Chapter 2 Review of literature - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/77695/4/13...

Chapter 2 Review of Literature

12

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


13

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


14

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 -


15

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


16

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


17

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


18

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).


19

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).


20

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


21

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


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


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).


24

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,


25

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


26

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)


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,


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).


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


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


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


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


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


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.


35

References

Abdel-Kader, M. S. 1998. DNA damaging steroidal alkaloids from Eclipta alba from the

suriname rainforest. J. Nat. Prod. 61(10): 1202-08.

Agarwal, S. S. and Gayatri, D. 2011. Evaluation of Eclipta alba gel for its hair growth

promoting activity. Ethnopharmacology, 12(2): 23-28.

Akhtar, M. F. Chemical and biological investigations of medicinal herbs Phyla nodiflora,

Ruellia patula and Ruella brittoniana Ph.D. Thesis. 1993, Pakistan: Univ. of

Karachi.

Ananthi, J., Prakasam, A., Pugalendi, K.V. 2003. Antihyperglycemic activity of Eclipta

alba leaf on Alloxan - induced diabetic rats. Yale Journal of Biology and

Medicine. 76: 97-102.

Anonymous. Medicinal plants in the Republic of Korea. World Health Organization.

Manila. 1987. pp3.

Anonymous. Medicinal plants of Nepal. Dept. of medicinal plants. Nepal: 1993, pp. 45.

Anonymous. The Wealth of India, Raw Materials, Council of Scientific and Industrial

Research, New Delhi, 3rd ed, India (New Delhi): CSIR; 1952, pp. 127-128.

Arunachalam, G., Subramanian, N., Pazhani, G.P., Ravichandran, V. 2009. Anti -

inflammatory activity of methanolic extract of Eclipta prostrata L. (Astearaceae).

African Journal of Pharmacy and Pharmacology. 3(3): 97-100.

Baig, M. I., Bhagwat, V. G. 2009. Study the efficacy of Galactin Vet Bolus on milk yield

in dairy cows. Veterinary world. 2(4): 140-42.

Baishiyou, R., 1993. Hair tonic. J. Cosmetic Dermatology. 6: 103-107.

Balakrishnan, G., Janakarajan, L., Balakrishnan, A. and Lakshmi, B.S. 2011. Molecular

basis of the anti-inflammatory property exhibited by cyclo-pentano phenanthrenol

isolated from Lippia nodiflora., Archives of Pharmacy Practice, 39(7): 71.


36

Barnabas, C., Gunasingh, G. and Nagarajan, S. 1980. Flavonoids from the flowers of

Phyla nodiflora Linn. Indian Journal of Chemistry, Section B: Organic Chemistry

including Medicinal Chemistry, 19B(9): 822.

Barua, A. K., Chakrabarti, P., Sanyal, P.K. 1971. Structure of nodifloretin, new flavone

from Lippia nodiflora. Transactions of the Bose Research Institute (Calcutta), 33-

34(3): 5-8.

Basu, A. K., Chakraborty, P. and Sanyal, P. K. 1969. Nodifloretin - A new flavones from

Lippia nodiflora. J Indian chem. Society, 46: 271-272.

Bensky Dan and Andrew Gamble. 1986. Chinese Herbal Medicine: Materia Medica.

Seattle: Eastland Press.

Bhargava, K., Krishnaswamy, N., Seshadri, T. 1970. Isolation of demethyl

wedelolactone and its glucoside from Eclipta alba. Indian Journal of Chemistry,

8: 664-665.

Bhaskar Rao, D., Chravi kiran, Madhavi, Y., Koteshwara Rao, P., Raghava Rao, T. 2009.

Evaluation of antioxidant potential of Clitoria ternate L. and Eclipta prostrata L.

Indian journal of biochemistry and biophysics. 46: 247 - 52.

Bhattacharya, S. K., Kalkunte, S. S. and Ghosal, S. 1997. Antioxidant activity of

glywithanolides from Withania somnifera. Indian J. Exp. Biol. 35: 236-239.

Bina, S., Siddiger, Fayal Ahmed, Kashif Ali, Sobiya Parwaiz and Sabira Begam. 2009.

Steroidal constituent from the aerial parts of Lippia nodiflora Linn. Natural

product research. 436-441.

Bodoprost, J. and Rosemeyer, H. 2007. Analysis of phenacylester derivatives of fatty

acids from human skin surface sebum by reversed phase HPTLC:

chromatographic mobility as a function of physicochemical properties. Int. J. Mol.

Sci. 8: 1111-1124.

Bruce Milliman, W., Davis, W., Lamson M. S., Matthew Brignall, S. 2000. Hepatitis C:

A retrospective study, literature review, and naturopathic protocol. Alternative

Medicine Review. 5(4): 355-70.


37

Chandra, K. 1985. Traditional remedies of Baharaich and Gonda District of U. P,

Sachitra Ayurveda, Patna, 1985. P. 483-485.

Cheol, G. Ryu. 2004. Hair-restorer and manufacturing process thereof. KR20040016331.

Cheryl Lans. 2007. Comparison of plants used for skin and stomach problems in Trinidad

and Tobago with Asian ethnomedicine. Journal of Ethnobiology and

Ethnomedicine. 3(3): 1-12.

Chopra, R. N., Nayar, S. L. and Chopra, I. C. Glossary of Indian medicinal plants, New

Delhi: Council of Scientific and Industrial Research, 1955: 155.

Christybapita, D., Divyagnaneswari, M., Dinakaran Michael R. 2007. Oral administration

of Eclipta alba leaf aqueous extract enhances the non - specific immune responses

and disease resistance of Oreochromis mossambicus. Fish and shellfish

immunology. 23(4): 840-52.

Dae-Ik Kima, Sung-Hyen Lee, Jin-Ho Choia, Hyun Soon Lillehoj, Mi-Hee Yu and Gun-

Soon Lee. 2008. The butanol fraction of Eclipta prostrata (Linn) effectively

reduces serum lipid levels and improves antioxidant activities in CD rats.

Nutrition Research. 28: 550-54.

Dan, N. V. and Nhu, D. T. Medicinal plants in Vietnam. World Health Organization.

1989. pp.12-14.

Daniel, M. Medicinal Plants, Chemistry and Properties, Oxford and IBH publishing Co.

Pvt. Ltd, New Delhi, 2006, 148-149.

Das, B. and Chakravarthy, A. K. Ecliptal, a new terthienyl aldehyde from Eclipta alba.

Indian Journal of Chemistry, 30, 1991, 1052 - 1053.

Datta, K., Singh, A. T., Mukherjee, A., Bhat, B., Ramesh, B. and Burman, A. C. 2009.

Eclipta alba extract with potential for hair growth promoting activity. Journal of

Ethnopharmacology. 124: 450-456.

Dhandapani, R. 2007. Hypolipidemic activity of Eclipta prostrata (L.) L. leaf extract in

atherogenic diet induced hyperlipidemic rats. 45: 617-19.


38

Durairaj, A., Mazumder, U. K., Gupta, M. and Selvan, V. T. 2009. Effect on inhibition of

proliferation and antioxidant enzyme level of Lippia nodiflora in EAC Cell line

treated mice. Journal of Complementary and Integrative Medicine, 6(1): 713-714.

Durairaj, A. K. and Gupta, M. 2007. Antimicrobial and lipid peroxide scavenging activity

of Lippia nodiflora (Verbenaceae), Pharmacologyonline, (3): 177-189.

Durairaj, A., Vaiyapuri, T. S., Mazumder, U. K. and Gupta, M. 2008. Protective activity

and antioxidant potential of Lippia nodiflora extract in paracetamol induced

hepatotoxicity in rats. Iranian Journal of Pharmacology & Therapeutics, 7(1): 83-

89.

Falodun, A., Siraj, R. and Choudhary, M. I. 2009. GC – MS analysis of insecticidal leaf

essential oil of Pyrenacantha staudtii Hutch and Dalz. (Icacinaceae). Tro. J.

Pharm. Res. 8: 139-143.

Forestieri, A. M., Monforte, M. T., Ragusa, S., Trovato, A. and Iauk, L. 1996.

Antiinflammatory, analgesic and antipyretic activity in rodents of plant extracts

used in african medicine. Phytotherapy Res. 10: 100-106.

Girish, H. V. and Satish, S. 2008. Antibacterial activity of important medicinal plants on

human pathogenic bacteria – a comparative analysis. World applied Sciences

Journal. 5(3): 267-271.

Han, Y., Xia, C., Cheng, X., Xiang, R., Liu, H., Yan, Q. and Xu, D. 1998. Preliminary

studies on chemical constituents and pharmacological action of Eclipta prostrate

L. Zhongguo Zhong Yao Za Zhi, 23: 680 - 682.

Haveliwala, M. D. The role of 'Sapera Forte Tablet' in the management of hypertension.

1963; 9: 837-39.

Hemalatha, S., Ayyappan, T., Shanmugan, S., Nagavalli, D. and Shrivijaya kirubha, T.

2006. Evaluation of antidiabetic and diuretic activity of polyherbal formulation.

Indian Journal of Traditional Knowledge. 5(4): 468-70.


39

Iqbal Hussain, Naeem Khan, Riaz Ullah, Shanzeb, Shabir Ahmed, Farhat Ali khan and

Sultan Yaz. 2011. Phytochemical, physiochemical and anti-fungal activity of

Eclipta alba. African Journal of Pharmacy and Pharmacology, 5(19): 2150-2155.

Jadhav, V. M., Thorat, R. M., Kadam, V. J. and Salaskar, K. P. 2009. Chemical

composition, pharmacological activities of Eclipta alba. Journal of Pharmacy

Research. 2(8): 1129-1231.

Jain, S. and Singh, P. A. 1988. Dithienylacetylene ester from Eclipta erecta Linn. Indian

Journal of Chemistry, 27: 99-100.

Jayathirthaa, M. G. and Mishraa, S. H. 2004. Preliminary immunomodulatory activities

of methanol extracts of Eclipta alba and Centella asiatica. Phytomedicine. 11(4):

361-65.

Joshi, B. C. 1970. Chemical examination of Lippia nodiflora. Vijnana Parishad

Anusandhan Patrika, 11(4): 214-219.

Karthikumar, S., Vigneswari, K., Jegatheesan, K. 2007. Screening of antibacterial and

antioxidant activities of leaves of Eclipta prostrata (L). Sci. Res. Essays. 2(4):

101-04.

Kaur, A. and Shukla, J. V. 2010. Chromatographic methods of fractionating several

chemical constituents in Phyla nodiflora. International Journal of

Pharmaceutical Sciences and Research. 1(1): 46-55.

Kaushik-Basu, N., Alain Bopda waffo, Tanaji Talele, T., Amartya Basu, Paulo Costa, R.

R, Alcides da Silva, J. M, Stefan Sarafianos G and Francois Noel. 2008.

Identification and characterization of coumestans as novel HCV NS5B

polymerase inhibitors. 36(5): 1482-96.

Khalil, A. T., Lahloub, M. F. and Salama, O. M. 1995. Phenolic compounds from Lippia

nodiflora. Journal of Pharmaceutical Sciences, 11(2): 256-26.

Khan, A. V and Khan, A. A. 2008. Ethnomedicinal uses of Eclipta prostrate. Indian

journal of traditional knowledge. 7(2): 316-20.


40

Khanna and kannabiran. 2008. Anticancer-cytotoxic activity of saponins isolated from

the leaves of Gymnema sylvestre and Eclipta alba on HeLa cells. International

journal of green pharmacy. 1: 227-29.

Khargava, K. K. and Seshadri, T. R. 1974. Chemistry of medicinal plants: Eclipta alba

and Wedelia calandulaceae. Journal of Research in Indian Medicine, 9: 915.

Kim, S. H., Hyun, S. H. and Choung, S. Y. 2008. Anti-diabetic effect of cinnamon extract

on blood glucose in db/db mice. J. Ethnopharmacology, 104: 119-123.

Kirtikar, K. R. and Basu, B. D. 1975. Chronica Botanica Indian Medicinal plants: New

Delhi. p.39.

Kirtikar, K. R. and Basu, B. D. 1991. Indian Medicinal Plants, 2nd edition. Dehradun:

Bishen Singh and Mahendra Pal Singh. 1916-1917.

Kosuge, T., Yokota, M., Sugiyama, K., Yamamoto, T., Ni, M. and Yan, S. 1985. Studies

on antitumor activities and antitumor principles of Chinese herbs. Yakugaku

Zasshi, 105: 791-795.

Kumar, S., Kumar, V. S., Sharma, A., Shukla, Y. N. and Singh, A. K. 1997. Traditional

medicinal plants in skin care. Central Institute of Medicinal and Aromatic Plants,

Lucknow, p. 103.

Kumar, G. S., Jayaveera, K. N., Kumar, C. K. A., Sanjay, P. U., Swamy, B. M. V. and

Kumar, D. V. K. 2007. Antimicrobial effects of Indian medicinal plants against

acne-inducing bacteria. Tropical Journal of Pharmaceutical Research. 6(2): 717-

723.

Lal, V. K, Amit Kumar, Prashant Kumar and Kuldeep Singh Yadav. 2010. Screening of

Leaves and Roots of Eclipta alba for hepatoprotective activity. Arch. Appl. Sci.

Res. 2(1): 86-94.

Lee in Geol, 2004. Kit for hair growth. KR20040039550.

Lee Sang Kuk, Ha Byong-Jo, Mun Song-Jun and Kang Kil-Sung. 1995. Hair growth

composition. KR950006061B.


41

Lee Won Gyu. 2001. Agent for preventing hair loss and stimulating or promoting hair

growth using skin of peach. KR20010044451.

Majumdar, M., Nayeem, N., Kamath, J. V. and Asad, M. 2008. Evaluation of Tectona

grandis leaves for wound healing activity. Pak. J. Pharm. Sci. 20: 120-124.

Malaya Gupta, Upal K. anti Mazumdera, Palla K. Haldar, Chandi C. Kandar, Laxmanan

Manikanda and Senthil, G. P. 2005. Anticancer Activity of Indigofera

aspalathoides and Wedelia calendulaceae in swiss albino mice. Iranian journal of

pharmaceutical research. 6(2): 141-45.

Manjunath, B. L. Medicinal plants in India. The wealth of India. New Delhi: CSIR, 1962:

142-143.

Meena, A. K., Rao, M. M., Komalpreet Kaur and Panda, P. 2010. Comparative

evaluation of standardization parameters between Wedelia genus species. Int. J.

Ph. Sci. and Res. 1(3): 207-210.

Melo, P. A., Do Nascimento, M. C., Mors, W. B. and Suarez-Kurtz, G. 1994. Inhibition

of the myotoxic and hemorrhagic activities of crotalid venoms by Eclipta

prostrate (Asteraceae) extracts and constituents. Toxicon. 32:595-603.

Mi Kyeong Lee, Na Ry Ha, Hyekyung Yang, Sang Hyun Sung, Gun Hee Kim and Young

Choong Kim. 2008. Antiproliferative activity of triterpenoids from Eclipta

prostrata on hepatic stellate cells. 15(9): 775-80.

Mitesh, D. Phale, Purnima, D, Hamrapurkar, Manasi, A. Chachad, Priti S. Patil, Sandeep

B. Pawar. 2010. Precise and sensitive HPTLC method for quantitative estimation

of wedelolactone in Eclipta alba Hassk. Pharmacophore, 1 (2), 103-111.

Mukherjee, D. R. and Poddar, H. 1976. Pilex therapy in Piles - a Preliminary Report. The

antiseptic. 10: 541.

Nair, A. G. R., Ramesh, P., Nagarjan, S. and Subraimanam, S. 1973. A new flavones

glycosides from Lippia nodiflora. Indian journal chem., 2: 1316-1317.


42

Nakaguchi, O., Okamoto, H., Matsuyama, Y., Karsurada, M. and Sakano, T. 2001. Hair

growth stimulants containing wedelolactone from Eclipta alba. Chemical

Abstracts, 134(2): 917.

Narayanan, N. M. E., Ranganathan, C. K. H., Narayanan, M. and Rao, G. V. 2008. A

process for manufacturing synergistic antimicrobial compositions for dandruff

treatment. India patent application IN 2002-MA 628, 2008: 101-105.

Nazim Uddin, Atiar Rahman, Nazim Uddin Ahmed, Sohel Rana, Rasheda Akter,

Masudul Azad and Chowdhury, A. M. 2010. Antioxidant, cytotoxic and

antimicrobial properties of Eclipta alba ethanolic extract. Int J Biol Med Res.

1(4): 341¬46.

Otilia Banji, David Banji, Annamalai Ar and Manavalan, R. 2007. Investigation on the

effect of Eclipta alba on animal models of learning and memory. Indian J physiol

pharmacol. 51(3): 274-78.

Pal, S. and Narasimham, N. 1943. The alkaloid in Eclipta alba (Hassk). Journal of Indian

Chemical Society, 20: 181.

Pascual, M. E., Slowing, K., Carretero, E., Sanchez Mata, D. and Villar, A. 2001. Lippia:

traditional uses, chemistry and pharmacology: a review. J. Ethnopharmacology,

76: 201-214.

Phadke, S. A. and Kulkarni, S. D. 1989. Screening of medicinal plants for antimicrobial

activity. Indian J. Med. Sci, 43(5): 113-117.

Pirzada, A. J., Iqbal, P., Shaikh, W., Kazi, T. G. and Ghani, K. V. 2005. Studies on the

elemental composition and antifungal activity of medicinal plant L. nodiflora

against skin fungi. Journal of Pakistan Assoc. Dermatology. 15(2): 113-118.

Pithayanukul, P., Lapett, B., Bavovada, R., Pakmanee, N. and Suttisri, R. 2004. Inhibition

of proteolytic and hemorrhagic activities by ethyl acetate extract of Eclipta

prostrate against Malayan pit viper venom. Pharmaceutical Biology, 45:282-288.

Pulak, M. Quality control of herbal drug; 1st Edition; (Horizan Publishing): 2002; 303-

305.


43

Rangachari Balamurugan and Savarimuthu Ignacimuthu. 2011. Antidiabetic and

Hypolipidaemic effect of methanol extract of Lippia nodiflora L in Streptozotocin

induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine. 30-36.

Ravikanth, V., Ramesh, P., Diwan, P. V. and Venkateswarlu, Y. 2000. Halleridone and

Hallerone from Phyla nodiflora as taxonomic markers. Biochemical Systematic

and Ecology, 28(9): 905-906.

Ravikumar, V. R and Sudha, T. 2011. Phytochemical and microbiologica observations on

Phyla nodiflora, Internat. J. Res. Pharmaceutical Chem. 1(2): 117-120.

Rolf teschke and Ruediger bahre. 2009. Severe hepatotoxicity by Indian herbal products:

A structured causality assessment. 8(3): 258-66.

Roy, R. K., Mayank Thakur and Dixit, V. K. 2007. Development and evaluation of

polyherbal formulation for hair growth promoting activity. J. Cosmetic

Dermatology. 6: 108-112.

Roy, R. K., Mayank Thakur and Dixit, V. K. 2008. Hair growth promoting activity of

Eclipta alba in male albino rats. Arch Dermatol Res. 300: 357-64.

Sahu, M and Srivastava Pankaj. 2001. Clinical study of pilex combination therapy Vs

conventional ayurvedic therapy in the management of haemorrhoids. The Indian

Practitioner. 54(11): 799-805.

Samudram, P., Rajeshwari Hari, Vasuki, R., Geetha and Sathiya moorthi, P. 2008.

Hepatoprotective activity of Bi-herbal ethanolic extract on CCl4 induced hepatic

damage in rats. AJBR. 2(2): 61-65.

Sangita Shukla, Rashmika Patel and Rajiv Kukkar. 2009. Study of phytochemical and

diuretic potential of methanol and aqueous extracts of aerial parts of Phyla

nodiflora Linn, International Journal of Pharmacy and Pharmaceutical Sciences,

1(1): 85-91.

Sawangjaroen, N., Subhadhirasakul, S., Phongpaichit, S., Siripanth, C., Jamjaroen, K and

Sawangjaroen, K. 2005. The in vitro anti - giardial activity of extracts from plants


44

that are used for self - medication by AIDS patients in southern Thailand.

Parasitol Res. 95(1): 17-21.

Sawant, M., Jolly C. Isaac and Shridhar Narayanan. 2004. Analgesic studies on total

alkaloids and alcohol extracts of Eclipta alba (Linn.) Hassk. Phytotherapy

research. 18(2): 111-13.

Saxena, A. K., Singh, B., Anand, K. K. 1993. Hepatoprotective effects of Eclipta alba on

subcellular levels in rats. Journal of ethnopharmacology. 40(3): 155-61.

Shin Endo, 2006. Hair growing and beautifying agent. JP2006151934.

Shukla. S, Saluja, A. K and Pandya, S. S. 2009. ,In-vitro antioxidant activity of aerial

parts of Lippia nodiflora Rich. Pharmacologyonline; 2: 450-459.

Siddiqi, B. S., Ahmed, F., Sattar, F. A and Begum, S. 2007. Chemical constituents from

the aerial part of L.nodiflora linn. Arch Pharma Res, 30(12): 1507-1510.

Sikroria, B. C., Srivastava, S. J and Niranjan, G. S. 1982. Phytochemical studies on

Eclipta alba. Journal of Indian Chemical Society, 59: 905.

Singh, I. and Singh, V. P. 2000. Antifungal properties of aqueous and organic solution

extracts of seed plant against Aspergillus flavus and A. niger. Phytomorphol. 50:

151-157.

Singh, A., Samir malhothra and Ravi subban. 2008. Anti-inflammatory and analgesic

agents from Indian medicinal plants. International journal of integrative biology.

3(1):58-72.

Sujatha Dodala, Ranganayakula Diviti, Bharathi Koganti and Prasad. 2010. The effect of

ethanolic extract of Phyla nodiflora Greene against calculi producing diet induced

urolithiasis, Indian Journal of Natural Products and Resources, 1(3): 314-321.

Supinya Tewtrakul, Sanan Subhadhirasakul and Sopa Kummee. 2006. Anti-HIV-1

integrase activity of medicinal plants used as self medication by AIDS patients.

Songklanakarin J. Sci. Technol. 28(4): 785-90.


45

Terblanche, F. C. and Kornelius, G. 1996. Essential oil constituents of the genus Lippia

(Verbenaceae) – A literature review. Journal of essential oil res. 8: 471-485.

Tewtrakul, S., Subhadhirasakul, S., Cheenpracha, S and Karalai, C. 2007. HIV-1 protease

and HIV-1 integrase inhibitory substances from Eclipta prostrate. Phytother Res.

21(11): 1092-95.

Thakur, V. D. and Mengi, S. A. 2005. Neuropharmacological profile of Eclipta alba (L.)

Hassk. J. Ethnopharmacol. 102: 23-31.

Thorat, R., Varsha jadhav, Vilasrao kadam, Ninad sathe, Ashwini save and Vikas

ghorpade. 2009. Evaluation of a herbal hair oil in reducing hair fall in human

volunteers. 6: 974-79.

Tomas – Barberan, F. A., Harborne, J. B and Self, R. 1987. Twelve 6- oxygenated

flavone sulphates from Lippia nodiflora and L.canescens, Phytochemistry, 26(8):

2281-2284.

Upadhyay, R. K., Pandey, M. B., Jha, R. N. and Pandey, V. B. 2001. Eclalbatin, a

triterpene saponin from Eclipta alba. J Asian Nat Prod Res. 3(3): 213-17.

Vianna-da-silva, N. M., Moraes ram, Da silva AJM, Costa PRR and Melo P. A. 2003.

Antivenom effect of a new synthetic coumestan analog of wedelolactone. J.

Venom. Anim. Toxins incl. Trop. Dis. 9(2): 381.

Wagner, H. 1986. Coumestans as the main active principles of the liver drugs Eclipta

alba and Wedelia Calendulaceae. Planta Med. 5: 370-74.

Wiart, C., Mogana, S., Khalifah, S., Mahan, M., Ismail, S., Buckle, M. and Narayanan,

A. K. 2004. Antimicrobial screening of plants used for traditional medicine in the

state of Perak, Peninsular, Malaysia. Fitoteropia, 75(1): 68-73.

Xiong - Hao Lin, Yan - Bin Wu, Shan Lin, Jian - Wei Zeng, Pei - Yuan Zen and Jin -

Zhong Wu. 2010. Effects of volatile components and ethanolic extract from

Eclipta prostrata on proliferation and differentiation of primary osteoblasts 15:

241-50.


46

Xiulan Wang. 1997. Hair growth, beauty-care and health care medicinal liquor and

method for preparing same. CN1154250.

Yahara, S., Ning, D. and Teshihire, N. 2006. Six new oleanane triterpene glycosides,

eclalbasaponins I - VI isolated from Eclipta alba (L.) Hassk. Chemical and

Pharmaceutical Bulletin, 42: 1336-1338.

Zhang, J. S. and Guo, Q. M. 2001. Studies on the chemical constituents of Eclipta

prostrate (L.). Yao-Xue-Xue-Bao, 36: 34-37.

Zhang, M., Chen, Y. Y., Di, X. H and Liu, M. 1997. Isolation and identification of

ecliptasaponin D from Eclipta alba (L.) Hassk. Yao-Xue-Xue-Bao, 32: 633-634.

Zheng, L. 2008. Application of Lippia nodiflora extract to preparing medicinal

preparation for treating hepatitis. China patent application CN 2007 – 10084260

20070224.

Web Source

http://www.ncbi.nlm.nih.gov/pubmed/18396809

http://www.bluvenus.com/SW/herbal/index.html

http://www.kettlecare.com/index.html

http://www.agriinfotech.com

http://www.reviveholisticbeauty.com

http://www.womenfitness.net

http://www.cosmeticsdesign.com/news/news-ng.asp

Chapter 2 Review of literature - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/77695/4/13...

Documents

Transcript of Chapter 2 Review of literature - Shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/77695/4/13...