Neem (Azadirachta indica)
Neem (Azadirachta indica)
Introduction
Neem (Azadirachta
indica) is an omnipotent and sacred gift of nature to
humankind. The wisdom of use of Neem as a medicinal plant dates back to the ancient Harappa
and Mohenjo-Daro civilizations in India. The medical practitioners of that
period studied the therapeutic value of Neem tree. The earliest indication of
Neem tree being employed for its medicinal properties as a household remedy
began nearly 5000 years ago. On the Indian sub-continent the earliest documentation
of use of the seeds, oil, bark, leaves and fruit of Neem (Azadirachta indica) for their medicinal properties dates back to more than 4500 years. In
the first millennium BC the Neem tree was called “Sarwa-Roga-Niwaaranee” (= one
that could cure all ailments). The ‘Upawanawinoda’ an ancient Sanskrit treaty
dealing with forestry and agriculture, describes Neem as a ‘cure’ for ailing
soils, plants and livestock. Neem has been widely used in Ayurveda and is also
extolled in earliest Indian scriptures of medicine- the Charaka Samhita (second
century AD) and Sushruta Samhita (fourth century AD).
[1], [2], [3], [4], [5]
The tree derives its name from the Sanskrit word
‘Nimba’ meaning a sprinkler, a short term for sprinkler of nectar (Ambrosia).
However the etymology of its generic name Azadirachta is nebulous. It is said
to be derived from the Persian words: azad
meaning free, drakhat meaning a tree.
When the specific word indica is
added the meaning of the botanical term becomes ‘A free tree from India’ which
does not convey any significance of the name. According to some scholars the epithet Azadarach itself means a poisonous plant. This
explains the meaning of generic name in a better way than the Persian version.
Unani scholars named it as ‘Shajar-e-Munarak’ (=the blesses tree) [6], [7], [8]
In Sanskrit Neem (Azadirachta indica) is also
called ‘Arishta’ (=perfect, complete, imperishable), Nimba (= to impart good
health), Pichumada (= destroyer of leprosy, healer of skin infections). [9], [10]
Synonyms in Sanskrit –Pichumarda,
Pichumanda, sarvatibhadra, Hinguniryasa, yavaneshta, Shukaprya, Neta, Subhadra,
Prabhadra, Sutikta [11]
The name Bead Tree comes from the use of the hard
nuts to make rosary beads. In the southern United States it was once believed
that if a horse ate the fruit of Neem, it would be protected against attacks of
'bots' (also botts = the larva of a botfly) [12]
In India Neem is used in households for giving bath
to newly born infants to protect them from skin diseases and people from insect
bites. It is also used to ‘cure’ many skin ailments. [13]
From teeth decay to
mouth ulcers, from pyrexias of unknown origin to malaria and from simple skin
rashes to fungal skin infections Neem ‘cures’ many ailments. Not only bed bugs or
agricultural insects, but Neem also kills many other pests. Hence the rural
Indians call Neem as their “Village Pharmacy”, “Village Drugstore”, “Village Dispensary”,
“Living Pharmacy” etc. [14], [15], [16],[17]
The Neem tree has
much to offer people in Africa’s drylands including food, medicine, timber and
shade.
In Kiswahiti language of eastern
Africa, Neem is known as ‘Mwarunaini’ meaning reliever of 40 human disorders.
[18], [19]
The Neem tree being
an incredible plant has been declared by the United Nations as the “Tree of the
21st century” [20]
In admiration of
this ‘plant wonder’ the US National Academy of Science published a report in
1992 titled “Neem: A tree for solving global problems”[21]
Since 1920, the
pioneering work on the possible commercial use of neem oil had been done by the
Indian Institute of Science, Bangalore, India. Researchers also began
investigating the active chemical ingredients responsible for the insecticide
and pesticide activity of Neem. Till now more than 140 active principles have
been isolated [22]
Neem is said to be non-toxic, though not really so, (see below) to humans
and each part of the tree is used as an active ingredient in different
industries. For long Neem had been used in households for giving bath to
infants, to protect people from insect bites, to cure skin ailments and also to
protect a number of plants as it contains a number of pesticides.
A number of researches have begun to unfold the powers and potential of
this revered tree. Their findings on international level vindicate the benefits
of Neem described in Ayurveda. Neem is being used on a commercial basis and
now, it finds immense use in a number of products in industries ranging from
cosmetics to agriculture and pharmaceuticals.
The
tree is now being cultivated and grown in a number of countries to fully tap
its potential and used on a commercial basis.
Other
Names
Latin/Botanical/
Taxonomical: Azadirachta indica
A.
Juss, Melia azadirachta
Sanskrit: Nimba and many more
English: Neem, Indian Lilac, Margosa Tree,
Crackjack, Paradise Tree, White Cedar, Chinaberry
Assamese: Neem
Bengali: Nim, Neem, Neemgachh
Gujarati: Limba, Limbado, Leemgo, Danu-jhada,
Nimuri
Hindi: Nim, Neem, Bal-nimb, Nind
Kannada: Bevinamara bevu, Hebbevu, Kiri-bevu, Nimb
Konkani: Nim
Malayalam: Aryaveppu, Veppu, Aryaveshnu, Rajavedhu,
Vepe
Marathi: Kadu Nimba, Kadukhajur, Limba,
Balanti-limb, Bal-nimb
Oriya: Kakopholo, Limbo, Nimbu, Nimo
Punjabi: Bakam Bukhain Drekh, Nim, Neem, Mahaneem
Rajasthani: Neem, Neemro
Tamil: Aruhundi, Kaduppagi, Kaingi, Vembu, Veppam, Nimbamu,
Nim-Banu
Telugu: Nimbanuv, Vepa, Yeppa, Yapa, Vemu [23], [24]
Taxonomic Classification
Kingdom: Plantae
(Unranked): Angiosperms
(Unranked): Eudicots
(Unranked): Rosids
Division: Magnoliophyta
Order: Sapindales
Family: N.O. Meliaceae [25], [26]
Geographical Distribution
Neem (Azadirachta indica) is native to India and the Indian
subcontinent including Nepal, Pakistan, Bangladesh and Sri Lanka. It is grown
in tropical and semi-tropical regions. Now it is grown in islands located in
southern part of Iran. [27]
Neem
has ‘poly-climax’ distribution in nature. In other words it can grow in more
than one habitat i. e. sandy plains habitat, gravel formations, hilly habitat
and aquatic habitat. [28]
Neem is a hardy tree which is resistant to draught. It can
tolerate saline, alkaline as well as slightly acidic soils. It does not grow in
naturally forested areas but grows in areas where there is man-nature
interaction. It is now found globally.
It is one of the very few shade giving
evergreen trees that thrive in drought prone areas. It can grow in regions with
an annual rainfall below 400 mm, but in such cases it depends largely on the
ground water levels. Neem can grow in many different types of soil but it
thrives best on well drained deep and sandy soils.
The oak like deciduous tree from 30 to 50 feet in
height is widely distributed throughout the subtropics. It is believed to be
native to China, but most definitely native to southwest Asia. It is also found
growing in southern France and Spain in avenues. It is widely cultivated and
naturalized in the West Indies and southern United States as a crop tree. In
parts of Africa it is grown in hedges for easier harvesting. [29], [30], [31]
Plant Morphology
[These images
show “poly-climax” distribution of Neem (Azadirachta indica) Hence it is
regarded as sacred gift of nature to humankind]
Neem is a
fast-growing tree that can reach a height of 15-20 meters (49-66
feet), rarely 35-40 meters (115-131 feet). It is evergreen but in severe
draught may shed nearly all of its leaves. Its dense crown is roundish and may
reach a diameter of 15-20 meters (49-66 feet). The Neem tree is very similar in
appearance to its relative, the Chinaberry (Melia azedarach)
[Roots of Neem ((Azadirachta
indica) show that the plant can thrive in any habitat]
The Root is a strong taproot with well developed lateral roots having bitter taste and
an unpleasant odor.
Root bark is available as quilled or
curved pieces of varying sizes with a thickness of 0.25 to 0.50 cm; outer
surface irregular, rough, scaly, fissured, reddish brown or grayish-brown;
inner surface, yellowish brown with parallel striations; fracture, splintery
and fibrous; odour like that of saw dust; taste, bitter
The Trunk is short, straight and may reach
a diameter of 1. 2m with spreading
branches.
The Bark has a rusty
grey color. Inside it is yellow, foliated, coarsely fibrous, hard,
fissured. Inside it is
yellow, foliated and coarsely fibrous.
The Branches are covered with furrowed bark, rusty-gray in
appearance, wide and spreading.
[Very young and mature
leaves of Neem ((Azadirachta indica)]
The Leaves alternate, opposite, pinnate, from 15 to 25 cm long with 20-30 medium to dark green,
pointed, sharply serrate or
lobed leaflets about 7 to 8.5 cm long,
ranging in shape from ovate and elliptic to lanceolate. The terminal leaflet
is often missing. The petioles are
short. Very young leaves are reddish to purplish in colour.
[Flowers of white and
lilac variety of Neem (Azadirachta indica)]
The Flowers white, fragrant, lilac-colored arranged in
more or less axillary panicles. The Inflorescences, which branch up to the third
degree, bear 150-250 flowers. An individual flower is about 5-6 mm long and
8-11 mm wide. Protandrous bisexual flowers
i. e. male flowers come to maturity before female flowers and bloom in
early spring; calyx has 5 parts, corolla has 5 petals, stamens are a deep
violet in color, the anthers yellow.
More information:
Dried flowers are brown to deep brown,
individual flower 5to 6 mm long and 6 to 11 mm wide, pentamarous, bisexual,
regular and hypogynous; Calyx 5, short, united at base; Corolla 5, free,
spatulate, spreading, 4.5 to 5.5 mm long, and 2 mm wide; Stamens 10,
monoadelphous, staminal tube inserted at base of corolla, Gynoecium
tricarpellary,
syncarpous, superior, trilocular, two ovules in each locule, Style one, Stigma 3 lobed; taste
mildly bitter, odour indistinct
[Raw, Ripe fruits of white and lilac variety and Nimbuli of Neem
((Azadirachta indica)]
The Fruit is a glabrous olive-like drupe ( having bony
nut) varying in shape from elongate oval to roundish, 1/2 to 3/4 inch
by 0.3-0.5 inch with 5 cells, indehiscent, deeply wrinkled, enclosing a single
seed in a brownish leathery pulp, odour strong and somewhat sweet or
bitter-sweet to taste. The exocarp (the fruit skin) is thin; the mesocarp
(pulp) yellowish white and very fibrous, 0.12-0.20 inch thick; the endocarp
(inner shell) white, hard, encloses the seed.
Seeds of Neem (Azadirachta
indica)
The Seed usually one but
rarely two or three, convex dorsally, up to 1.5 cm long and 0.6 cm wide; brownish,
seed-coat thin, brownish, shell like, cracks to touch, inside of cracked pieces
golden yellow; seed kernel light brown, oily; odour strong, taste bitter [32],
[33], [34]
Microscopic
Structure
Root:
Root
bark shows cork, cortex and phloem; cork generally 6-7 layers of polygonal and
thin-walled cells with reddish-brown contents; outer cortex of tangentially
elongated large rectangular cells with tangentially elongated sclereids; singly
or in groups in isolated patches; sclereids vary in size and wall thickness,
distinctly striated, pitted and often associated with cells containing crystal;
inner cortex of polygonal parenchymatous cells with bundles of sclerenchymatous
fibres, thick walled with irregular lumen; secondary phloem composed of
alternating tangential bands of bast fibers and parenchymatous tissues intercepted
by uni or biseriate phloem rays; abundant starch grains present in
parenchymatous cells of cortex and phloem; starch grains simple, or more usually,
compound with 2 or 3 components; hilum cleft or radiate, each grain 5 to 20µ in
diameter; abundant prismatic calcium oxalate crystals in cortex of 10 to 15 µ
in diameter also associated with phloem fibres; idioblasts with reddish brown
contents seen in cortex cells with fat droplets seen in inner cortex and phloem
[35]
Powder
of Root bark:
Reddish-brown,
shows cork cells; numerous prismatic crystals of calcium oxalate both isolated
and in association with phloem fibres; individual fibres with narrow lumen and
elongated tapering ends; pitted macrosclereids with wide lumen and distinct
striations; simple and compound starch grains with 2 or 3 components of 5 to 20
µ in diameter in size; parenchymatous cells large and occasionally filled with
brown contents. [36]
Stem
Bark:
Stem
bark shows outer exfoliating pieces hard, woody considerably thick in older
trunks; almost entirely dead elements of secondary phloem, alternating with
discontinuous tangential bands of compressed cork tissue, former composed of
several layers of stone cells occurring in regularly arranged groups together
with collapsed phloem elements filled with brown contents; in between the
successive zones of cork tissue 3-5 layers of fiber groups with intervening
thin-walled and often collapsed phloem elements present; each zone of cork
tissue consists of several layers of regular thin-walled cells occasionally
with a few compressed rows of thick-walled cells towards outer surface; within
exfoliating portion a number of layers of newly formed cork composed of
thin-walled rectangular cells and one or two layers of cork cambium, below
which a wide zone of secondary phloem present; secondary cortex absent in most
cases; secondary phloem commonly composed of well-developed fibre bundles traversed
by 2-4 seriate phloem rays and transversely separated by bands of
parenchymatous tissue of phloem; phloem element of outer bark mostly collapsed;
a few fairly large secretory cavities also occur in phloem; most of phloem
parenchyma contain starch grains and prismatic crystals of calcium oxalate;
starch grains simple, round with central hilum, measuring 2.75-5µ; structure of
bark varies considerably according to gradual formation of cork bands.
Powder
of Stem Bark: Reddish-brown; shows
numerous prismatic calcium oxalate crystals, phloem fibres with narrow lumen
and pointed ends; cork cells, stone cells mostly in groups, lignified
rectangular to polygonal having wide lumen and distinct striations, simple
starch grains, measuring 2.75-5µ in diameter. [37]
Leaf:
Midrib- leaflet through midrib shows a biconvex
outline; epidermis on either side present; stele composed of one
crescent-shaped vascular bundle towards lower and two to three smaller bundles
towards upper surface; rest of tissues composed of thin-walled, parenchymatous
cells having secretory cells and rosette crystals of calcium oxalate; phloem
surrounded by non-lignified fibre strand; crystals also present in phloem
region.
Lamina- shows dorsi-ventral structure; epidermis on
either surface, composed of thin-walled, tangentially elongated cells, covered
externally with thick cuticle; anomocytic stomata present on lower surface
only; palisade single layered; spongy parenchyma composed of 5-6 layered,
thin-walled cells, traversed by a number of veins; rosette of calcium oxalate
crystals present in a few cells; palisade ratio 3.0-4.5; stomal index13.0-14.5
on lower surface and 8.0-11.5 on upper surface
Powder
of leaf: green; shows vessels,
fibres, rosette crystals of calcium oxalate, fragments of spongy and palisade
parenchyma. [38]
Flower:
Calyx: Sepal
shows thin-walled polygonal papillose epidermis; elongated thin-walled
unicellular conical trichomes of varying lengths; rosette crystals in cells of
epidermis
Petals: Petals
shows epidermis of rectangular cells papillose at margin, non-glandular
unicellular trichomes, over 150µ long, tubular and hyaline; glandular trichomes
of about 20µ numerous rosette crystals in epidermal cells
Androecium: Epidermis
of stamina tube composed of thick-walled rectangular parenchymatous cells and
the endothecium of the anther walls
Gynoecium: Stigma
sticky, parenchymatous epidermal cells, elongated into extensive papillae,
style thin-walled, rectangular, ovary superior, trilocular
Pollen Grain: Porous,
4-colporate, spherical 105 to 161 µ in diameter with a smooth exine
Powder of Flower: Yellowish brown, fragments of parenchymatous papillose epidermal cells,
trichomes, numerous vessels, rosette calcium oxalate crystals, and yellowish
brown pollen grains
Fruit:
Pericarp well-differentiated into epicarp, mesocarp
and endocarp; epidermis more than one layered; squarish to rectangular cells
containing yellowish brown contents and oil droplets; mesocarp many layered of
loosely packed cells with large elongated sclereids scattered in outer layers;
endocarp of 2 distinct layers, outer of closely packed lignified stone-cells, inner
fibrous, loosely packed, lignified
Seed:
Seed kernel shows a thin brown testa of isodiametric
stone cells overlying integument of loosely packed parenchymatous cells;
cotyledon consisting of parenchymatos cells containing abundant oil droplets
Powder of Neem Seeds:
Dark brown; shows abundant brachysclereids, columnar
sclereids and pitted stone cells with wide lumen and distinct wall striations;
groups of lignified fibres, thin-walled, arranged in network of loose strands;
parenchymatous cells of cotyledon containing aleurone grains and oil globules;
fragments of testa showing distinctly striated isodiametric stone cells; a few
scattered rosette crystals of calcium oxalate [39]
Parts
Used
All parts of the tree (seeds, leaves,
flowers and bark) are used for preparing many different medical preparations.
Phytochemistry
Till today more than 140 compounds have
been isolated from different parts of Neem. Detailed discussion of each one is
out of scope of this work. Only important ones will be discussed here. [40]
Chemical
constituents
Moisture
|
59.4%
|
Proteins
|
7.1%
|
Fats
|
1.0%
|
Carbohydrates
|
22.9%
|
Fiber
|
6.2%
|
Calcium
|
510mg/100g
|
Phosphorus
|
80mg/100g
|
Iron
|
17mg/100g
|
Thiamine
|
0.04mg/100g
|
Niacin
|
1.40mg/100g
|
Vitamin C
|
218mg/100g
|
Carotene
|
1998microgram/100g
|
Glutamic acid
|
73mg/100g
|
Tyrosine
|
31.50mg/100g
|
Aspartic acid
|
15.50mg/100g
|
Alanine
|
6.40mg/100g
|
Proline
|
4.00mg/100g
|
Glutamine
|
1.00mg/100g
|
[41]
Classification
of chemical constituents
Terpenoids
|
A. Protolimonnoids
B. Limonoids
Subgroup:
(1) Azadirachtin (2) Salannin (3) Nimbin
(4) Nimbolinin
(5) Gedunin (6) Azadirone (7)
Amoorastatin (8) Vepinin
(9) Vilasinin
C. Pentatriterpenoids
D. Hexatriterpenoids
|
Neem oil fatty acids
|
Omega-3: Alpha-linoleinic acid?
Omega- 6: Linoleic acid 6-16%
Omega-9: Oleic acid 25-54%
Palmitic acid: Hexadecanoic acid 16-33%
Stearic acid: Octadecanoic acid 9-24%
Palmitoleic acid: 9-Hexadecenoic acid ?
|
Sterols
|
Campesterol
β-sitosterol
Stigmasterol
Fucosterol
|
Bitter principles
|
|
Tannins
|
|
Flavonoids
|
|
Sesquiterpene
|
[42], [43], [44]
Chemical Constituents of various
parts of the plant
(Based on zero moisture per 100
grams)
Seed
|
Protein 28.7g, fat 44.0g (oleic
acid, palmitic acid, linoleic acid, stearic acid and margosa) and two new
triterpenoids: azadiractin H and azadirachtin I, nimbin, nimbidin, nimbolide,
gedunin, mahmoodin, sodium nimbidate
|
Leaves/Leaf extract
|
Paraisine, isomeldenin, nimbin,
nimbinene, 6-desacetylnimbene,
nimbandiol, nimocinol, quercetin,
beta-sitosterol, tannin and two tetracyclic triterpenoids
|
Fruits
|
Azadirine, azadirachtin and resin
|
Bark
|
Margosine, margolone, margolonone,
isimargolonone, gallic acid, catechin, epicatechin, polysaccharides G1 A-
G1B, polysaccharides G2A, G2 B, NB-2-peptidoglucan
|
Cortex
|
Vanillic acid and dl-catrchol
|
Pericarp
|
Bakayanin and bakayanic acid
|
Fruit oil
|
Glycerides of
palmitic-oleic-linoleic and stearic acid.
Does NOT contain
linolenic-chaulmoogric or hydnocarpic acids
|
Tree (all parts)
|
Azadirachtin
|
[45], [46], [47], [48], [49], [50]
Properties of
the chemicals
Azadirachtin
|
Insect repellant, anti-fedent,
anti-hormonal, antimalarial
|
Nimbin
|
Anti-inflammatory, anti-histaminic,
anti-pyretic, anti-bacterial and antifungal, spermicidal
|
Nimbidin
|
Anti-inflammatory, analgesic, anti-bacterial,
anti-fungal, anti-arthritic, anti-arrhythmic, anti-ulcer, hypoglycemic,
spermicidal
|
Nimbolide
|
Anti-pyretic, antibacterial,
anti-tubercular, antimalarial, anti-protozoal
|
Sodium nimbinate
|
Anti-inflammatory, Anti-arthritic,
diuretic and spermicidal
|
Gedunin
|
Anti-fungal, anti-malarial and
vasodilator
|
Salannin
|
Insect repellant
|
Quercetin
|
Anti-inflammatory, anti-oxidant,
anti-bacterial and anti-
Protozoal
|
Mahmoodin
|
Antibacterial
|
Gallic acid, Catechin and Epicatechin
|
Anti-inflammatory, immunomodulatory
|
Margolone, Margolonone and
Isomargolonone
|
Anti-bacterial
|
Cyclic trisulphide and Cyclic
tetrasulphide
|
Anti-fungal
|
Polysaccharides
|
Anti-inflammatory
|
Polysaccharides G1A, G1B
|
Anti-tumor
|
Plysaccharides G2 A
G3 A
|
Anti-inflammatory
|
NB-2 peptidoglucan
|
Immunomodulatory
|
Nimbidol
|
Anti-pyretic, anti-tubercular, anti-protozoan
|
[51], [52], [53], [54], [55], [56]
Identity, Purity and Strength (of root-bark extract):
Foreign matter: Not more than 2%
Total Ash: Not more than
15%
Acid-insoluble ash: Not more than 3%
Alcohol soluble extractive: Not less than 6%
Water-soluble extractive: Not less than 7%
[57]
T. L. C. of Root-bark
TLC of the alcoholic extract on pre-coated silica gel
‘G’ plate (0.2 thick) using hexane: ethylacetate (1:1) shows spots at Rf 0.08,
0.12, 0.19 (all violet), 0.25 (mustard yellow), 0.33, 0.39, 0.46 (all light
violet) and 0.82 (purple) on spraying with 1 % Vanillin-sulphuric acid reagent
followed by heating the plate at 1050 C for about ten minutes.
Identity,
Purity and Strength (of stem-bark extract):
Foreign
matter Not more than 2%
Total
Ash
Not more than 7%
Acid-insoluble
ash Not more than 1.5%
Alcohlo-soluble
extractive Not less than 6%
Water-soluble
extractive Not less than 5%
T.
L. C. of Stem Bark
T.
L. C. of the alcoholic extract of the drug on Silica gel ‘G’ using Chloroform:
Ethyl acetate; Formic acid (5:4: I:) shows UV (366nm) three fluorescent zones
at Rf. 0.72 (blue), 0.86 (blue) and 0.90 (green). On spraying with 5%
Methanolic phosphomolybdic acid reagent and heating the plate for about 10
minutes at 1050 C four spots appear at Rf. 0.20, 0.45, 0.63 and 0.90
9all blue) [58]
Identity,
Purity and Strength (of leaf extract):
Foreign
matter: Not more than 2%
Total
Ash: Not more than 10%
Acid-insoluble
Ash: Not more than 1%
Alcohol-soluble
extractive: Not less than
13%
Water-soluble
extractive: Not less than 19 % [59]
Identity,
Purity and Strength (of flower extract):
Foreign
matter: Not more than 2%
Total
Ash: Not more than 14%
Acid-insoluble
Ash: Not more than 5%
Alcohol-soluble
extractive: Not less than 5%
Water-soluble
extractive: Not less than 12 % [60]
T.
L. C.
TLC
of the alcoholic extract on pre-coated silica gel ‘G’ plate (0.2 mm thick)
using chloroform: octane (20: 1) shows spots at Rf 0.12 (violet), 0.17 (light
pink), 0.33 (violet), 0.5 (purple), 0.64 (dark purple) 0.80 (light purple),
0.85 (light purple), 0.92 (purple) on spraying with 1 % Vanillin-Suphuric acid
reagent followed by heating the plate at 1050 C for about fifteen
minutes [61]
Identity,
Purity and Strength (of fruit extract):
Foreign
matter: Not more than 2%
Total
Ash: Not more than 8 %
Acid-insoluble
Ash: Not more than 20 %
Alcohol-soluble
extractive: Not less than
16 %
Water-soluble
extractive: Not less than 19 % [62]
T.
L. C.
T.
L. C. of the alcoholic extract on pre-coated silica gel ‘G’ plate (0.2 mm
thick) using chloroform: acetone (18. 5: 1.5) shows spots at Rf 0.11 (grayish
violet), 0.16 (yellow), 0.19 (green),
0.24 (violet), 0.29 (grey), 0.33 (mustard yellow), 0.42 (pink), 0. 49 (grayish
black), 0.57 (violet) and 0.76 (light purple) on spraying with 1%
Vanillin-Sylphuric acid reagent and heating the plate at 1050 C for
about ten minutes [63]
Cytological
Identity
13
chromosome count in Azadirachta indica A. Juss [64]
Genetic study
Genus Azadirachta belongs to family
Meliaceae which includes 600 species. To avoid confusion regarding
identification and prevent adulteration when used for medicinal purpose,
scientists have established DNA fingerprinting of the plant. [65]
By using RAPD molecular markers R. S. Dhillon et al
established the accurate genetic identity of Neem (Azadirachta indica)
[66]
Safety
Tests
No
safety data for each specific species of herb is available. Here are general guidelines:
Heavy
Metals:
Arsenic: Not
more than 5.0 mg/kg
Mercury: Not
more than 0.5mg/kg
Lead: Not
more than 10.0 mg/kg
Chromium: Not
more than 0.3 mg/kg
Microbial
Limits:
Total
bacterial count: Not more than 105cfu/g
Total
yeast and mould count:
Not more than 104cfu/g
Bile
tolerant gram negative bacteria:
Not more than 104cfu/g
Specific
Pathogens:
Salmonella
spp: Absent in 25 g
Escherichia
coli: Absent
in 1g
Staphylococcus
aureus: Absent
in 1g
Pseudomonas
aeruginosa: Absent
in 1g [67]
Properties
and Pharmacology
Ayurvedic
Properties
Ganas
(Classical categories)
Charaka Samhita:
Kandughna: Antipruritic group
Tiktaskandha:
Bitters
Sushrut
Samhita:
Aaragwadhaadi, Guduchyaadi
and Laakshaadi group
Energetics:
Rasa (Taste): Tikta (Bitter), Kashaya (Astringent)
Weerya (Potency): Sheeta (Cold in nature)
Wipaaka: Katu
Gunas: (Qualities and properties)
Sheeta: Has cooling effect
Laghu: Easy to digest
Graahee: Herbs that help solidify the stool, increase the
appetite and improve the digestion and improve the absorption of fluids.
Katu: Acrid, pungent
Tikta: Bitter
Agnikrut: Appetizer, improves digestion
Waatakrut: Increases waat-flatulence
Ahrudya: Not benevolent for heart
Shramapranut (Shramhara): Relieves fatigue
Trut-nut (Trusha-hara): Quenches thirst
Kaasa-nut (Kaasahara): Antitussive, relieves cough
Jwara-nut (Jwarahara): Antipyretic (? Diaphoretic)
Aruchi-nut (Aruchihara): Relieves dyspepsia, loss of appetite
Krumi-prnut (Krumihara): Anthelmintic
Wrnahara: Heals wound quickly
Pittahara: Relieves hyperacidity, allergies
Kaphahara: Reduces phlegm, reduces expectoration
Chhardi-hrullasa-nut (Chhardi-hrullasa-hara): Anti-emetic, relieves retching, relieves
gastro-esophageal-reflux
Mehanut (Mehahara): Useful in diabetes and increased frequency of urination
Kushthahara: Antileprotic and useful in skin diseases [68], [69],
[70]
Properties of Neem root:
While most of the properties of root are similar to
those mentioned above, only those showing some special and different properties
are mentioned here—
Kanduhara: Antipruritic
Graahee: see above
Sheeta: Has cooling effect
Ahrudya: see above
Kaphahara: Relieves phlegm, expectotation
Pittahara: Anti-histaminic, relieves hyperacidity
Ruchya: see above
Deepana: Appetizer
Wishghna: Antidotes poisons
Wranashodhana: Relieves wound infections, reduces wound
discharges etc. [71]
Properties of Neem stem-bark:
While most of the properties of stem-bark are similar
to those mentioned above, only those showing some special and different
properties are mentioned here—
Kandughna: Antipruritic
Kaphahara: See above
Pittahara: See above
Wishghna: See above
Wranashodhanakara: See above
Hrudaya-widaaha-shantikara: Relieves heart-burn [72].
Properties of Neem leaf:
While most of the properties of leaf are similar to
those mentioned above, only those showing some special and different properties
are mentioned here—
Nertya: Beneficial to eyes
Krumi-nut (Krumihara): Anthelmintic
Pittanut (Pittahara): Relieves hyperacidity, allergies
Wishnut (Wishahara): Antidotes poisons
Waatala: Increases waata, induces flatulence
Arochakanut: Relieves dyspepsia, improves appetite
Kushthnut (Kushthahara)): Antileprotic, useful in skin diseases [73], [74], [75]
Properties of Neem flower:
While most of the properties of neem flower are
similar to those mentioned above, only those showing some special and different
properties are mentioned here—
Chakshushya: Useful
in ophthalmic disorders
Krumighna:
Anthelmintic
Kaphahara:
See above
Pittahara: See
above
Waatakara: May
be harmful to nervous system
Wishghna: See
above
Kushthghna: See
above
Graahee: See
above [76]
Properties of Neem fruit:
While most of the properties of neem fruit are similar
to those mentioned above, only those showing some special and different
properties are mentioned here—
Tikta Rasa: Bitter
in taste
Bhedana: Relieves
constipation, laxative, softens stool
Snigdh: Unctous
(Oily, greasy)
Laghu: Easy
to digest, light to digest
Ushna: Hot
in potency
Kushthghna: Antileprotic,
useful for skin diseases
Gulmanut:
Exhibits antitumor properties
Arshnut (Arsha-hara, Arshaari): Relieves fissures and piles (hemorrhoids)
Kruminut (Krumihara, Kruminaashaka): Anthelmintic
Mehanut (Mehahara): Antidiabetic, relieves increased frequency of micturition
[77], [78], [79]
Sushrut Samhitaa:
Raktapittanut: Relieves
bleeding disorders
Shothahara: Anti-inflammatory,
relieves edema
Netrya: Twigs
and flowers are useful in ophthalmic disorders
Effects on Doshas: Kapha and Pitta
Effects on Dhatus: Predominantly Rakta (Blood and hematopoetic system)
Effects on Srotas: Rasawaha (Lymphatic), Raktawaha (Blood), Praanawaha
(Respiratory system), Annawaha (Digestive system) [80]
Modern view
Azadirachtin
Molecular formula: C35H44O16
Structural formula:
Azadirachtin belongs to the limonoid group
of chemical compounds. It is a secondary metabolite present in the seeds, bark
and leaves of Neem tree.
Azadirachtin fulfils many of the criteria
of a good insecticide. In addition it has anti-bacterial, anti-viral and
anti-fungal properties. [81]
Nimbolide
Molecular formula: C27H37O7
Structural formula:
Structural formula:
[82], [83], [84]
Nimbolide is a terpenoid lactone derived from leaves
and flowers of Neem tree. It displays a
vatiety of biological activities. Of these proapoptotic and anticancer
activities have attracted the attention of research scholars
Nimbolide exhibits anticancer activity via selective
modulation of multiple cell signaling pathways linked to inflammation,
survival, growth, invasion, angiogenesis and metastasis.
In cancer cells Nimbolide induces apoptosis through
reactive oxygen species, downregulation of cell survival proteins and
upregulation of pro-apoptotic proteins. [85], [86], [87]
Nimbolide,
a natural triterpenoid isolated from the leaves and flowers of Neem inhibits
the cell proliferation and development of metastasis of cancer cells by
inducing apoptosis and cell cycle arrest. [88]
Salannin
Molecular formula: C34H44O9
Structural formula:
[89], [90]
[89], [90]
Azadirachta, salannin, nimbin and 6-desacetylninbin
inhibit E-20-M activity in insects. Thus they exhibit insecticidal activity
[91]
Nimbin
Molecular formula: C30H36O9
Structural formula:
Nimbin is a triterpenoid isolated from Neem. It is
responsible for much of the biological activities of neem oil. It is
anti-inflammatory, anti-pyretic, anti-histaminic, antiseptic and fungicidal.
[92]
Nimbin in a dose dependent manner arrests
the growth of mosquito larve thus preventing the spread of vector borne
diseases. [93]
Nimbolinin
Molecular formula: C35H46O10
Structural formula:
Nimbolinin D [94]
Nimbolinin A [95]
Nimbolinin C
[96]
Nimbolinin B [97]
Nimbolinin compounds are anti-inflammatory.
They also prevent neurodegenerative disorders such as Parkinsonism and
Alzheimer’s disease. [98]
Gedunin
Molecular formula: C28H34O7
Structural formula:
Hps90
(heat shock protein 90) stabilizes a number of proteins required for tumor
growth. That is why Hsp90 inhibitors are investigated as anti-cancer drugs.
[99]
Gedunin is a naturally occurring Hsp90 inhibitor found
in neem [100], [101], [102], [103]
Recently gedunin was investigated for its
anticancer potential against ovarian cancer. Its effect was evaluated on SKOV3,
OVCAR4 and OVCAR8 ovarian cancer cell lines proliferation, alone and in
presence of cisplatin. The study showed that gedunin alone produced up to 80%
decrease in cell proliferation and
combining gedunin with cisplatin up to 47%
decrease in cell proliferation compared with treatment by cisplatin alone. The
molecular mechanism of anticancer activity of gedunin is complex and may
involve modulation of cell survival and apoptosis pathways. [104]
P23 is simple protein having complex function. It is a
part of Hps90.
Gedunin directly binds to p23, inhibits its activity,
blocks its cellular interaction with Hsp90 and interferes with p23 mediated
gene regulation. That is how gedunin leads to the death of cancer cells. [105],
[106]
Azadirone
Molecular formula: C28H36
Structural formula:
[107]
Azadirone, a limonoid tetranortriterpene,
sensitizes human cancer cells to tumor necrosis factor-related
apoptosis-inducing ligand through a p53 protein independent mechanism and
inhibits tumor growth [108]
Amoorastatin
Molecular formula: C28H36O10
Structural formula:
[109]
Amoorastatin has anti-neoplastic
properties. [110]
Vepinin
Molecular formula: C28H36O5
Structural formula:
[111]
As of today there is no authentic information about
pharmacology of Vepinin
Vilasinin
Molecular formula: C39H46O9
Structural formula:
[112]
Vilasinin is found in the
seed extract of Neem. It has antifeedant activity towards Epilachna
varivastis (Mexican bean beetle).
(Antifeedant= a chemical agent that causes a pest to stop eating.) [113]
Pharmacology
at a glance
Anti-inflammatory
|
Nimbidin, sodium
ninbidate, gallic acid, catechin, polysachharides
|
Anti-oxidant
|
Extract of Neem seed
|
Immunomodulatory
|
NB-II peptoglycan, gallic
acid, epicatechin and catechin
|
Anti-pyretic,
Anti-arthritic
|
Nimbidin
|
Antimicrobial
|
Nimbidin, nimbolide, mahmoodin, margolone,
isomargolonone
|
Antifungal
|
Nimbidin, gedunin, cyclic trisulfide
|
Anthelmintic
|
Vanellic acid
|
Anti-malarial
|
Nimbolidfe, gedunin, azadirachtin, bakayanin and bakayanic acid.
|
Larvicidal on malarial
vector
|
Neem oil formulations
|
Anti-peptic ulcer
|
Nimbidin
|
Regenerative effect on the
mucosa of the stomach and the ileum
|
Aqueous extract of the plant
|
Hepatoprotective
|
Aequeous extract of Neem leaf
|
Hypoglycemic
|
Nimbidin
|
Diuretic
|
Nimbidin
|
Spermicidal
|
Nimbin, nimbidin
|
Anti-cancer
|
Polysaccharides
|
[114]
Some testimonials from modern research
Anti-inflammatiry
activity:
Neem was in vogue for the treatment of
rheumatoid arthritis and osteoarthritis.
There are several chemical compounds of
Neem having a proven anti-inflammatory activity that antagonize histamine and
other mediators of inflammation in the body. The important chemicals that
contribute to this effect are nimbidin, limonoids, and catechin. Warmed Neem oil is also recommended
for external use to reduce pain and inflammation in affected joints.
The chloroform extract of stem bark of Neem is
effective against carrageenin-induced paw edema in rats. The bark extract of
Neem cures inflammatory stomatitis in children. [115], [116], [117]
Neem
oil has been reported to exhibit anti-inflammatory and antipyretic activity.
[118]
The
methanol extract of Neem leaves exerts anti-inflammatory and antipyretic action
in rabbits [119]
Neem
exhibits analgesic activity. It is mediated through opiod receptors in
laboratory animals [120]
The
major active principle of Neem seed oil is nimbidin. It is a mixture of tetranortriterpenes.
It possesses a potent anti-inflammatory activity. In an experimental study on
rats, oral administration of 5 to 25 mg/kg body weight of nimbidin for 3
consecutive days inhibited inflammatory activity. Nimbidin inhibited nitric
oxide (NO) and prostaglandin E2 production in lipopolysaccharide stimulated macrophages,
where as interleukin-1 was weakly inhibited. Investigating the mechanism of NO
inhibition revealed that nimbidin ameliorated the induction of inducible NO
synthase without inhibition in its catalytic activity. Nimbidin also attenuated
degranulation in neutrophils. Thus nimbidin can be valuable in treating
inflammatory diseases. [121]
Antioxidant activity
On the basis of free radical scavenging activity the
extracts of leaf and bark of Neem were shown by Ghimeray et al in 2009 to possess
anti-oxidant activity. [122], [123]
In an experimental study the antioxidant activity of
neem seed has been demonstrated. An antioxidant principle, a potent inhibitor
of plant lipooxigenase has also been isolated [124]
Immunomodulatory activity
The aqueous extract of Neem bark possesses
immunostimulant effect.
The aqueous extract of Neem stem bark enhances the
immune response of Balb-c mice to sheep red blood cells in vivo.
Humoral and cell mediated response shows that the
aqueous extract of Neem leaf has potent immunostimulatory activity.
Via cell mediated mechanism Neem oil shows potent
immunostimulatory activity. [125]
Antibacterial activity
Neem stick extract even at concentration as low as
5% shows antibacterial activity against Streptococcus mutan, Streptococcus
salivavius, Streptococcus mitis, and
Streptococcus sanguis [126]
Neem leaf extract is effective against E.
faecalis, Staphylococcus aureus, Streptococcus mutans and Candida albicans.
[127], [128]
Extracts of various parts of neem exert bactericidal
effect on Staphylococcus aureus, Escherichia coli, Pseudomonas aerugenosa
and fungicidal effect on Candida albicans [129]
A
wide range of antibacterial agents present in neem leaves, bark and seed show
antibacterial actions against Gram-positive, Gram-negative microorganisms
including streptomycin resistant strains of Micobacterium tuberculosis. In
vitro studies show that neem inhibits Vibrio cholera, Klebsiella
pneumonia, Micobacterium tuberculosis. [130]
Antiviral activity
The extract of neem seed kernel was found to be
effective against duck plaque virus (DPV) infecting ducks. The extract
increased the cell viability by reducing cytopathic effects caused by DPV and
the amount of protein expressed in virus-infected cells. [131]
In another study neem bark extract significantly
blocked Herpes simplex virus type-1 from entering cells at concentrations
ranging from 50 to 100µg/ml. When the extract was directly incubated with
virus, the activity of virus was blocked. This suggests that neem extract has
anti-HSV-1 property. Further virions treated with neem bark extract failed to
bind the cells. This highlights the cell-attachment-blocking activity of neem
bark extract. Cells treated with neem bark extract also inhibited HSV-1 glycoprotein
mediated cell to cell fusion and polykaryocytes formation. This suggests that
neem bark extract blocks viral fusion. These findings are important for the
development of anti-herpetic microbicide from neem. [132]
Methanolic extract of leaves of neem was found to be
useful against Coxsackie B group of viruses. It exhibits virucidal activity at
concentration 1000µg/ml. The virucidal action is complete in 96 hours. The
antiviral activity of neem is attributed to flavonoids, triterpenoids and
Neuronal ceroid lipofuscinoses (NCL) present in the plant.
Recently an in vitro
study shows that aqueous extract of neem leaves exhibits antiviral activity
against Vaccinia, Chikungunia and measles viruses. [135], [136]
Norterpenoid compounds isolated from the seeds of
Neem inhibit the Epstein-Baar virus antigen activation induced by Tissue
Plasminogen Activator (TPA) [137]
Antifungal activity
Various studies were conducted with water
extract/methanol extract/ethanol extract/ethyl acetate extract of neem leaf, neem
seeds and neem seed oil. The extracts were found to exhibit antifungal/ fungicidal
activity against Tricophyton rubrum, Tricophyton mentagragrophytes,
Tricophyton violaceaum, Microsporum nanum, Epidermophyton floccosum,
Aspergillus flavus, Aspergillus fumigantus, Aspergillus niger, Aspergillus
terreus, Candida albicans, Microsporum gypseum, Microsporum nanum and
Microsporum canis. The main component responsible for this activity was
said to be nimonol. [138], [139], [140], [141], [142]
Antiparasitic activity
The
alcoholic extract of neem leaf and seed is effective against both chloroquin
resistant and sensitive strains of malarial parasites. Neem seed extract and
its purified fractions inhibit the growth and development of asexual and sexual
stages of Plasmodium falciparum. [143]
Chloroform, diethyl ether, methanol and ethanol
extracts of neem leaves show antifilarial and anthelmintic activity. All the
solvents show significant anthelmintic activity at the concentration of 200 µg/
ml after 135 minutes of incubation. Highest mortality rate of microfilariae was
observed in methanol and ethanol extracts. [144]
To evaluate the utility of Neem leaves as
anthelmintic, experimental studies were arranged in the Department of Animal
Nutrition, Madras Veterinery College, Tamilnadu, India during 2006. The studies
revealed that Neem leaves are anthelmintic. The anthelmintic activity was
attributed to azadirachtin [145]
Actions
on the Skin
Neem leaves have antiseptic, anti-bacterial,
anti-viral, anti-fungal and anti- head lice properties. These properties are
useful for the treatment of pimples, non- specific skin inflammations, fungal
skin infections, dandruff, lice infestation and hair fall. Neem sooths the oily
skin without drying the skin. [146]
These activities of Neem are attributed to various
anti-oxidants present in it. Neem imparts the skin a youthful glow. [147]
Herbalists and naturalists recommend Neem leaf tea
orally and application of Neem oil locally for the treatment of eczema and
psoriasis.
Anti-inflammatory, antiseptic and anti-oxidant
properties of Neem are said to be useful in this regard.
However there is no internationally accepted
research data. [148]
Of
thirty one norterpenoid complounds found in Neem seeds six newly isolated
limonoids, (1)7-benzoyl-17-epinimbocinol, (2) 3-acetyl-7-tigloylnimbidin, (3)1-isovaleroyl-1-detigloylsalanninolide,
(4) 2,3-dihydro-3α-methoxylimbonide, (5) deacetyl-20, 21,-epoxy-20,
22-dihydro-21-deoxyisonimbinolide, (6)
deacetyl-20,21,22,23-tetrehydro-20,22-dihydroxy-21,23-dimethoxynimbin inhibit
the effect of melanogenesis and melanin in the B16 melanoma cells. Furthermore,
azadirachtin B inhibits carcinogenesis of mouse skin induced by peroxynitrite. [149],
[150], [151]
Wound healing
To study the effect of Neem oil on wound healing,
patients with chronic non healing wounds of more than six weeks duration were
selected. The wounds were biopsied before initiating the local application of
the oil. The dressings were changed daily. Every two weeks the wound area,
formation of granulation, microscopic angiogenesis were assessed. The results
showed that Neem oil dressings were useful for wound healing. [152]
Neem oil directly accelerates the process of wound
healing. According to R. L. Bhardwaj, an associate professor of veterinary
Anatomy and Histology, COVAS, CSKHPKV, Palampur, India; a high content of
essential fatty acids in Neem oil adds moisture and softness to the skin during
wound healing. This supported by anti-inflammatory, anti-bacterial, ani-viral
and anti-fungal properties of Neem oil. [153]
Neem oil processed from seeds of the plant is used
in veterinary practice in Nigeria for the management of surgical wounds, both
clean and infected wounds. There Neem oil is used in veterinary practice for
dressing of wounds after drainage of abscesses. [154]
Actions
on Hematopoetic System
Nimbolide
is cytotoxic to human B-lymphocyte cancer. Its anticancer activity is is
mediated through mitochondrial apoptosis. Nimbolide is also effective in
killing B-lymhocyte cancer cells resistant to some chemotherapeutic drugs.
[155]
Norterpenoid
compounds present in Neem seeds show cytotoxic activity against leukemia (HL
60) cells. [156]
Actions on Nervous System
The leaf extract of Neem shows varying degrees of
CNS depressant activities in mice. Leaf extract up to a dose of 200mg/kg body
weight produces significant anxiolytic activity in rats. [157], [158]
In
a number of animal models investigated nimbidin a bitter principle isolated
from seed oil of Neem exhibited sedative activity. Further, in vitro
studies showed that nimbidin has a pronounced anticholinergic, antihistaminic,
antiserotonin and antinicotinic activities. But in vivo studies did not
show any anticholinergic or antihistaminic activities. Nimbidin did not show
any local anaesthetic activity in rodents. [159]
In
a study on rats, leaf extract of Neem 500mg/kg body weight and seed oil 2ml/kg
body weight exhibited antinociceptive effect. Leaf extract was more potent than
the seed oil. [160]
Actions on the eye
In diabetic rats with diabetic retinopathy aqueous
extract of Neem leaves at a dose of 250mg/kg body weight 16 weeks reversed
retinopathy. [161]
By causing cell cycle arrest nimbolide found in Neem
directly inhibits retinoblastoma and suppresses the growth of glioblastoma
[162]
Actions on Endocrine System
Oral
administration of Neem leaf extract up to 100mg/kg body weight for 20 days to
male rats did show adverse effects on thyroid function. But administration of
higher doses increased thyroxine levels in the blood. [163]
Actions on CVS
The ethanol extract of stem bark and root bark of
Neem showed hypotensive effect. The anti-histaminic nimbidin present in Neem
leaves is a potent vasodilator. It reduces elevated blood pressure. Neem leaf
extract, tincture or capsules when taken for a month lower cholesterol levels.
[164], [165]
In an experimental study on rats, intravenous
administration of alcoholic extract of neem leaf at doses of 100, 300,
1000mg/kg resulted in bradycardia and fall in blood pressure. Bradycardia was
later followed by cardiac arrhythmia. All these effects were dependent on the
dose administered. Pretreatment with either atropine or mepyramine failed to
prevent the hypotensive effect of the extract. [166]
Actions on RS
Asprgillosis an opportunistic fungal infection can
be acute or chronic. It is often found in immuno-compromised patients, in
patients on prolonged antibiotic or steroid therapies. It is characterized by
invasion of blood vessels which can result in dissemination to other organs.
Aspergilloma is a fungal ball that develops in previous cavitary lesions in the
lungs. Inhalation of essential oil of Neem kills the fungi attached to the
inner lining of the respiratory tract. [167]
Actions on GI System
The antioxidant, antibacterial and antifungal
activities of Neem make it vary suitable for periodontal and endodontic
diseases. The bitter taste can be masked by sweeteners and agreeable flavors.
[168], [169], [170]
Antioxidant activity of
limonoids from Neem leaf show inhibitory effect on 7,
12-dimethylbenzanthracin-induced hamster buccal pouch carcinogenesis. On a
comparative basis, nimbolide was found to be a potent antiproliferative and
apoptosis inducing agent. [171], [172]
Nimbidin a bitter
principle found in Neem exhibited significant antisecretory activity in
pylorus-ligated rats and cats. On intra venous administration of 40mg/kg body
weight, nimbidin suppressed basal as well as histamine and carbachol stimulated
gastric secretion. However nimbidin had no effect on aspirin induced gastric
secretion. The anti secretory activity of nimbidin was found to be similar to
H-2 receptor antagonists. [173]
At 500 mg/kg body weight aqueous extract of Neem leaf
extract showed gastric ulcer healing effects in diabetic as well as non
diabetic rats. This effect was studied on various parameters of offensive
acid-pepsin secretion in 4 hour pylorus ligation, pentagastrin (Dose:
5µg/kg/hr) stimulated acid secretion and gastric mucosal proton pump activity.
Pretreatment with aqueous extract of Neem significantly decreased gastric
secretion. Further the extract inhibited the rat-gastric mucosal proton pump
activity. This effect was comparable to omeprazole. This shows that the
gastroprotective activity of the extract was due to proton pump inhibition. No
toxicity was observed up to the dose of 1g/kg for 28 days in this study.
In another study by Dorababu and his co-researchers on
rats, at 500 mg/kg body weight aqueous extract of Neem showed significant anti-gastric
ulcer and ulcer healing activity in non-diabetic and non-insulin-dependent
diabetic rats. [174], [175]
Cold-restraint stress is a method used to produce experimental
stomach ulcers. In this process by exposing gastric mucosa to 40C
for 2 hours gastric ulceration is produced. Hypothermia, ischemia of gastric
mucosa following extreme cold and possibly some other factors are responsible
for the ulceration and depressed gastric motility.
To evaluate antisecretory and anti-ulcer effect of
aqueous extract of Neem bark, in experiments on rats, Bandopadhyay U et al used
pyloric ligation, cold-restraint stress method, and indomethacin to produce
gastric ulceration. The bark extract showed very potent antisecretory and ulcer
healing activity. The researchers found that the extract was equipotent to
ranitidine but more potent than omeprazole in inhibiting pylorus
ligation-induced acid secretion. In the model of stress ulcer, the extract was
more effective than ranitidine but equipotent to omeprazole. The researchers
think that the pharmacological effects of the bark extract are due to a
phenolic glycoside. [176], [178], [179], [180], [181]
To evaluate the anticancer effects of Neem,
N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) was used to induce gastric cancer
in Wistar rats. By intragastric intubation 200mg/kg body weight, ethanolic
extract of neem leaf was administered three times per week. To assess the
results all the animals were killed after 26 weeks. The results of the study
suggest that ehtanolic extract of Neem leaf exerts chemoprotective effect on
gastric carcinoma by modulating lipid peroxidation and antioxidant status in
the stomach, liver and erythrocytes
[182]
Proinflammatory microenvironment plays an important
role in the development of colorectal cancer. Nimbolide can suppress the growth
of human colorectal cancer by suppressing the proinflammatory microenvironment.
[183]
·
Development of cancer implies dysregulation of multiple cell signaling
pathways.
·
Chemoprevention can block, retard or reverse carcinogenesis
·
Nimbolide exhibits anticancer activity by inducing apoptosis and
inhibiting tumor cell proliferation in vitro and in vivo.
For more details of mechanisms of suppression of
colorectal cancer by nimbolide see above. [184]
Actions on the Pancreas
Nimbolide inhibits pancreatic cancer growth and
cancer metastasis. It inhibits the generation of Reactive Oxygen Species (ROS) thereby
regulating the apoptosis in pancreatic cancer cells. Inhibition of generation
of ROS inhibits proliferation and development of metastasis of pancreatic
cancer via mitochondrial-mediated apoptosis. [185], [186]
Actions on the Liver
In
a study Bhanwara et al induced hepatotoxicity in rats by administering a single
dose of paracetamol 2 g/kg. The liver damage was evidenced by elevated levels
of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl
transpeptidase and by histological studies. Administration of aqueous extract
of Neem leaves at the dose of 500mg/kg reduced the elevated levels of enzymes.
The liver necrosis also reduced as observed macroscopically and
microscopically. [187]
Chattopadhyay
RR and Bandopadhyay M. also observed hepatoprotective effects of Neem leaf
extract on paracetamol-induced liver damage.
They
attribute hepatoprotection by Neem to antoxidants present in the plant. [188],
[189]
To
investigate hepatoprotective activity of fresh juice of young stem bark of Neem,
carbontetrachloride was administered to albino rats to induce hepatic damage.
Administration of fresh juice (200 and 500mg/kg) of tender Neem stem bark
showed reversal of hepatic damage. The best results were observed at the dose
of 500mg/kg body weight. The effect was comparable to silymarin. The effect was
attributed to antioxidant phytochemicals present in the plant. [190]
N.
S. Baligar et al used higher doses (500 to 2000 µg/kg bodyweight) of the
phytochemical Azadirachtin A present in Neem to counteract the hepatotoxicity
produced by carbontetrachloride. They confirmed the usefulness of Azadirachtin
A by increased levels of decreased levels of liver enzymes, improvement in
ultrastructure as evidenced on sonography and improvement of the liver
architecture as noted by liver histology. This study reveals that Azadirachtin
A in pure form, when used at higher doses, posseses a very potent
hepatoprotective activity. But the effective concentration and the dose needs
to be determined.[191]
To
probe the utility and mechanism of action of Neem leaf-powder in the treatment
of alcoholic liver damage, alcoholic liver damage was induced in Wistar rats.
After treatment with Neem leaf-powder the liver damage was reversed. The
effects were comparable to those of silymarin. The leaf powder normalized the
decreased levels of glutathione, superoxide dismutase and catalase caused by
alcoholic liver damage. [192]
Actions on metabolism
Experiments
conducted on rats by R.R. Chattopadhyay and M. Bandyopadhyay showed that fresh
extract of mature leaves of Neem normalized the lipid profile in non diabetic
and diabetic rats. [193]
Antidiabetic activity
There are many research papers showing antidiabetic
activity of various parts of Neem plant. Here are some important
references:
Aqueous extract of leaves of Neem significantly
decreases elevated blood blood sugar in non diabetic and diabetic rats. [194]
Epinephrine
increases hepatic glucose production by stimulating glycogenolysis and
gluconeogenesis. Glycogenolysis wanes rapidly but gluconeogenesis and glucose
disposal persist longer. Hence epinephrine-induced hyperglycemia continues for
a long time. Thus epinephrine is an important contributory factor to
stress-induced hyperglycemia and susceptibility of diabetics to complications
of metabolic ill effects of stress. Neem does not show any action on peripheral
utilization of glucose and on hepatic glycogen. Neem acts as an antidiabetic
agent by blocking the action of epinephrine [195]
Administration of 500mg of Neem seed kernel powder
for 30 days to alloxan induced diabetic rabbits, reduced elevated blood sugar
serum lipids. [196]
To
evaluate antidiabetic effect of Neem root bark, alcoholic extract of Neem root
bark was administered orally at 200, 400 and 800 mg/ kg body weight for 15 days
to alloxan-induced diabetic Wister rats. The hypoglycemic activity was
significant only at doses of 800mg/kg body weight. The activity was not as
significant as that of glibenclamide. [197]
Dixit V. P. et al demonstrated hypoglycemic activity
of Neem seed oil in nondiabetic and diabetic rats. [198]
Actions on Urinary System
Nimbidin a bitterprinciple on Neem shows moderate
diuretic activity [199]
Actions on Male Reproductive System
Neem oil exhibits spermicidal activity. The
mechanisms involved are:
1. Neem oil decreases the motility of sperms. The
motility of sperms depends on mitochondrial activity present in mid-piece of
sperms. The researchers found that neem oil significantly decreases the
mitochondrial activity. As the duration of contact between the oil and sperm
increases the mitochondrial activity decreases significantly. Thus Neem oil
applied to vagina before coitus kills sperms.
NIM-76 is the odorus and volatile fraction of Neem
oil. Its antifertility activity was investigated in animal models. The fraction
applied to vagina of rats, rabbits and rhesus monkeys before coitus killed
sperms. There was no alteration in the valuse of estradiol (E2) and
progesterone (P) suggesting that the action of the drug was local and
independent of female hormones.
It is suggested that active compounds present in
Neem oil are absorbe through the vaginal mucosa and exert antifertility effect.
[200], [201], [202]
Oral administration of aqueous extract of Neem leaf,
purified extract of Neem seed exhibited antifertility effect in various
experimental animal models [203]
The
effect of antifertility activity of Neem can be produced in the male by
interference at the following steps:
1.
Secretion and release of Follicle Stimulating Hormone Releasing Factor (FSHRF)
and Leuteinizing Hormone Releasing Factor (LHRF) from the hypothalamus
2.
Secretion and release of Follicle Stimulating Hormone (FSH) and Leutinizing
Hormone (LH) from the pituitary
3.
Production of spermatozoa and androgenic hormone
4.
Transport of sperms into the epididymis with simultaneous maturation of
spermatozoa.
5.
Passage of spermatozoa through through vas deferens to ampula
6.
Suspension of sperms in seminal plasma during ejaculation
7.
Passage of ejaculate through cervix.
8.
Ascent of sperms through the uterus and oviducts.
9.
Penetration of ovum by spermatozoa.
This
preliminary report on the antifertility activity of Neem in male mice shows
that the antifertility activity of Neem is not due to inhibition of
spermatogenesis. The mechanism may be much complex than thought of.
[204],
[205], [206]
The
antifertility effect of Neem is possibly due to activation of cell-mediated
immune reaction. The mechanism of action of neem oil appears to be non-hormonal,
probably mediated through its spermicidal effect and may have fewer side
effects than steroidal contraceptives. [207]
More
likely mechanisms for abortive effects involve the activation of macrophages by
neem and subsequent secretion of cytokines that may alter immune and non-immune
cells. In rats, CD4 and CD8 cells (particularly CD8 cells) increased in the
spleen 96 hours after treatment onset and tumor necrosis factor alpha and
gamma-interferon increased in serum, mesenteric lymph nodes, and fetoplacental
tissue. [208]
The
ethanol extract of Neem leaves showed anticancer activity against prostate
cancer. The phytochemicals 2’ 3-dehydrosalannol, 6-desacetyl nimbinene and
nimolinone exhibit this activity. [209], [210], [211]
Actions on Female Reproductive System
Local application of Neem to vagina before coitus
and instillation of a single dose of Neem oil in the uterus blocks the
fertilization of ovum. [212]
Antioxidant and antiproliferative activity of
limonoids found in Neem suppress the growth of cancer of the cervix of the
uterus. [213]
Antitumor activity
Prophylactic
treatment on Swiss albino mice with Neem leaf preparation once a week for four
weeks restricted the growth of Ehrlich’s carcinoma. [214]
Nimbolide,
a natural triterpenoid present in Neem inhibits the growth of carcinoma of the
colon by cell cycle arrestin the G2/M phase. [215]
Nimbolide
induces apoptosis by both intrinsic and extrinsic pathways in breast cancers.
The studies by Arumugam A et al suggeast that Neem leaf extract inhibits human
breast cancer by altering cell proliferation, apoptosis and angiogenesis.
[216], [217]
Culinary
uses
Neem gum is a rich source of protein. It
is used as a bulking agent and for the preparation of special purpose foods for
diabetics.
The tender shoots and flowers are eaten as
a vegetable in India. Neem flowers are popular for
their use for soup-like pickle in South India.
Neem is also used as a culinary item in
parts of mainland Southeast Asia, particularly
in Cambodia.
The taste of Neem is quite bitter and thus
the food is not enjoyed by all inhabitants of these nations, though it is
consumed since it is said to be good for one's health.
Toxicity
The epithet Azadarach itself means a
poisonous plant.
Neem indeed is Nature’s drug house but
injudicious, unscrupulous use of the drug can take its toll.
Nimbidin produces sub-acute toxicity in
adult rats after daily administration of 25, to 100 mg/kg for six weeks. A
significant hypoglycaemic effect was observed by feeding nimbidin. It has
spermicidal activity.
Nimbolide and nimbic acid were found to be
toxic to mice when given intravenously or intraperitoneally. At a lethal dose
they cause death in most animals by hepato-renal failure as well as by marked
and sudden drop of arterial blood pressure.
Due to lack of sufficient data regarding
the clinical trials and possible toxicity, it is inadvisable for children and
pregnant or lactating mothers to use Neem.
Those who have impaired liver or kidney
function should also use great caution. Large doses of seed or seed components
may be toxic.
Even the hardcore traditional Ayurvedic
practitioners advise against the use of Neem if the patient suffers from
consumption (old term for tuberculosis), wasting and acute or chronic fatigue. Excess of neem causes diarrhea,
vomiting, and symptoms of narcotic poisoning.
Ripe fruits more poisonous than green ones and sometimes cause human fatalities.
NOT TO BE GIVEN TO WEAK, OLD, OR VERY YOUNG [218]
Some Case Reports:
Case: 1
In an attempt to commit suicide, a 35 year
old female consumed 150 ml of Neem oil on 12-12-2009. She was hospitalized in
nearby government hospital and treated with induced vomiting after about 2-3
hours of consumption of the oil. She was asymptomatic for about 2 days. Later
she developed sudden bilateral visual loss on 16-12-2009.
Ophthalmic examination:
No perception of light in both eyes
Dilatation of both pupils (6mm),
sluggishily reacting to light
Fundus examination showed hyperemic,
edematous discs in both eyes with extention of edema along the superior and
inferior temporal arcuate fibers for about 2-3 disc diopters from the disc
margins. The veins around the disc were tortuous and dilated. The vitreous
revealed no abnormality.
Neurological examination showed exaggerated
deep tendon reflexes and extensor bilateral plantar reflex.
MRI: Bilateral putaminal regions showed altered signal
hypointensities in T1W images, Hyperinensities on T2W
Treatment given:
Intravenous prednisolone 1g for three days
followed by oral prednisolone 50 mg/day for11 days with intramuscular injection
of methyl cobalamine 1000µg every five days for 8 weeks.
The patient did not show any visual
improvement but papillary reactions improved. During follow up after 15 days
her vision in both eyes improved. At one month follow up her vision was 20/200
in both eyes, papillary reactions improved, fundus examination showed reduced
disc edema in both eyes.
At follow up after two months her vision
was 20/ 200 in both eyes.
Intramuscular injection of methyl
cobalamine was continued [219]
Report 2
Neem oil was considered as a ‘cure
all’medicine in many countries. It has been considered to be ‘safe’ to use. But
not really. In fact the oil is poisonous. In rats oral LD 50 of Neem
oil is 14 ml/kg and rabbits 24ml/kg. The features of poisoning are: stupor,
convulsions, diarrhea, respiratory depression and death.
Thirteen infants who received Neem
oil at the doses of 5 to 30 ml orally developed severe poisoning within hours
of ingestion. Clinically they developed vomiting, drowsiness, convulsions,
metabolic acidosis, coma, hepatoencephalopathy and death. Blood count showed
polymorphoneuclear leucocytosis. Liver biopsy of one infant and necropsy
examination showed pronounced fatty infiltration of the liver. The kidney
biopsy showed edema of proximal tubules. Brain showed cerebral edema. Electron
microscopy demonstrated mitochondrial damage. These findings suggest that
margosa oil (Neem oil) may be involved in the etiology of Reye’s syndrome among
Indiansin Malaysia. For want of known antidote they were treated
symptomatically, but did not show any improvement. [220], [221], [222]
Report 3
Margosa oil (Neem oil) causes toxic
encephalopathy particularly in infants and children. The usual features are
vomiting, drowsiness, tachycardia, recurrent convulsions, metabolic acidosis
and leucocytosis. The management is aimed at controlling convulsions and
treatment of encephalopathy. If infants and children survive neurological
deficits have been reported. [223], [224]
Report 4
Both neem seed oil and azadirachtin impair
intrauterine development and alter antioxidant/oxidative status during
pregnancy. [225]
Report 5
In experimental studies on animal models, Adult Wistar
rats who received ethanolic extract of neem root bark orally at doses of 500,
1000 and 2000 mg/kg body weight for three weeks developed nephrotoxicity. The
results were confirmed by histological study. [226]
AL RESEARCH
Medicinal Actions and Uses
Traditional Uses
Neem has been
used internally for intermittent fevers, malaria, tuberculosis, rheumatism,
arthritis, jaundice, and skin diseases, intestinal worms and candidiasis. For
its internal use usually combined with Glycyrrhiza glabra to reduce
toxicity.
It has been used externally for ringworm, eczema, lice-fungal infections.
Juice of the leaf is anthelmintic, antilithic, emmenagogue; decocotion of the leaf is astringent, stomachic.
Flower has been used for nervous headache, neuralgia, prickly heat.
Stembark is anthelmintic and has been used for dyspepsia, and gastralgia. Can it be used for H. pylori infection?
Fruit has been used for abdominal pain, urethritis, cystitis, delirium, ringworm, endometritis, weeping eczema; pulp of fruit has been used to make ointment to destroy lice and other skin diseases.
Root bark has been used against ringworm, scabies and for ascariasis.
Root bark has been used externally for vaginal infections.
Oil from the bark has been used medicinally as an anthelmintic and emetic.
Bark
of the tree is bitter and astringent and has been used in India as a tonic.
Oil from the nuts and seeds has been used for cramps, obstinate ulcers, and elimination of intestinal worms; also applied externally for rheumatism.
Decoction has been used as a cathartic and in large doses slightly narcotic; possible febrifuge; has also been used for hysteria; either the decoction or the powdered root bark has been taken for worms (dose is followed by a purgative).
Decoction has been used in the southern United States to expel intestinal worms. A drink was prepared using 100 grams of the bark boiled in 1 litre of water until it was reduced to half (500ml). Dose = 15ml every 3 hours being accompanied by a purgative such as castor oil or Cascara sagrada).
The
tender twigs are used as crude form of tooth brush to scrub teeth and the powder as
dentifrice (Marathi: Dantamanjan). Probably the Ayurvedic scientists were not
conversant with the chemical constituents of the plant but their wisdom of
using the plant for medicinal purpose is commendable.
In modern era
the liquid extract is used in toothpastes. [227], [228], [229], [230]
Here are medicinal uses of Neem plant from myths to
medicine:
Used by the folk:
Fresh leaf tea = Malaria
Decoction, infusion of all parts of tree, root
and bark = Malaria, viral
fevers, viral hepatitis, bronchitis, coughs, and helminthiasis.
Edible
pulp of the fruit =
Hemorrhoids.
Externally
poultice of leaves= Acute
and chronic lymphadenitis, contusions, sprains, abscesses.
It is said, that it treats 40 different
diseases.
Uses in Ayurvedic medicine:
Leaf- Leprosy, helminthiasis, ophthalmic problems, skin wounds, contusions, ulcers, hematomas, anorexia, biliary dyspepsia.
Bark – Analgesic and PUO.
Flower – Viral hepatitis, helminthiasis, bronchitis
Fruit - Hemorrhoids, helminthiasis, UTI, (?)Urinary calculi, urinary disorder, epistaxis, bronchitis, ophalmic disorders, diabetes, wounds and leprosy.
Twig – Scrubbing teeth, dentifrice, cough, asthma, hemorrhoids, intestinal worms, spermatorrhea, urinary disorders, diabetes.
Gum - Ringworms, scabies, wounds and ulcers.
Seed pulp and oil- Leprosy and intestinal worms.
Leaf's oil is used as local antiseptic and insecticide.
Neem oil may be useful for gingivitis, stomatitis, aphthous ulcers.
Neem oil may be useful for gingivitis, stomatitis, aphthous ulcers.
In the rural areas, burning of leaves and
seeds is used as mosquito repellant. The extract is used as larvicidal spray
for prophylaxis of malaria.
Some studies
show that even chloroquine-resistant strains of malaria are sensitive to Neem,
particularly a component called Irodin A. The recommended preventative measure
is to chew and consume the leaves on a daily basis. [231], [232], [233], [234]
Preparations and Dosages
There are many forms and routes of use for
Neem.
Neem oil: Used
as hair oil for dandruff and head lice.
For topical use Neem oil and leaf extracts are incorporated into
soaps, lotions, creams, ointments etc. These act to relieve inflammation and
kill bacteria, fungi, insects and skin parasites.
It is applied externally for pain relief
in RA and OA.
The oil from the nuts is useful for
cramps, burns, wounds and refractory, obstinate indolent ulcers, etc.
Neem oil is spermicidal. Its intravaginal application exerts anti
fertility action and also prevents embryo-implantation.
Neem oil is used for preparing soap, shampoo,
balms and creams. It is useful for skin care such as acne, keeping skin
elasticity.
Neem oil can be mixed with
olive oil and gently massaged into the hair serves to treat dandruff and
dispose of headlice if left without washing for one hour. Following the hour,
hair should be rinsed normally with shampoo. Dandruff and headlice will usually
subside within three weeks of a once-weekly treatment course.
Pure Neem oil can also be
applied to the nose like nasal drops in order to clear sinustis.
Lepa
(Paste for topical skin application): Neem powder is mixed with water or honey
to make paste. It is used to dress wounds, ulcers
The paste prepared with Neem and Turmeric
is effective in the treatment of scabies.
Ointment is used to destroy lice is made from the pulp. It is also
used for bald head and other skin diseases.
Aahaar (Diet): Neem is used as vegitable.
Snaana (Bath): Some 5-6 leaves are placed in a bucketful of water.
This helps reduce skin irritation, skin eruptions (especially measles) [235],
[236], [237], [238]
Neem tea made of
boiled neem leaves, sometimes combined with other herbs such as ginger, can be
ingested to fight intestinal parasites.
Lotion derived from Neem leaf, when locally applied, can cure
ringworm, eczema and scabies within 3-4 days in acute stage or a fortnight in
chronic stage.
Kwath (Decoction): The
decoction of the bark is used externally for hemorrhoids. Bark extracts are also bactericidal.
The decoction of Neem is cathartic and in
large doses slightly narcotic. It also has febrifuge properties. It is used as
a remedy for hysteria.
To prepare an infusion ten
clean Neem leaves are boiled in a litre of water for precisely ten minutes and
left to cool. It can be used as eyewash, gargle for stomatitis, aphthous
ulcers, pharyngitis, laryngitis etc.
The decoction is made from 50 grams of
bark to 400ml of water boiled down to 200ml. One tablespoonful of this taken
every two or three hours followed by a purgative is an effective dose for
intestinal parasites.
Neem leaf extract has been prescribed for
oral use for the treatment of malaria.
Other many preparations: Neem Kwath, Nimbaarishta,
Nimbaharidrakhanda, Brihatpanchanimbachoorna, Neem Malahara, Nimbawaarunee and
many more commonly used in Ayurvedic practice is available in Ayurvedic textbooks.
Dosages:
Neem
Churna: 1 to 3 gms.
Leaf
Juice: 10 t0 20 ml.
Oil:
5 to 10 drops. [239], [240], [241], [242]
References:
1. http://ssnaneem.weebly.com/neem-history.html
8.
http://www.natureneem.com/index_fichiers/Neem_history_Neem_and_India.htm
9. The Student’s New Sanskrit
Dictionary by Dr. G. V. Dewasthalee, Y. B. Joshi and G. R. Kulkarni, 3rd
edition, 1984
11.
http://easyayurveda.com/2012/11/28/neem-in-ayurveda-benefits-usage-side-effects-full-reference/
12. Cepeda-Palacious R et al, In vitro and in vivo effects of neem tree
(Azadirachta indica A. Juss) products on larvae of the sheep nose bot fly
(Oestrus ovis L. Diptera: Oestridae), Vet Parasitol, 2014 Feb 24; 200(1-2):
225-8
13.
http://www.neem-products.com/neem-history.html
14.
Azadirachta indica: Neem tree, the “village pharmacy” Eleonora Mugnai ele.mugnai@fastwebnet.it ASAT -
Associazione Scienze Agrarie Tropicali ASAT Sci-Tec - Vol. 1, 2009
15.http://www.banyanbotanicals.com/info/ayurvedic-living/living-ayurveda/herbs/neem/#
16. Xin
Tinghui, Malcolm Wegener, Michael O’Shea, Ma Deling, World Distribution and
Trade in Neem Products with Reference to their Potential in China, http://ageconsearch.umn.edu/bitstream/126066/2/Xin.pdf
17. Sunday E. Atawodi, Joy C. Atawodi,
Azadirachta indica (neem): A plant of multiple biological and pharmacological
activities, Phytochemistry Reviews, October 2009, Volume 8, Issue 3, pp 601-620
18.
Azadirachta indica : Neem tree, the “village pharmacy” Eleonora Mugnai ele.mugnai@fastwebnet.it ASAT -
Associazione Scienze Agrarie Tropicali ASAT Sci-Tec - Vol. 1, 2009
19.
http://www.natureneem.com/index_fichiers/Neem_history_Neem_and_India.htm
20. United Nations Environment Programme
Neem: The UN’s tree of the 21st Century. Nairobi: United Nations
Environment Programme; 2012; Available on line:
http://www.unep.org/wed/tree-a-day/neep.asp.
21. National Academy of Science.
Washington, DC: NAS; 1992. Neem, a tree for solving global problems [R]
23.
http://www.goodhealthnyou.com/library/reading/neem/apendix4.asp
24.
https://en.wikipedia.org/wiki/Azadirachta_indica
25.
http://www.goodhealthnyou.com/library/reading/neem/apendix4.asp
26.
https://en.wikipedia.org/wiki/Azadirachta_indica
28. Dr. Ramkishore Sharma, Dr.
Mukesh Kumar Sharma, Phytogeographical Distribution of Azadirachta indica in
Churu District, Rajasthan, International Journal of Geogology, Agriculture and
Environmental Sciences, Volume 2, Issue 1, February 2014, Website: www.woarjournals.org/IJGAES
29.Anjana Chowdhary and Vinod
Singh, Geographical Distribution, Ethnobotany and Indigenous Uses of Neem
31. www.boloji.com/ayurveda
33. The Ayurvedic
Pharmacopoeia of India, Part I, Volume V
34. google
images
35. The Ayurvedic
Pharmacopoeia of India, Part I, Volume V
36. The Ayurvedic
Pharmacopoeia of India, Part I, Volume V
37. The Ayurvedic
Pharmacopoeia of India, Part I, Volume II
38. The Ayurvedic
Pharmacopoeia of India, Part I, Volume II
39. The
Ayurvedic Pharmacopoeia of India, Part I, Volume II
40.
emedtv.com, healthjockey.com, indianscience.org
center/plant-profiler/azadirachta-indica.html
47.
Tomar Lokeshwar et al, Review on Neem (Azadirachta indica): Thousand problems
one solution, IRJP, 2011, 2 (12): 97-102
49.www.springerlink.com
50.www.ncbi.nlm.nih.gov/pubmed
52.
www.neemfoundation.org
53.
Tomar Lokeshwar et al, Review on Neem (Azadirachta indica): Thousand problems
one solution, IRJP, 2011, 2 (12): 97-102
55.
Neem: The Village Pharmacy, 2007, from http://netowne.com/alt-healing/ayurveda
56.
P. Sudhir Kumar, Debasis Mishra, Gautam Ghosh, Chandra S. Panda, Biological
action and medicinal properties of various constituent of Azadirachta indica
(Meliaceae) an Overview, Scholars
Research Library, Annals of Biological Research, 2010, 1 (3): 24-34, Available
online at www.scholarsresearchlibrary.com
57.
The Ayurvedic Pharmacopoeia of India, Part I, Vovume V
58. The Ayurvedic
Pharmacopoeia of India, Part I, Volume II
59. The Ayurvedic
Pharmacopoeia of India, Part I, Volume II
60. The Indian Pharmacopoeia
of India Part I, Volume V
61. The Indian Pharmacopoeia
of India Part I, Volume V
62. The Indian Pharmacopoeia
of India Part I, Volume V
63. The Indian Pharmacopoeia
of India Part I, Volume V
64. Chromosome Count Data
Base, http://ccdb.tau.ac.il/Azadirachta
65.
Seham S. El-Hawary et al, DNA fingerprinting and botanical study of Azadirachta
indica A, Juss. (neem) family Meliaceae, Beni-Suef University Journal of Basic
and Applied Sciences, Volume 2, Issue 1, March 2013, pages 1-13
66.
R. S. Dhillon et al, Assessment of genetic diversity in Azadirachta indica
based on DNA fingerprinting, Indian Journal of Biotechnology, Volume 6, October
2007, pp 519-524
68. Bhaawaprakaash
71. The
Ayurvedic Pharmacopoeia of India Part I, Volume V
72. The
Ayurvedic Pharmacopoeia of India Part I, Volume II
73.
Bhaawaprakaash
74. The
Ayurvedic Pharmacopoeia of India Part I, Volume II
76. The
Ayurvedic Pharmacopoeia of India Part I, Volume V
77.
Bhaawaprakaash
78. The
Ayurvedic Pharmacopoeia of India Part I, Volume V
80.
http://www.banyanbotanicals.com/info/ayurvedic-living/living-ayurveda/herbs/neem/#
82.
http://www.biovision.com/nimbolide-4818.html
83.
http://www.scbt.com/datasheet-397039-casnumber-25990-37-8.html
86.
Laxmi Narendra Bodduluru et al, Chemopreventive and therapeutic effects of
nimbolide in cancer: The underlying Mechanisms, Toxicology in Vitro, Volume 28,
Issue 5, August 2014, Pages 1026-1035
87.
Takashi Kikuchi et al, Cytotoxic and Apoptosis-Inducing activities of Limonoids
from the seeds of Azadirachta indica (Neem), Journal of Natural
Products, 2011, 74 (4), pp 866-870
88. Elumalai P, Arunakaran J,
Review on molecular and chemoprotective potential of nimbolide in cancer,
Genomics Inform 2014, Dec; 12(4): 156-64
89.
http://www.ebi.ac.uk/chebi/searchId.do?chebiId=67309
91.Mitchell
MJ, Smith SL, Johnson S, Morgan ED, Effects of the neem tree compounds
Azadirachta, salannin, nimbin and 6-desacetylninbin on ecdysone
20-monooxygenase activity, Arch Insect Biochem Physiol. 1997; 35 (1-2): 199-209
97.
https://www.google.co.in/search?q=Nimbolinin&biw=1366&bih=673&noj=1&tbm=isch&imgil=FS1jHWXdEIICbM%253A%253B7OOC-
98.
Tao L et al, 1-O-tigloyl-1-O-deacetyl- nimbolinin B inhibits LPS-stimulated
inflammatory responses by suppressing NF-κB and JNK activation in microglia
cells, Pharmacol Sci 2014; 125 (4): 364-74 Epub 2014 Jul 11
100.
https://nl.wikipedia.org/wiki/Gedunine
101.
http://www.tocris.com/dispprod.php?ItemId=220954#.Vr7XobR97VQ
103.
https://pubchem.ncbi.nlm.nih.gov/compound/12004512#section=Top
104. Kamath SG et al, Gedunin, a novel
natural substance, inhibits ovarian cancer cell proliferation, Int J Gynecol
Cancer 2009 Dec; 19(9): 1564-9
105. Sara J, Felts, David O. Toft, p23, a simple protein with complex
activities, Cell Stress Chaperones. 2003, Apr; 8(2): 108-113
106. Patwardhan et al, Gedunin
inactivates the co-chaperone p23 protein causing cancer cell death by
apoptosis; J Biol Chem. 2013 Mar 8; 288(10):
7313-25
107.
http://www.chemspider.com/Chemical-Structure.9081498.html
108. Gupta SC, Francis SK,
Nair MS, Mo YY, Aggarwal BB, Azadirone, a limonoid tetranortriterpene, induces
death receptors and sensitizes human cancer cells to tumor necrosis
factor-related apoptosis-inducing ligand (TRAIL) through a p53
protein-independent mechanism: evidence for the role of the ROS-ERK-CHOP-death
receptor pathway, J Biol Chem. 2013 Nov 8; 288(45): 32343- 55
109.http://www.molbase.com/en/71590-47-1-moldata-1498406.html
110.Judith Polonsky et al, Antineoplastic agent. 61.
Isolation and structure of amoorastatin, J. Am. Chem. Soc., 1978, 100 (24),
pp7731-7733
111.
http://chem.sis.nlm.nih.gov/chemidplus/rn/24021-78-1/US
National Library of Medicine/Toxinet Toxicology Data Network
112.
http://pubchem.ncbi.nlm.nih.gov/compound/102403692#section=Top
113.
http://dictionary.reference.com/browse/antifeedant
114.
http://www.infinityfoundation.com/mandala/t_es/t_es_agraw_neem.htm
115. Tidjani, M. A., Dupont,
C. and Wepierre, J., Planta Med. Phytother., 1989, 23, 259–266.
116. Prakash Kumar
Singh,Bechan Sharma, Certain Traditional Indian Plants and Their Therapeutic
Applications: a Review VRI Phytomedicine Volume 1, Issue 1, July 2013.
117. Lorenz, H.K.P.J. Praxis
1976, 8, 231-233
118. Kaushik Biswas et al,
Biological activities and medicinal properties of neem (Azadirachta indica),
Current Science, Volume 82, No 11, 10 June 2002
119. Okpanvi S. N., Ezeukwu G.
C. Anti-inflammatory and Antipyretic activities of Azadiracta indica, Planta
Med, 1981, 41, 34-39
120. Vohra S. B. Dandiya P. C.
Phytoterapia, 1992, 63, 195-207
121. Kaur G et al, Nimbidin
suppresses functions of macrophages and neutrophils: relevance to its
anti-inflammatory mechanisms, Phytother Res. 2004 May; 18(5): 419-24
122. Amal Kumar
Ghimeray et al, Antioxidant activity and quantitative estimation of
azadirachtin and nimbin in Azadirachta indica A. Juss grown in foothills of
Nepal, African Journal of Biotechnology Vol. 8 (13), pp. 3084-3091, 6 July 2009
123. Gayatri Nahak and R. K. Sahu,
Antioxidant activity in bark and roots of Neem (Azadirachta indica) and
Mahaneem (Melia azedarach) , Continental J. Pharmaceutical Sciences
4:28-34 2010
124. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an
overview, Annals of Biological Research,
2010, 1, (3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
125. Kausik Biswas et al, Biological activities and medicinal
properties of neem (Azadirachta indica), Current Science, Vol. 82, No. 11, June
2002; http://repoitory.ias.ac.in/5193/1/305.pdf
126. Prashant GM et al, The effect of mango and neem extracts on four
organisms causing dental caries: Streptococcus mutan, Streptococcus
salivavius, Streptococcus mitis, and
Streptococcus sanguis: An in vitro study, Indian J Dent Res.
2007, 18: 148-51
127. Bohora A, Hegde V, Kokate S. Comparison of
antibacterial efficiency of neem leaf extract and 2% sodium hypochlorite against
E. faecalis, C. Albicans and mixed culture. Endodontology. 2010;
22:10–3.
128. Dhanya Kumar NM, Sidhu P. The antimicrobial
activity of Azadirachta
Indica, Glycyrrhiza glabrat, Cinnamum zeylanicum, Syzygium aromaticum, Acacia
nilotica on Streptococcus
mutans and Enterococcus
faecalis: An in vitro study. Endodontology. 2011;
23:18–25.
129. Okemo
P.O. et al, The kill kinetics of Azadirachta indica A. Juss (Meliacae) extracts
on Staphylococcus aureus, Escherichia coli, Pseudomonas aerugenosa and Candida
albicans African Journal of Science
and Technology (AJST) Science and Engineering Series. 2001; 2(2): 113-118
130. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an
overview, Annals of Biological Research,
2010, 1, (3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
131. Xu J et
al, Antiviral activity and mode of action of extracts from neem seed kernel
against duck plaque virus, Poult Sci. 2012 Nov; 91 (11): 2802-7
132. Vaibhav
Tiwari et al, In vitro antiviral activity of neem (Azadirachta indica
L.) bark extract against herpes simplex virus type-1 infection, Phytotherapy
Res. 2010 Aug; 24 (8): 1132-1140
133.
Badam L, Joshi SP, Bedekar SS, ‘In vitro’ antiviral activity of neem
(Azadirachta indica. A. Juss) leaf extract against group B coxsackie viruses, J
Commun Dis. 1999; Jun 31 (2): 79-90
135. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an
overview, Annals of Biological Research,
2010, 1, (3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
136. Rao, A.R., Kumar, S.S.U.,
Paramasivam, T.B., Kamalakshi, S., Parashuraman, A.R., and Shantha, M. (1969)
Study of antiviral activity of tender leaves of margosa tree (Melia
azadirachta) on vaccinia and variola virus - A preliminary report. Indian
Journal of Medical Research 57: 495-502.
137. Akihisa
T et al, Melanogenesis inhibitory, anti-inflammatory and chemoprotective Sci.
2009; 58(11): 581-94
138.
Bhatnagar et al, The inhibitory effect of of neem (Azadirachta indica)
leaf extracts on aflatoxin synthesis in Aspergillus parasiticus. Journal
of the American Oil Chemists’ Society. 1998; 65(7): 1166-1168
139.
Bohra N. K. , Purohit D. K., Effect of some aqueous plant extracts on toxigenic
strain of Aspergillus flavus , Advances in Plant Sciences, 2002;15 (1):
103-106
140.
Charmaine Lloyd A. C. et al, Anticandidal activity of Azadirachta indica,
Research Paper, 2005; 37(6): 386-389, http:// www.ijp-online.com
141.
Natarajan V et al, Antidermatophytic
activity of Azadirachta indica (neem) by in vitro study, Med Chem
Anticancer Agents, 2002; 5(2): 149-156
142.
Natarajan V, Venugopal P. V. Menon T., Effect of Azadirachta indica
(neem) on the growth pattern of dermatophytes, Indian Journal of Medical
Microbiology, 2003, 21(2): 98-101
143. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an overview,
Annals of Biological Research, 2010, 1,
(3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
144. Sharba Kausar et al, In vitro evaluation of antifilarial effect of
Azadirachta indica leaves extract in different solvents on the microfilariae of
Setaria cervi, Journal of parasitic diseases, January 2016
145. L. Radhakrishnan, S.
Gomathinayagam, V. Balakrishnan,
Evaluation of Anthelmintic Effect of Neem (Azadirachta indica) Leaves on
Haemonchus contours in Goats, Research Article, http://scialert.net/fulltext/?doi=jp.
2007.57.67
148. http://www.discoverneem.com/neem-oil-eczema.html
149. Akihisa
T et al, Melanogenesis inhibitory, anti-inflammatory and chemoprotective Sci.
2009; 58(11): 581-94
150. Manosroi
A et al, Limonoids from Azadirachta indica var. siamensis extracts and their
cytotoxic and melanogenesis-inhibitory activities, Chem Biodiverse. 2014 Apr;
11 (4): 505-31
151. Takagi M
et al, Cytotoxic and melanogenesis-inhibitory activities of limonoids from the
leaves of Azadirachta indica (Neem), Chem Biodivers. 2014 Mar; 11 (3): 451-68
152. Anjali Singh et al, Effect of Neem oil and Haridra on non-healing
wounds, Ayu, 2014 Oct-Dec; 35 (4): 398-403
153.
http://www.hillagric.ac.in/edu/covas/vpharma/winter%20school/lectures/32%20Neem%20medicinal%20values.pdf
154. Bwala DG et al, Management of surgical wounds using crude neem oil
in one year old ram: A successful report, National Veterinary Research
Institute, Plateau State, Nigeria; Journal of Veterinary Medicine and Animal
Health, Volume 36(6) pp75-78, October 2011
155. K. Chitta et al,
Nimbolide targets BCL2 and induces apoptosis in preclinical models of
Waldenstroms macroglobulinemia, Citation: Blood Cancer Journal (2014) 4, e260;
Published on line 7 November 2014
156. Manosroi
A et al, Limonoids from Azadirachta indica var. siamensis extracts and their
cytotoxic and melanogenesis-inhibitory activities, Chem Biodiverse. 2014 Apr;
11 (4): 505-31
157. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an
overview, Annals of Biological Research,
2010, 1, (3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
158. Jaiswal AK, Bhattacharya
SK, Acharya SB, Anxiolytic activity of Azadirachta indica leaf extract in rats,
Indian J Exp Biol 1994; 32(7): 489-491
159. N. R.
Pillai, G. Santhakumari, Johannes Laping, Some pharmacological actions of
‘Nimbidin’ – A bitter principle of Azadirachta indica-A Juss (Neem), Anc Sci Life, 1964 Oct-Dec; 4(2):
88-95
160. P. Khosla
et al, Antinociceptive activity of Azadirachta indica (Neem) in rats, Indian
Journal of Pharmacology 2000; 32: 372-374
161. Halim Eshrat M, Ali Hussain, Reversal of diabetic retinopathy in
streptozotocin induced diabetic rats using traditional Indian anti-diabetic
plant Azadirachta indica (L.), Indian Journal of Clinical Biochemistry,
July 2002, Volume 17, Issue 2, pp 115-123
162. Karkare S et al, Direct inhibition of retinoblastoma
phosphorylation by nimbolide causes cell cycle arrest and suppresses
glioblastoma growth, Clin Cancer Res. 2014 Jan 1; 20(1): 199-212
163. Sunanda Pandya, Anandkar, How safe is neem
extract with respect to Thyroid function in male mice? Pharmacological
Research, Volume 41, Issue 4, April 2000, pages 419-422
164. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an
overview, Annals of Biological Research,
2010, 1, (3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
165. Klaus Ferlow, HMH-10/2007, The Miraculous Neem, http://www.energygrid.com/health/2014/02kf-neem.html
166. Koley KM, Lal J, Pharmacological effects of Azadirachta indica
(neem) leaf extract the ECG and blood pressure of rat,Indian J Physiol
Pharmacol, 1994 Jul; 38 (3): 223-5
167. Veena Uniyal, R. P. Bhatt, Seema Saxena, Amitabh Talwar,
Antifungal activity of essential oils and their volatile constituents against
respiratory tract pathogens causing Aspergilloma and Aspergillosis by gaseous
contact, Journal of Applied and Natural Science; 4(1): 65-70 (2012)
168. Botelho M, Santos AD, Martin J, Carvalho C, Paz
M, Azenha C, et al. Efficacy of a mouthrinse based on leaves of neem in the
treatment of patient s with chronic gingivitis. J
Med Plant Res. 2008; 2:341–6.
169. Behl M, Sidhu O, Kumar V, Singh D, Saimbi C.
Efficacy of neem active metabolites for prevention of dental plaque and
gingivitis. Neem Foundation. 2002
170. Botelho M, Santos AD, Martin J, Carvalho C, Paz M,
Azenha C, et al. Efficacy of a mouthrinse based on leaves of neem in the
treatment of patient s with chronic gingivitis. J
Med Plant Res. 2008; 2:341–6.
171. Manikandan P, Letchoumy PV, Gopalkrishnan M,
Nagini S, Evaluation of Azadirachta indica leaf fractions for in vitro
antioxidant potential and in vivo modulation of biomarkers of chemoprevention
in hamster buccal pouch carcinogenesis, Food Chem Toxicol. 2008 Jul; 46(7):
2332-43
172. Harish Kumar G et al, The neem limonoids
azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in
an animal model of oral oncogenesis, Invest. New Drugs. 2010 Aug; 28 (4):
392-401
173. Pillai NR, Santhakumari G, Effect of nimbidin on
gastric acid secretion, Anc Sci Life 1985, Oct; 5(2): 91-7
174. Dorababu M, Joshi MC, Kumar MM, Chaturvedi A, Goel RK, Effect of
aqueous extract of neem (Azadirachta
indica) leaves on offensive and diffensive gastric mucosal factors in rats,
Indian J Physiol. Pharmacol, 2006, Jul-Sep; 50(3): 241-9
175. Dorababu M, Prabha T, Priyambada S, Agrawal VK, Aryya NC, Goel RK,
Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and
healing in experimental NIDDM rats, Indian J Exp Biol. 2004 Apr; 42(4): 389-97
176.
Koo MW, Cho CH, Ogle CW, Effect of cold-restraint stress on gastric ulceration
and motility in rats, Pharmacol Biochem Behav.
1986 Oct; 25(4): 775-9
178.
Bandopadhyay U etal, Gastroprotective effect of Neem (Azadirachta indica) bark
extract: possible involvement of H (+)-K(+)-ATPase
inhibition and scavenging of hydroxyl radical, Life Sci. 2002, Nov 1; 71(24):
2845-65
179.
Chattopadhyay l et al, Mechanism of antiulcer effect of Neem (Azadirachta
indica) leaf extract: effect on H+K+ATPase, oxidative damage and apoptosis,
Inflammopharmacology, 2004; 12(2): 153-76
180. Maity P et al, The use of neem for controlling gastric
hyperacidity and ulcer, Phytother Res. 2009 Jan; 23(6): 747-55
181. Raji Y, Ogunwande IA, Osadebe CA, John G, Effects of Azadirachta
indica extract on gastric ulceration and acid secretion in rats, J
Ethnopharmacol, 2004 Jan; 90(1): 167-70
182. R Subapriya, S Nagini,
Ethanolic Neem Leaf Extract Protects Against N-methyl
-N’-nitro-N-nitrosoguanidine-induced Gastric Carcinogenesis in Wistar Rats,
http://www.apocpcontrol.com/paper_file/issue_abs/Volume4_No3/S%20Nagini.pdf,
Neem Leaf Inhibition of MNNG Gastric Carcinogenesis, RESEARCH COMMUNICATION
183. Gupta SC et al, Nimbolide, a limonoid triterpene, inhibits growth
of human colorectal cancer xenografts by suppressing the proinflammatory
microenvironment, Clin Cancer Res. 2013 Aug 15; 19 (16): 4465-76
184.
Laxmi Narendra Bodduluru et al, Chemopreventive and therapeutic effects of
nimbolide in cancer: The underlying Mechanisms, Toxicology in Vitro, Volume 28,
Issue 5, August 2014, Pages 1026-1035
http://www.sciencedirect.com/science/article/pii/S0887233314000745
185. Ramadevi Subramani et al, Nimbolide inhibits pancreatic cancer
growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal
transition, Scientific Reports 6, Article number 19819, published 25 January
2016, htto://www.nature.com/articles/srep 19819
186. Veeraraghavan et al, Impact of Curcumin, Raspberry Extract and
Neem Leaf Extract on Rel Protein-Regulated Cell Death / Radiosensitization in
pancreatic Cancer Cells, Pancreas: October 2011-Volume 40-Issue7-pp1107-1119
190. Pravin V Gomase, Vinod D
Rangari, R. R. Verma, Phytochemical Evaluation
and Hepatoprotective Activity of Young Stem (Tender) Bark of Azadirachta
indica A. Juss, International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491 Vol 3, Suppl 2, 2011
191. N. S. Baligar et al,
Hepatoprotective activity of the neem-based constituent azadirachtin-A in
carbon tetrachloride intoxicated Wistar rats, Canadian Journal of Physiology
and Pharmacology, 2014, 92(4) 267-277
192.
Hepatoprotective effect of Azadirachta indica (Neem) leaves against alcohol
induced liver injury in albino rats, ARTICLE
193. R.R. Chattopadhyay, M.
Bandyopadhyay, Effect of Azadirachta indica leaf extract on serum lipid profile
changes in normal and streptozotocin induced diabetic rats, African Journal of
Biomedical Research, Vol. 8 (2005); 101 - 104 ISSN 1119 – 5096 © Ibadan
Biomedical Communications Group Available online at
http://www.bioline.org.br/md
194.
Singh, P. P., Junnarkar, A. Y., Thomas, G. P., Tripathi, R. M. and Varma, R.
K., ibid, 1980, 61, 164–168, CURRENT SCIENCE, VOL. 82, NO. 11, 10 JUNE 2002,
http://repository.ias.ac.in/5193/1/305.pdf
195. Chattopadhyay RR,
Possible mechanism of antihyperglycemic effect of Azadirachta indica leaf
extract. Part IV, Gen pharmacology: The Vascular System, 1966 Apr; 27 (3):
431-4
196. KN Bopanna, J Kannan, Gadgil Sushma, R Balaraman, SP Rathod,
Antidiabetic and antihyperlipaemic effects of neem seed kernel powder on
alloxan diabetic rabbits, Indian Journal of Pharmacology, 1997; 29 (3): 162-167
197. Prabhakar Patil et al,
Antidiabetic activity of alcoholic extract of Neem (Azadirachta indica) root
bark, National Journal of Physiol Pharm Pharmacol, 2013; 3(2): 142-146
198. V. P. Dixit, Rakesh Sinha, Rita Tank, Effect of neem seed oil on
the blood glucose concentration of normal and alloxan diabetic rats, Journal of
Ethnopharmacology, Volume 17, Issue 1, July 1986, Pages 95-98
199. N. R.
Pillai, G. Santhakumari, Johannes Laping, Some pharmacological actions of
‘Nimbidin’ – A bitter principle of Azadirachta indica-A Juss (Neem), Anc Sci Life, 1964 Oct-Dec; 4(2):
88-95
200. Prashant Patil et al, Effect of Neem oil on Sperm Mitochondrial
Activity, Free Online Journal Published
Quarterly: Mangalore, South India: ISSN 0972-5997 Volume 8, Issue 4; Oct - Dec
2009
201. S. S. Riar et al, Antifertility activity of volatile fraction of
neem oil, Contraception, Volume 44, Issue 3, September 1991, pages 319-326
202. Jaya Bardhan et al, A
fertility controlling agent in rhesus monkey, Indian Journal of Physiol
Pharmacol, 1991; 35(4) 278-280
203. Despande, V. Y., Mendulkar, K. N. and Sadre, N. L., Male antifertility
activity of Azadirachta indica in mice, J. Postgrad. Med. (Bombay) Year: 1980,
Volume: 26, Issue: 3, page: 167-70
204.
Jackson, H.: Development of antifertility substances, Progress in Drug
Research, 7: 133-192, 1964
205. Despande, V. Y.,
Mendulkar, K. N. and Sadre, N. L., Male antifertility activity of Azadirachta
indica in mice, J. Postgrad. Med. (Bombay), Year: 1980, Volume: 26, Issue: 3,
Page: 167-70
206. Mukharjee S, Garg S,
Talwar G. P., Early post implantation contraceptive effects of purified
fraction of Neem (Azadirachta indica) seeds, given orally in rats: Possible
mechanisms involved, J Ethnopharmacol 11-30-1999; 67 (3): 287-296
207. P. Sudhir Kumar, Debasis Mishra, Goutam Ghosh, Chandra S.
Panda, Biological action and medicinal
properties of various constituents of Azadirachta indica (Meliaceae), an
overview, Annals of Biological Research,
2010, 1, (3): 24-34; http://scholarsresearchlibrary.com/abr-vol-1-iss3.html
208.Talwar, G. P., Shah, S.,
Mukherjee, S., and Chabra, R. Induced termination of pregnancy by purified
extracts of Azadirachta Indica (Neem): mechanisms involved. Am J Reprod Immunol 1997; 37(6):485-491.
209. Mahapatra S et al, Novel
molecular targets of Azadirachta indica associated with inhibition of tumor
growth in prostate cancer, AAPS J. 2011 Sep; 13 (3): 365-77
210. Wu Q et al, Preclinical evaluation of the
supercritical extract of Azadirachta indica (neem) leaves in vitro and in vivo
on inhibition of prostate cancer tumor growth, Mol Cancer Ther 2014 May; 13
(5): 1067-77
211. Kumar S et al, Anticancer effects of ethanolic neem
leaf extract on prostate cancer cell line (PC-3), J Ethnopharmacol, 2006 Apr
21; 105 (1-2): 246-50
212. Shakti N et al, Antifertility Effects of Neem (Azadirachta indica)
Oil by Single Intrauterine Administration: A Novel Method for Contraception,
proceedings of the Royal Society B, Biological Sciences, 22 December 1990.
213. Priyadarshini RV, Murugan RS, Sripriya P, Karunagaran D, Nagini S,
The neem limonoids azadirachtin and nimbolide induce cell cycle arrest and
mitochondria-mediated apoptosis in human cervical cancer HeLa) cells, Free
Radic Res. 2010 Jun; 44 (6): 624-34
214. Haque E, Mandal I, Pal S,
Barel R, Prophylactic dose of neem (Azadirachta indica) leaf preparation
restricting murine tumor growth is nontoxic, hematostimulatory and
immunostimulatory, Immunopharmacol Immunotoxicol. 2006; 28(1): 33-50
215. Roy MK, Kobori M,
Takenaka M, Nakahara K, Shinmoto H, Tsushida T. Inhibition of colon cancer
(HT-29) cell proliferation by a triterpenoid isolated from Azadirachta indica
is accompanied by cell cycle arrest and up-regulation of p21. Planta Med 2006;
72: 917–923.
216. Elumalai P et al,
Induction of apoptosis in human breast cancer cells by nimbolide through
extrinsic and intrinsic pathway, Toxicol Lett. 2012, Nov 30; 215(2): 131-42
217. Arumugam A et al, Neem
leaf extract inhibits mammary carcinogenesis by altering cell proliferation,
apoptosis and angiogenesis, Cancer Biol. Ther. 2014 Jan; 15 (1): 26-34
218.
http://www.ncbi.nlm.nih.gov/pubmed/24722271
219. AR Suresh,
P Rajesh, KS Anil Raj, Radhika Torgal, A rare case of toxic optic neuropathy
secondary to consumption neem oil, Indian J Ophthalmol. 2014 Mar; 62(3):
337-339, drsureshaar@yahoo.co.in
220. Gandhi M et al, Acute toxicity study of the oil
from Azadirachta indica seed (neem oil) J Ethnopharmacol, 1988; 23 (1): 39-51
221. Brahmachari G, Neem- an omnipotent plant: a
retrospection, Chembiochem, 2004; 5(4): 408-421
222. Sinniah D, Margosa oil poisoning as a cause of
Reye’s syndrome, Lancet, 1981, Feb 28; 1 (8218): 487-9
223. Lai SM, Lim KW, Cheng HK, Margosa oil poisoning
as a cause of toxic encephalopathy, Singapore Med J. 1990 Oct; 31 (5): 463-5
224. Dhongade
RK, Kavade SG, Damle RS, Neem oil poisoning, Indian Pediatr. 2008 Jan; 45(1):
56-7
225. Bruna
Dallaqua et al, Treatment with Azadirachta indica in diabetic pregnant
rats: Negative effects on maternal outcome, Journal of Ethnopharmacology,
Volume 143, Issue 3, 11 October 2012, pages 805-811
226. Onimisi
BO, Nadabo YA, Musa SA, Musa MA, Nephrotoxic Effects of Methanolic Extract of
Azadirachta Indica (Neem) Root Bark on The Adult Wistar Rats, International
Journal of Health Sciences and Research (IJHSR) 2015; 5 (4): 116-121
230. https://
en.wikipedia.org
234. https:/en.wikipedia.org
238. http://en.wikipedia.org
242. https://en.wikipedia.org
Comments