Bhumyamalaki (Phyllanthus niruri, Phyllanthus amarus)
Bhumyamalaki
(Phyllanthus
niruri, Phyllanthus amarus)
By
Dr. Hemant Vinze M. S.
Introduction
Bhumyamalaki (Phyllanthus niruri- Phyllanthus amarus) is principally a kharif
crop (growing in rainy season) growing as a contaminant weed in cultivated
fields and in wasteland. Traditionally though a trusted medicine, it is not
cultivated as “medicinal plant” but is gleaned from fields or is gathered
directly from forests or wastelands. Since the weed reduces the crop yield by
10 to 15% it is considered a ‘nuisance’ by farmers. However it obliges the
medical fraternity and mankind by its pleiotropic actions. The herb is extolled
in Ayurveda and by herbalists. The herbalists
used to sell it in fairs and marketplaces. It is their wont even
today. It has a long history in herbal systems of medicine in every tropical
country where it grows. The way indigenous people employ it (standard infusion
or weak decoction of the whole plant) is also very similar worldwide. [1], [2]
As
the shrub grows close to the ground and its leaves resemble those of Aamalakee
(Amalaki) its Sanskrit epithet is Bhumyamalaki (Bhumamalaki). Another Sanskrit
epithet is Bhoodhaatree (Bhoodhatri). Bhoo stands for earth and Dhaatree means
a foster mother. Indigenous to India, for eons, this was a valuable drug in the
medicinal chest of the proverbial grandmothers and the laity. In India, even today, it is a common household remedy for
asthma, bronchitis, extreme thirst, jaundice and tuberculosis.
Also indigenous to the
Bahamas, it is called hurricane weed or gale-wind grass. It is used there for
poor appetite, constipation, fever, cough and cold. [3]
The Spanish name for P. amarus / P.niruri is Chanca Piedra. Translated in English
it means “Shatter stone” or “Stone breaker” because the indigenous peoples of
the Amazon have been using it to eliminate kidney stones and gallstones and is
still in vogue there. “Stone breaker”! Quite an epithet to live up to! [4],
[5]
In
South America even in modern times, P. amarus is the most popular remedy
for the treatment of gallstones and kidney stones.
It
is very popular in Peruvian herbal medicine for the treatment of hepatitis,
urinary tract infection (UTI) and as diuretic.
In Brazilian herbal medicine
it is considered an excellent remedy to remove urinary stones especially uric
acid stones. [6]
The flowers that seem to be
borne on the leaves are called foliage flowers. Hence the epithet of the genus of this herb is Phyllanthus. [7]
Charles von Linne was a Swedish
physician, botanist and zoologist. Better known as Carl Linnaeus, he was the
father of modern taxonomy and ecology. The epithet of this species niruri (“Shatter stone” or “break
stone”) was assigned to this plant by Carl Linnaeus, and comes from its Indian
vernacular name. [8]
Though
the plant has been used to treat/cure afflictions of various systems, for want
of scientific documentations and clinical research, the skeptics considered the
claims of cure more as a bluff than as a plant wonder. However phytochemical
research since 1960 and clinical research thereafter established its pleiotropic actions. These actions were
attributed to its remarkably complex chemical composition. [9], [10]
Other Names
Taxonomic: Phyllanthus niruri L. Phyllanthus fraternus Webster
Phyllanthus
amarus, Phyllanthus urinaria
Sanskrit: Bhumyamalaki (Bhumamalaki),
Bhoodhaatree
English: Stone
breaker, Seed under leaf
Aassamese: Bhui Aamala,
Bengalee: Bhumamala, Bhumi-Aamalakee
Gujarati: Bhoy aawalee, Bhoy aamalee, Kanocha, Ranavli
Hindi: Bhueeaaolaa,
Kanocha, Kanochha, Ranavli, Jar-Aamalaa
Kannada: Madarasa nelli, Nelanelli
Malayalam:
Keezharnelli
Marathi: Bhueeaawalaa,
Bhueeaawalee.
Tamil: Mela nelli, Keezharnelli
Telugu: Nullausereki, Nallausirike
AKA
Spanish: Chanca Piedra, Portuguese: Quebra
Pedra [11], [12]
Taxonomic classification
Kingdom: Plantae
(Unranked):
Angiosperms
(Unranked): Eudicots
(Unranked):
Rosids
Phyllum: MAG/agnoliphyta
Phyllanthus is the largest genus in the family Phyllanthaceae. It includes 500 to 1200 species
growing in temperate and tropical zones. Many of them are of medicinal value.
The genus has a remarkable diversity of growth forms but the species express more or less similar pattern. In recent times the family Phyllanthaceae is divided
into four genera.
Phyllanthus urinaria, Phyllanthus amarus
and Phyllanthus
niruri are similar species. The
difference is that P. amarus has
larger leaves than the other two and its fruit is wart-like.
Geographical distribution
This annual plant is a widespread tropical and
subtropical plant commonly found as a weed in coastal areas and sandy regions.
Although its botanical center of origin is unknown; it is regarded as
indigenous to central and southern India, China, tropical areas of the Bahamas
and other tropical areas throughout the world and the rainforests of Amazon. [15],
[16]
Plant Morphology
Bhumyamalaki Phyllanthus amarus Leaves and Plant
Bhumyamalaki Phyllanthus niruri/Phyllanthus amarus Flowers
Bhumyamalaki
Phyllanthus niruri/Phyllanthus amarus Fruits
Macroscopic Characteristics
This
is a small, glabrous and erect annual herb. It grows 10 to 70 cm tall.
Root:
is small, 2.5-11 cm long, nearly
straight, gradually tapering with a number of fibrous secondary and tertiary
roots; external surface light brown in color; fracture is short.
Stem: is slender, glabrous, yellowish or light brown, woody, terete
(cylindrical), 20-75 cm long; branching is profuse, bearing 5-10 pairs of
leaves; with internode 1-3.5 cm long.
Bark: is smooth and light green. Younger parts are rough.
Leaf: Leaves are numerous. The leaf is compound,
leaflets are arranged in two rows with a rachis; alternate, opposite, elliptic-oblong
or obtuse, distichous (arranged alternately in two vertical rows on opposite
sides of the axis), sessile, stipulate, entire, 1.5 cm long and 0.5 cm wide;
greenish brown in color.
Flowers: numerous,
pale green which are often flushed with red. They are axillary, monoecious (having the male and female reproductive organs on
different parts). In the South Hemisphere, they bloom from July to April
and in the North Hemisphere, from January to October.
Fruits: are
tiny, 1.8 mm in diameter, rounded smooth capsules.
Seeds: about 0.9 mm long,
triangular, with 6-7 longitudinal ribs and many
transverse striations on the back [18], [19], [20], [21], [22]
Microscopic
Characteristics
Root: The transverse section shows 4-6 layers of cork
consisting of thin-walled, rectangular, tangentially elongated and radially
arranged cells filled with reddish-brown contents; the secondary cortex
consists of 8-10 layers of thin-walled, elongated, parenchymatous cells. The
secondary phloem narrow, consists of sieve elements, phloem parenchyma is
traversed by narrow phloem rays. The secondary xylem is represented by a broad
zone of tissue composed of vessels, tracheids, fibers and parenchyma, all
elements being thick-walled and lignified with simple pits; xylem rays are
uniseriate.
Stem:
The transverse section shows a single
layer of epidermis, composed of thick-walled, flattened tangentially elongated
cells. An older stem shows 4-5 layers of cork composed of thin-walled, tabular,
tangentially elongated and radially arranged cells filled with reddish brown
contents. The cortex is composed of 4-6 layers of oval, tangentially elongated
thin-walled, parenchymatous cells and some cortical cells filled with yellowish
brown content. The endodermis is quite distinct. The pericycle represented by a
discontinuous ring composed of several tangentially elongated strands of
lignified fibers with thick walls and narrow lumen; secondary phloem is narrow,
composed of sieve elements, dispersed in a mass of phloem parenchyma; secondary
xylem is composed of vessels, fibers and parenchyma and is traversed by
numerous uniseriate rays. The vessels are mostly simple pitted with a few show
spiral thickenings. The fibers are narrow, elongated, with narrow or sometimes
blunt ends with simple pits; the centre is occupied by a pith composed of
thin-walled, circular to oval parenchymatous cells and occasionally clustered
crystals of calcium oxalate are present in parenchymatous cells of brown
tissue.
Leaf:
The transverse section of leaf shows
a biconvex outline. The epidermis on either side is a single layer covered
externally by a thick cuticle; a palisade layer is present beneath the upper
epidermis, intercepted by a few parenchymatous cells in the middle. The
meristele is composed of small strands of xylem towards the upper surface and
phloem towards the lower surface; the rest of the leaf tissue is composed of
thin-walled parenchymatous cells, some having clusters of calcium oxalate
crystals. The lamina shows a dorsi-ventral structure, with mesophyll
differentiated into palisade and spongy parenchyma. The epidermis on either
side is composed of thin-walled tangentially elongated cells covered externally
by a thick cuticle; anisocytic-type stomata are present on both epidermises;
single layer palisade; mesophyll is composed of 3-5 layers of loosely arranged
cells with a number of veins traversing this region; a few clusters of calcium
oxalate crystals are present in spongy parenchyma.
Powder: The drug powder is brown in color; under the
microscope it shows fragment of cork cells, vessels and fibers. [23], [24],
[25]
Parts Used
Root,
leaves, fruits, milky juice, and whole plant
Phytochemistry
The
phytochemical constituents are:
1. Flavonoids: Rutin, Quercetin,
Quercitrin, Astragalin, Catechin, Prenylated flavone glycoside, Nirurin,
Niruriflavone,
2.
Terpenes: Linonene, p-chymene,
Lupeol, Lupeol acetate
3.
Coumarins: Ellagic acid,
Methylbrevifolincarboxylate,
4.
Major lignans: Phyllanthin and Hypophyllanthin, Phylltetralin,
Niranthin, Hdroxyniranthin,
Dimethylenedioxyniranthin, Nirtetralin, Isolintetralin, Lintetralin.
5. Minor lignans: Phyllanthusiin D, Amariin, Amarulone, Amarinic acid.
6. Tannins: Repandusinic acid, Geranin, CorilAG/agin.
7. Saponins: Diosgenin
8. Alkaloids: Norsecurinines, Nirurine, Phyllanthine,
Phyllochrysine,
Sobubbialine,
Epibubbialine, Diarylbutane, Nyrphyllin and alkaloids of the quinazolidine
type.
9. Other compounds: Beta-glucogallin, Linear and complex hetero xylans,
Nirurisise
10. Hydrocarbons: Triacontanal, Triacontanol
11. Common lipids
12. Phytosterols
Table 1. Phytochemicals
of Phyllanthus niruri/ Phyllanthus amarus
Flavonoids
|
Rutin, quercetin,
quercitrin, astragalin, catechin,
prenylated flavone glycoside,
nirurin, niruriflavone
|
Terpenes
|
Linonene, p-chymene, lupeol, lupeol acetate
|
Coumarins
|
Ellagic acid, methylbrevifolincarboxylate
|
Major lignans
|
Phyllanthin and hypophyllanthin, phylltetralin,
niranthin,
hdroxyniranthin,
dimethylenedioxyniranthin, nirtetralin, isolintetralin,
lintetralin
|
Minor lignans
|
Phyllanthusiin D, amariin,
amarulone, amarinic acid
|
Tannins
|
Repandusinic acid, geranin, corilagin
|
Saponins
|
Diosgenin
|
Alkaloids
|
Norsecurinines, nirurine, phyllanthine, phyllochrysine,
sobubbialine, epibubbialine, diarylbutane, nyrphyllin and alkaloids of the quinazolidine
type
|
Other compounds
|
Beta-glucogallin, linear and complex hetero xylans,
niruriside
|
Hydrocarbons
|
Triacontanal, triacontanol
|
Common lipids
|
Exact information not available
|
Phyosterols
|
Exact information not available
|
[26]
Table 2. Phytochemicals in Various Parts of Phyllanthus niruri/ Phyllanthus amarus
The whole plant
|
Rutin, Quercetin, Quercitrin, Prenylated flavone glycoside, Nirurin,
Ellagic acid, Hypophyllanthin, Repandusinic acid, Geranin, Corilagin,
Diosgenin, Norsecurinines, Beta-glucogallin, Linear and complex hetero
xylans, Nirurisise
|
Leaf
|
Quercitrin, Astragalin, p-chymene, Phyllanthin, Niranthin,
Hdroxyniranthin, Dimethylenedioxyniranthin, Nirtetralin, Isolintetralin,
Lintetralin. Phyllanthine
|
Root
|
Catechin, Lupeol,
Phyllanthine
|
Stem
|
Phyllanthine
|
Aerial parts
|
Nirurine,
Triacontanal, Triacontanol
|
[29], [30]
Identity, Purity and strength Tests
(1)
Foreign matter:
Not more than 2 percent
Total ash: Not
more than 16 percent
Acid-insoluble ash: Not more than 7 percent
Alcohol-soluble extractive: Not less than 3 percent
Water-soluble extractive: Not less than 13 percent [31]
(2) Standards accepted by I.P. in 2010
Foreign organic matter: Not more than 2.0 %
Ethanol-soluble extractive: Not less than 6.0 %
Water-soluble extractive: Not less than 15.0 %
Total Ash: Not more than 8.0 %
Acid-insoluble ash: Not more than 5.0 %
Heavy metals 1.0 g complies with the limit test for heavy metals, Method
B (20 ppm).
Loss on drying Not more than 12.0 per cent, determined on 5 g by drying in
an oven at 105°C.
Microbial contamination Complies with the microbial contamination tests. [32],
[33]
Color
Tests for identification
Observed
colors after treating the solution of P. amarus ( Phyllanthus amarus)
are:
1.
Conc. HCl Green
2.
NaOH (5%) Brown
3.
KOH (5%) Brown
4.
FeCl3
Green to dark green.
TLC
Patterns
Recently
TLC, HPLC patterns are also used for the identification of P. amarus. [34]
Various
assays are also available to establish the identity of P. amarus [35]
Cytological
Identification
The no of chromosomes in Phyllanthus amarus (Schumach & Thonn) is 7 [36]
Genetic Identification
Although above-mentioned tests are useful to identify P.niruri genetic identification method is gold standard.
Recently
SCAR markers are developed for the correct identification of Phyllanthus
species. [37]
Purity Tests (Accepted
Internationally)
Foreign
Matter: Not more than 2%
Ash
content:
Total
Ash: Not more than 9%
Acid-soluble
Ash: Not more than 2%
Loss
on drying: Not more than 10%
Extractive
Values:
(A) Water-soluble Extract
Hot Method: Not less than 21%
Cold Method: Not less than 14%
(B) Ethanol-soluble Extract
Hot Method: Not less
than 13%
Cold Method: Not less
than 7%
Safety Tests
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
[38]
Aflatoxins (as per international guidelines)
Preferably Aflatoxins should be below
detectable limits (BLD) [38c], [38d]
Specific
Pathogens: (as per international guidelines)
Salmonella species: Absent in 25 g /none
Escherichia coli: Absent in 1g / maximum 102 to 104
per gram
Staphylococcus aureus: Absent in 1g
Pseudomonas aeruginosa: Absent
in 1g
Shigella
species:
Enterobacter
species: maximum 104 per gram
Other
enterobacteria: maximum 103
per gram
Aerobic
bacteria: maximum 105
to 107 per gram
Mould
propagules: maximum 103 to 105 per
gram
Yeasts
and Mould: maximum
103 to 104 per gram [38a], [38b]
Aflatoxins (as per international guidelines)
Aflatoxin
B1, Aflatoxin B2, Aflatoxin G1, Aflatoxin G2
Preferably Aflatoxins should be below
detectable limits (BLD) [38c], [38d]
Pesticide residues (as per
international guidelines)
In recent times various pesticides are used to protect and preserve the
food and medicinal values of plants.
To avoid toxicity of herbal medicine, International Society for
Standardization of Drugs and World Health Organization (WHO) have laid the guidelines
for permissible levels of pesticides in herbal medicines.
In general, the pesticide contamination in any herbal medicine should
be less than 1 percent of total intake from all sources, including food
and drinking water.
Aldrin and dieldrin are broad spectrum pesticides
commonly used in agriculture. The recommended maximum limit of these pesticides
is Not more than 0.05 mg/kg. [38e],
[38f]
Radioactive residues (as per
international guidelines)
A certain amount of exposure to ionizing radiation of plants cannot be
avoided since there are many sources, including radionuclides occurring
naturally in the ground and the atmosphere.
The World Health Organization (WHO), in close collaboration with
several international organizations, has developed guidelines for permissible
and acceptable limits for radioactive residues in herbal medicines.
The amount of radiation in plants depends on intake of radionuclides.
Significant risk is associated only with consumption of quantities over 20 kg
of plant material per year so that the risk to health is most unlikely to be
encountered given the amount of medicinal plant materials need to be ingested.
Additionally, the level of contamination might be reduced during the
manufacturing process. Therefore World Health Organization (WHO) has not
proposed strict limits regarding the acceptability for radioactive
contamination. [38g]
Properties and Pharmacology
Ayurvedic Properties
Ganas (Classical Categories)
Charaka Ganas: None
Sushruta+Ganas: None
Energetics
Wipaaka/ Vipak (End result, Post digestive effect): Madhura (sweet)
Note: Here I wish to clarify the
meaning of these technical words:
Virya (Weerya): Potency, power,
vigor
Vipak (Wipaak): After digestion change of taste. The food we take is
acted upon by jatharagni (digestive activity) and the taste of the food
changes. The original rasa (taste) changes to vipak (new or same taste.)
Prabhav (Prabhaawa): Effect, prominent, peculiar or special action of an
herb. Innate and specific property [39]
Effects
on Doshas: Kapha, Pitta
Actions
on Dhaatus (Tissues):
Asthi (Bones: Healing fractures), Rasa (Lymphatics), Rakta (Blood)
Actions
on Srotas (Systems): Annawaha (Gastro-Intestinal Tract), Raktawaha
(Hemopoetic System), Mootrawaha (Urinary System)
Deepana:
Appetizer
KaphAG/aghna:
Allays
catarrhal inflammations
KushthAG/aghna:
Antileprotic
and useful in skin disorders
Krimighna:
Anthelmintic
and anti microbial
JwarAG/aghna:
Anti-pyretic
Mootrala:
Diuretic
Paachana:
Digestive
(Digestant)
Rakta-Pradara:
Allays menorrhagia
Rakta
pitta shaamaka: Allays rakta pitta (innate haemorrhage,
internal bleeding)
Rakta
shodhaka: Blood purifier
Shweta
pradara: Relieves leucorrhea
Wranaropana: Vulnerary (Wound
healer)
Yakruduttejaka:
Stimulates
the functions of the liver [40], [41]
According
to Ayurvedic system of medicine it is considered alexipharmic (acting as
antidote to poisons) and vulnerary.
Modern View
Some recent studies show
that P. amarus is febrifuge,
antiseptic, astringent, stomachic and diuretic.
The fresh plant extract and the methanol extract show
antioxidant activity.
Some therapeutic properties
of P. amarus include
anti-hepatotoxic, anti-lithic, anti-hypertensive, anti-HIV and anti-hepatitis B
activity. [42]
Given orally to mice the whole plant extract shows marked
radioprotective activity by decreasing the damage to intestinal cells,
decreasing the percentAG/age of chromosomal aberration, decreasing the lipid
peroxidation levels and by elevating the levels of antioxidant enzymes in the
intestines, liver and blood.
Radioprotective activity of P. amarus is attributed to ellagitannins
(amariin, 1-galloyl-2, 3-dehydrohexahydroxydiphenyl (DHHDP)-glucose,
repandusinic acid, geraniin, corilagin, phyllanthusiin D) and flavonoids
(rutin, and quercetin 3-O-glucoside). [43]
To study the protective
effect of the extract of P. amarus AG/against
the damage induced following radiation, 250mg/kg and 750mg/kg of the extract
were administered orally to mice for five days prior to and for one month after
6 Gy whole body radiations. Treatment with P.
amarus extract significantly increased the total white cell count in the
blood, cellularity of the bone marrow and alpha-esterase activity as compared
to untreated animals exposed to radiation. The treatment also increased the
activity of Superoxide Dismutase (SUPEROXIDE DISMUTASE (SOD)), Catalase (CAT),
Glutathione-S-Transferase (GST), Glutathione Peroxidase (GPX), and Glutathione
Reductase (GR), both in the blood and in the tissues, which were reduced by
radiation treatment. There was also a significant increase in the glutathione
(GSH) levels of blood and tissues. Lipid peroxidation levels, which were
increased after radiation, were significantly reduced by the treatment, both in
serum and liver. These results indicate that P. amarus extract increases the antioxidant defense mechanism in
mice and thereby protects the animals from damage induced by radiation. [44]
Administration of 75%
methanolic extract of P. amarus at
doses 250 and 750 mg/kg body weight significantly reduced the myelosuppression
caused by cyclophosphamide. It improved the WBC count, bone marrow cellularity
and the number of maturing monocytes. It reinstated glutathione levels. When administered simultaneously with
cyclophosphamide it did not interfere with anticancer activity of cyclophosphamide
but reduced its toxic effects thus exhibiting chemoprotective activity. [45]
When given orally to male mice the aqueous crude extract causes
varying degrees of decline in fertility. When given orally to female rats at
the dose of 100 mg/kg bodyweight for 30 days, the alcoholic extract of the
whole plant shows significant contraceptive effect.
The methanol extract of the leaves of P. amarus (Dose: 50 to 800 mg/kg) caused a significant
decrease in the elevated levels of total
cholesterol, AST, ALT, urea, uric acid, alkaline and acid phosphatases, thus
exhibiting cardioprotective, hepatoprotective and nephroprotective properties. [46]
Rutin
Molecular
formula: C27H30O16
Structural
formula:
Other
names: Rutoside, Phytomelin, Sophorin, Birutan, Eldrin and
many more.
Rutin
is the glycoside between the flavonol quercetin and the disaccharide rutinose.
Its chemical structure is very much similar to that of quercetin.
Rutin
is a plant pigment found in fruits and vegetables and contributes to the antibacterial
properties of the plants.
Rutin
is anti-inflammatory, stronger anti-oxidant than quercetin. Rutin inhibits
platelet aggregation, decreases capillary permeability and improves
circulation. It inhibits vascular endothelial growth factor, thus inhibiting
angiogenesis in tumors.
In
rats rutin increases iodine uptake by thyroid without raising serum T3 T4 [47]
Quercetin
Molecular formula: C15H10O7
Strucural formula:
[48]
Quercetin is a flavonoid (plant pigment).
Quercetin is found in fruits, vegetables,
leaves, grains and various types of honey. It is found in red wine, onions,
green tea, apples, berries, Ginkgo biloba and St. John’s wort.
It is used in beverages and as a food
supplements. [49]
Quercetin is anti-inflammatory (hence used
in fibromyalgia rheumatoid arthritis and gout). It is anti-oxidant. It is
anti-microbial and anti-viral. It inhibits reverse transcriptase, part of the
replication process of retrovirus. It is anti-allergic hence is used in hay
fever, bronchial asthma and eczema. It is used to treat diabetes and metabolic
syndrome. It is Monoamine-Oxidase (MAO) inhibitor. It is used in treating
dyslipidemia and atherosclerosis. It is also used to boost immunity, increase
endurance and improve athletic performance.
Quercetin competitively binds to bacterial DNA gyrase. Hence it is
contraindicated with some antibiotics especially fluoroquinolones. [50]
Quercetin
and Alcoholic Liver Disease
Disorder of lipid metabolism
and oxidative stress are the important factors in the pathogenesis and
progression of Alcoholic Liver Disease (ALD). The mitochondria compartment of
the hepatocytes is the main target of this oxidative stress. Therefore
antioxidants and free radical scavengers should counter this damage.
In animals pretreated with
quercetin, ethnol-stimulated mitochondrial dysfunction was ameliorated. [51]
Quercetin
downregulates the ethanol-induced expression of glutathionine peroxidase 4
(GPX4). Quercetin reduces the ethanol-induced expression of SUPEROXIDE
DISMUTASE (SOD) 2 to downregulate the expression of Gadd45b which can damage
DNA of hepatocytes which in turn culminates in ALD. [52]
Quercetin AG/against HCV
Infection
Quercetin and its
five derivatives have shown selective anti-HCV activity. These molecules by
inhibiting NS3 and heat shock proteins suppress the replication of hepatitis C
virus. (Heat shock proteins are essential for HCV replication). Quercetin has a
direct inhibitory action on HCV NS3 protease. The inhibition of NS3 by
quercetin is dose dependent. [53], [54]
Quercetin AG/against HBV
Infection
The flavone glucoside in the
structure of quercetin plays an important role in exhibiting anti-hepatitis B
activity. In addition, substitution of acyl group on glucoside may be important
for anti-HBV activity. Quercetin does not show activity against HBeAg
secretion. This is due to the absence of saccharide group in the structures of
quercetin. [55], [56]
For
more information about quercetin ref. to Aamalakee (Emblica officinalis)
Quercitrin
Molecular
formula: C21H20O11
Structural
formula:
Quercitrin is a glycoside formed from
quercetin and rhamnose. It is anti-inflammatory. It exhibits antioxidant and
free radical scavenging activity probably via some different mechanism hitherto
not clearly understood [57]
Catechin
Molecular
formula: C15H14O6
Structural
formula:
Catechin has
been found to be the most powerful antioxidant and free radical scavenger among
different members of the different classes of flavonoids. [58]
Lupeol
Molecular Formula: C30H50O
Structural Formula of
Lupeol:
Lupeol is a pharmacologically active triterpenoid. It is anti-inflammatory.
It decreases IL4 production by T-helper type 2 cells. Lupeol has complex
pharmacological actions in humans, displaying antimicrobial, antiprotozoal,
antitumor and chemoprotective properties. In laboratory models it inhibits
prostate and skin cancers. [59]
Phyllanthin and Hypophyllanthin:
Molecular formula: Phyllanthin C24H34O6
Structural formula: Phyllanthin
[60]
Phyllanthin
Molecular formula: Hypophyllanthin C24H30O7
Structural formula: Hypophyllanthin
[61]
Hypophyllanthin
Phyllanthin and Hypophyllanthin are major lignans. They inhibit DNA polymerase and
reverse transcriptase of hepatitis B virus, Woodchuck hepatitis virus and
retroviruses. Thus they arrest their replication.
Phyllanthin and hypophyllanthin present in P. amarus inactivate
hepatitis B virus, both in vitro and in vivo. [62]
Chanca
piedra (Phyllanthus amarus)
lowers blood cholesterol, low density lipoprotein and very low density
lipoprotein by reducing the ability of the liver to synthesize cholesterol and
by increasing the fecal (faecal) bile acid excretion. These effects on blood
and liver were attributed to phyllanthin and hypofhyllanthin found in P.
amarus. [63]
KB
cell culture is a cell line derived from a human carcinoma of the nasopharynx.
Since 1960 it has been used by the National Cancer Institute (NCI) as an anti
tumor assay for screening antitumor activity of plant extracts. This in
vitro assay is more sensitive than in vivo assay. It is less
expensive, requires less test material and less time. Phyllanthin and
Hypophyllanthin enhance the cytotoxic response mediated by vinblastine with
multidrug-resistant KB cells. [64]
These
lignans show activity AG/against Ehrlich ascites carcinoma in mice. They have
protective effect in doxorubicin induced toxicity. [65]
Along
with phyllanthin and hypophyllanthin the hexane extract contains nirtetralin,
niranthin. They exert cytotoxic effects on 2 human leukemia cell lines. They
reverse the multidrug resistance of many cancer cells as well.
The
ethanolic extract of P. amarus is
valuable in preventing BPH in rats.
Phyllteralin, Nirtetralin, Niranthin
Phyllteralin,
Nirtetralin, Niranthin are lignans. They
exhibit anti-inflammatory and anti-allodynic actions. Of these nirtetralin is
the strongest one. These actions are probably mediated through their direct antAG/agonistic
actions on the PAF binding receptor sites. (Allodynia means ‘other pain’ i.e.
pain due to a stimulus which normally does not provoke it. It can be static or
moving or migrating. It can be perceived in areas other than the one
stimulated. This is not ‘referred’ or ‘radiating’ as it is not perceived along
a dermatome.)
In studies conducted by
Department of Pharmacology, Center of Biological Sciences, Universidade Federal
de Santa Catarina (UFSC), Florianopolis, SC, Brazil, to study anti-inflammatory
effects of P. amarus the hexane extract and lignans; phyltetralin,
nirtetralin, niranthin isolated from P.
amarus were given orally to experimental animals. These lignans inhibited
carrageenan induced paw edema, neutrophil influx and interleukin-1 beta tissue
levels. They also significantly inhibited paw edema induced by bradykinin (BK),
platelet activating factor (PAF) and endothelin-1 (ET-1); while the edema
induced by histamine and substance P was unaffected.
Nirtetralin
and niranthin are reported to possess hepatoprotective action. Cytotoxic
actions of nirtetralin, niranthin, and phyllanthin on two human leukemia cell
lines, K-562 and Lucena-1, suggest that they may be MDR reversing AG/agents in
the realm of chemotherapy of malignancies.
Nirtetralin
and nirtetralin A and B effectively suppress the secretion of HBV antigens in a
dose-dependent manner. [66], [67], [68]
Diosgenin
Molecular formula: C27H47O3
Structural formula:
Diosgenin a steroid sapogenin is the
product of hydrolysis by acids, strong bases or enzymes of saponins.
Diosgenin is the precursor for the semi
synthesis of progesterone which in turn was used in early combined oral
contraceptive pills. The unmodified steroid has estrogenic activity. It can
reduce the serum cholesterol levels.
Diosgenin is used for the commercial
synthesis of cortisone, pregnenolone, progesterone and many other steroid
products. [69]
In obesity, adipocyte hypertrophy and
chronic inflammation in adipose tissue cause insulin resistance and type-2
diabetes. Diosgenin decreases the size of adipocytes and reduces inflammation
of the adipose tissue by inhibiting macrophage infiltration of the adipocytes.
Thus diosgenin ameliorates diabetes. [70]
The steroidal saponin diosgenin induces apoptosis in
HT-29 human colon cancer cells (at least in part) by inhibition of bcl-2 and by
induction of capsase-3 protein expression. It also inhibits azomethane-induced
aberrant crypt foci (ACF) formation in F344 rats or preneoplastic colonic
lesions. Further detailed studies show that, in rats, diosgenin prevents
azoxymethane-induced colon carcinogenesis during initiation and promotion stages.
Thus diosgenin seems to have potential as a novel colon cancer preventive agent.
[71]
Phenylpropanoids (Niruriside)
Molecular formula: C38H42O17
Structural
formula:
Phenylpropanoids are
a group of natural products with a wide range of biological and pharmacological
importance. They show anti-inflammatory activity by inhibiting cyclo-oxygenase
enzymes. Of these, Cox 2 is inhibited more than Cox 1. They also possess free
radical scavenging property. They exhibit smooth muscle relaxant, antispasmodic
and analgesic properties.
The
Rev protein of HIV is sequence specific RNA binding protein required for viral
replication. Niruriside shows specific inhibitory activity against binding of
Rev Protein. The anti-HIV activity of P. amarus is attributed to repandusinic acid 11, a tannin and
niruriside a phenylpropanoid. [73]
Polyphenols,
ellagitannins, flavonoids
Some
principal constituents of P. amarus namely amariin,
1-galloyl-2,3-dehydrohexahydroxydiphenyl (DHHDP)-glucose, repandusinic acid,
geraniin, corilagin, phyllanthusiin D, rutin and quercetin 3-O-glucoside exhibit very strong antioxidant and free
radical scavenging activity. Amariin, repandusinic acid and phyllanthusiin D
show higher degree of antioxidant activity among the ellagitannins and were
comparable to flavonoids, rutin and quercetin 3-O-glucoside.
In
addition, they protect rat liver mitochondria and pBR322 plasmid DNA AG/against
radiation damage. The protection conferred is probably due to their efficient
hydroxyl radical scavenging activity. The inhibitory effect of ellagitannins on
lipid peroxidation in liver mitochondria was due to their efficient superoxide
radical scavenging ability. [74], [75]
Alkaloids
The
alkaloids in P. amarus exhibit very
potent antifungal, antimicrobial, anti-inflammatory and analgesic activity. The
analgesic activity seems to be unrelated to the activation of opioid mechanism.
Some of the alkaloids also show anti-malarial actions.
The
alkaloid phyllanthoside is smooth muscle relaxant. Its spasmolytic action helps
to expel urinary calculi. [76]
Geraniin and
1346TOGDG
They
are very potent antiviral AG/agents. At the dose 5 mg/kg geraniin shows
antihypertensive activity by lowering systolic and diastolic BP. [77]
Arabinogalactan (AG/ag)
The
aqueous extract of the whole plant contains acidic arabinogalactan. This
molecule can furnish ample material for a ‘Monograph’. The author does not
intend to write one though, he would certainly write all that really matters in
the present context.
Arabinogalactan
(AG/ag) is a biopolymer. It consists of two monosaccharides arabinose and
galactose. In nature two classes of arabinogalactan found are: plant
arabinogalactan and microbial arabinogalactan. In plants, it is a major
constituent of gums such as gum Arabic.
AG/
ag is a soluble, fermentable fiber found in high concentrations in P. amarus, North American larch trees,
leeks (Allium fistulosum Linn,
Vilaayati lasoona or Marathi: Khorat), carrots, radishes, pears, wheat, red
wine, tomatoes and many flowering plants.
The
non-absorbed fiber of AG/ag is eagerly fermented by the fiber avid microflora
of the distal gut. This increases the production of short-chain fatty acids
(SCFAs), mainly butyrate and propionate. SCFAs are important to the health of
the colon as they are the principal energy source for the colonic epithelial
cells. AG/ ag works in the colon by activating immune cells. By fermenting
fibers, it promotes growth of probiotic bacteria (such as Pet Flora) in the
colon and contributes to healthy microflora levels. AG/ ag furnishes food
supply to ‘gut friendly’ bacteria such as bifidobacteria and lactobacillus. It
controls the acid balance in the large bowel. It thus acts as prebiotic and
probiotic. It also eliminates some pathogens. (The author regrets his inability
to find exactly which pathogens!)
Some
studies have shown that AG/ag reduces ammonia generation in the colon. Because
ammonia has damaging effects on the colonic cells, reduction of ammonia is
significant for the health of the colon. The patients with liver disease cannot
detoxify ammonia which results in hepatic encephalopathy. AG/ag may therefore
benefit patients with liver disease.
AG/ag
is a potent immunomodulator. In immunological studies conducted in several
universities and at major US institutions, AG/AG was found to stimulate SUPEROXIDE
DISMUTASE (SOD) production, activate immune cells especially killer cells and
macrophages, promote cytokine production and communication and signaling
compounds of immune cells. A recent, randomized 4-week trial in healthy adults
showed that AG/ag also potentiates the complement system. Antioxidants, such as
vitamin C, may enhance its activity. AG/ag thus helps the body to fight
infections.
Recent
scientific
studies have shown that AG/ag blocks invading bacteria and
viruses from attaching to cell membranes in the liver and other organs. In
Yonsei University, Seoul, South Korea, the researchers investigated the
immunomodulating effects of AG/ag and fucoidan in vitro. At
concentrations of 10 to 100 microgram/ml of AG/ag and fucoidan, the activated
mouse spleen lymphocytes became cytotoxic to tumor cells. The data suggests
that arabinogalactan and fucoidan are activators of lymphocytes and macrophages.
This property may contribute to their effectiveness in the immunoprevention of
cancer. [78], [79], [80]
A
study conducted by Desai et al.
concluded that mice pretreated with AG/ag were protected against endotoxin-induced sepsis.
In these mice, there was
complete protection against lipopolysaccharide-induced mortality. AG/ag exhibits similar actions in
patients with septic shock. [81]
The
Royal Society of Medicine of Great Britain is of the opinion that ninety
percent of chronic diseases are caused by unhealthy intestinal tract. Since AG/ag
promotes the growth of ‘health friendly’ bacteria, retards the growth of intestinal
pathogens and activates immune system, AG/ag is recommended to preserve and
promote health. AG/ag is approved by FDA as dietary fiber and food additive. In
July 2009, the Australian Authorities approved AG/ag as a therapeutically
active ingredient for oral use.
AG/ag
has been shown to block the metastasis of tumor cells in the liver and to
stimulate Natural Killer cell (NK cell) cytotoxicity. AG/ag has been shown to
reduce tumor cell colonization and increase survival time of subjects with
various cancers. Hence AG/ag may be important in cancer treatment.
Some testimonials from modern research
Antioxidant and Detoxification Activity
The
methanolic extract of P. amarus
and dried powder of the whole plant, exhibit free-radical scavenging and
strong antioxidant activity.
The
liver is the largest chemical factory responsible for detoxification of
substances detrimental to the body. Glutathione is the prime antioxidant
helping the liver in this process. Rising levels of toxins result in depletion
of glutathione causing oxidative damage to the liver. The protein fraction of P. amarus reinstates the levels of
glutathione, boosts the levels of SUPEROXIDE DISMUTASE (SOD) and CAT thereby
neutralizing the excessive amounts of free radicals and various toxins to
provide hepatoprotection. [82]
P. amarus is effective for detoxification of toxicities induced by paracetamol,
nimesulide, cyclophosphamide and many other drugs and chemicals.
Anti-Inflammatory Activity
Methanol
and aqueous extracts inhibit all phases of inflammation in experimental rats.
When
given orally, the hexane extract, the lignan-rich fraction or the lignans
phyltetralin, nirtetralin, niranthin of P. amarus inhibited carrageenan
induced paw edema and neutrophil influx. They also inhibited the increase of
IL1-β tissue levels induced by bradykinin; PAF and endothelin-1 induced paw
edema.
P. amarus exhibits anti-inflammatory activity by inhibition of
iNOS, COX2 and cytokines via NF-kappa B pathway. [83]
Further
study suggested that anti-inflammatory and antiallodynic (countering allodynia
i.e. neuropathic pain) actions of P. amarus are probably mediated
through its direct antagonistic action on the PAF receptor binding sites. [84]
Immunomodulatory activity
Albino
rats treated with 400mg/kg of P. amarus exhibited immunostimulant/ immunebooster activity. (Decrease in ESR,
increase in RBC, WBC: TC DC counts etc.)
Antimicrobial Activity/ Antiviral
Activity
S.
P. Thyagarajan et al treated hepatitis B virus carriers with P. amarus, 600 mg/day for 30 days. When
tested 15-20 days after the
treatment, the carriers lost the surface antigen. Some subjects who have been
followed up to 9 months the antigen did not return. [85]
To study the mechanism of action of P. amarus
in controlling hepatitis B infection transgenic mice were used as animal model.
When P. amarus was administered to transgenic mice hepatic HBsAg, mRNA levels decreased. In cell culture P.
amarus inhibited hepatitis B virus polymerase activity, decreased hepatitis
B virus DNA content and suppressed virus release into culture medium. P.
amarus also suppressed hepatitis B virus mRNA expression after
glucocorticoid stimulation. [86]
An aqueous extract of Phyllanthus niruri
inhibits replication of hepatitis virus. In vitro it inhibits endogenous
DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis
B virus. By same mechanism Phyllanthus niruri inhibits Woodchuck
hepatitis virus. [87]
A flavonoid molecule isolated from Phyllanthus
urinaria showed anti hepatitis B activity. It was identified as ellagic
acid. Ellagic acid blocks HBeAg secretion in HepG2 2.2.15 cells. Since HBeAg is
involved in immune tolerance during hepatitis B infection, ellagic acid may be
a new therapeutic agent against immune tolerance in HBV-infected individuals. [88]
Extracts
of P. amarus have been shown by B. S.
Blumberg and many other research workers to inhibit the DNA polymerase of HBV
and woodchuck hepatitis virus (WHV) in vitro. These activities are
attributed to a virucide hitherto unnamed. [89]
In a study
conducted by Liu et al., 88 patients with chronic hepatitis B were given P. amarus
(Quebra pedra) in powder form. There was a substantial increase in
antibodies to the hepatitis virus, which
is a positive step in the recovery of host defense.
Seven species of
Phyllanthus with different formulations and
additives showed
their ability to
inhibit
hepatitis B virus
DNA replication (i.e. the HbsAg and HbeAg expression). This inhibition occurs at both the HBV DNA synthesis level and translation of
viral mRNA.
[90]
Mehrotra et al. conducted a study, in which the whole
plant material
of P. amarus
was dried,
powdered,
and
extracted with ethanol. This extract was subsequently
fractionated in hexane, chloroform, butanol, and water. All
fractions were tested for in vitro effects on HbsAg, HbeAg, and HBV-DNA in serum samples positive
for
HBV antigens, followed by screening of respective antigens by ELISA.
The extracts were effective against HBV
antigens, the butanol extract being
the most potent of them. [91]
A study conducted by Xia et al. used various combinations of Phyllanthus, interferon-α,
lamivudine,
adefovir dipivoxil, thymosin,
vidarabine and conducted 16 trials and included 1326 patients in the
study. They
concluded there is no evidence to prove that Pyllanthus can be used in the management of chronic HBV infection. Phyllanthus with an antiviral
drug may help better than just the antiviral drug. However, the validity of the
study conclusions depends on heterogeneity, systemic errors, and random errors.
Some more clinical trials should be conducted with bigger sample size and low risk. In future,
the trials should also report the species and dose at which it is effective. [92], [93],
[94], [95]
The author is very much
impressed by the conclusions of the researchers Xia Y et al. They used various
combinations of Phyllanthus, interferon alpha, lamivudine, adipovir,
dipivoxil, thymosin, vidarabine; conducted 16 trials and included 1326 patients
in their study. Their conclusions:
“There is no convincing evidence that Pyllanthus
compared with placebo benefits patients with chronic HBV infection. Phyllanthus
plus an antiviral drug may be better than the same antiviral drug alone.
However, heterogeneity, systemic errors, and random errors question the
validity of the results. Clinical trials with large sample size and low risk of
bias are needed to confirm our findings. Species of Phyllanthus should
be reported in future trials, and a dose-finding design is warranted.” [96], [97], [98], [99]
The human hepatoma cell line, PLC/PRF/5, also known as
Alexander cell line was shown to produce hepatitis B surface antigen. This cell
line has the property of secreting HbsAg (surface antigen) in the supernatant tissue
culture medium. The supernatant was used to study the antiviral property of Phyllanthus
amarus. It was found that Phyllanthus amarus at 1mg/ml concentration
on a single dose inhibited the secretion of HbsAg for a period of 48 hours.
This experiment proved the anti hepatitis B virus property of Phyllanthus
amarus at cellular level and further confirmed its beneficial use in the
treatment of acute and chronic hepatitis B infections and also in eradicating
HBV from healthy carriers. [100], [101]
Transfection is the process
of deliberately introducing nucleic acids into cells. In animal cells, the term
transfection is used to refer to progression to a cancerous state
(carcinogenesis) in these cells. Transfection can result in unexpected
morphologies and abnormalities in target cells. [102]
Yeh et
al. designed a study to evaluate the role of P. amarus in the treatment of
hepatitis B virus infection. HepA2 cell line
was transfected
with tandemly
arranged HBV DNA,
which initiated synthesis and secretion of HbsAg and HbeAg. Aqueous extract
of P. amarus resulted in
reversible inhibition
of cellular
proliferation and suppression
of HbsAg production,
but HbeAg
production in
HepA2 cells was
not affected. HbsAg gene expression was suppressed at mRNA
level in a
time-dependent manner and the HbsAg gene promoter-driven
CAT
activity was
selectively abolished. This study concludes that specific components in P. amarus suppress the
HbsAg gene
expression in human hepatoma cells, which contributes to antiviral activity of
Phyllanthus amarus
in
vivo. [103]
A study was designed to
evaluate the role of Phyllanthus amarus in the treatment of hepatitis B
virus infection. HepA2 cell line had been transfected with tandemly arranged
HBV DNA and continued to synthesize and secrete both HbsAg and HbeAg. Aqueous
extract of Phyllanthus amarus reversibly inhibited cellular
proliferation and suppressed HbsAg production but not HbeAg production in HepA2
cells. Phyllanthus amarus suppressed HbsAg gene expression at mRNA level
in a time-dependent manner, and selectively abolished the HbsAg gene promoter
driven CAT activity. This shows that Phyllanthus amarus contains some
active components which can supress the HbsAg gene expression in human hepatoma
cells. Such suppression may contribute the antiviral activity of Phyllanthus
amarus in vivo. [104]
The polyprotein processing and viral RNA replication necessitate the presence of viral enzymes NS3 protease and NS5B RNA-dependent RNA polymerase. Methanolic extract
of P. amarus
root inhibited HCV-NS3 protease enzyme significantly, whereas methanolic extract
of
P. amarus leaf inhibited NS5B considerably in in vitro assays.
Besides, monocistronic
replicon
RNA and HCV H77S
viral RNA
were effectively inhibited
in HCV
cell
cultural
system.
Furthermore, P. amarus root
extract with IFN-α inhibited HCV RNA replication. [105]
The viral enzymes NS3
protease and NS5B RNA dependent RNA polymerase are essential enzymes
polyprotein processing and viral RNA replication. Methanolic extract of Phyllanthus
amarus root showed significant inhibition of HCV-NS3 protease enzyme and
methanolic extract of Phyllanthus amarus leaf showed considerable
inhibition of NS5B in the in vitro assays. Further, both these extracts
significantly inhibited monocistronic replicon RNA and HCV H77S viral RNA in
HCV cell cultural system. Furthermore, the extract of Phyllanthus amarus
root together with IFN-alpha showed additive effect in the inhibition of HCV
RNA replication. [106]
[Note: Monocistronic
is a term used in biochemistry to describe the capacity of eukaryotes to code
one gene per one mRNA, as opposed to many genes or sometimes all genes
(polycistronic)
A replicon is a DNA
molecule or RNA molecule, or a region of DNA or RNA that replicates from a
single origin of replication] [107]
Nikam et al.
studied the hepatoprotective property of P. amarus. The study
included 50 patients with hepatitis C infection in the age
group of 20–60 years, and they were treated with P. amarus.
The plasma LPO levels were significantly decreased,
whereas the activity of SUPEROXIDE DISMUTASE (SOD), GPx, catalase, vitamin E, and vitamin C were significantly increased after
5 and 10 weeks of the treatment. Oxidative stress due
to hepatitis
C is
responsible for hepatocellular damage. The treatment with P. amarus increases antioxidant levels in
the
liver, reduces lipid peroxidation of
hepatic cell
membranes,
and
protects the
liver from free
radical insult caused by hepatitis C virus.
[108]
In one study 50 patients
with hepatitis-C infection ranging between age groups 20-60 were selected for
the treatment with Phyllanthus amarus. The study was also aimed at
hepatoprotection offered by Phyllanthus amarus. After Phyllanthus
amarus therapy (dose not mentioned) for 5 and 10 weeks, the plasma LPO
levels were significantly decreased and activity of SUPEROXIDE DISMUTASE
(SUPEROXIDE DISMUTASE (SOD)), GPx, catalase, vitamin E and vitamin C were
significantly increased. Hepatitis-C increases oxidative stress that is
responsible for hepatocellular damAG/age. The therapy with Phyllanthus
amarus increases antioxidant levels in the liver, reduces lipid
peroxidation of hepatic cell membranes and protects the liver from free radical
insult caused by hepatitis-C virus. [109]
Hepatoprotective Activity
Phyllanthin and Hypophyllanthin are said to protect hepatocytes against
carbon tetrachloride and galactosamine induced toxicity. The crude extract of P. amarus has a significant regenerative
activity on the hepatocytes following alcohol induced liver damage. The
ethanolic extract of P. amarus
administered orally to rats has a significant protective effect on aflatoxin
B-1 induced liver damage.
In one experiment albino rats were treated with oral
administration of ethanol for 30 days to induce alcoholic damage. As expected triglyceride, cholesterol and phospholipid deposits
were found in liver, brain, kidney and heart. They were then treated with 200
mg. per day for 45 days with powder of the whole plant of P. amarus. The increased levels of all these were brought
back to normal on administration of powder of P. amarus.
At
doses of 35mg/kg and 70 mg/kg the biochemical parameters were restored to
normal within 48 hours in jaundiced calves.
In another study in rats
the powder of the whole plant of P. amarus at the dosage of 0.66g/kg
showed hepatoprotective activity against CCl4 induced hepatocyte damage.
In
summary phyllanthin, hypophyllanthin, niranthin and nirtetralin, are said to
possess anti-hepatitis B activity.
For
more details see above.
Mechanism
of Hepatoprotection
The
hepatoprotective mechanism of this plant is neither related to inhibition on
cytochrome p450, nor induction on sulfate and glucuronide conjugation pathways
of paracetamol, but partly due to the antioxidant activity and the protective
effect on the decrease of hepatic reduced glutathione. [110]
Actions on Metabolism
In two clinical trials
diabetic, mild hypertensive and dyslipidemic patients were treated with the
preparation of the whole plant of P. amarus for 10 days. Their elevated
sugar and lipid levels decreased and mild diuretic action of the herb helped
control hypertension. However the sample size was too small (9 and 25 patients)
and the duration of treatment was too short (only 10 days) to declare the herb
to be a trustworthy remedy for diabetes, dyslipidemia and hypertension!
The hydroalcoholic extracts
of P. amarus at doses of 300 and 500
mg/kg possess significant hypolipidemic activity against cholesterol rich diet
induced hyperlipidemia in Wister rats. These extracts also reverse the
morphological and histopathological damage of the liver induced by high lipid
levels. [111]
During
one study administration of triton WR- 1339 in rats caused increase in
cholesterol 3.5 folds, phospholipids 2 folds and triglyceride 1.2 fold. At dose
200mg/kg administration of P. amarus
lowered their levels by 27, 25, and 24 percent respectively. At dose 100mg/kg P. amarus lowered elevated levels of
cholesterol and LDL in rats fed with high cholesterol diet.
The
Lipid lowering activity (LLA) is mediated through hepatic cholesterol
synthesis, increased faecal excretion of bile acids and enhanced plasma
lecithin: cholesterol acyltransferase activity. [112]
In
one study the ethanolic extract (1 or 10 microgram/ml) of P. urinaria (P. amarus) exhibited antioxidant and cytoprotective
effects against doxorubicin induced cardiotoxicity. [114]
Culinary uses
Not
used as food.
Toxicity
At a dose more than 800 mg/kg body weight, P. amarus
is toxic.
Histologically, there were protein casts in the
kidney
tubules with tubular necrosis, lymphocytic infiltration at the portal areas of
the liver and marked testicular degeneration with severe disorganization of the
seminiferous tubules, which were devoid of spermatic cells. [115]
Contraindications/
Drug-interactions
P. amarus may be contraindicated in individuals on medications for heart ailments. At high
dosages, it has
been
considered
abortifacient as well as menstrual promoter,
hence, it should
be contraindicated during
pregnancy. It is
also contraindicated for people with diabetes, especially if they are on insulin therapy and in
various other medical conditions
where diuretics are not advised. The doctor has to be consulted before consuming P. niruri for longer than 3 months.
No drug interactions
have been reported till date.
Medicinal Actions and Uses
Traditional Uses
Phyllanthus plants have been used in folk medicine to treat a wide number of diseases. In Ayurvedic medicine, various Phyllanthus
species are known as bhuiamla.
The name was previously assigned to P. amarus only. Bhuiaamla is
recommended for jaundice, gonorrhea and diabetes; skin ulcer, scabies and other skin afflictions as well as for poultices for abscesses.
World over P. amarus has been recommended for more or less same
afflictions as in Ayurveda.
Usages in
Ayurveda
It is used to quench thirst, to treat bronchitis,
tuberculosis, asthma, biliousness, hiccups, leprosy, anemia, urethral discharge
and as diuretic.
It is recommended to treat jaundice and hepatic
disorders, acid peptic disease, many GI disorders, bleeding disorders,
metabolic disorders and leucorrhea. [116]
Usages in
Modern Medicine
After
extensive research P. amarus is used
to prevent and treat hepatitis B infection.
Preparations and dosages
Paste prepared
from the leaves crushed with salt is used to treat fractures, applied on wounds,
applied on edematous surfaces and to treat dermatitis. For this it is used for
external applications.
Powder: of
the whole plant given with rice water is useful in menorrhagia, leucorrhoea,
dysuria, diabetes and some skin disorders.
Root: mixed with sugar is instilled in nose to treat
hiccups.
Whole plant: Dosage of whole plant decoction is 10-20 ml.
Powder: 3-6gm.,
600-900mg (recommended by some experts) [117]
Tincture: 1 - 4 ml / daily.
Infusion: One cup/day
P. amarus is administered in the form of infusion or tincture
or capsules for the treatment of chronic dysentery.
Phyllanthin and Hypophyllanthin are major components of many
popular liver tonics.
In
India, a cupful of the leaf decoction is drunk daily to cure diarrhea.
Fruits
useful for tubercular ulcers, wounds, sores, scabies and ring worm [118], [119]
The
fresh root is believed to be an excellent remedy for jaundice.
Poultice
of the leaves with salt cures scabies and without salt is applied on bruises
and wounds. The milky juice is a good application to offensive sores.
The
infusion of the root and leaves is a good tonic and diuretic when taken
in repeated doses. [120], [121]
In
many parts of India, it is commonly used for the treatment of snake bite.
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http://bhumiamalaki.com/aboutbhumiamalaki.html
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