Bhringraj (Eclipta alba)

Bhringraj (Eclipta alba)



Introduction 
Since the time of Ayurveda till today Bhringraj (Eclipta alba) is a top-notch herb used in hair care industry. Bhringraj is a widely celebrated medicinal plant, especially in India, used singly or in combination with other herbs such as amala, shikaakai for making a vast range of hair care, hair rinse and conditioner products. Bhringraj oil when massaged on to the scalp; imparts a (Eclipta alba)calming effect and promotes a good sleep. [1]
Descriptions of the medicinal properties of the herb by Arab writers are similar to those by their Indian counterparts. According to J.J. Wood, in hepatic derangements Eclipta prostrata is of greater service than Taraxacum.
The Sanskrit word Bhringraj literally means that which imparts hair the splendid color like that of a humming bee. It has numerous epithets describing its properties of promoting the growth of hair, preventing balding and premature graying and making them black and lustrous.  Kesharaaja, literally means king of the hair or king for hair care, ruler of the hair, unravels its inbuilt qualities regarding the health of the hair, Markava that which prevents premature graying and Keshranjanaa that which imparts beautiful tinge to hair.
According to Waagbhata, a person who consumes a fresh juice of Bhringraj daily for a month and stays on a diet predominantly of milk, is rejuvenated and lives a strong, healthy and happy life of 100 years. [2], [3], [4]
The name of the genus Eclipta (Ek-lip-tuh --) is derived from Greek ‘ekleipo’ meaning ‘deficient’ referring to the absence of calyx. [5]
Though it is not described by Brihat-trayee in ganas and wargas, in therapeutics it is an important herb. Charaka recommended it for raktapitta. In Raja-Nighantu the blue Bhringraj is extolled to be the best (? One of the best) rasaayana (rejuvenator)
In modern times its hepatoprotective role is well documented. [6]
Other Names
Latin/Botanical/Scientific: Eclipta alba L,Hassk; Eclipta prostrata L,Eclipta erecta, Verbesina alba, Verbesina prostrata
Sanskrit : Kesharanjanaa, Tekaraaja, Bhringa, Maarkawa, Bhringaja
Assamese : Bhringraj, Kehraaj                  
Bengali : Bheemaraaja, Kesuriyaa, Kesaree
English : --
Gujrati : Bhaangaro, Bhangro  
Hindi :  Bhaangaraa, Bhaangraiyaa
Kannada :  Garujalu, Gurugada, Soppu, Keshawardhanaa (Keshawardhana), Kodigaraju
Malayalam : Kayyonni,  
Marathi : Bhaangaraa, Bhringraj, Maakaa
Punjabi : Bhaangaraa
Tamil :  Karisalankanni, Karisalai              
Telugu : Guntakalagara, Guntagalagara  
Urdu : Bhaangaraa  
AKA False Daisy, Yerba de tago, Babri [7]
 Taxonomic classification
Kingdom: Plantae
Unranked:  Angiosperm
Unranked:  Eudicots
Unranked:  Asterids
Division:     Magnoliophyta
Class:         Magnoliopsida
Order:        Asterales
Family:      Asteraceae  [8]

Geographical Distribution
Bhringraj is a creeper growing commonly in moist places. It grows as a common weed on the hills and up to the height of 6,000 ft in the Himalayas. Though the plant is widely distributed throughout India it is more common in areas of upper Gangetic plains, in pasture lands, along roadsides in Chhota Nagpur, all districts of Bihar and Orissa, Punjab, Western India and South India. It is found in China, Thailand, Brazil  and Southwestern America. Now it is cultivated all over the world. [9], [10]
Bhringraj (Eclipta alba) is a moisture-loving creeper. It is an annual, erect or prostrate, much branched, entirely pubescent (covered with hairs), rooting at the nodes. It grows 3 feet tall. The plant flowers in September and fruits in November





Roots of the plant are well developed, cylindrical and grayish in color. A number of secondary branches arise from main root











Stem is short, up to about 7 mm in diameter, flat, round or cylindrical, grayish or brown in color, rough due to hairy branches, node distinct



  



Leaves are opposite, sessile, usually oblong and lance shaped, 2.5 to 8.5  cm long, 1.2 to 2.3 cm wide, blackish green in color with white appressed (lying flat or pressed closely against something as hairs on certain plant stems) hairs on both sides and serrated edges








 Flower solitary or 2, together on unequal axillary peduncles; involucral bracts (inflorescence in a specialized leaf), about 8, ovate, obtuse or acute, herbaceous, strigose (having short, stiff, appressed hair); white disc flowers tubular, corolla often 4 toothed; stamen 5, filaments epipetalous, free, anthers united into a tube; ovary inferior, unilocular with one basal ovule. In Indian conditions the flowering time is from October to December






Fruit is achene (a type of simple dry fruit) compressed, narrowly winged and 6-8 mm in diameter, having one black colored seed









Seed 0.2 to 0.25 cm long, 0.1 cm wide, dark brown or black in color, resembling cumin seeds, cuneate (wedge shaped) with a narrow wing, hairy and non endospermic




According to the colors of the flowers the herb bears; in Ayurveda three varieties of Bhringraj are described:
1.  White (Eclipta alba) 
2.  Yellow (Widelia calendulacea)
3.   Neela Bhringraj, Neeli Bhringraj (Indigofera tinctoria) [14]
Probably this is why there are many taxonomic names. In this article the author lays stress on E. alba. In fact Eclipta alba L. andEclipta prostrata L. are synonyms. In their research works some scholars preferred E. prostrata to E. alba. I have not altered their terminology but honored it. [15]
Although the names Eclipta alba and Eclipta prostrata are used as synonyms Rechinger (1977) they are two different species.
Among North Indian populations, three morphotypes of Eclipta alba are identified i. e. erect, semierect and prostrate. The erect plants are tall and upright while the prostrate variety has all creeping branches. The semierect variety has lower parts of branches creeping and tips are ascending.[16]
Microscopic Characteristics
Root- Mature root show poorly developed cork, consisting of 3-5 rows of thin-walled, tangentially elongated cells; secondary cortex consists of outer one or two rows of tangentially elongated or rounded cells with air cavities, inner secondary cortex of tangentially elongated or irregular shaped, parenchymatous cells with conspicuous air cavities; stone cells found scattered in secondary cortex and cork, in singles or in groups of various shape and  size; pericyclic fibers in tangentially arranged bands of many cells or in singles; secondary phloem consists of sieve elements including phloem fibers traversed by multiseriate phloem rays; phloem rays broader towards periphery, consisting of rounded cells; xylem composed of vessels, fiber tracheids, fibers and xylem parenchyma, traversed by xylem rays; vessels numerous, found scattered throughout wood, in macerated preparation vessels small, drum-shaped, cylindrical elongated with pitted walls and perforations, simple, rarely slightly oblique; fiber tracheids, pitted, with very pointed tips, xylem fibers long with pointed tapering ends and short lumen, a few fibers show peg-like outgrowths towards the tapering ends; xylem panihar manwatkarrenchyma sparse usually squarish to rectangular having simple pits on their walls, xylem ray distinct, run straight in tangential section, generally 5-32 cells in height and 3-5 cells in width although very rarely uniseriate and biseriate rays also found, ray cells pitted.  
 Stem- Mature stem shows single layered epidermis, externally covered with cuticle, a few epidermal cells elongate to form characteristic non-glandular trichomes, the cork where formed, poorly developed consisting of  rectangular cells; secondary cortex consists of large, rounded or irregular shaped parenchymatous cells having wide air spaces; endodermis single layered consists of tangentially cells; pericyclic fibersdistinct, arranged in tangential strands; vascular bundles in a ring, collateral, endarch (xylem whose early development is towards the center), of varying sizes traversed by medullary rays; phloem a narrow strip composed of sieve elements and phloem parenchyma; xylem consists of large number of vessels, xylem fibers and xylem parenchyma; xylem vessels appear evenly distributed throughout the xylem; in macerated preparation vessels barrel-shaped, some elongated with simple perforations, pitted with spiral thickening; xylem fibers with wide lumen, pointed tips and pitted walls, a few often bifurcate and a few other large, peg-like outgrowth; xylem parenchyma rectangular with pitted thickening; xylem rays trirseriate to pentaseriate, normally biseriate and uniseriate, 8-15 cells in height and 3-5 cells in width; centre occupied by a wide pith consisting of isodiametric cells of parenchyma.
Leaf-
Petiole- shows single layered upper and lower epidermis consisting of tubular cells, covered with striated cuticle; trichomes of two types, non-glandular, uniseriate, 1-5 celled, warty, and with pointed apical cell; epidermis followed by wide cortex, consisting of 2-5 layered collenchymas on both, upper arid lower side with distinct angular thickening; parenchyma 4-6 layered on upper side and 5-8 layered on lower side consisting of isodiametric, thin-walled cells with intercellular spaces; five vascular bundles central one largest while four others small flanking to either side of central bundle, consists of xylem on dorsal side and phloem on ventral side; xylem vessels arranged in radial rows traversed by xylem rays. 
Midrib- cut at basal region shows both upper and lower single layered epidermis, externally covered with cuticle, a few epidermal cells elongate outwards to form uniseriate hairs; epidermis followed by cortex, consisting of 3-5 layered 22 collenchymatous cells on both sides; section cut at middle region shows 3-4 layered collenchymatous cells on dorsal and 1-3 layered on ventral side, while the section cut at apical region, shows 2 layered collenchymatous cells on both sides, transverse section cut at a basal, middle and apical regions shows 4-6 layered parenchymatous cells on dorsal side and 6-9 layered parenchyma on ventral side, in section cut at basal region 4-6 layered parenchyma on both the sides in the middle region with thin-walled cells and intercellular spaces, 2-3 layered parenchymatous cells on both side in the apical region; section in the basal region shows vascular bundle similar to that of petiole while in the section cut at middle and apical region shows 4 smaller bundles shifting towards lamina.
Lamina- shows a dorsi-ventral structure, epidermis single layered, externally covered with cuticle, followed by single layered palisade parenchyma containing chlorophyll contents; spongy parenchyma irregularly arranged with distinct intercellular spaces and filled with chlorophyll contents; mesophyll traversed by number of veins; anisocytic (of unequal size) and anomocytic stomata ( irregular cell type stomata) present on both surface, more abundant on lower surfaces; stromal index 20.0- 22.5 on upper and 23.5-26.0 on lower surface; palisade ratio 3.8-4.5; hairs stiff, pointed, wide at the base, about 3 celled, uniseriate, middle cells longest, uppermost generally not exceeding the basal cell length, septa thick-walled.
Powder- dark green; shows vessels in large groups or single broken pieces with pitted walls, numerous fibers entire or in pieces, trichomes entire or in pieces, warty, a few attached with epidermal or subsidiary cells, aniscytic or anomocytic stomata. [17]
Parts Used
Leaves, roots, seeds and entire plant         
Phytochemistry
The plant extract is resinous in nature and contains the alkaloid ecliptine. The herb is a rich source of ascorbic acid and thiophene derivatives.
The chief constituents of the herb are coumestan derivatives such as wedelolactone, demethylwedelolactone and desmethyl-wedelolactone-7glucoside. Wedelolactone is classified as a coumestan. Coumestan is a derivative of coumarin. Because of the estrogenic and steroid-like activity of some coumestans, a variety of synthetic coumestans have been developed so as to explore their pharmacological effects.
The other constituents are ecliptal, ß-amyrin, luteolin-7-O-glucoside, apigenin, wedelic acid, hentriacontanol, heptacosanol, stigmasterol, polypeptides, polyacetylenes, thiophene-derivatives, steroids, triterpenes and flavonoids, alkaloid ecliptine and nicotine.
The occurrence of mono-, di- and tri- thiophene acetylenes together with a-terthenyl in some species is noteworthy.
  
The chemical constituents of various parts of the plant

Roots
Thiophene acetylenes, Hentriacontanol, Heptacosanol, Stigmasterol, Ecliptal, Eclalbatin  

Stems
Wedelolactone
Leaves
Rich in protein, Wedelolactone, Desmethylwedelolactone,  Desmethyl-wedelolactone-7-glucoside, Stigmasterol
Seed
Sterols, Ecliptalbine
Aerial parts
P-amyrin & Luteolin-7-O-glucoside, Wedelolactone, Apigenin, Cinnaroside, Sulphur compounds, Eclalbosaponins I-VI, Trithienyl aldehyde, Ecliptal, Stigmasterol, ß-Sitosterol, and Volatile Oils.
Whole plant
Resin, Ecliptine, Reducing sugar, Nicotine, Nicotinic acid, Stigmasterol, Triterpene saponin, Eclalbatin, Ursolic acid, Oleanolic acid.     


Recently isolated chemicals:

The polypeptides isolated from the plant yield cystine, glutamic acid, phenylalanine, tyrosine and methionine on hydrolysis.
From the dried whole plant, in 1994, Yahara et al, isolated new oleanane tritriterpene glycosides named Eclalbasaponins I-IV; in 1997 they isolated new taraxastane triterpene glycisides named Eclalbasaponins VII-X. In 2001Zao et al isolated triterpenoid saponins named Eclabasaponins XI and XII and in the same year Upadhyay et al isolated Eclabatin and α-amyrin. [18], [19], [20]
Classification of chemical ingredients

Triterpenes             
Eclalbatin, Ecliptasaponins A-B-C and D, Eclalbasaponins I-XII, Oleanolic acid, α-amyrin, β-amyrin, Ursolic acid, Wedelic acid.
Coumarins
Wedelolactone, Dimethylwedelolactone 7-glucoside, Nor-wedelolactone, Demethylwedelolactone, Isodemethylwedelolactone.
Alkaloids
Ecliptine, Nicotine, Steroidal Alkaloids.
Sterols
β- glucoside Daucosterol, Stigmasterol-3-O-glucoside, Stigmasterol, β-sitosterol
Hydrocarbons
Dithienylacetylene ester, Ecliptal, α-terthienyl-methanol, Heptacosanol, Hentriacontanol.
Flavonoids
Apigenin, Leuteolin, leuteolin-7-glucoside
Steroids
Diosgenin, Tigogenin, Lansosterol,
Thiopenes
Polyacetylenic thiopenes
Miscellaneous
Nonacosanol, Stearic acid, Lacceroic acid, α-terthienyl 3,4-dihydroxy benzoic acid.

The polypeptides isolated from the plant yield cystine, glutamic acid, phenylalanine, tyrosine and methionine on hydrolysis. [21], [22]
Identity, Purity and Strength
Foreign matter: Not more than 2 %
Total ash: Not more than 22 %
Acid-insoluble ash: Not more than 11 %
Alcohol-soluble extractiveNot less than 5 %
Water-soluble extractive: Not less than 15 % [23]
Heavy metals 1.0 g complies with the limit test for heavy metals
Loss on drying; Not more than 15 %
Microbial contamination complies with the microbial contamination test. [24]
(2) Standards accepted by I.P in 2010
Tests Foreign organic matter: Not more than 2 .0 %.
Ethanol-soluble extractive: Not less than 5.0 %
Water- soluble extractive: Not less than 15.0 %
Total Ash: Not more than 22%.
Acid-insoluble ash: Not more than 11%
Heavy metals: 1.0 g complies with the limit test for heavy metals.
Loss on drying:  Not more than 15.0%, determined on 5 g by drying in an oven at 105º. (0C or 0F is not mentioned)
Microbial contamination: Complies with the microbial contamination tests.
Assay-- Determine by liquid chromatography [25]
TLC Pattern
Petroleum ether extract:  Solvant system: Tolune: Acetone: Formic Acid (9:6:1) Rf value (Rf x 100) yellow (70), Spraying system: Iodine vapour: Yellow Rf value 90
Acetone extract: Solvent system: Tolune: Acetone: Formic Acid (9:6:1), Rf value (Rf x 100) 68( Light brown), 58 (Violet), 42 (Brown), Spraying system: Iodine vapour: Rf value (Rf x 100) 68( Light brown), 58 (Violet), 42 (Brown)
Alcoholic extract: Solvent system: Tolune: Acetone: Formic Acid (9:6:1), Rf value (Rf x 100) 35(Light brown), 60 (Violet), 90 (Brown), Spraying system: Iodine vapour: Rf value (Rf x 100) 35(Light brown), 60 (Violet), 90 (Brown)
Methanolic extract: Solvent system: Tolune: Acetone: Formic Acid (9:6:1), Rf value (Rf x 100) 10, (Green), 15 (Green), 20 (Green), 60 (Green), 90 (Green), Spraying system: Day light: Rf value (Rf x 100) 10(Green), 20 (Green), 60 (Green), 90 (Green) [26]

Cytological Identity

32 Chromosome counts in Eclipta alba (L) Hassk [27]

Genetic study

Recently Yadav et al have developed RAPD-based SCAR markers to identify accurately the species: Eclipta alba [28]

With the help of molecular techniques like Random Amplified Polymorphic DNA (RAPD), Amplified Fragment Length Polymorphic DNA (AFLP), Restricted Length Polymorphic DNA (RFLP) and Inter Simple Sequence Repeat (ISSR) etc the identification of plant species has now become very accurate. [29]

TLC identification
Botanists have done High Performance Thin Layer chromatographic identification of E. alba. [30]
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    [31]

Properties and Pharmacology

Ayurvedic properties
Ganas (Classical Categories) and Wargas
 

Charak Ganas

                      None 

Sushruta Ganas

                      None

Dhanvantari Nighantu

Karaweeraadi Warg


Shodala Nighantu

Karaweeraadi Warg

Bhaawaprakaash Nighantu

Guduchyaadi Warg

Raaja Nighantu

Moolakaadi Warg

Shaaligraama Nighantu

Guduchyaadi Warg

Aadarsha Nighantu

Sahadewyaadi Warg

 [32]


Energetics


 

Rasa (Taste)

Katu (Acrid, Spicy, Pungent, Piquant), Tikt (Bitter)

Virya (Energy State)

Ushna (Hot)

Wipaaka

Katu (acrid, Spicy, Pungent)

Praabhaav

None


Gunas (Qualities) and effects on Doshas
  
GunasRooksha ( Dry), Laghu (Light), Teekshna (Penetrating)
Effects on DoshasKapha-Waat Shaamaka


Actions on Dhatus and Srotasas
 

Actions on Dhaatus

Rasa (Lymph), Rakta (Blood), Asthi (Bone), Majjaa (Bone marrow), Shukra (Semen)

 

Actions on Srotasas (Systems)

Rasawaha (Lymphatic System), Raktawaha (Hematopoetic System), Annawaha (GI

System), Majjaawaha (Bone marrow), Mootrawaha (Urinary System), Shukrawaha (Male Reproductive System) 

 

 


 

Ayurvedic Actions
                           
Aamahara
Eradicates free radicals
Balya
Imparting Strength
Chakshushya
Beneficial to eyes
Deepana
Appetizer
Dantya
Beneficial to teeth
Kaphahara/Kaphashaamaka
Expectorant, Reduces phlegm
Keshya
Beneficial for hair
Kushthaghna
Anti-leprotic
Medhya/
Nootropic, Memory and intelligence enhancer
Paachana
Digestive or Digestant
Rasaayana
Rejuvenator or Adaptogen
Twachya
Beneficial to skin
Waataanulomana
Carminative, Prokinetic
Yakriduttejaka
Stimulates Liver functions
[33]
In Ayurveda Bhringraj is said to be astringent and styptic, benevolent to body tissues, blood, alterative, antipyretic, cholagogue, hepatoprotective, laxative, nervine tonic, adaptogenic, and vulnerary. [34], [35]
Modern View   
According to modern science it has anti-inflammatory, analgesic, antioxidant, antibacterial, antiviral, antileprotic, anthelmintic (ovicidal), antimyotoxic, styptic, hepatoprotective, spasmogenic, hypotensive and anticancer properties.
E. alba plant is a rich source of thiophene derivatives which are active against nematodes. Its roots are emetic and purgative.
The herb is cardio-depressant when used for hepatic congestion. It gives symptomatic relief in gastralgia, nausea and vomiting in patients suffering from acid peptic disease [36]
                       Chemical constituents and their pharmacological activities

Wedelolactone
Anti-inflammatory, Antioxidant, Antiseptic, Antibacterial, Hair tonic, Styptic (Anti-hemorrhagic), Hepatoprotectant, Antituomr
Eclalbosaponins
Anthelmintic, Hair tonic, Antiproliferative
Demethylwedelolactone
Cosmetic (Dye), Hair tonic, Styptic (Anti-hemorrhagic), Anti-venom
Dasyscyphin C
Anti-viral, Anti-proliferative
Eclalbatin
Anti-oxidant
Ecliptalbine, Verazine
Analgesic, Hypolipidemic
Coumarins
Anti-inflammatory, Anti-oxidant, Immunemodulatory, Anti-bacterial, Anti-fungal, Anti-HIV, Adrenergic, Antipyretic, Anti-highprotein lymphedema (Filarial), Anti-coagulant, Vasoconstrictor, Anti-tumor (anti-cancer)
α-amyrin and β-amyrin
Sedative, Analgesic, Antidepressant, Anti-pruritic, Anti-scratching
Ursolic Acid
Muscle growth, Anabolic
Stigmasterol
Anabolic, Adaptogen, Vit. D precursor
Apigenin
Hepatoprotective
Wedelic Acid
Hepatoptotective
Luteolin
Hepatoprotective
[37]
Wedelolactone
Molecular formula: C16H10O7                                                
Structural formula:
          [38]
Wedelolactone (WDL) belongs to the flavonoids category of phytoestrogens. It was originally extracted from Eclipta alba(Eclipta prostrata). Later extracted from Wedelia chinensi, is a major coumestan ingredient of the herb.
In one study wedelolactone has been shown to inhibit caspase-11 which is a key regulator of proinflammatory cytokine IL-1Beta maturation and pathological apoptosis. It also inhibits IKKy, a kinase that activates NF-kB.
Wedelolactone showed hepatoprotective activity protecting cultured liver cells from the toxicity of CCl4, Phalloidin and Galactosamine.
Wedelolactone inhibits 5-LO (lipoxygenase) activity in porcine leucocytes. [39]
The synthetic wedelolactone stimulates RNA synthesis in isolated nuclei from hepatocytes  [39], [40]
Previous findings that wedelolactone inhibited IKK activity and caspase-11 expression which resulted in the activation of NF-kB pathway suggested that wedelolactone could be a potential lead compound in anti-inflammatory therapy. However according to some experts the mechanism of anti-inflammatory activity of wedelolactone is unclear.
Previous studies have shown that wedelolactone has antihepatotoxic, antiandrogenic and anti- human immunodeficiency activities. In China it has been in vogue to treat septic shock, viral hepatitis and venom poisoning. [41], [42]
In Punjab and Gujarat, India Bhringraj has been used externally as antiseptic to treat infected wounds and ulcers in cattle and to treat many microbial infections in rural areas of India. The results of recent studies revealed that wedelolactone may be the main constituent in Bhringraj, (Eclipta alba) responsible for antimicrobial activity of the herb. Studies have also shown that wedelolactone has anti-bacterial, anti-viral and anti-fungal activity. Wedelolactone showed antibacterial activity against S. typhimurium, S. epidermidis, B. subtilis and E. coli. [43]
Wedelolactone shows a significant anti-HIV-1 activity [44]
Wedelolactone induces caspase-dependent apoptosis in prostate cancer cells. Wedwlolactone has bee found to modulate androgen receptor (AR) activation of transcription from prostate specific antigen (PSA) promoter in prostate cancer cells. [45], [46]
The anticancer activity of wedelolactone has also been shown in androgen receptor negative breast cancer cells. Wedelolactone arrested the growth of cancer cells at the S and G2/M phase of the cell cycle by damaging DNA. [47]
Human Epithelial type-2 cells originate from human laryngeal carcinoma. wedelolactone induces apoptosis in these cells in combination with LPS and Poly-isnosinic acid: Polycytidylic acid. [48]
Coumarins                      
Coumarins possess anti-inflammatory, anti-oxidant, anti-coagulant, analgesic, immunemodulatory, anti-bacterial, anti-HIV and anti-tumor (anti-cancer) activities. [49]
Coumarins are vasoconstrictors, decrease capillary permeability, inhibit histamine release from mast cells. They possess mild adrenergic activity.
Coumarins also exhibit anti-inflammatory, antipyretic, antibacterial, antifungal properties. Coumarins are also useful in the treatment of High Protein Lymphedema (HPLO), chronic infections, disorders of immune system and cancers.[50]
Oleanolic acid
Molecular formula: C30H48O3
Structural formula:
Oleanolic acid is a naturally occurring triterpenoid widely distributed in food and medicinal plants. It exhibits antiviral, hepatoprotective and anti tumor properties. [51]
Oleanolic acid has anti-inflammatory, hypolipidemic and hepatoprotective properties.
Oleanolic acid is useful in neurodegenerative disorders like Alzheimer’s disease [52], [53]
Amyrins
Molecular formula: C30H50O
Structural formula:
       
   α  Amyrin                                         β Amyrin
Amyrins are a pair of closely related triterpenes. They are designated as α Amyrin and β Amyrin. Each has the chemical formula C30H50O. They are isolated from a variety of plant sources. [54]
In mice 500mg/kg acetaminophen caused fulminant liver damage. Pre-treatment with α and β Amyrins with 50 and 100 mg/kg at 48, 24and 2 hours before acetaminophen, attenuated acute liver injury as was proved by biochemical and histopathological studies. [55]
Animals pre-treated with the oral dose of 50, 100 and 200 mg/kg of α and β Amyrins block histamine and serotonin receptors and relieve itching. In addition α and β Amyrins at the dose of 100mg/kg prevent degranulation of mast cells and are now known as mast cell stabilizers. Amyrins do not show sedative activity. These properties of Amyrins found in Bhringraj (Eclipta alba) (E. alba) can be exploited to treat pruritus associated with jaundice. These actions are due to the stabilizing action of Amyrins on the mast cell membrane. [56]
Beta-amyrin palmitate at doses of 5, 10 and 20mg/kg body weight exhibit sedative activity; the effect of course is dose dependant. [57] 

Orally administered α and β amyrins (found in E. alba) selectively bind to CB (1) and CB (2) receptors and inhibit inflammatory and persistent chronic neuropathic pain. [58]
The anti-inflammatory activity of amyrins is attributed to their ability to inhibit prostaglandins and suppress COX-2. Amyrins also block the activation of NF-κB. [59] 
Antilipoxygenase activity of amyrins suggests that they have a beneficial role in the treatment of arthritis. [60]
The mixture of α-β-amyrins exhibit anti nociceptive properties [61]

In mice α and β amyrins demonstrated significant anti-nociceptive activities against subplantar or intracolonic application of capsaicin [62]

In mice α and β amyrins demonstrated significant anti-nociceptive activities against cyclophosphamide induced bladder pain and intracolonic administration of mustard oil [63]

Alpha and beta amyrins exhibit anxiolytic activity. [64]
To evaluate beneficial effects of α and β amyrins in pancreatitis, by using cerulein acute pancreatitis was induced in mice. The animals were then treated with α and β amyrins. The treatment decreased the elevated levels of tumor necrosis factor-α, interleukin-6, lipase, amylase, myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS). Further more α and β amyrins suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis and expression of TNF-α and iNOs suggesting α and β amyrins are useful for the treatment of acute pancreatitis.
Similar protective effects of α and β amyrins were observed in acute pancreatitis induced in rats by using L-arginine [65], [66]
In mice α and β amyrins showed gastroprotective effect against ethanol-induced gastric mucosal damage. At the dose of 100mg/kg the gastroprotective effect was maximum. The gastroprotective effect involves the activation of capsaicin-sensitive primary afferent neurons. [67]
By suppressing inflammatory cytokines and COX-2, possibly via NF-κB and CREB (cAMP response element-binding protein)-signaling pathways α and β amyrins demonstrated protective effect against trinitrobenzene sulphonic acid-induced colitis in Swiss male mice
Protective effect of α and β amyrins was also observed in mice against dextran sulphate-induced colitis. It was hypothesized that the cannabinoid pathway may be involved in this regard. [68], [69]

In experimental on isolated rabit jejunum preparations triterpene compounds α and β amyrins expressed antispasmodic activity. [70]

In mice pretreatment with α and β amyrins at the doses of 50 and 100mg/kg at 48, 24 and 2 hours before administration of acetaminophen attenuated the acetaminophen-induced liver damage [71]

In mice, α-amyrin, by reducing elevated bold sugar levels improved diabetes in streptozotocin-iduced diabetes [72]

In streptozotocin-induced diabetic rats α-β-amyrins reduced elevated levels of blood glucose, total cholesterol and serum triglycerides. At the dose of 100mg/kg there was significant reduction in TC, TG, L and VLDL levels and elevation in the level of HDL cholesterol. These amyrins also lowered the lipid levels in normoglycemic rats. [73]

Ursolic acid
Molecular formula: C30H48O3
Structural fopmula 
 
Ursolic acid is a pentacyclic triterpenoid. It is present in many medicinal plants such as Bhringraj  (E. alba), basils, apples, cranberries etc. In vitro by inhibiting the STAT3 activation pathway and inducing apoptosis, ursolic acid inhibits the proliferation of various cancer cells. Ursolic acid also inhibits JNK expression and IL-2activation of JURKAT leukemic T cells leading to the reduction in proliferation and T cell activation.
Ursolic acid can serve as a starting material for synthesis of more potent bioactive derivatives such as experimental antitumor agents. [74]
Ursolic acid has anti-inflammatory, antioxidant, anti-microbial, anti-HIV, hepatoprotective, anti-tumor, cytotoxic and anti-cancer properties. Ursolic acid prevent wrinkling of the skin. [75], [76]
Ursolic acid increases the amount of muscle and brown fat and decrease white fat. By increasing Akt activity in skeletal muscle it inhibits muscle atrophy and promotes muscle growth. Consistent with increased skeletal muscle and brown fat, ursolic acid increases energy expenditure, improves glucose tolerance and decreases fatty liver disease. Thus it is useful in the treatment of obesity. [77]
To take the advantage of these activities Korean sport scientists advise the athletes to consume 450mg of ursolic acid every day. The study of the use of ursolic acid by athletes is recorded in the Korean Journal of Physiology and Pharmacology. [78]
In experimental studies ursolic acid has been shown to target cell cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects. [79]
By inducing cell cycle arrest and apoptosis ursolic acid exhibits anticancer effects in various human cancer cell lines in vitro, especially in gall bladder cancer. [80] 

Luteolin

Luteolin has anti-inflammatory, anti-oxidant, antiallergic cardioprotective properties. The cardioprotective role has been shown in cardiomyocytes following ischemia-reperfusion. This suggests that leuteolin can be used for preventing and treating ischemic heart disease. [81], [82]

By blocking carcinogenic stimuli, inhibiting tumor cell proliferation and induction of cell cycle arrest or apoptosis luteolin blocks the development of cancer cells both in vitro and in vivo. [83]

By suppression of cell cycle pathways and stimulation of apoptosis leuteolin sensitizes cancer cells to anti-cancer chemotherapeutic drugs. [84]

Apigenin

Apigenin has anti-inflammatory and anti-oxidant properties. It has beneficial effect in cardiovascular and neurological disorders. [85]

A recent study shows that apigenin can inhibit the growth of cancer cells, sensitize cancer cells to chemotherapeutic agents, induce apoptosis in cancer cells and inhibit neoangiogenesis [86]
Sterols:
β- glucoside Daucosterol
Molecular formula: C35H60O6
Structural formula:
                                                     [87]
 β- glucoside Daucosterol is immunomodulator. [88]
Stigmasterol
Molecular formula: C29H48O
Structural formula: 
Stigmasterol is also known as Wulzen anti-stiffness factor. It plays an important role in the tissue rebuilding mechanisms. It acts as an intermediate in the biosynthesis of androgens. It is also used as the precursor of Vitamin D3. It is also most commonly abused as anabolic steroid in sports. [89]
Eclalbasaponins
Eclabasaponin isolated from Eclipta alba have antibacterial activity against Gram-positive and Gram-negative bacteria. By bringing about changes in the cell surface structure and disrupting the bacterial cell membrane they act as antibacterial agents. [90]
Eclalbasaponin VI shows α-glucosidase activity.
Eclalbasaponin I inhibit proliferation of hepatoma cells.
Eclalbasaponins have antiproliferative effect on hepatic stellate cells. [91]
Some testimonials from modern research:
Anti-Inflammatory Activity
The plants of the genus Eclipta show anti-inflammatory activity. Their chemical constituents inhibit even the higher levels of histamine.
The methanolic extract of E. alba shows free radical scavenging activity for DPPH and hydroxyl radicals.
In laboratory experiments milk injections are used to induce leukocytosis. Treated with the aqueous extract of E. alba such animals exhibited normalization of white blood cell count. [92] 

The methanolic extract administered by the oral route at a concentration of 100 and 200 mg/kg showed the significant dose dependent anti-inflammatory activity in carrageenan and egg white induced hind paw edema in rats. Anti-inflammatory activity of the tested extract was comparable with that of the standard drug indomethacin (10 mg/kg) and cyproheptadine (8 mg/kg) [93]
Antioxidant Activity
In an experimental study on Charles River Sprague-Dawly CD rats Eclipta prostrata at doses of 50mg/kg and 100mg/kg exhibited antioxidant effect. [94], [95], [96]
In an experimental study on rats global ischemia reperfusion injury was induced by occluding both common carotid arteries for 30 min, followed reperfusion for 4 hrs. Pretreatment with hydroalcoholic extract of E. alba significantly reduced the edema, the size of cerebral infarct and reversed the biochemical markers [97]
Immunomodulatory activity
Wedelolactone and demethyl-Wedelolactone in E. alba enhance the non-specific immune response and resistance to various diseases. The aqueous extract of leaves of E. alba enhances humoral and cellular immunity.
The results of the study suggest that dietary intake of the extract of E. alba leaves can enhance immunity in humanbeings. [98], [99]
Antimicrobial Activity
The wedelolactone contained in E. alba shows antibacterial action against Staphylococcus aureus, Staphylococcus epidermidis(at concentration of 15.0 μg /ml), Salmonella typhimurium (at the concentration of 25.0 μg /ml) and E. coli. [100]   
Anti-viral Activity
E.alba shows antiviral activity against Ranikhet viral disease.  Dasyscyphin-C, a newer saponin compound extracted from the leaves of E. prostrata shows antiviral activity against fish nodavirus, grouper nervous necrosis virus (GNNV).   
The methanolic extract of leaves of E. alba (Dose: 250-750 mg/kg) produced schizonticidal effect on Plasmodium berghei in mice. [101]
In an experimental study the ethanolic extract of whole plant of Eclipta alba at concentrations 1.0, 2.0, 5.0, and 10.0 mg/ ml exhibited antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli, Proteus mirabilis, Pseudomonas fluroescens, Pseudomonas aeruginosa and Salmonella typhi. The antibacterial activity was comparable with that of the standard antibiotic penicillin (10mg/L). [102]
Antifungal Activity:
25beta-hydroxyverazine showed good activity against Candida albicans (Abdel Kader et al., 1998). The in vitro antifungal activity of whole plant of E.alba extract was investigated against Candida tropicalis, Rhodotorula glutinis and Candida albicans. The extract showed high degree of activity against all test fungi. The inhibitory effects of extracts are very similar to those of standard antibiotics used
The extract of whole plant of E. alba and particularly 25 beta-hydroxyverazine fraction of it showed good antifungal activity against Candida albicans, Candida tropicalis and Rhodotorula glutinis and many other fungi tested. The inhibitory effects were very much similar to those of standard antifungal antibiotics. 
According to some research workers E. alba works better than Amphotericin B in fighting fungal infections.  [103] 
Anti-protozoal Activity   :
The anti-malarial activity of Eclipta alba leaves extract was evaluated against Plasmodium berghei ANKA strain in mice. A standard inoculum of 1 x 10(6) infected erythrocytes was used. The methanolic leaf extract (250-750 mg/kg) produced a dose-dependent chemosupression or schizontocidal effect during early and established infection and high mean survival time values particularly in the group administered 750 mg/kg/day of extract. [104]
Its effects on the other species of Plasmodium need be evaluated.
Eclalbosaponins are active against Giardia intestinalis.
Dasyscyphin C extracted from E. prostrata is leishmanicidal. At the concentration 450μg/ml death of the parasite L. major, was 73 percent. The other species viz. L. aethiopica and L. tropica were less sensitive to the saponins of E. prostrata.
Thiophene derivatives are active against nematodes. Triterpenoid and saponins are antiproliferative and Leishmanicidal. [105]
Antimalarial Activity
At doses 250-750 mg/kg bodyweight the methanolic extract of E. alba produced a dose-dependent schizonticidal effect against Plasmodium berghei. [106]  
Hexane, ethyl acetate, benzene, chloroform and methanol extract of leaves of E. alba exhibit larvicidal and ovicidal activities. Thus E. alba can be useful in combating malaria through its larvicidal and ovicidal activities. [107], [108]
Anthelmintic Activity
Anatomically and physiologically earthworm (Pheretima posthuma) resembles roundworm (Ascaris lumbricoides). To evaluate anthelmintic activity of Eclipta prostrata, in an experimental study, earthworm was used instead of roundworm.
At concentration with 100mg/ml ethanol and aqueous extracts of Eclipta prostrata caused paralysis in 2.5 minutes and death in 24.8 minutes of worms studied. This showed that ethanol and aqueous extracts of E. prostrata have significant anthelmintic activity against Ascaris lumbricoides (round worms). The anthelmintic activity was dose dependent. In this regard the ethanolic extract was superior to aqueous extract. The anthelmintic activity of E. prostrata was comparable to Albendazole. [109]
Actions on CNS
Ecliptalbine and verazine show analgesic activity.
In one study on albino mice, analgesic effect of E. alba was studied using ethanolic and alkaloidal extracts of E. alba in standard experimental models. Both the extract showed analgesic activity but the alkaloidal fraction was the most efficacious in all models tested. [110], [111]
The aqueous, hydroalcoholic extracts and hydrolyzed fraction of the aqueous extract of E. alba were subjected to neuropharmacological activities (sedative, muscle-relaxant, anxiolytic, nootropic and antistress activities) in rats. The findings indicated nootropic activity of the aqueous extract (300 mg/kg, p.o.) and its hydrolyzed fraction (30 mg/kg, p.o.). The aqueous extract and the hydrolyzed fraction exhibited gastro protective effect (anti-stress activity) and normalized the white blood cell count in the milk induced leukocytosis challenge model [112]
The aqueous extract of leaves of Eclipta alba when administered to mice at doses of 100 1nd 200mg/kg body weight improved their cognitive function. This activity was attributed to the presence of leuteolins present in the extract [113]
In animal model (rat) the methanolic extract of the whole plant of E. alba at the dose of 200mg/kg ameliorated oxidative stress, improved memory and arrested the progression of Alzheimer’s disease [114]
Antiepilepsy Activity
The methanol extract of leaf powder of E. alba administered to rats (Dose: 50, 100 and 200mg/kg body weight) exhibited anti-convulsant activity. This effect was attributed to wedelolactone, α and β-amyrins and luteolin present in the extract. [115], [116]
The suspension of E. alba containing 100 and 200 mg/kg was administered to rats to evaluate Transfer Latency on an elevated plus maze. Mice were placed at the center of open field apparatus to assess spatial habitual learning, observed for 20 minutes for rearing and time spent during rearing using varied doses for 30 minutes, 24 hours and 96 hours and 144 hrs. The results revealed significant improvement of retrieval memory [117]
Actions on Behavior
The aqueous extract of E. alba at the dose of 300mg/kg acts as memory enhancer and cognitive enhancer (nootropic) in rats.
The suspension of E. alba at the doses of 100 and 200 mg/kg revealed significant improvement in special habitual learning and retrieval of memory in rats [118]
Anti aggressive effect:
In rats E. alba (200mg/kg) significantly minimized dominance which is correlated to the level of aggression. A tangible behavioral submission was also observed with the dose 100 and 200 mg/kg.
It has been suggested that these effects of E. alba are probably due to its immunomodulatory action on the nervous system. [119]
Actions on Skin and Hair growth
An Ayurvedic formulation containing powder of E. alba has been shown to provide complete remission and prevent the recurrence of eczema in dogs. [120]
The antioxidant property of aqueous extract of E. alba protects the skin against ultra-violet irradiation-induced skin damage. [121]
The study was aimed to investigate the efficacy of methanol extract of E. alba as hair growth promoter. Pigmented C57/BL6 mice, preselected for their telogen phase of hair growth were used. The extract was applied topically to assess telogen to anagen transition. The methanol extract of whole plant when tested for hair growth promoting potential, exhibited dose dependent activity in C57BL6 mice (Datta et al., 2009) [122]
Bhringraj (Eclipta alba) is a topnotch herb for hair care. Hair regrowth has been noted in repeated studies with the petroleum ether extract of E. alb leaf. Its potency rivals that of 2% solution of Minoxidil. According to one study, combination thrapy of Eclipta Alba with two other herbs (Citrullus Colocynthis andCuscuta Reflexa) has outperformed Minoxidil in hair groth activity. [123]
Eclipta alba promotes hair growth and maintains its luster and black color. The appropriate concentration for this activity is 10%w/v. In the reported work, petroleum ether and ethanolic extracts were incorporated into water in oil cream base were applied topically on shaved skin of albino rats. The results of this application were better than the use of 2% and 5% minoxidil treatment [124], [125], [126]
Bhringraj (E. alba) oil is useful for the treatment of graying of hair.
A simple hair pack made with fresh leaves is effective in preventing baldness. Apply the paste of fresh leaves on the scalp. Wait for 15-20 minutes before washing. Use this once a week for good results. [127]
Effects on wound healing
Due to its antioxidant, anti-inflammatory, free radical scavenging and antimicrobial activities it promotes wound healing. (Dose: Ethanolic extract 150 to 300 mg/kg body weight).  [128]
Actions on the Eye
Eye health does not have any direct studies on it despite its historical claims, although the one human intervention noted that 7.5% of the sample consuming 3g of the leaves daily claimed they had better eyesight; this study was blinded, and constitutes the only evidence for eye health claims. In a way it is promising (3g of the leaves themselves over 60 days improving eye health even when paricipants were unaware this could be an effect of treatment) but it does not constitute sufficient evidence in and of itself.
Beyond the possible eye/hair benefits and the liver protection, other possible benefits of Eclipta Alba are lessened anger (two animal studies, moderate oral doses), pain reduction (dose dependent, which outperfomed Aspirin when consumed at higher doses of 500mg/kg rats; 80mg/kg ethanolic extract in humans) a reduction in blood pressure, diuretic effects, with at least one study suggesting some benefit to the immune system (increasing macrophage and white blood cell activity).
A possibly promising herb for wellness and beauty, but requires more studies on it. [129]
Actions against snake bite
Wedelolactone and demethylwedelolactone found in E. alba and E. prostrata have trypsin inhibitory and styptic (antihemorrhagic) activity against Malayan Pit Viper venom.
Walter B. Mors et al, Maria Helena da Silva et al and Paulo A. Melo et al showed that in Swiss mice, the ethanolic extract of the aerial parts of E. prostrata neutralized the lethal activity of South American rattle snake venom. According to them the aqueous extract of E. prostrata inhibits the release of creatine kinase from isolated rat muscles exposed to the crude venom. They attribute these effects to wedelolactone, sitosterol and stigmasterol.
Ethanolic extract of the aerial parts of E. alba neutralizes three lethal activity of the venom of South American rattle snake (Crotalus durissus terrificus) by inhibiting snake venom phospholipase A2 activity. The inhibitory activity has been attributed to wedelolactone, demethylwedelolactone, coumestan, stigmasterol, and sitosterol present in the extract.
In one study aqueous extracts of E. alba inhibited the release of creatinine kinase from isolated rat muscle exposed to crude venom. This protection was also observed in vivo, when the venom was preincubated with the plant extract in mice.
In neutralizing myotoxins wedelolactone was more effective than sitosterol and stigmasterol. Wedelolactone inhibited the hemorrhagic effects of B. jararaca venoms. This activity was attributed to inhibition of proteolytic activity of B. jararaca venom [130], [131]
Actions on Musculo-Skeletal System
Flavonoid, diosmetin, and isoflavonoids, 3’hydroxybiochanin A, and 3’O-methylorobol, isolated from the methanol extract of E. prostrata significantly increased osteoblast differentiation as assessed by the alkaline phosphatase activity [132]
Actions on RS
Wedelolactone which is anti-allergic, is a potent phytochemical against bronchial asthma. [133]
Actions on CVS
To evaluate antihypertensive effect of E. alba, dried leaf powder of E. alba was administered to mild hypertensive subjects, six capsules of 500mg each for 60 days. The sudy indicated that the leaf powder possessed diuretic, hypotensive and hypocholesterolemic properties [134]
The ethanolic extract of leaves of E. alba showed negative inotropic and negative chronotropic effects on frog heart. The extract reduces cardiac output. It antagonizes the effects of adrenaline. [135], [136]
Effect on proteolytic and hemorrhagic activities
Wedelolactone and demethylwedelolactone, isolated from E.alba demonstrated significant trypsin inhibitory effects. The partially purified ethyl acetate extract of E. prostrata (containing 47% of wedelolactone) and wedelolactone demonstrated strong antiproteolytic and antihemorrhagic activity against Malayan Pit Viper venom in a dosedependent manner. The extract, at 5 mg/ml, inhibited proteolytic activity of 100 µg of the venom and hemorrhagic activity of 3 minimum hemorrhagic doses to 95% and 65% respectively. At the same concentration, wedelolactone neutralized the proteolytic activity at around 76% and, at doses of 0.25-1.0 mg/ml, offered protection against hemorrhagic activity of the venom in the range 3-3.5%. [137]
Actions on GI System
The aqueous extract and the hydrolyzed fraction exhibited gastro-protective effect and normalized the white blood cell count in the milk injection induced leukocytosis in laboratory models. [138]
E. alba significantly reduces the gastric acid secretion, occurrence of gastritis and gastric ulcers and gastric inflammation. Its potency as anti-ulcer agent is comparable to that of various PPIs. [139]
The ethanolic extract of E. alba administered orally at doses of 50, 100 and 200 mg/kg body weight twice a day exhibits antiulcer activity in several peptic ulcer rat-models in a dose dependent manner. The antisecretary activity of the extract was evident by reduction in volume of gastric juice, total acid output and increase in gastric pH. [140]

To evaluate anti-peptic ulcer efficacy of E. alba, by administering aspirin or ethanol peptic ulcer was induced in Sprague Dawley rats. Administration of methanolic extract of E. alba prior to induction of peptic ulcer, protected the animals against drug-induced peptic ulcer. This activity of the extract of E. alba was comparable to proton pump inhibiting drug rabaprazole. [141]

Hepatoprotective Activity
CCl4 inflicts insult on the liver. The parenchyma undergoes fatty degeneration culminating into cirrhosis and death. CCl4inhibits the hepatic microsomal drug metabolizing enzymes. In experimental animals the ethanol-water (1:1) extract of E. albasignificantly restored the loss of hepatic lysosomal acid phosphatase and alkaline phosphatase caused by CCl4. [142]
In another study the ethanolic extract of leaves of E. alba and seeds of Piper longum (50mg/kg body weight) was administered orally once a day for fourteen days. All the biochemical markers of the liver function were restored to normal levels. The triterpenoid eclabasaponin fraction contained in the methanolic extract of the leaves restored the liver functions to normal levels. The coumestan fraction and triterpenoidal saponin fraction contained in the chloroform extract of roots very significantly reduced CCL4 induced increase in lysosomal enzyme levels in the blood. [143]
Administration of fresh leaf powder of E. alba at the dose of 500mg/kg bodyweight to rats exhibited a significant hepatoprotective activity against paracetamol-induced hepatotoxicity [144]
In albino rats, the ethanol extract of the whole plant of E. alba exhibits hepatoprotective activity against alcohol-induced liver dmage. Moreover the toxic effects of alcohol can be reversed with co-administration of the ethanol extract of the whole plant. E. alba not only normalizes the biochemical markers of liver injury but also reverses the histopathological changes that occur in the liver after the alcoholic liver disease. [145] 
The hepatoprotective effect of E. alba is attributed to the coumestans (wedelolactone and demethylwedelolactone) [146]
In another Indian study Eclipta alba extract and its isolates;  wedelolactone, luteolin and apigenin exhibited anti HCV activity in vitro and in cell culture system. It was further established that the inhibition of HCV replication in cell culture system was via inhibition of HCV replicase activity in the cell. Researchers suggest, standardized extract of Eclipta alba or its isolates can be used as an alternative and/or complimentary treatment against HCV. [147], [148]
Two studies by Dixit and Achar (1979 and 1981) reported efficacy of E. alba for the treatment of jaundice due to viral hepatitis in adults and in children. [149], [150]    
In my opinion E. alba, Piper longum (Pippalee), Picrorhiza kurroa (Kutakee), Phyllanthus niruri / Phyllanthus amarus(Bhoomyaamalakee, Bhui Aamalaa)  and many other hepatoprotective drugs from plant kingdom should be tried either singly or in combinations in patients with hepatitis B and C infections, alcoholic liver disease, NASH, cirrhosis of the liver etc.
The other species E. prostrata is also hepatoprotectant. In rats the alcoholic extract of aerial parts of this plant (Dose: 62.5 to 500mg/kg) restored the liver functions to normal following CCl4 induced liver injury. When administered orally or intraperitoneally the extract did not show toxicity. In mice the lethal dose was greater than 2g/kg. 
Stigmasterol and alpha-terthenyl are hepatoprotectants.
Researchers from Chandigarh, India have reported Eclipta alba to be effective in converting the HbsAg positive patients to HbsAg negative. [151], [152]
Wedelolactone present in E. alba exhibits antifibrotic effect on human hepatic stellate cell line LX-2. Hepatic stellate cells (HSC) are a major fibrogenic cell type that contributes to collagen accumulation during chronic liver disease which subsequently culminates into liver fibrosis. By inhibiting the activation of HSCs wedelolactone prevents the development of liver cirrhosis. [153]
Antidiabetic Activity
Oral administration of suspension of leaf of E. alba at doses of 2 and 4 g/kg bodyweight to alloxan-induced diabetic rats resulted in significant reduction in blood glucose from 372mg/dl to 117mg/dl and glycosylated hemoglobin, Hb A(1)c;
a decrease in the activities of glucose-6 phosphatase and fructose 1,6-bisphosphatase, and increase in the activity of liver hexokinase. These activities control diabetes and diabetes-related complications
Similar results were observed in streptozotocin (STZ)-induced diabetic rats by other researchers. [154], [155]
Actions on Metabolism
Adipocytes arise from multipotent adipogenic stem cells in the vascular stroma of adipose tissue and remote stem cells of other organs. Adipocyte hyperplasis is associated with obesity [156]
Wedelolactone has been observed to inhibit the adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells. [157]
The alcoholic extract of whole plant of E. prostrata, in albino rats reduces elevated serum cholesterol, LDL and triglyceride. Needless to say the response is dose dependent. Like E. alba, E. prostrata is rich in wedelolactone which is effective in lowering the lipids. Ecliptalbine and verazine show lipid lowering activity.
The aqueous extract of the leaf of E. alba at the dose of 200mg/kg body weight administered orally to rats significantly reduced total cholesterol, triglycerides and increased high density lipoprotein cholesterol levels. [158], [159]
Actions on Urinary System
The powder of dried leaves of E. alba (3g/day) is a very good diuretic. When used at this dose the urine volume increased by 34% and excretion of urinary sodium increased by 24%. [160]
Actions on Male Reproductive System
In an experimental study male Wister rats were fed orally with boric acid at a dose of 350mg/kg bodyweight for 30 days. From 15 days onwards the toxic effects on testis, kidney and liver were evident. After 30 days the damage to testis was complete. After 30 days, the hydroalcoholic extract of Eclipta alba was administered orally to the rats at a dose of 500mg/kg body weight for 60 days. In the rats treated with the plant extract there was a complete reversal of toxicity. The levels of testosterone, estrogen and FSH returned to normal. The fertility was restored and the altered tissue morphology showed significant signs of recovery. However the mechanism of action of E. alba is not clear and needs further study. [161]
Anti-Tumor Activity
By inducing apoptosis, wedelolactone present in E. alba, kills both androgen-sensitive and androgen-independent prostate cancer cells [162]
Methanolic extract of E. alba exhibited anticancer activity against Ehrlich Ascites Carcinoma in Swiss albino mice. [163]
Recently a new saponin, Dasyscyphin-C is isolated from Eclipta prostrata. It has anticancer activity against human cervical carcinoma [164]
The hydro-alcoholic extract of E. alba inhibits the cell proliferation in a dose-dependent manner in HepG2, A498 and C6 glioma cells. The extract downregulates nuclear factor κB (NFκB) and damages the DNA of malignant cells [165]
The hydro-alcoholic extract of the plant (E. alba) demonstrated antiproliferative activities in multi-drug resistant hepatocellular carcinoma cell line [166] 
Juice obtained from E. alba inhibits the migration of liver, lung and breast cancer cells. Thus E. alba plant extract prevents cancer metastasis
The juice also demonstrates anti-angiogenic activity [167]
The methanol extract of E. alba has been shown to inhibit the growth of colonic cancer cells. [168], [169]
Culinary uses
Not used routinely. In some countries it is included in diet to prevent breast and prostate cancer.
Medicinal Actions and Uses
Traditional Uses
In folk medicine a black dye obtained from E. alba is in vogue for dyeing hair and tattooing. Externally it is used to treat athlete foot, eczema and dermatitis, hair loss and to prevent graying of hair. Its leaves are used to treat scorpion sting. It is used for the treatment of jaundice (infective hepatitis, now viral hepatitis) and ascites (due to cirrhosis of the liver). It is believed by folk to rejuvenate hair, teeth, bone, improve memory, sight and hearing. Thus the herb prevents and retards aging in general.
In Taiwan E. alba is used to arrest bleeding anywhere in the body especially hemoptysis, hematemesis, bleeding piles and hematuria. It is used for diarrhea and infective hepatitis. Externally it is used to allay itching and some skin allergies.
In China E. prostrata is a cooling and restorative herb. It is used for its actions on the mind, nerves, liver, kidney and eyes. 
In China and Brazil it is used to promote hair growth, to improve hair color, and as anti-snake venom medicine.
Usages in Ayurveda
In Ayurveda the plant is considered a Rasaayana (Adaptogen) for rejuvenation of hair, teeth, bones, memory, sight, hearing and body systems imparting longevity.
It is used to promote deep sleep.
It is used for the hair care and to improve complexion.
It is used to relieve gastralgia, nausea and vomiting. 
The Roots are used as emetic and purgative.
It is strongly recommended for the treatment of jaundice, ascites and enlarged spleen (probably due to portal hypertension and not due to any other cause). It is especially rejuvenating for hair, skin and teeth. According to Ayurveda the liver is the controller of hair, nails, skin and teeth. Hence by improving the liver functions Bhringraj acts as rejuvenator for these tissues.
Bhringraj improves iron metabolism and improves the quality of the blood.
Acting as appetizer it increases bile flow from the liver into the intestines. [170]
By sedating the nervous system it relieves headache and vertigo.
It reduces BP and edema
It has been used in night blindness and myopia to improve vision.
It is useful in skin disorders and improves complexion. [171]
It is used to relieve dysuria and improve kidney function.
The leaves are used to treat Dysfunctional Uterine Bleeding (DUB) and repeated abortions.
It is used to treat scorpion stings.
Recently nasal instillation (nose drops) of Bhringraj Tailam (Bhringraj Oil) along with administration of Kaasis Bhasma internally has been used to treat premature graying of hair (Palitam, palitham). Vide infra (Additional Information)
Indications mentioned in Ayurvedic texts:
Dhanwantaree Nighantu: Shotha (edema), Aama (for scavenging free radicals), Kapha (expectoration), Paandu (anemia), Kushtha (leprosy), Kandu (itching)
Shodala Nighantu: Shwitra (leucoderma), Akshiroga (ophthalmic disorders)
Bhawaprakaasha Nighantu: Krimi (helminthiasis), Kaasa (cough), Shwaasa (dyspnea), Shotha (edema), Aama (for scavenging free radicals),  Paandu (anemia), Kushtha (leprosy), Netraroga (ophthalmic disorders), Shiroroga (ailments of the head)
Shleepada, Granthi, Vrana, Kshala, Netraroga, Palitya,Kesharoga, Bhrama,Naktandhya, Kamala, Arsha, Ajeerna, Kushtha,Kilasa, Jwara, Kasa, Pandu, Shotha, Shwasa,Daurbaya,Charmaroga
Kaiyadeva Nighantu: Netraroga (ophthalmic disorders), Shiroroga (ailments of the head), Krimi (helminthiasis), Kaasa (cough), Shwaasa (dyspnea), Shotha (edema), Kushtha (leprosy), Shotha (edema), Aama dosha (for scavenging free radicals),  Paandu roga (anemia).
Madanaphala Nighantu: Kushtha (leprosy), Netraroga (ophthalmic disorders), Shiroroga (ailments of the head). [172]
Therapeutic recommendations mentioned in Ayurvedic texts:
Charaka Samhitaa:
Graying of hair: Bhringraj Taila (Ch. Chi-26/264)
Sushruta Samhitaa:
Inflammations caused by nail scratching-Bhringraj swarasa (the juice of fresh leaves) (Su. Kalpasthaana-8/56)
Kaasa-Shwaasa (cough-dyspnea)- Oil (?Sesame oil) cooked with 10 times fresh juice of Bhringraj, when used judiciously alleviates cough and dyspnea (Su. Uttarsthaana -51/30)
Psoriasis- Tagara (Tabernaemontana coronarea ), Kushtha (AkA Pushkaramoola, Saussurea lappa/ Saussurea costus), Apaamaarga (Achyranthes aspera), pounded with Bhringraj juice for local application (Su. Kalpasthaana -8-54)
Ashtaanga Hridayam:    
Those who drink the fresh juice of Bhringraj leaves for one month and consume milk as staple food attain a life of 100 years endowed with strength and vigor (Ashtaanga. us.-34/136)  
Shaarngadhara Samhitaa:
Iron ore and Saariwaa (Hemidesmus indicus L.) are made into bolus, mixed in oil (?Sesame oil) and Bhringraj swaras (juice) and boiled to the consistency of oil. It is applied to get rid of dandruff, premature graying of hair, pruritus and alopecia. 
Nimba beeja (seeds of Citrus limonum) are macerated with Bhringraj juice and decoction of wood of Asana (Pterocarpus marsupium) tree to make paste. The paste is cooked in Sesame oil. Few drops of this oil are instilled in each nostril. During the treatment the patient consumes rice and milk as staple diet. This cures premature graying of hair in men.
Chakradatta:
To relieve gastritis, hyperacidity and vomiting mix Hareetakee (Terminalia chebula) powder, Bhringraj and old jiggery and consume small pills frequently.
For healthy hair- Cook Sesame oil with Bhringraj juice, paste of triphalaa, Neelotpala (Nymphaea stellata Wild), Saariwaa (Hemidesmus indicus L.) and slag of iron (partially vitreous by-product of smelting iron ore). Use this hair oil daily. This hair oil makes the hair curled, dense and firm. [173]
Usages in Siddha Medicine
In many afflictions E. alba is used as in the Ayurvedic system. Some different uses are mentioned here.
Its leaves are steeped in boiling water. The steam arising from it is used to treat piles.
Paste made by leaves ground in sesame oil is applied on the body part inflamed due to filariasis. 
The juice of entire plant is given to treat hepatomegaly, splenomegaly, indigestion, jaundice etc. in the dose of 20-30 ml twice a day.
Paste made from leaves is rubbed well and bandage applied at the site of scorpion bite. 
Usages in Modern Medicine
In modern times E. alba is a precious herb in hair care and cosmetic industry.   
In southern Thailand E. alba fresh plant is used as self medication by HIV positive patients. There it is also used to treat giardiasis.
In some countries it is used to treat dyslipidemia, edema and paronychia.   
Extract of E. prostrata is used to treat lethal and myotoxic effects of South American rattlesnake venom.  
Alas! Despite the data accumulated from various animal studies E. alba is underused in clinical practice in modern medicine.More studies are warranted to unravel its therapeutic potentials in hepatology.
Formulations:
Kayyanyadi Tailam: Swarasa of Bhringaraja, Amritha And Dhatri 8%, Yashti (Kalka) 2.26%, Thailam 84%, Milk 5%, Anjana (Pathrapakam) 0.58%
Grahani Mihira Tailam: Contains 12 gm drug/ 4 litres of taila.Recommended in case of fevers, acidity problems and respiratory problems.
Nilakadya Tailam: Contains 12 gm drug/ 3 litres of taila.Used for abhyanga(bath)
Nilibrngadi Tailam: Contains Bhringaraja svarasa – 768 ml/ 6.5 liters used externally for headache
Siddha
The leaves are ground and prepared into a karkam (paste) and mixed with the leaf juice of this plant. It is then added into gingelly oil and boiled to proper patham or paste and the oil is extracted. This oil is applied daily over the head and is helpful to cure hair loss, body pain and diminution of vision. The samoolam (root) of this plant is ground and the juice from it is given in the dose of 20-30 ml daily twice for hepatomegally, spleenomegally, indigestion, jaundice etc. Root powder is given internally in the dose of 5 gram daily for diseases of liver, spleen and skin diseases. The leaves are ground well and the karkam prepared from it is rubbed well and tied as a bandage over the site of scorpion bite. The steam coming from the leaves with boiling water is exposed over pile mass. The leaves are ground with gingelly oil and applied over the inflamed limb due to filariasis.
For heamaturia, the leaf juice in the dose of 5-15 ml is given daily twice a day.The 2-3 drops of leaf juice is mixed with equal quantity of honey and given internally to infants for common cold.
The choornam (powder) of samoolam (root) of this plant is given as an adjuvant with Aya chendooram is a very effective remedy for anemia, dropsy and jaundice. For intestinal worms one ounce of castor oil is mixed with 1/2 ounce of karisalai juice is given internally early morning or alternate days.Samoolam of this plant is made into choornam (powder) and 2-5 grams of this is given internally for one month with tender coconut water and second month with honey. This medicine is a kayakarpam.
Chinese:
Eclipta alba: Han lian cao (prostrata) Eclipta is one of the few "yin tonics" among Hawaiian medicinals.
Korea:
 The plant is used as an antidote for snake bites in Korea.
Philippines:
A decoction of the dried plant is used for heamoptysis and heamtemesis. For dysentery and heamturia urine, a decoction of the dried herb or tincture is used. Medicated tea or tinctures are used as household remedies for sprains, furuncle and dermatitis; the tea or tincture is excellent 
Nepal: 
Plant juice, mixed with an aromatic (essential oil), is used in the treatment of catarrhal problems and jaundice. The leaves are used in the treatment of scorpion stings [174]
Toxicity
Use of E. alba can cause severe chills in some patients.
Drug Interactions 
Not reported
Preparations and dosages
Fresh juice: For hematuria, 5-15 ml twice a day. For common cold in infant 2-3 drops with equal quantity of honey or mixed with goat’s milk. To expel intestinal worms, given in the morning with 15 ml. of castor oil. 
Powder: As adaptogen given orally for a month with honey, 2-5 grams. Also used for anemia, dropsy and jaundice. The powder of the root is given internally in the dose of 5 gram daily for diseases of the liver, spleen and skin diseases.
Powder of the whole plant: 3 to 5 grams
Tincture: 0.5 - 3 ml. daily.
Infusion: 100- 200 ml. daily.
Seeds: 0.5 to 1.5 G
Decoction: Is used orally to treat leprosy. Decoction with black pepper and sugar is used as anti-inflammatory
Bhringraj Ghana Sattwa: For viral hepatitis 1g three times a day
Bhringraj watee (Tablet): For viral hepatitis 1g three times a day 600 mg. three times a day
Medicated oil: In hair care and cosmetic industry, it is massaged on to the scalp, to impart calming effect and to promote good sleep. It is rubbed on the head to relieve headache. It is massaged on the affected part to relieve lymphedema. Modern Bhringraj oils are enriched with natural proteins, polysaccharides, vitamin E, minerals, peppermint oil, mint leaf extract and many other nutrients for hair care.
Bhringraj seeds promote spermatogenesis, hence is used for virilisation. [175]
The mixture of roots, leaves and Ajamoda is useful in all urinary disorders. [176]
Bhringraj ghrita (Medicated ghee): Dose not found
Important Combinations:
Bringaraaja taila, Shadbinu taila, Bhringrajadi choorna [177]
With honey the leaf extract is used to treat catarrh, urinary problems and to expel worms in infants and children. [178]
Additional Information:
(A)  Yogaratnaakar 
In view of the author of Yogaratnaakar paste or pulp of fresh leaves of E. alba be applied at the site of scorpion sting and bandage be fastened. Simultaneously a few drops of fresh juice of leaves be instilled in each nostril.
While local application relieves edema, nasal instillation ‘drains’ the poison.
(B)  Dr. Nadkarni agrees with Yogaratnaakar.
(C)  In addition to the measures mentioned above, in Chennai (old Madras) the patient with scorpion bite is given fresh juice ofE. alba to drink.
(D) Vaidya  Appaashaastree Saathe’s prescriptions
  1.   For cough, cold and bronchitis in infants and children
Fresh juice                10 ml
Honey                      6 grams      (Given frequently in small quantity as lambative (Marathi: catan, chaatana) or linctus.)
2.    For vertigo and migrane
Fresh juice                 10 ml
Sugar candy                 3 grams
Coconut milk              50 ml
To be taken two or three times
Or instil 2-3 drops in each nostril.
3.   As adaptogen, to enhance intellect and memory
Powder                        1 gram
Honey                          3 grams
Sugar candy                6 grams
Cow ghee                    6 grams
One dose to be taken every day for at least 40 days.
4. For conjunctivitis, trachoma 
Instill a drop or two of fresh juice in the eyes every morning  and at bed time swallow: 
Powder                        1 gram
Honey                          3 grams
Cow ghee                    6 grams
5. For jaundice, viral hepatitis
Fresh juice                    10 ml
Sugar candy                  10 grams
Miree (Piper nigrum)       4 grams
One dose of this to be taken twice a day till jaundice abates.
6. For thickening of the skin due to filariasis, Hypothyroidism, multiple lipomatosis, adiposo dolorosa
Massage fresh juice on the affected parts. 

          (E) In Dr. Desai’s opinion:     

      It is appetizer, digestant, laxative, diuretic, vulnerary, antipruritic and adaptogen. It improves complexion and imparts luster to the skin. It is the remedy par excellence for jaundice.


(F) Clinical Management of Palitham (Grey Hair) with Bhringraj Thaila Nasyam and Kasisa Bhasma Internlly [179]

References
1. http://www.agriculturalproductsindia.com/herbal-products/herbal-products-bhringraj.html
4. http://www.dreddyclinic.com/ayurvedic/herbs/bb/bhringaraj.htm
5. https://sites.google.com/site/efloraofindia/.../a.../eclipta/eclipta-prostrata
https://books.google.co.in/books?id=YC_lAgAAQBAJ&pg=PA1518&lpg=PA1518&dq=etymology+of+Eclipta&source=bl&ots=cU-lyfd6ZA&sig=DVnmfaQro-K5KkdROCAsGiCi3E0&hl=en&sa=X&ved=0CDQQ6AEwA2oVChMIrNKYzJWLyQIVY9imCh2LqAKv#v=onepage&q=etymology%20of%20Eclipta&f=false
6. http://reddybams.page.tl/Bhringraj.htm
7. http://www.ayurveda.hu/api/API-Vol-2.pdf, The Ayurvedic Pharmacopoeia of India; The Ayurvedic Pharmacopoeia of India; http://www.ayurveda.hu/api/API-Vol-2.pdf        
9.
(Review of Literature)
10.  http://www.femineus.pl/index.php?topic=7378.0
13.  www.google images
14. http://www.imispharma.com/Products/Medicine-Neeli-Bhringaraja-Taila.htm
15
http://www.imispharma.com/Products/Medicine-Neeli-Bhringaraja-Taila.htm
16
17. http://www.ayurveda.hu/api/API-vol-2.pdf
(Review of Literature)
22 http://en.wikipedia.org/wiki/Eclipta_prostrata
24.  http://ipc.nic.in/writereaddata/linkimages/Admin9640017989.pdf
25. http://ipc.nic.in/writereaddata/linkimages/Admin9640017989.pdf
26. http://ipc.nic.in/writereaddata/linkimages/Admin9640017989.pdf
27. Chromosome Count Data Base, http://ccdb.tau.ac.il/Angiosperms
28. Yadav et al, Development of Sequence Characterized Amplified (SCAR) Marker for the Authentication of Bacopa monnieri (L.) Wettst Aradhana, European Journal of Medicinal Plants, 2(3): 186-198; 2012
32
http://reddybams.page.tl/BHRINGRAJ (ECLIPTA ALBA).htm
33. Neeraja P.V., Elizabeth Margaret Eclipta alba (L.) Hassk: A Valuable Medicinal herb; IJCPR, November 2011-January 2012; 2(4); 188-197
34. http://www.ayurveda.hu/api/API-Vol-2.pdf 
35.  http://reddybams.page.tl/BHRINGRAJ.htm
37.
http://www.pharmatutor.org/articles/phytochemical-and-pharmacological-profile-of-eclipta-alba?page=0,1
38. http://enwikipedia.org/wiki/Wedelolactone
40. S. M. Wong et al, Wedelactone and coumestan derivatives as new antihepatotoxic and antiphlogistic principles, Arzneimittel-Forschung, vol. 38, no. 5, pp 661-665, 1988
41. M. Kobori et al, Wedelolactone suppresses LPS-induced caspase-11 expression by by directly inhibiting the IKK complex
42. F. Yuan J. Chen et al, Wedelolactone inhibits LPS-induced pro-inflammation via NF-κB Pathway in RAW 264.7 cells, Journal of Biomedical Science, vol. 20, no. 1, article 84, 2013
43. S Dalal, S Rana, K Sastry, K Kataria, Wedelolactone as an Antibacterial Agent extracted from Eclipta alba (Original Article); The Internal Journal of Microbiology Volume 7, Number 1.                                                                                             
44. S. Tewtrakul et al, HIV-1 protease and HIV-1 integrase inhibitory substances from Eclipta prostrata, Phytotherapy Research vol.21, no. 11, pp. 1092-1095
45. Sarveswaran S, Gautam SC, Ghosh J; Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKC without inhibiting Akt; Int J Oncol 2012 Dec 41 (6): 2191-9

46. F. M. Lin et al, Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells, Carcinogenesis, vol. 28, no. 12, pp2521-2529, 2007
47. P. Benes et al, Inhibition of topoisomerase Iiα: novel function of wedelolactone, Cancer Letters, vol. 303, no. 1, pp. 29-38, 2011
48. W. M. Huston et al, Apoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innate immune activation compounds and the inhibitor wedelolactone, The American Journal of Reproductive Immunology, vol. 65, no. 5, pp. 460-464, 2011
49. Wu L, Wang X, Xu W, Farzaneh F, Xu R, The structure and pharmacological functions of coumarins and their derivatives, Curr Med Chem 2009; 16(32): 4236-60
50. Denise Egan et al, The pharmacology, metabolism, analysis and applications of coumarin and coumarin-related compounds, Drug Metabolism Reviews, 22(5), 503-529 (19900
52. J. Liu, Pharmacology of oleanolic acid and ursolic acid, Journal of Ethnopharmacology, vol. 49, no. 2, pp. 57-68, 1995
53. K. Y. Yoo and S. Y. Park, Terpenoids as potential ant-Alzheimer’s disease therapeutics, Molecules, vol. 17, no. 3, pp. 3524-3538, 2012 
55. Oliveira FA et al; Protective effect of alpha-and beta- amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. Trunk wood resin, against acetaminophen-induced liver injury in mice, J Ethpharmacol 2005 Apr 8:98(1-2): 103-8
56. Oliveira FA et al; Pentacyclic triterpenoids, alpha and beta amyrins suppress the scratching behavior in a mouse model of pruritus, Pharmacol Biochem Behav 2004 Aug: 78(4): 719-25.
57. Subarnas A et al, Pharmacological properties of beta-amyrin palmitate, a novel centrally acting compound, isolated from lobelia inflata leaves, J. Pharmacol, 1993 Jun; 45(6):545-50
58. Chicca A, Marazzi J, Gertsch J, The antinociceptive triterpene β-amyrin inhibits 2- arachidonoylflycerol (2-AG) hydrolysis without directly targeting cannabinoid receptors, Br. J Pharmacol 2012 Dec; 167(8):1596-608
59. R. Medeiros et al, Mechanisms underlying the inhibitory actions of the pentacyclic triterpene α-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate, European Journal of Pharmacology, vol. 559, no. 2-3, pp. 227-235, 2007
60. G. Kweifio-Okai and T. A. Macrides, Antilipoxygenase activity of amyrin triterpenes, Research Communications in Chemical Pathology and Pharmacology, vol. 78, no. 3, pp.367-372   
61. Otuki MF. et al; Antinociceptive Properties of Mixture of α-Amyrin and β- Amyrin Triterpenes: Evidence for Participation of Protein Kinase C and Protein Kinase A Pathways; JEPT April 2005 Vol. 313 no. 1 310-318

62. F. A. Oliveira et al, Attenuation of capsaicin-induced acute and visceral nociceptive pain by α and β amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in mice, Life Sciences, vol. 77, no. 23, pp. 2942-2952, 2005
63. R. C. P. Lima Jr., Attenuation of visceral nociception by α and β amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in mice, Planta Medica, vol. 72, no. 1, pp. 34-39, 2006
64. G. F. Aragao et al, A possible mechanism for anxiolytic antidepressant effects of α and β-amyrin from Protium heptaphyllum (Aubl.) March, Pharmacology Biochemistry and Behavior, vol. 85, no. 4, pp. 827-834, 2006
65. C. M. Melo, T. C. Morais et al, Anti-inflammatory effect of α-β-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice, Inflammation Research, vol. 60, no. 7, pp. 673-681, 2011
66. C. M. Melo, K. M. M. B. Carvalho et al, α-β-amyrin, a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in rats, World Journal of Gastroenterology, vol. 16, no. 34, pp. 4272-4280; 2010
67. F. A. Oliveira et al, Gastroprotective effect of the mixture of α and β-amyrin from Protium heptaphyllum: role of capsaicin-sensitive primary afferent neurons, Planta Medica, vol. 70, no. 8, pp. 780-782, 2004
68. C. E. Vitor et al, Therapeutic action and underlying mechanisms of a combination of two pentacyclic treterpenes, α-β-amyrin, in a mouse model of colitis, British Journal of Pharmacology, vol. 157, no. 6, pp. 1034-1044, 2009
69. I. Matos et al, Preventive and therapeutic oral administration of the pentacyclic triterpene α, β-amyrin ameliorates dextran sulphate sodium- induced colitis in mice: the relevance of cannabinoid system, Molecular Immunology, vol. 54, no. 3-4, pp. 482-492, 2013
70. N. Ali, Brine shrimp cytotocxcity of crude methanol extract and antispasmodic activity of α and β-amyrin acetate from Tylophora hirsuta Wall, BMC Complimentary and Alternative Medicine, vol. 13, article 135, 2013

71. F. A. Oliveira et al, Protective effect of α and β-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. Trunk wood resin, against acetaminophen-induced liver injury in mice, Journal of Ethnopharmacology, vol. 98, no. 1-2, pp. 103-108, 2005 

72. A. B. Singh et al, Antihyperglycemic activity of α-amyrin acetate in rats and db/db mice, Natural Product Research, vol. 23, no. 9, pp. 876-882, 2009

73. F. A. Santos et al, Antihyperglycemic and hypolipidemic effects of α, β- amyrin, a triterpenoid mixture from Protium heptaphyllum in mice, Lipids in health and Disease, vol. 11, article 98, 2012
74. https://en.wikipedia.org/wiki/Ursolic_acid
75. Y. Ikeda et al, Ursolic acid: an anti- and pro-inflammatory triterpenoid, Molecular Nutrition and Food Research, vol. 52, no. 1, pp. 26-42, 2008
76. N. Sultana Clinically useful anticancer, antitumor and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product, Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 26, no. 5, pp. 616-642
77. Steven D. Kunkel et al, Ursolic acid Increases Skeletal Muscle and Brown fat and Decreasea DietiInduced Obesity, Glucose Intolerance and Fatty Liver Disease; PLoS One, 2012: 7(6): e39332  
Source:
Bang HS et al, Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men, Korean J Physiol Pharmacol 2014 Oct; 18(5): 441-6
79. Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A; Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies, Biochem Pharmacol 2013 Jun 1: 85(11): 1579-87 

80. Hao Weng et al; Ursolic acid induces cell cycle arrest and apoptosis of gall bladder carcinoma cells, Cancer Cell Int. 2014; 14: 96

81. G. Seelinger et al, Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin, Planta Medica, vol. 74, no. 14, pp. 1667-1677, 2008

82. X. Tongda, D. Li, D. Jiang, Targeting cell signaling and apopttic pathways by luteolin: cardioprotective role in rat cardiomyocytes following ischemia/reperfusion, Nutrients, vol. 4, no. 12, pp. 2008-2019, 2012 

83. G. Seelinger et al, Anti-carcinogenic effects of the flavonoid luteolin, Molecules, vol. 13, no. 10, pp. 2628-2651, 2008

84. Y. Lin et al, Luteolin, a flavonoid with potential for cancer prevention and therapy, Current Cancer Drug Targets, vol. 8, no. 7, pp. 634-646, 2008

85. S. Shukla and S. Gupta, Apigenin: a promising molecule for cancer prevention, Pharmaceutical Research, vol. 27, no. 6, pp. 962-978, 2010

86. M. Piantelli et al, Flavonoids inhibit melanoma lung metastasis by impairing tumor cells endothelium interactions, Journal of Cellular Physiology, vol. 207, no. 1, pp. 23-29, 2006
88. Lee JH et al, Immunoregulatory activity by daucosterol, a beta sitosterol glycosterol, induces proactive Th1 immune response against disseminated Candiasis in mice; Vaccine 2007 May 10; 25(19): 3834-40  
89. https://en.wikipedia.org/wiki/Stigmasterol
90. Ray A., Bharali P., Konwar B. K., Mode of antibacterial activity of Eclalbasaponin isolated from Eclipta alba, Appl Biochem Biotechnol, 2013 Dec; 171(8): 2003-19
92. Thakur VD, Mengi SA, Neuropharmacological profile of Eclipta alba (Linn) Hassk, J Ethnopharmacol 2005 Oct 31; 102(1): 23-31
93. Amrit Pal Singh et al. / International Journal of Phytopharmacology, 1(2), 2010, 57-63.
94. Karthikumar S, Vigneswari K, Jegatheesan K, Screening of antibacterial and antioxidant activities of leaves of Eclipta prostrata (L). Sci. Res. Essays. 2007; 2(4): 101-104
95. Bhaskar Rao D et al, Evaluation of antioxidant potential of Clitoria ternate L. and Eclipta prostrata L. Indian Journal of Biochemistry and Biophysics. 2009; 46: 247-52
96. http://www.pharmatutor.org/articles/phytochemical-and-pharmacological-profile-of-eclipta-alba?page=0,1
97. K. P. Mansoorali, T. Prakash, D. Kotresha, K. Prabhu, N. Rama Rao, Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats, Phytomedicine, vol. 19, no. 12, pp. 1108-1116, 2012
98. Christybapita D, Divyagnaneswari M, Dinakaran Michael R. Oral administration of Eclipta alba leaf aqueous extract enhances the non-specific immune responses and disease resistance of Oreochromis mossambicus, Fish and Shellfish, Immunology, 2007; 23(4): 840-52
99. Jayathirthaa MG, Mishraa SH, Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica, Phytomedicine. 2004; 11(4): 361-65 
100. Dalal S, Rana S, Sastri K, Kataria S, Wedelolactone as an Antibacterial Agent extracted from Eclipta alba, International Journal of Microbiology, 7, 2009, 1 
101. Amrit Pal Singh et al, Eclipta alba Linn- Ancient Remedy with Therapeutic Potential, International Journal of Pharmacology, 1(2), 2010, 57-63
102. S. Selvamani, S. Balamurugan, In vitro antibacterial activity of Eclipta alba (L) Hassk, International Letters of Natural Sciences 16 (2014) 28-34 ISSN 2300-9675
103. Venkatesan S, Ravi R. Antifungal activity of Eclipta alba, Indian Journal of Pharmacology, 66, 2004, 97-98
104. Bapna et al, Anti-malarial activity of Eclipta alba against Plasmodium berghei infection in mice, Journal of communicable Diseases, 39, 2007, 91-94
105. Amrit Pal Singh et al, Eclipta alba Linn- Ancient Remedy with Therapeutic Potential, International Journal of Pharmacology, 1(2), 2010, 57-63
106. B. Saroj et al, Anti-malarial activity of Eclipta alba against Plasmodium berghei infection in mice, Journal of communicable Diseases, vol. 39, no. 2, pp. 91-94, 2007
107. M. Govindan, Evaluation of indigenous plant extract against the malarial vector, Anopheles stephensi (Liston) (Diptera: Culicidae) Parasitology Research, vol. 190, no. 1, pp. 93-103, 2011
108. http://www.hindawi.com/journals/isrn/2014/385969/
109. Somnath D. Bhinge et al, In vitro Anthelmintic Activity of Herb Extract of Eclipta prostrata L. against Pheretima posthuma, Asian Journal of Pharmaceutical and Clinical Research Vol. 3, Issue 3, 2010 
110. Amrit Pal Singh et al, Eclipta alba Linn- Ancient Remedy with Therapeutic Potential, International Journal of Pharmacology, 1(2), 2010, 57-63
111. Mahesh Sawant, Jolly C, Isaac, Shridhar Narayanan, Analgesic studies on total alkaloids and alcohol extracts of Eclipta alba (Linn) Hassk. Phytotherapy research, 2004; 18(2): 111-13 
112. Thakur VD, Mengi SA, Neuropharmacological profile of Eclipta alba (Linn) Hassk, J Ethnopharmacol 2005 Oct 31; 102(1): 23-31
113. O. Banaji, D. Banaji et al, Investigation on the effect of Eclipta alba on animal models of learning and memory, Indian Journal of Physiology and Pharmacology, vol. 51, no. 3, pp. 274-278, 2007
114. M. Bhaskar, M. Chintamaneni, Withania somnifera and Eclipta alba ameliorate oxidative stress induced mitochondrial dysfunction in an animal model of Alzheimer’s disease, The American Journal of Phytomedicine and Clinical Therapeutics, vol. 2, pp. 140-152, 2014
115. M. F. Shaikh, J. Sancheti, Sathaye, Phytochemical and pharmacological investigations of Eclipta alba (Linn.) Hassak leaves for antiepileptic activity, International Journal of Pharmacy and Pharmaceutical Sciences, vol. 4, no. 4, pp. 319-323, 2012
117. Otilia Banji, David Banji, Annamalai Ar, Manavalan R. Investigation on the effect of Eclipta alba on animal models of learning and memory. Indian J physiol pharmacol 2007; 51(3): 274-78.
118. Banji et al 2008 (improvement of retrieval memory), www.onlineijp.com/download.php?=77_57-63.pdf&id=77
119. Lobo OJ et al, Evaluation of anti-aggressive activity of Eclipta alba in experimental animals, Pak J. Pharm. Sc. 2008, Vol. 21, No. 2; 195-199 
120. M. Kaur, H. M. Chandola, Role of rasayana in cure and prevention of recurrence of vicharchika (eczema), Ayu, vol. 31, no. 1, pp. 33-39, 2010
121.C. F. Chan et al, Potent antioxidative and UVB protective effect of water extract of Eclipta prostrata L. The Scientific World Journal, vol. 2014, Article ID 759039, 8 pages
122. Amrit Pal Singh et al. / International Journal of Phytopharmacology,
1(2), 2010, 57-63.
124. Roy RK, Mayank Thakur, Dixit VK, Hair growth promoting activity of Eclipta alba in male albino rats, Arch Dermatol Res 2008; 300: 357-364
125. Rupali Thorat et al, Evaluation of a herbal hair oil in reducing hair fall in human volunteers, 2009; 6: 974-979
126.http://www.pharmatutor.org/articles/phytochemical-and-pharmacological-profile-of-eclipta-alba?page=0,1
127. http://www.wildturmeric.net/2014/10/7-amazing-skin-health-benefits-of-bhringraj-karisalankanni.html
128. Shalini Sharma, Mukesh S Sikawar, Wound healing activity of ethanolic extract of leaves of Eclipta alba, Pharmacognosy Magazine, Year: 2008, Volume: 4, Issue: 13, Page: 108-111; http://www.phcog.com
130. L. C. Diogo et al, Inhibition of snake venoms and phospholipases A2 by Extracts from native and genetically modified Eclipta alba: isolation of active coumastans, Basic and Clinical Pharmacology and Toxicology, vol. 104, no. 4, pp. 293-299, 2009
131.W. B. Mors et al, Neutralization of lethal and myotoxic activities of south American rattlesnake venom by extracts and constituents of the plant Eclipta prostrata (Asteraceae), Toxicon vol 27, no. 9, pp. 1003-1009, 1989
132. Lee MK et al, Stimulatory constituents of Eclipta prostrata on mouse osteoblast differentiation. Phytotherapy Research, 3, 2008, 145-148
133.H. Deng, Y. Fang, Anti-inflammatory gallic acid and wedelolactone are G protein-coupled receptor-35 agonists, Pharmacology, vol. 89, no. 3-4, pp. 211-219, 2012
134. V. Rangineni, D. Sharada, S. Saxena, Diuretic, hypotensive and hypocholesterolemic effects of Eclipta alba in mild hypertensive subjects: a pilot study, Journal of Medicinal Food, vol. 10, no. 1, pp. 143-148, 2007
135. R. Zafar, B. P. S. Sagar, Hepatoprotective and cardiac inhibitory activities of ethanolic extracts from plant leaves and leaf callus of Eclipta alba, Pharmaceutical Biology, vol. 38, no. 5, pp. 357-361, 2000
136. http://www.hindawi.com/journals/isrn/2014/385969/
137. Pimolpan Pithayanukul et al, Inhibition of Proteolytic and Hemorrhagic Activities by Ethyl Acetate Extract of Eclipta prostrate, Against Malayan Pit Viper Venum, Pharmaceutical Biology, 10/2008; 45(4): 282-288
138. Thakur VD, MengiSA , Neuropharmacological profile of Eclipta alba (Linn.) Hassk, Journal of Ethnopharmacology, 102, 2005, 23-31, www.onlineijp.com/download.php?f-77_57-63.pdf&id=77
139. http://www.tropilab.com/ecliptatincture.html
140. S. P. Kumar et al, Antisecretary and antiulcer activities of Eclipta alba Linn in rats, in Proceedings of the 5th World Ayurveda Congress, Oral Presentation, Abstract no. OAO1.03, Bhopal, India, December 2012

141. A. Babergee et al, Antiulcer activity of extract of Eclipta alba, Indian Journal of Pharmaceutical Sciences, vol. 67, no. 2, pp. 165-168, 2005
142. A. K. Saxena, B. Singh, K. K. Anand, Hepatoprotective effects of Eclipta alba on subcellular levels in rats, Journal of Ethnopharmacology, vol. 40, no. 3, pp. 155-161, 1993
143. R. Vasuki, R. Hari, S. Pandian, G. Arumugam, Hepatoprotective action of ethanolic extracts of Eclipta alba and Piper longum Linn and their combination on CCl4 induced hepatotoxicity in rats, International Journal of Pharmacy and Pharmaceutical Sciences, vol. 4, no. 1, pp. 455-459, 2012
144. K. Prabhu, N. Kanchana, A. M. Sadiq, Hepatoprotective effect of Eclipta alba on paracetamol induced liver toxicity in rats, Journal of Microbiology and Biotechnology Research, vol. 1, pp. 75-79, 2011
145. K. Arun, U. Balasubramanian, Comparative study on hepatoprotective activity of Aegle marmelosand Eclipta alba against alcohol induced in albino rats, International Journal of Environmental Science, vol. 2, pp. 389-402, 2011
146. H. Wagner et al, Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendulacea, Plant Medica, vol. 5, pp. 370-37, 1986
147. Dinesh Manvar et al, Identification and evaluation of anti-hepatitis C virus phytochemicals from Eclipta alba, Journal of Ethnopharmacology, vol.144, no. 3, pp. 545-554, 2012

148. http://www.hindawi.com/journals/isrn/2014/385969/
149. Dixit S, Achar M, Bhringaraja (Eclipta alba Linn.) In the treatment of infective hepatitis, Curr. Med. Prac. 23, 1979, 237-242   
150. Dixit S, Achar M, Study of Bhringaraja (Eclipta alba) therapy in jaundice in children, Journal of Research in Indian Medicine, 2, 1981, 96-100
151. Bhringaraja- Official Website of Chandigarh Administration, http://chandigarh.gov.in/green_herb_bhring.htm
152. http://shodhganga.inflibnet.ac.in/bitstream/10603/4494/8/08_chapter%202.pdf
153. Y. Xia et al, Wedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2, European Journal of Pharmacology, vol. 714, no. 1-3, pp. 105-111, 2013
154. J. Ananthi, A Prakasam, K. V. Pugalendi, Antihyperglycemic activity of Eclipta alba on alloxan-induced diabetic rats, Yale Journal of Biology and Medicine, vol. 76, no. 1-6, pp. 97-102, 2003

155. N. Jaiswal et al, Antidiabetic effect of Eclipta alba associated with the inhibition of α-glucosidase and aldose reductase, Natural Product Research, vol. 26, no. 24, pp. 2363-2367, 2012
156. S. W. Qian, Characterization of adipocyte differentian from human mesenchymal stem cells in bone marrow, BMC Developmental Biology, vol. 10, article 47, 2010
157. S. Lim et al, Wedelolactone inhibits the adipogenesis through the ERK pathway in human adipose tissue-derived mesenchymal stem cells, Journal of Cellular Biochemistry, vol. 113, no. 11, pp. 3436-3445
158. Dhandapani R, Hypolipidemic activity of Eclipta prostrata (L) leaf extract in atherogenic diet induced hyperlipidemic rats, 2007; 45: 617-19  
160. Vasavi Ranginei et al, Diuretic, Hypotensive and Hypocholesterolemic Effects of Eclipta alba in Mild Hypertensive Subjects: A Pilot Study, Journal of Medicinal Food 04/2007; 10(1): 143-8
161. Pooja Nair et al, Evaluating the reversal potentials of hydroalcoholic extract of Eclipta alba in Boric acid induced male reproductive toxicity, Scholars Research Library, Central European Journal of Experimental Biology, 2012, 1 (3): 77-93 (http://scholarsresearchlibrary.com/archive.html)
162. S. Sarveswaran, S. C. Gautam, J. Ghosh, Wedelolactone, a medicinal plant derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt, International Journal of Oncology, vol.41, no. 6, pp. 2191-2199, 2012
163. Malaya Gupta et al, Anticancer activity of Indigofera aspalathoides and Wedelia calendulaceae in Swiss albino mice, Iranian Journal of Pharmaceutical Research, 2005; 6(2): 141-45

164. Khanna et al, Anticancer-cytotoxic activity of saponins isolated from the leaves of Gymnema sylvestra and Eclipta alba on HeLa cells. International Journal of Green Pharmacy, 2008, 1: 227-29
165. H. Chaudhary et al, Evaluation of hydro-alcoholic extract of Eclipta alba for its anticancer potential: an in vitro study, Journal of Ethnopharmacology, vol. 136, no. 2, pp. 363-367, 2011
166. H. Chaudhary, P. K. Jena, S. Seshadri, Evaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistance reversal potential: an in vitro study, Nutrition and Cancer, vol. 65, no. 5, pp. 775-780, 2013
167. K. Lirdprapamongkol et al, Juice of Eclipta prostrate inhibits cell migration in vitro and anti-angiogenic activity in vivo, In Vivo, vol, 22, no. 3, pp. 363-368, 2008
168. R. B. Desireddy et al, Screening of Eclipta alba extracts for anticancer activity, International Journal of Research and Development in Pharmacy & Life Sciences vol. 1, pp. 203-205, 2012
169.http://www.hindawi.com/journals/isrn/2014/385969/
172. http://reddybams.page.tl/BHRINGRAJ.htm         
173.  http://reddybams.page.tl/BHRINGRAJ.htm  
174. Eclipta alba (L.) Hassk: A Valuable Medicinal herb Neeraja P.V., Elizabeth Margaret, IJCPR, November 2011-January 2012; 2(4); 188-197
179. Dr. T. Shripathi Rao, Dr. C. Srinivasulu, S. Sunil Kumar, Research Database on Ayurveda, Siddha, Other Traditional Medicine and Related Sciences, Vol. 1, 2010, Page 12. 


Comments

Unknown said…
Wedelolactone isolated from the herbs of Eclipta prostrata. It could significantly inhibit the activation of LX-2 cells. Wedelolactone

Unknown said…
Thanks for sharing this useful information.If you want to buy ayurvedic oil online then I will suggest you to Go here Bhringraj Hair Oil

Popular posts from this blog

Bhumyamalaki (Phyllanthus amarus, Phyllanthus niruri)

AMALAKI (Phyllanthus emblica, Emblica officinalis)

Methee-Fenugreek (Trigonella foenum-graecum L)