Chapter 2 Review of Literature
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Chapter 2 Review of literature
Research and scientific literature is the collection of research information and as
such, serves as the reservoir of knowledge about a subject. The literature codifies the
subject material, maintains a historical record on experimental trials, and aids in problem
solving through education and communication about facts and ideas. A close examination
of the literature indicates the amount of research on most herbs, spices and medicinal
plants remains quite limited. This relatively low average number of published research
papers must be viewed with caution, of course as great variation in economic value and
commercial use exists. As the scientific literature on the herbs, spices and medicinal
plants develops, more exchange of information should occur, helping to advance the
science of these plants. Modern research on herbs, spices and medicinal plants has
expanded to study a wide variety of tropical areas connected to botany, horticulture and
pharmacology of these plants. With this increased interest in herbs, spices and medicinal
plants, professional and field specialists associated with trade, horticulture and chemistry
have made an ever increasing demand for recent and accurate information on plants, its
pharmacognosy and pharmacology.
2.1 Literature survey of Eclipta alba (l.) Hassk.
The review of literature encompasses information of folklore claims,
pharmacognosy, phytochemistry, pharmacological and cosmeceutical activities of Eclipta
alba Hassk.
2.1.1 Folklore claims
The literature survey on the ethnomedical uses of E. alba reveals that in many
parts of the world it is grown commercially as a medicinal crop (Anonymous, 1952).
Aerial parts of the plant are used in medicine (Chopra et al., 1956).
India: According to Ayurvedic philosophy E. alba is bitter; alterative and anthelmintic. It
is useful in inflammations, hernia, eye diseases, bronchitis, asthma, leucoderma, anemia,
heart and skin diseases, night blindness and syphilis. It is reported as beneficial for
complexion, hair, eyes, and teeth. Expressed juice of E. alba mixed with goat’s milk is
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used in frontal sinusitis and nasal cattarh in children. Bhringraj taila and Bhringrajadi
churana are official preparations (Anonymous, 1952; Chopra et al., 1956). In Unani
system, the juice of E. alba is used in 'Hab Miskeen Nawaz' along with aconite, Croton
tiglium, “triphala”, Piper nigrum, Piper longum, Zingiber officinale, and minerals like
mercury, sulphur, arsenic and borax. for various types of pains in the body. It is also a
constituent of 'Roghan Amla Khas' for applying on hair and of Ma'jun Murrawah-ul-
arwah (Anonymous, 1952).
Korea: The plant is used as an antidote for snake bites in Korea (Anonymous, 1987).
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 (Dan and Nhu, 1989).
Nepal: The 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
(Anonymous, 1993).
Table 2.1: Biological activites of various parts of Eclipta alba
S. No. Plant parts Activity
1 Whole plant
Rejuvenating, Age – sustaining tonic, Detoxifying, Deobstruent, Antiseptic herb in vitiated blood, Anaemia, Splenic and liver enlargements, Catarrhal jaundice, Hyperacidity, Gastritis, Dysentery, Anti - catarrhal, Spasmogenic, Hypotensive properties
2 Juice of leaves
Skin diseases, Allergic Urticaria, Asthma, Inflatulence, Colic and liver affections, Bronchitis, Enlarged glands, Dizziness, Vertigo, Blurred vision
3 Paste of leaves Applied over swelling
4 Powder Bronchitis, Cough, Rheumatism and Skin diseases
5 Decoction Invigorate the liver, Graying of hair, Bleedings, Spermatorrhoea, Menorrhagia
6 Paste of herb Healing effect, Headache, Toothache
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7 Root Liver tonic, Emetic, Purgative, Antiseptic to ulcers, Wounds in cattle
2.1.2 Phytochemistry
Preliminary Phytochemical screening showed the presence of proteins,
aminoacids, essential oils, volatile oils, tannins, steroids, carbohydrates, glycosides,
alkaloids, flavones glycosides in plant of E. alba (Pulak et al., 2002). E. alba contains
wide range of active principles which includes coumarins, alkaloids, flavanoids,
glycosides, polyacetylenes, triterpenoids. The leaves contain stigmasterol, a -
terthienylmethanol, wedelolactone, demethyl wedelolactone and demethyl wedelolactone
- 7 - glucoside (Wagner et al., 1986). The roots give hentriacontanol and heptacosanol.
The roots contain polyacetylene substituted thiophenes. The aerial part is reported to
contain a phytosterol, P-amyrin in the n - hexane extract and luteolin – 7 - glucoside, P -
glucoside of phytosterol, a glucoside of a triterpenic acid and wedelolactone in polar
solvent extract. The polypeptides isolated from the plant yield cystine, glutamic acid,
phenyl alanine, tyrosine and methionine on hydrolysis. Nicotine and nicotinic acid are
reported to occur in this plant (Jadhav et al., 2009).
Coumarins
The dried leaves of E. alba have been reported to contain wedelolactone, a
complex coumarin and its derivatives dimethylewedelolactone – 7 - glucoside and nor -
wedelolactone (Bhargava et al., 1970; Wagner et al., 1986; Yahara et al., 2006; Mitesh et
al., 2010). Demethyl wedelolactone, isodemethyl wedelolactone, and strychnolactone
have been reported from by percolation and hot extraction of E. alba whole plant (Zhang
and Guo, 2001).
Alkaloids
Alkaloids including ecliptine and nicotine (Pal and Narasimham, 1943; Khargava
and Seshadri, 1974; Sikroria et al., 1982) were identified. Bio - active steroidal alkaloids,
verazine, 20 – epi – 3 – dehydroxy – 3 – oxo - 5, 6 – dihydro - 4, 5 - dehydroverazine
ecliptalbine, (20 R) - 4s - hydroxyverazine, 4s - hydroxyverazine, (20 R) - 25s -
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hydroxyverazine and 25s -hydroxyverazine have been identified from the methanolic
extract (Abdel Kader et al., 1998).
Hydrocarbons
Dithienylacetylene ester (Jain and Singh, 1988), ecliptal or α - terthienyl aldehyde
(Das and Chakravarty, 1991), α – terthienyl - methanol (Han et al., 1998) and α -
formylterthienyl (Zhang et al., 1997).
Triterpenes
Ecliptasaponin C and D (Zhang et al., 1997), new triterpenoid glucosides, have
been isolated from the whole plant of E. alba. A new triterpene saponin, eclalbatin,
together with α-amyrin, β - amyrin, ursolic acid, oleanolic acid and wedelic acid has been
isolated (Upadhyay et al., 2001). From the whole parts of six new oleanane triterpene
glycosides, eclalbasaponins I - VI have been isolated (Yahara et al., 2006).
Volatile oils
The volatile components were isolated from the aerial parts of this plant by
hydrodistillation and analysed by GC - MS. A total of 55 compounds, which were the
major part (91.7 %) of the volatiles, were identified by matching mass spectra with a
mass spectrum library (NIST 05.L). The main components were as follows: heptadecane
(14.78 %), 6, 10, 14 – trimethyl – 2 - pentadecanone (12.80 %), w - hexadecanoic acid
(8.98 %), pentadecane (8.68 %), eudesma - 4 (14), 11 - diene (5.86 %), phytol (3.77 %),
octadec – 9 - enoic acid (3.35 %), 1, 2 -benzenedicarboxylic acid diisooctyl ester (2.74
%), (Z, Z)- 9, 12 - octadecadienoic acid (2.36 %), (Z) - 7, 11 – dimethyl – 3 – methylene -
1, 6, 10 - dodecatriene (2.08 %) and (Z, Z, Z) -1, 5, 9, 9 – tetramethyl - 1, 4, 7 -
cycloundecatriene (2.07 %) (Xiong – Hao Lin, 2010).
Saponins
From the whole plant of E. alba, a new triterpene saponin, named eclalbatin,
together with α - amyrin, ursolic acid and oleanolic acid were isolated. The structure of
eclalbatin has been established as 3 – O – beta – D – glucopyranosyl – 3 – beta –
hydroxyl – olean – 12 – en – 28 – oic acid, 28 – O – beta – D – arabinopyranoside (1) on
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the basis of chemical and spectral data (Upadhyay et al., 2001). Dasyscyphin C was
isolated from Eclipta prostrate which were studied on the HeLa cells for the anticancer
activity (Khanna and Kannabiran, 2008).
Fig. 2.5. Chemical structure of major constituents of Eclipta alba
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Table 2.2: Chemical Constituents of Eclipta alba
Triterpenes Eclalbatin
Coumarins Wedelolactone
Alkaloids Ecliptine
Sterols β glucoside
Ecliptasaponin A,B,C(1) & D
Dimethylewedelolactone- 7- glucoside
Nicotine Daucosterol
Eclalbasaponins I-XII Oleanolic acid
Nor-wedelolactone Demethylwedelolactone
Steroidal Stigmasterol-3 -O-glucoside
α-amyrin Isodemethyl wedelolactone Alkaloids Stigmasterol β- amyrin, β-sitosterol Ursolic acid Wedelic acid
Flavonoids Hydrocarbons Apigenin Steroids Miscellaneous Dithienylacetylene ester
Luteolin Diosgenin Nonacosanol
Ecliptal Luteolin-7-glucoside Tigogenin Stearic acid α-terthienyl-methanol Lanosterol Lacceroic acid Heptacosanol Thiopenes alpha-terthienyl Hentriacontanol Polyacetylenic thiopenes 3,4-dihydoxy
benzoic acid
Table 2.3. Chemical constituents of parts of Eclipta alba
S. No. Parts Chemical constituents
1 Leaves Wedelolactone [1.6 %], Desmethylwedelolactone, Desmethyl -wedelolactone – 7 – glucoside, Stigmasterol
2 Roots Hentriacontanol, Heptacosanol & Stigmasterol, Ecliptal, Eclalbatin.
3 Aerial parts α - amyrin & Luteolin – 7 – O – glucoside, Apigenin, Cinnaroside, Sulphur compounds, Eclalbasaponins I - VI
4 Stems Wedelolactone
5 Seeds Sterols, Ecliptalbine (alkaloid)
6 Whole plant Resin, Ecliptine, Reducing sugar, Nicotine, Stigmasterol, Triterpene saponin, Eclalbatin, Ursolic acid, Oleanolic acid
Chapter 2 Review of Literature
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2.1.3 Pharmacology
Crude extract
The crude extract has been found to have wound healing properties. It has been
reported to counteract CCl4 - induced inhibition of the hepatic microsomal drug
metabolizing enzymes. The loss of hepatic lysosomal acid phosphatase and alkaline
phosphatase by CCl4 was significantly restored by E. alba. The study shows that
hepatoprotective activity of E. alba is by regulating the levels of hepatic microsomal drug
metabolizing enzymes (Saxena et al., 1993). The fresh plant is used as self medication by
AIDS patients in southern Thailand and showed potential as a therapeutic agent against
Giardia intestinal infections (Sawangjaroen et al., 2005; Supinya et al., 2006). The leaf
extract showed hypolipedemic activity in atherogenic diet induced hyperlipedemic rats
(Dhandapani, 2007). It has antimicrobial and antioxidant properties (Karthikumar et al.,
2007) and also 3 % extract of E. alba is used in pilex formulation with other ingredients.
It has been reported to decrease bleeding time (Mukherjee and Poddar, 1976). Leaf
extract has been used in edema. It is used in the treatment of paronychia (Khan and Khan,
2008).
Antihepatotoxic properties
The hepatoprotective effect of the ethanol / water (1 : 1) extract of E. alba has
been studied at subcellular levels in rats against CCl4 - induced hepatotoxicity. E. alba
significantly counteracted CCl4 - induced inhibition of the hepatic microsomal drug
metabolizing enzymes. The loss of hepatic lysosomal acid phosphatase and alkaline
phosphatase by CCl4 was significantly restored by E. alba. The study shows that
hepatoprotective activity of E. alba is by regulating the levels of hepatic microsomal drug
metabolizing enzymes (Saxena et al., 1993). Bi - herbal ethanolic extract (BHEE) from
the leaves of E. alba and seeds of Piper longum at a dose level of 50 mg / kg body weight
was administered orally once for 14 days which restored elevated serum marker enzymes
such as SGOT, SGPT, ALP, LDH, ACP, GGT and 5' Nucleotidase, due to CCl4
treatment. All the biochemical parameters like total protein, total bilirubin, total
cholesterol, triglycerides, and urea were also restored towards normal levels (Samudram
et al., 2008).
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Hepatoprotective activity of methanolic extract and sub fractions of leaves and the
chloroform extract and sub fractions of roots of E. alba were carried out using carbon
tetrachloride - induced liver damage and lysosomal enzymes level in wistar albino rats.
The methanolic extract of leaves and the chloroform extract of roots of E. alba showed
significant activities and respectively causing 72.8 % and 47.96 % reduction of lysosomal
enzyme. The triterpenoid eclabasaponin fraction from methanolic extract of leaves
produced significant (78.78 %) and the alkaloidal fraction (60.65 %) reduction of carbon
tetra chloride induced increase in lysosomal enzyme in blood. Coumarin fraction and
triterpenoidal saponin fraction from the chloroform extract of roots produced very
significant (75.6 %) and (52.41 %) respectively reduction of carbon tetra chloride
induced increase in lysosomal enzyme levels in blood (Lal et al., 2010).
Antihyperlipedemic properties
It has been reported that in the atherogenic diet induced hyperlipedemic model,
the aqueous leaf extract of the E. prostrata was given orally to the rats which
significantly reduced total cholesterol, triglycerides, total protein. There was a significant
elevation in the high density lipoprotein cholesterol levels and 200 mg / kg of extract
showed better results compared to 100 mg / kg (Dhandapani, 2007). Animal model
containing Charles River Sprague - Dawley CD rats (specific pathogen – free / viral
antibody - free Crj/Bgi male, 180 ± 10 g) were fed experimental diets supplemented with
0 mg (control), 25 mg (E25), 50 mg (E50), or 100 mg (E100) of a freeze-dried butanol
fraction of E. prostrata per kilogram of diet for 6 weeks which reported significant
reduction of serum triacylglycerol and total cholesterol, low-density lipoprotein-
cholesterol levels and elevation in the high-density lipoprotein in the E50 and E100 groups
respectively when compared with the untreated control group (Dae-Ik Kima et al., 2008).
Antioxidant properties
The antioxidant effects of E. prostrata was reported when 50 mg / kg and 100 mg
/ kg dose were fed orally into Charles River Sprague - Dawley CD rats which reduced
serum hydroxyl radical (nmol / mg protein per minute) and serum lipid peroxide (nmol /
mg protein) levels compared to untreated group. 100 mg / kg dose significantly reduced
carbonyl content of oxidatively modified proteins (Dae-Ik Kima et al., 2008).
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Antioxidant activity of E. prostrata was determined by FRAP, radical scavenging
activity, reducing activity and DPPH assay. The antioxidant capacity was increased by
increasing the concentration of the extracts from 25 to 100 mg / ml (Bhaskar Rao et al.,
2009).
The antioxidant activity of the hexane, ethyl acetate, ethanol and water extracts of
E. prostrata was determined by ferric thiocynate (FTC). FTC method was used to
determine the amount of peroxide formed and that react with ferrous chloride (FeCl2) to
form a reddish ferric chloride (FeCl3) pigment. In this method, the concentration of
peroxide decreases as the antioxidant activity increases. Hexane, ethyl acetate, ethanol
and water extract at various concentration (50, 100, 250 and 500 in µg / mL), showed
antioxidant activities in a concentration dependent manner. Ethanolic extract at the
concentration of 500 µg / mL showed (77.62 %), which is close to the reference
compound α - tocopherol (80.06 %) (Karthikumar et al., 2007). E. alba is reported to
have free radical scavenging action (Bhattacharya et al., 1997). Kim et al. (2008) found
that butanol fraction of E. alba improves antioxidant activities in rats. Ethanol extract of
the aerial parts of E. alba showed significant free radical scavenging for DPPH and for
hydroxyl radical (Unnikrishnan et al., 2007; Majumdhar et al., 2008).
Immunomodulatory activities
It has been reported that protection of neuronal tissues may be possibly due to the
immunomodulatory action of E. alba. Therefore, E. alba can serve as a potential memory
modulator (Otilia Banji et al., 2007). Experimentation made to assess the
immunomodulatory activity of methanol extracts of whole plant of E. alba (1.6 %
wedelolactone) at five dose levels (dose - response relationship) ranging from 100 to 500
mg/ kg using carbon clearance, antibody titer and cyclophosphamide immunosuppression
parameters significantly increased phagocytic index and antibody titer and the F ratios of
the phagocytic index and WBC count were also significant (Jayathirthaa and Mishraa,
2004). The aqueous leaf extract E. alba was fed into a fish (tilapia, Oreochromis
mossambicus) at 0, 0.01, 0.1 or 1 % levels as a diet for 3 weeks. After each week, non -
specific humoral (lysozyme, antiprotease and complement) and cellular
(myeloperoxidase content, production of reactive oxygen and nitrogen species) responses
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and disease resistance against Aeromonas hydrophila were noted which resulted in
increased activity of non - specific immune parameters. The results indicate that dietary
intake of E. alba aqueous leaf extract enhances the non - specific immune responses and
disease resistance of O. mossambicus against A. hydrophila (Christybapita et al., 2007).
Analgesic and Anti-inflammatory activity
Albino wistar rats were used to investigate anti-inflammatory activity in which
methanolic extract was administered orally. 100 and 200 mg / kg showed significant anti-
inflammatory activity in carrageenin and egg white induced hind paw edema in rats
which was compared with indomethacin (10 mg / kg) and cyproheptadine (8 mg / kg)
(Arunachalam et al., 2009). Analgesic effect was studied on albino mice using ethanolic
and alkaloidal extract of E. alba. Standard experimental models such as the tail clip
method, the tail flick method and the acetic acid induced writhing response were used
which showed both the ethanol extract as well as the total alkaloids produced good
analgesic activity in all the different models of analgesia used. The total alkaloidal
fraction was the most efficacious in all models tested (Singh et al., 2008; Sawant et al.,
2004).
Antidiabetic activity
Leaf suspension of E. alba (2 and 4 g / kg) orally in alloxan induced diabetic rats
resulted in reduction in blood glucose level, glycosylated haemoglobin. There was
decreased activity of glucose - 6 phosphatase and fructose1, 6 - bisphosphatase, and an
increase in the activity of liver hexokinase. Thus oral administration of E. alba
suspension possess potent antihypergylcemic activity (Ananthi et al., 2003). E. alba as an
ingredient in polyherbal formulation Pan-five were scientifically and clinically proved to
possess antidiabetic and diuretic activity by acting upon pancreas by restoration and
regeneration of pancreatic β - cell activity (Hemalatha et al., 2006).
Antimicrobial activity
Antimicrobial potentials of Eclipta plants have been investigated by a number of
workers. The shoot extract of E. alba possess antimicrobial activity (Anonymous, 1952;
Kosuge et al., 1985). The alcoholic extract of E. alba has shown antiviral activity against
Chapter 2 Review of Literature
22
Ranikhet disease (Dhar et al., 1968). E. alba plants have been screened for antifungal
(Nene et al., 1968; Farouk et al., 1983; Singh and Singh, 1997; Thyagarajan and
Krishnaswamy, 1999) and antibacterial (Phadke and Kulkarni, 1989) properties. E. alba
seeds frequently observed growing on cattle dung heaps were screened for their
antibacterial properties against Bacillus subtilis, Escherichia coli, Pseudomonas cichorii
and Salmonella typhimurium (Kumar et al., 1997). Direkbusarakom et al. (1998) has
evaluated E. alba plants for antibacterial activity against the fish and shrimp pathogenic
bacteria: Aeromonas hydrophila, a Streptococcus species and ten strains of Vibrio.
Abdel-Kader et al. (1998) has reported eight steroidal alkaloids obtained from methanol
extracts of E. alba leaves as DNA damaging agent or antifungal agent against three
strains of Saccharomyces cerevisiae. Wiart et al. (2004) have also investigated methanol
extract of E. alba for antibacterial and antifungal activities. The ethyl acetate and ethanol
extracts of E. alba were found to be active against Escherichia coli, Klebsiella
pneumonia, Shigella dysenteriae, Salmonella typhimurium, Pseudomonas aeruginosa,
Bacillus subtilis and Staphylococcus aureus (Karthikumar et al., 2007).
Ethanol extracts of fruits of E. alba has been found to possess strong inhibitory
effects on acne-inducing bacteria Staphylococcus epidermidis (Kumar et al., 2007).
Girish and Satish (2008) tested the aqueous and methanol extracts of E. alba against
some human pathogenic bacteria and found that methanol extracts had wider range of
activity. Yasmin et al. (2008) studied that the aqueous extracts of E. alba leaves showed
mild antifungal activity on Fusariam moniliforme. Khanna and Kannabiran (2008)
evaluated the antimicrobial activity of pure saponins fraction from leaves of E. alba for
pathogenic bacteria and fungi. The antileptospiral (antibacterial) activity of E. alba was
well studied by Prabhu et al. (2008) and results showed better inhibitory action against
various serogroups of Leptospira species inhibited by both water and ethanol extracts.
Hair growth promoting effects
Eclipta alba (L.) Hassk. is one of the best known ayurvedic herb with purported
claims of hair growth promotion. A black dye obtained from E. alba is used for dyeing
hair and tattooing. Bhringaraja oil is a famous hair tonic for maintaining dark hair and
reversing baldness. It may be used along with Centella asiatica (Brahmi) and Phyllanthus
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23
emblica (Amla). E. alba extracts have been used in traditional chinese medicine as well
as by middle-eastern ayurvedic doctors for thousands of years to prevent hair loss. It is
reported to improve hair growth and color (Chopra et al., 1956; Kritikar and Basu, 1975).
Taken internally, it is believed to blacken the hair and beard (Boulos et al., 1984).
Topical application of fresh Eclipta juice mixed with neem oil reportedly stimulated hair
growth and in some cases changed gray hair to black (Chandra, 1985). The leaf juice of
plant is applied as hair tonic on the scalp (Jamir, 1997). Roy et al. (2007) developed and
evaluated a polyherbal formulation containing E. alba for hair growth-promoting activity.
Although the chemical component which promotes hair growth has not yet been
identified, it is believed that its ability to promote hair growth seems from its bioactive
steroidal alkaloids (McCarthy, 2008). Petroleum ether extracts of E. alba with other herbs
was prepared and evaluated their hair growth promoting activity in albino rats
(Nakaguchi et al., 2001; Roy et al., 2008; Datta et al., 2009). The extracted juice of E.
alba if taken internally and applied to the scalp blackens the hair (Chopra et al., 1955;
Kritikar and Basu, 1975). E. alba has been reported in various polyherbal formulation
(Baishiyou, 1993; Cheol, 2004; Lee, 1995, 2001, 2004; Shin, 2006; Xiulan, 1997) for hair
growth promotion.
Datta et al. (2009) investigated the efficacy of methanol extract of E. alba as hair
growth promoter. E. alba is used in hair oil preparations since it promotes hair growth
and maintains hair black. 10 % w/v of E. alba was a main ingredient in the preparation of
herbal formulation for hair growth (Thorat et al., 2009). Alopecia is a dermatological
disorder with psychosocial implications on patients with hair loss. E. alba is a well -
known ayurvedic herb for hair growth. In the reported work petroleum ether and
ethanolic extracts were incorporated into oleaginous cream (water in oil cream base) and
applied topically on shaved denuded skin of albino rats. The time (in days) required for
hair growth initiation as well as completion of hair growth cycle was recorded. Minoxidil
2 % solution was applied topically and served as positive control for comparison. The
result of treatment with 2 and 5 % petroleum ether extracts were better than the positive
control minoxidil 2 % treatment (Roy et al., 2008).
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Thakur et al. (2008) investigated that -sitosterol and wedelolactone were
responsible for hair growth activity. 5α - reductase inhibition contributes in treatment of
androgenic alopecia. Daniel (2006) also reported that E. alba herbs were used for
promoting hair growth activity. Iqbal Hussain et al. (2011) reported that the medicated
oils of E. alba is widely used as hair tonic and to prevent hair fall and premature graying
of the hair. Bhringaraja is the most common ingredient incorporated in numerous market
preparations of various hair oils.
According to Agarwal and Gayatri (2011) herbal formulations containing
petroleum ether extracts of E. alba, methanolic extracts of E. alba and various fixed oil
like mustard oil, coconut oil and sesame oil are used for evaluating the formulations for
hair growth promoting potential activity. The results showed that the animals treated with
the methanolic extract of E. alba shows highest number of hair follicle and the earliest
hair growth seen in methanolic extract gel formulation.
Anticancer activity
Methanolic extract of E. alba was evaluated for its anticancer activity against
Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice. On day 1, the extract of E. alba
at a dose of 250 and 500 mg/kg body weight were administered orally and continued for
9 consecutive days. The anticancer activity was examined by determining the tumor
volume, tumor cell count, viable tumor cell count, nonviable tumor cell count, mean
survival time and increase in life span in experimental animal models. The extract
increased the life span of EAC treated mice and restored the hematological parameters as
compared with the EAC bearing mice. Thus, study revealed that the methanolic extract of
E. alba showed anticancer activity in the tested animal models (Malaya Gupta et al.,
2005). Coumarins are also known to act as phytoestrogens. These compounds are present
in soyabeans and clover. In many countries it is used as diet which acts as
chemopreventive agent in breast and prostate cancer (Kaushik Basu et al., 2008).
Dasyscyphin - C (saponins) a newer isolated compound from E. prostrata
reported to have anticancer - cytotoxic activity. It was tested under in vitro conditions in
HeLa (Human cervical carcinoma) and vero cell lines. At the concentration of 50 g / ml it
showed a good anticancer - cytotoxic activity on HeLa cells (Khanna and Kannabiran,
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2008). A rat hepatic stellate cell line (HSCs) was used as in vitro assay system, the
methanolic extract of aerial parts of E. prostrate showed significant inhibitory activity on
HSCs proliferation (Mi Kyeong Lee et al., 2008).
Anti-venomous activity
The constituents of E. alba have found to neutralize the lethal and myotoxic
activities of venom of south american rattle snake (Mors et al., 1989) and rattle snake at
Tamil Nadu (Samy et al., 2008). Fresh aerial parts are used to treat snakebites in Brazil
(Martz, 1992). Melo et al. (1994) found that E. prostrata extracts inhibit the myotoxic
and hemorrhagic activities of crotalid venom. Pithayanukul et al. (2004) isolated
demethyl wedelolactone from butanolic extracts of E. prostrata and evaluated for its anti-
venom potential against the lethal action of the venom of the Jararaca (Bothrops
Jararaca). Secondary metabolites wedelolactone and demethyl wedelolactone isolated
from extracts of natural and genetically modified E. alba with Agrobacterium rhizogenes
LBA 9402, were found to inhibit the myotoxic activities induced by basic phophlipases
A2 isolated from venoms of Crotallus durissus terrificus and Bothrops jararacussu
(Diogo et al., 2009).
Combination therapy
E. alba (whole plant), Mimosa pudica (whole plant), Vitex negundo (whole plant)
and Solanum nigrum (aerial parts) possessed styptic and anti-inflammatory properties and
help in regeneration of the vascular endothelium (Sahu and Pankaj, 2001). Combination
of herbs like Anethum sowa (Shatapushpa), Piper longum (Pippali mool), Valeriana
wallichii (Tagar), Cassia fistula (Aragvadh), Withania somnifera (Ashwagandha) and
Triphala (A herbal combination of three fruits) with E. alba (Bhringaraj) pacify the
aggravated vata dosha and combination with Elaeocarpus ganitrus (Rudraksha),
Herpestris monniera (Brahmi) showed a tranquilizer effect (Haveliwala, 1963). Herbal
mixture containing Phyllanthus nigrum, Picrorrhiza kurroa, Zingiber officinale,
Boerhaavia diffusa, Andrographis paniculata, Cichorium intybus, Emblica officinalis,
Embelia ribes, Terminalia chebula, Terminalia arjuna, Piper longum with E. alba is used
as a good digestive tonic (Bruce Milliman et al., 2000). Galactin Vet Bolus a polyherbal
ingredient containing E. alba increased the yield of milk in the Holstein and jersey
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crossbred cows (Baig and Bhagwat, 2009). E. alba with Acacia catechu leaves reduced
severe hepatotoxicity (Rolf teschke and Ruediger bahre, 2009).
Other pharmacological activities
It has been reported that the importance of free carboxylic acid at C-28 position in
echinocystic acid derivatives from the methanolic extract E. prostrata showed antifibrotic
activity (Mi Kyeong Lee, 2008). Ethanolic and ethyl acetate fractions of E. prostrata
were tested for its antibacterial activities against Escherichia coli, Klebsiella pneumoniae,
Shigella dysenteriae, Salmonella typhi, Pseudomonas aeruginosa, Bacillus subtilis and
Staphylococcus aureus (Karthikumar et al., 2007). E. prostrata is combined with a non-
plant material which is used to bath children suffering from malnutrition for 9 days and
used as self medication by AIDS patients in southern Thailand (Sawangjaroen et al.,
2005; Cheryl Lans, 2007). 16 parts of E. prostrata (bhringaraj), 1 part of Triphala
formula {Emblica officinalis (amalaki), Terminalia chebula, (haritaki), Terminalia
belerica (bibhitaki)}, 1 part of Caltropis gigantea (arka) and 1 part of Smilax officinalis
(sariva) mixed with 80 parts of sesame oil and boiled to make a medicated oil which is
reported to be used in skin diseases (Bensky Dan and Andrew Gamble, 1986).
Table 2.4. Pharmacological activities of the chemical constituents
S. No Chemical constituents Pharmacological activities
1 Wedelolactone Antihepatotoxic (Nazim Uddin et al., 2010), Antibacterial (Karthikumar et al., 2007), Trypsin Inhibitor, Antivenom (Vianna-da-silva et al., 2003)
2 Eclalbosaponins Hair revitalizing (Thorat et al., 2009), Antiproleferative (Khanna and Kannabiran, 2008; Kaushik-Basu et al., 2008), Antigiardial (Sawangjaroen et al., 2005)
3 Demethylwedelolactone Antihepatotoxic (Wagner et al., 1986), Antihaemorrhage (Mukherjee and Poddar, 1976), Antivenom (Vianna-da-silva et al., 2003), Dye (cosmetic) (Meena et al., 2010)
4 Dasyscyphin C Antiviral, Anticancer (Khanna and Kannabiran, 2008)
5 Eclalbatin Antioxidant (Tewtrakul et al., 2007)
6 Ecliptalbine, verazine Lipid lowering, Analgesic (Abdel-Kader et al., 1998)
Chapter 2 Review of Literature
27
2.2 Literature survey of Lippia nodiflora Linn.
2.2.1 Folklore claims
Phyla nodiflora (Lippia nodiflora) belongs to Verbenaceae family, distributed in
India, Ceylon, Baluchistan, South Africa and Central America. L. nodiflora L commonly
known as Booken, is a traditional medicine in many parts of Pakistan and used for the
treatment of various dermatomycoses (Ravikumar and Sudha, 2011) like tinea capitis,
tinea pedis, tinea manuum, tinea corporis etc. The plant is aromatic, runner plant with
scanty roots and cure adenopathy, chronic indolcent ulcers, bronchitis, fevers and cold
(Kirtikar and Basu, 1991). The plant is also used for boils, indigestion in children and for
the women after the delivery (Chopra et al., 1956). The plant is used as gastro protective
effect, anti inflammatory (Balakrishnan et al., 2011), antineoplastic, antioxidant and
diuretic (Shukla et al., 2009). The aerial parts of this plant are used as anodyne,
antibacterial, diuretic, emmenagogue, parasiticide, refrigerant and febrifuge agents.
Leaves and fruits are eaten for the treatment of irritation of the internal piles and for
joints and knee pain. It is effective against bronchitis, respiratory diseases, arthritis,
stomachic wounds, burning sensation, and asthma, loss of consciousness, neuralgia sores,
spasm and vertigo (Manjunath, 1962).
2.2.2 Phytochemistry
The plant is rich in many important medicinal useful compounds. The plant
contains a variety of constituents such as triterpenoids, flavonoids, phenols, steroids, and
many others. Among these flavonoids, the most commonly found in L. nodiflora are
Nodifloretin (3), β -sitosterol glycoside and stigmasterol glycoside from the leaves of L.
nodiflora (Barua et al., 1971). Nodifloridin A (1) and Nodifloridin B (2) along with
lactose, maltose, glucose, fructose and xylose were isolated from the plant (Joshi, 1970).
Two new flavone glycosides lippiflorin A (16) and lippiflorin B (17), along with the
known compound nepetin and batalilfolin from the ethanol extract of L. nodiflora were
isolated (Nair et al., 1973).
From the flowers of L. nodiflora, two flavones glycosides, 6 - hydroxyluteolin - 7
Oapioside and luteolin - 7 - O - glucoside, and three flavones 6 – hydroxyl luteolin,
Chapter 2 Review of Literature
28
nepetin and batatifolin were isolated (Barnabas et al., 1980). From the alcoholic extracts
of L. nodiflora, two phenylpropanoid compounds acteoside (18) and 2' - O -
acetylechinacoside and a flavone demethoxycentaureidin were isolated (Khalil et al.,
1995). From L. nodiflora, twelve flavones sulfates Hispidulin 7 - sulfate (4), Hispidulin 7,
4' - disulfate (5), Jaceosidin 7, 4' - disulfate (6), Nepetin 3', 4' - disulfate (7), Nodifloretin
6, 7 - disulfate (8), 6 - Hydroxyluteolin 6, 7 – disulfate (9), Nodifloretin 7 - sulfate (10), 6
- Hydroxyluteolin 6 – sulfate (11), 6 - Hydroxyluteolin 7 - sulfate (12), Jaceosidin 7 -
sulfate (13), Nepetin 7 - sulfate (14), and Hispidulin 4' - sulfate (15), along with the
known compounds Nepetin, Hispidulin, and Jaceosidin (Tomas – Barberan et al., 1987).
Halleridone and Hallerone as their acetyl derivatives were isolated from the leaves of
L. nodiflora (Ravikanth et al., 2000). From the methanolic extract of the aerial parts of L.
nodiflora, a new triterpenoid lippiacin, a new steroid 4', 5’- dimethoxybenzoloxy
stigmasterol along with the known stigmasterol and β - sitosterol [1, 6] were isolated
(Siddiqi et al., 2007).
The plant was fractionated several constituents from the L. nodiflora using multi
component solvent systems; Hexane : Toluene : Ethyl acetate (2 : 1.5 : 0.5) for methanol
extract and Hexane : Ethyl acetate (3 : 1) for chloroform and petroleum ether extract.
Five different phenolic components were isolated and were compared using a HPTLC,
among these extracts, the highest number of constituents were isolated from the butanol
extract (Kaur and Shukla, 2010). The molecular basis of a compound, cyclo pentane
phenanthrenol, which exhibit anti inflammatory property was also given (Balakrishnan et
al., 2011). Nodifloretin - A, a new flavone was also discovered (Basu et al., 1969).
Chemical and biological investigations of medicinal herbs Phyla nodiflora, Ruellia
patula and Ruella brittoniana were done (Akhtar, 1993). Steroidal constituent from the
aerial parts of Lippia nodiflora Linn was also obtained (Bina et al., 2009).
Chapter 2 Review of Literature
29
Table 2.5. Chemical constituents of plant parts of Lippia nodiflora
Plant part
Phytoconstituents isolated Author
Leaves Halleridone and Hallerone
β - sitosterol
2 – phenethyl alcohol, 1 – octen – 3 - ol, linalool, 2, 6 -dimethyloctane,methyl salicylate, calamenene, α – copaene, α – bergamotene, δ – cadinene, β – bisabolene, umbellulone
Stigmasterol, Phytol
Ravikanth et al., 2000
Forestieri et al., 1996
Terblanche and Kornelius, 1996
Gabay et al., 2010
Ogunlesi et al., 2009
Leaves and Roots
Flavonoides, β – caryophyllene, β – caryophyllene oxide
Duke and Ayensu, 1985; Pascual et al., 2001
Flowers 6 – hydroxyluteolin – 7 – O – apioside, luteolin – 7 – O – glucoside, 6 – hydroxyluteolin, nepetin, batatifolin
Barnabas and Nagarajan, 1980
Whole aerial parts
Lippiacin, Benzofuranone rengyolone (halleridone 2)
Cyclo – pentano phenanthrenol
n - hexa decanoic acid
Dodecanoic acid
Siddiqui et al., 2007
Balakrishnan et al., 2010
Falodun et al., 2009
Bodoprost and Rosemeyer, 2007
Whole plant
Lippiflorin A and Lippiflorin B
Aceteoside and 2’ – O – acetyl echinacoside
Nepetin, Jaceosidin, hispidulin aglycones, hispidulin, hydroxyluteolin, nodifloretin mono and disulphates, lippiflorin A and B glycosides, nodifloretin A and B, nodiflorin A and B glucosides, Alkaloids, resin
Nodifloridin A and B
Nodifloretin, β - sitosterol glycoside
Nair et al., 1973
Khalil et al., 1995
Tomas – Barberan et al., 1987
Forestieri et al., 1996
Joshi, 1970
Barua et al., 1971
Chapter 2 Review of Literature
30
2.2.3 Pharmacological activities
Hepatoprotective and Antioxidant potential of Lippia nodiflora
The methanolic extract of Lippia nodiflora (MELN) has been evaluated for
antioxidant activity and hepatoprotective effects in paracetamol induced liver injury (750
mg / kg, b.w). MELN was administered orally for 7 days at doses 200 and 400 mg / kg.
The higher dose (400 mg / kg) of MELN was found to be more effective than the lower
dose (200 mg / kg) in paracetamol induced liver damage. MELN produced significant (P
< 0.001) hepatoprotective effect by decreasing the activity of serum enzymes such as
SGOT, SGPT, ALP bilirubin and lipid peroxidation, while it significantly (P < 0.001)
increased the level of total protein, glutathione (GSH), catalase (CAT) and superoxide
dismutase (SOD) in a dose dependent manner (Durairaj et al., 2008). The MELN was
found to be equivalent to that of standard silymarin 25 mg / kg, thus the plant was found
to be hepatoprotective probably due to the antioxidantal potential on hepatocytes and the
methanol extract of L. nodiflora for total phenolic content, indicated by the Folin-
Ciocalteu phenol reagent was found to be 114.8 μg / mL total phenolics for 1 mg of the
extract.
Anti-diuretic activity
The diuretic potential of methanol and aqueous extracts of the aerial parts was
assessed in albino rats using in-vivo Lipschitz test model. The volumes of urine, urinary
concentration of sodium and potassium ions were the parameters of the study.
Furosemide was used as standard. The results indicate that methanol and aqueous extract
at 500 mg / kg body weight shows a significant (P < 0.05) increase in the urine volume
and electrolyte excretion (P < 0.001) when compared to control. Both the extracts show
significant diuretic activity (Sangita Shukla et al., 2009).
Antitumor activity
The methanolic extract of L. nodiflora has been evaluated for antitumor activity
using Erich’s Ascites Carcinoma (EAC) bearing swiss albino mice. The mice were
administrated with the methanol extract at 200 and 400 mg / kg of body weight daily for
nine days after 24 hours of tumor inoculation. The methanolic extract indicated
Chapter 2 Review of Literature
31
significant (P < 0.001) decrease in tumor volume, viable cell count and packed cell
volume, the life span of the mice was also found to be increased. For the mice treated
with the methanol extract the hematological profiles reverted to more/less normal levels,
while the serum enzymes, total proteins and billirubin were altered narrowly. The
methanol extract increased the levels of reduced glutathione (GSH), catalase (CAT) and
superoxide dismutase (SOD) and reduced the levels of lipid per oxidation. The plant was
found to bear good antitumor activity, which was supposed to be due to the increase of
antioxidant activity (Durairaj et al., 2009).
Anti-inflammatory activity
The crude methanol extract and the isolated compound of cyclo-pentano
phenanthrenol from L. nodiflora were assessed for anti-inflammatory activity. Human
peripheral blood mononuclear cells were used as models to examine intracellular protein
levels of pro-inflammatory mediators (MAPK and NF-KB) and the mitogen induced
lymphocyte proliferation, cytokine mRNA expression (TNF-α, IL-1β and IL-6). The NO
release levels, on treatment with the extract and the isolated compound were correlated
with the underlying iNOS mRNA expression in the murine macrophage cell line RAW
264.7. In the cell line RT-PCR for COX-2, MMP2 and MMP9 were also conducted. As
an in vitro model for the rat basophilic leukemia cell line RBL-2H3 was employed for
PLA2 activity. The crude extract (20 μg / mL) and the isolated compound (10 μg / mL)
were used to assess the activity. Cyclo-pentano phenanthrenol was found to inhibit TNF-
α, IL-1β and IL-6 expression, prostaglandin biosynthesis via PLA2, NO release via iNOS
suppression and COX-2 inhibition and the activation of intracellular targets, MAPK and
NF-KB. Thus the compound was concluded to exhibit anti-inflammatory activity
(Durairaj et al., 2009).
Antimicrobial activity
The methanolic extract of Phyla nodiflora had been evaluated for antibacterial (S.
aureus, M. luteus, P. mirabalis). The anti microbial screening was performed by agar
diffusion method using a paper disc. The sterilized (autoclaved at 120˚ C for 30 min)
medium was inoculated with the suspension of the micro organisms. The paper
impregnated with the extracts (1000 μg / ml) was placed on the solidified medium. The
Chapter 2 Review of Literature
32
Petri dishes were pre incubated for one hour at room temperature and incubated at 37˚C
for 24 hrs and 48 hrs for antibacterial and antifungal activity respectively. Gentamycin
was (1000 μg / ml) used as a standard for anti bacterial. The ethanol extract showed
significant antibacterial activity due to the presence of bio-active compounds when
compared with petroleum - ether and aqueous extract (Durairaj and Gupta, 2007).
Antifungal activity
The antifungal activity of crude extracts of L. nodiflora L. against the human
pathogenic fungi was reported. The crude extract of various solvents of Phyla nodiflora
had been screened for antifungal activity against Aspergillus niger, A. Flavus,
Paecilomyces varioti, Microsporum gypseum, Trichophyton rubrum. All crude extract
had significant inhibition activity against most of the fungi. Ethanol extract had
maximum inhibition activity (100 %) against tested organism as compared to aqueous
(82.6 %), Methanol (61 %), Ethyl acetate (87 %) extracts (Pirzada et al., 2005).
Antiurolithiatic activity
The ethanolic extract of L. nodiflora (Linn.) had been evaluated against calculi
producing diet induced urolithiasis. Calcium oxalate urolithiasis was induced by
administration of gentamycin and calculi producing diet (5 % ammonium oxalate in
standard rat pellet feed). The extract was also assessed for effect on in vivo antioxidant
parameters like lipid peroxidation, reduced glutathione, catalase in hyperoxaluric kidney
and in vitro scavenging of nitric oxide and 2 – diphenyl – 2 – picryl hydrazyl free
radicals. Ethanolic extract of L. nodiflora exhibited significant effect in preventing
calcium oxalate stone formation and also in dissolving the pre-formed calcium oxalate
stones in the kidney along with significant effect on both in vitro and in vivo antioxidant
parameters. The present study clearly demonstrates the antiurolithiatic activity of L.
nodiflora supporting the traditional claim (Sujatha Dodala et al., 2010).
Antidiabetic and Hypolipidaemic
The effect of methanol extract of L. nodiflora Linn. in streptozotocin induced
diabetic rats was reported by Rangachari and Savarimuthu (2011). The methanolic extract
of L. nodiflora at three dose levels were administered orally to streptozotocin (STZ) (40
Chapter 2 Review of Literature
33
mg / kg bw) induced diabetic rats for 15 days. The extract at three dose levels showed a
significant increase in the liver, muscle glycogen and serum insulin level and a significant
decrease in fasting blood glucose, glycosylated hemoglobin levels and serum marker
enzyme levels. The total cholesterol and serum triglycerides levels were also significantly
reduced and the high density lipoprotein level was significantly increased upon treatment
with the L. nodiflora methanol extract. Histochemical study of pancreas also confirmed
the biochemical findings. Acute toxicity studies revealed the non-toxic nature of the
methanol extract of L. nodiflora exerts significant antidiabetic and hypolipidaemic effect
in STZ-induced diabetic rats (Rangachari and Savarimuthu, 2011).
Neuropharmacological activity
The neuropharmacological profile of petroleum, chloroform and ethanolic
extracts of aerial part of L. nodiflora was reported with experimental models using test
such as potentiation of diazepam-induced sleeping time, locomotor activity, motor
coordination, exploratory behavior pattern, elevated plus maze and maximal electroshock
convulsions. It showed that the ethanolic extract of L. nodiflora at both doses (250 and
500 mg / kg p.o.) and its chloroform extract at a higher dose of 500 mg / kg produced
central inhibitory (sedative) effect, anticonvulsant effect and anxiolytic effect in mice.
Values were statistically significant (P < 0.05 and P < 0.01) when compared to the
control group. The petroleum ether extract of plant at both dose levels (250 and 500 mg /
kg p.o.) did not produce any central effects. The ethanolic and chloroform extracts
showed the central inhibitory activity due to the presence of flavonoids. The essential oils
of the leaves of Lippia alba, Lippia gracilis, Lippia microphylla and L. nodiflora were
tested for larvicidal activity against the instar larvae of Aedes aegypti. The higher
larvicidal activity (LC50 = 26.3 μg / mL) was observed for the oil of L. gracilis, while
appreciable activity was observed for the oil of L. nodiflora (Zheng, 2008).
Antidandruff activity
Zheng (2008) suggested that since L. nodiflora contains nodifloretin, β-sitosterol
glucoside, stigmasterol glucoside, nodifloridin A and nodifloridin B, it could be used in
proper doses for the treatment of hepatitis. Narayanan et al. (2008) suggested that the
Chapter 2 Review of Literature
34
plant extracts of any of the two plants, Datura metel, Murraya koenigii, L. nodiflora and
Wrightia tinctoria possess antidandruff application.
2.3 Justification for inclusion in the study
Cosmeceutical value of the plants is generally determined by the presence of
biologically active compounds. Such phytocompounds have been characterized as
flavonoids, alkaloids, tannins, terpenoids, saponins and so on. Standardization of herbal
cosmetics is an important task. The major problems faced by users are non-availability of
rigid quality control profile. Proper identification and standardization is a primary
condition. Eclipta alba and Lippia nodiflora has been used in traditional and folklore
medicine for the treatment of hair growth and dandruff control activity. An attempt have
been made to isolate new compounds from aerial parts of Eclipta alba and Lippia
nodiflora and systematic screening of the extracts may result in the discovery of novel
and effective compounds. The literature survey revealed that Eclipta alba and Lippia
nodiflora are not much scientifically explored for its folklore claims and phytochemical
constituents. Hence in this study, we had investigated the phytochemical characterization
of the active principle of Eclipta alba and Lippia nodiflora and the application of its
crude extracts in various cosmeceutical activities, selected on the basis of ethno
pharmacological lead and literature survey.
Chapter 2 Review of Literature
35
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