Traditional medicinal uses

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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, syphilis etc. It is reported to be beneficial for the complexion, hair, eyes, and teeth. Expressed juice of E. alba mixed with goat's milk is used in frontal sinusitis and nasal cattarh in children. Bhringraj taila and Bhringrajadi churana are official preparations.

In the Unani system, the juice of E. alba is used in 'Hab Miskeen Nawaz' alongwith aconite, Croton tiglium, 'triphala', Piper nigrum, Piper longum, Zingiber officinale, and minerals like mercury, sulfur, arsenic, borax etc. 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.

Korea: The plant is used as an antidote for snake bites.

The Philippines: A decoction of the dried plant is used for heamoptysis and heamtemesis. For dysentery and heamturia urine, a decoction of the dried herb or tincture is used.

Medicated tea or tinctures are used as household remedies for sprains, furuncle and dermatitis; the tea or tincture is excellent.

Nepal: 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.

22.3 Phytochemistry

Alkaloids: Alkaloids including ecliptine and nicotine have been reported. Bio-active steroidal alkaloids, verazine, 20-epi-3-dehydroxy-3-oxo-5, 6-dihydro-4, 5-dehydroverazine, ecliptalbine, (20R)-4£-hydroxyverazine, 4£-hydroxyverazine, (20R)-25£-hydroxyverazine and 25£-hydroxyverazine have been identified from the methanolic extract.

Coumarins: The dried leaves of E.alba have been reported to contain wedelolactone (Fig. 22.1), a complex coumarin and its derivatives dimethylewedelolactone-7-glucoside and nor-wedelolactone. Demethylwedelolactone, isodemethylwedelolactone, and strychnolactone have been reported by percolation and hot extraction of the whole plant of E. alba.

Fig. 22.1 Structure of Wedelolactone.

Hydrocarbons: Ddithienylacetylene ester, ecliptal or a-terthienyl aldehyde, a-terthienyl-methanol and a-formylterthienyl.

Triterpenes: Ecliptasaponin C and D, new triterpenoid glucosides, have been isolated from the whole plant of E. alba. A new triterpene saponin, eclalbatin, together with a-amyrin (Fig. 5.245), p-amyrin (Fig. 5.245), ursolic acid (Fig. 5.245), oleanolic acid (Fig. 5.245), and wedelic acid have been isolated. From the whole parts of six new oleanane triterpene glycosides, eclalbasaponins I-VI have been isolated.

Thiopenes: Polyacetylenic thiopenes 5'-senecioyloxymethylene-2-(4-isovaleroxybut-3-ynyl) dithiophene, 5'-tigloyloxymethylene-2-(4-isovaleroxybut-3-ynyl) dithiophene have been reported form the plant. The roots contain polyacetylene substituted thiophenes).

Sterols: The aerial parts of the plant have been reported to contain phytosterol; p glucoside of phytosterol, daucosterol and stigmasterol-

3-O-glucoside. The whole plant contains stigmasterol (Fig. 5.247) and ß-sitosterol (Fig. 5.247).

Flavonoids: Apigenin (Fig. 5.112), luteolin (Fig. 15.12) and luteolin-7-glucoside (Fig. 15.9).

Miscellaneous: Nonacosanol, stearic acid, lacceroic acid and 3,4-dihydoxy benzoic acid .

22.4 Ethnopharmacology

Anti aggressive effect: The present study investigated the ability of 100 and 200mg/kg of aqueous extract of E. alba to circumvent aggression. Foot shock induced aggression and the water competition test were utilized as models for screening of anti aggressive activity. E. alba significantly minimized dominance (p<0.05) which is correlated to the level of aggression particularly with 200mg/kg in the water competition test. A tangible behavioral submission was observed with 100 and 200mg/kg and of E. alba in the foot shock induced test.

Analgesic effect: The present experimental research investigated the analgesic activity of the total ethanol extract of E. alba, and isolated alkaloids in albino mice using the tail clip method, the tail flick method and the acetic acid induced writhing response. The ethanol extract and the total alkaloids produce significant analgesic activity in all the different models of analgesia used. However, the total alkaloidal fraction was the most efficacious in all the models tested.

Anti-inflammatory effect: The methanolic extract administered by the oral route at a concentration of 100 and 200 mgkg-1 showed the significant dose dependent anti-inflammatory activity in carrageenin and egg white induced hind paw oedema in rats. Anti-inflammatory activity of the tested extract was comparable with that of the standard drug indomethacin (10 mgkg-1) and cyproheptadine (8 mgkg-1).

Antibacterial effect: The antimicrobial activity of wedelolactone was evaluated using minimum inhibitory concentration and agar well diffusion method. The compound exhibited good activity against Staphylococcus epidermidis and Salmonella typhimurium. The MIC test showed the growth inhibition of S. epidermidis at a concentration of 15.0 ^g/ml, ZOI 10.24 mm and of S. typhimurium at a concentration of 25.0 ^g/ml, ZOI 9.16 mm. Antifungal effect: 25beta-hydroxyverazine showed good activity against Candida albicans (Abdel Kader et al., 1998). The in vitro antifungal activity of the whole plant of E.alba extract was investigated against Candida tropicalis, Rhodotorula glutinis and Candida albicans. The extract showed high degree of activity against all tested fungi. The inhibitory effects of extracts are very similar to those of standard antibiotics used.

Antimalarial effect: The anti-malarial activity of Eclipta alba leaves extract was evaluated against Plasmodium berghei ANKA strain in mice. A standard inoculum of 1 x 10(6) infected erythrocytes was used. The methanolic leaf extract (250-750 mg/kg) produced a dose-dependant chemosupression or schizontocidal effect during early and established infection and high mean survival time values particularly in the group administered 750 mg/kg/day of extract.

Antihyperglycemic effect: Oral administration of leaf suspension of E. alba (2 and 4 g/kg body weight) for 60 d resulted in significant reduction in blood glucose (from 372.0 ± 33.2 to 117.0 ± 22.8), glycosylated hemoglobin HbAlc, a decrease in the activities of glucose-6 phosphatase and fructose1,6-bisphosphatase, and an increase in the activity of liver hexokinase. E. alba at dose of 2 g/kg body weight exhibited better sugar reduction than 4 g/ kg body weight.

Hepatoprotective effect: 1. Ethanol / water extract 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 ethanol/water extract.

2. In another study, the EtOAc part of alcoholic extraction exhibited significant hepatoprotective activity against CCl4-induced liver injury in rats.

3. In yet another study, treatment with 50% ethanol extract of E.alba (100 & 250mg/100g body weight) was found to protect the mice from hepato-toxic action of paracetamol as evidenced by significant reduction in the elevated serum transaminase levels. Histopathological studies showed marked reduction in fatty degeneration and centrizonal necrosis in animals receiving different doses of E.alba along with paracetamol as compared to the control group.

Hypolipdimeic effect: 1. The total alcoholic extract of E. prostrata exhibited a dose-dependent activity in albino rats when compared to standard drugs. The activity was assessed by studying the lipid profiles of serum, liver and heart of the control and drug-treated animals.

2. Charles River Sprague-Dawley CD rats 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 wk. Serum triacylglyceride and total cholesterol levels were significantly lower in the E50 and E100 groups by 9.8% to 19.0% and by 10.7% to 13.4%, respectively, and low-density lipoprotein-cholesterol levels were significantly reduced in the same groups by 10.3% to 13.0% compared with the untreated control group.

Neuropharmacological effects: 1. The aqueous, hydroalcoholic extracts and hydrolyzed fraction of the aqueous extract of E. alba was subjected to neuropharmacological activities. in rats. The findings indicated nootropic activity of the aqueous extract (300 mg/kg, p.o.) and its hydrolyzed fraction (30 mg/kg, p.o.). The aqueous extract and the hydrolyzed fraction exhibited gastro protective effect and normalized the white blood cell count in the milk induced leukocytosis challenge model.

2. The suspension of E. alba containing 100 and 200 mg/kg was administered to rats to evaluate Transfer Latency on an elevated plus maze. Mice were placed at the center of open field apparatus to assess spatial habitual learning, observed for 20 min for rearing and time spent during rearing using varied doses for 30 min, 24 h and 96 and 144 h. The results revealed significant improvement of retrieval memory.

Hair growth promoting effects: The study was aimed to investigate the efficacy of methanol extract of E. alba as hair growth promoter. Pigmented C57/BL6 mice, preselected for their telogen phase of hair growth were used. The extract was applied topically to assess telogen to anagen transition. The methanol extract of whole plant when tested for hair growth promoting potential, exhibited dose dependent activity in C57BL6 mice.

Effect on proteolytic and hemorrhagic activities: 1. Wedelolactone and demethylwedelolactone, isolated from E.alba demonstrated significant trypsin inhibitory effects.

2. The partially purified ethyl acetate extract (PEE) of E. prostrata (containing 47% of wedelolactone) and wedelolactone demonstrated strong antiproteolytic and antihemorrhagic activity against Malayan Pit Viper venom in a dose-dependent manner. The extract, at 5 mg/ml, inhibited proteolytic activity of 100 ^g of the venom and hemorrhagic activity of 3 minimum hemorrhagic doses to 95% and 65% respectively. At the same concentration, wedelolactone neutralized the proteolytic activity at around 76% and, at doses of 0.25-1.0 mg/ml, offered protection against hemorrhagic activity of the venom in the range 3-3.5%.

Effect on osteoblast differentiation: Flavonoid, diosmetin (Fig. 22.2), and isoflavonoids, 3'hydroxybiochanin A (Fig. 22.3), and 3'O-methylorobol (Fig. 22.4), isolated from the methanol extract of E. prostrata significantly increased osteoblast differentiation as assessed by the alkaline phosphatase activity.

Fig. 22.2 Structure of Diosmetin.
Wedelolactone Structure

Fig. 22.4 Structure of 3'-0-methyllorobol. 22.5 Clinical studies: Two studies reported efficacy of E.alba in the treatment of infective hepatitis in adults and jaundice in children, respectively. A clinical study reported diuretic, hypotensive, and hypocholesterolemic properties of E. alba, which helps in the alleviating oxidative stress-induced complications in hypertensive patients.

Fig. 22.4 Structure of 3'-0-methyllorobol. 22.5 Clinical studies: Two studies reported efficacy of E.alba in the treatment of infective hepatitis in adults and jaundice in children, respectively. A clinical study reported diuretic, hypotensive, and hypocholesterolemic properties of E. alba, which helps in the alleviating oxidative stress-induced complications in hypertensive patients.

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