INTRODUCTION:

1. Wedelia chinensis Merrill

Wedelia chinensis Merrill (Syn. Wedelia calendulaceae, Solidago chinensis) (Asteraceae, Sunflower family) is a small much branched annual herb, commonly known as “Pilabhamgara” or “Bhringraj’in Hindi, Wedelia in Chinese, Pitabhrnga, Pitabhrngarajah in Sanskrit¹. Wedelia chinensis is a tender, spreading, and hairy herb, with the branches usually less than 50 cm long. The leaves are oblong to oblong-lanceolate, 2-4.5 cm in length, and narrowed at both ends. The margins are entire or obscurely toothed; and both surfaces are covered with sharp-pointed, appressed, straight, and stiff hairs. The heads are stalked, about 1 cm in diameter, and yellow. The involucral bracts are oblong-ovate. The ray flowers are 8-12, spreading, about equal to the bracts, and broad; the disk flowers number about 20, and are short, narrow, and pointed. The achenes are nearly cylindric, and hairy².

Wedelia chinensis is a reputed herbal medicine in both Ayurvedic, Siddha and Unani system of medicine. It is a scabrous procumbent perennial soft herb with high camphor like odor and has a gorgeous growth³.

The herb contains wedelolactone and demethylwedelolactone (Coumestans derivatives) possessing potent anti-hepatotoxic effect and is incorporated as a major ingredient in a number of developed potent anti-hepatotoxic phytopharmaceuticals formulations. It is useful in the treatment of osteoporosis of knee and also possesses anti-inflammatory activity^4-6. As it contains large amount of phenolic constituents and it is also effective in the treatment of inflammatory conditions, so its wound healing activity was studied in details. Extracts from the dried or fresh leaves of plants are applied as a paste on wounds in some rural communities. The fresh juice from the leaves of Wedelia chinensis has been used by Ayurvedic physicians in India for external use to treat skin problems, dermatitis, eczema and acne. Some work on the wound healing activity of the aqueous extract of the leaves of this plant on open wound and sutured wound models is already on record⁷

Wedelia Chinensis is a very useful herbal medicinal plant. Its leaves can be used in treatment of dermatological disorders, cough, headache, hair loss, lice, strengthening the nervous system, lack of blood, digestive system disorders. The leaves are used in dyeing grey hair and in promoting the growth of hair. They are considered tonic, alternative, and useful in coughs, cephalalgia, skin diseases, and alopecia. The juice of the leaves is much used as a snuff in cephalalgia. The seeds and flowers, as well as the leaves, are used in decoction, in the quantity of half of teacupful twice daily, as a deobstruent. In decoction, the plant is used in uterine haemorrhage and menorrhagia. Wedelia chinensis using home remedy Osteochondritis Dissecans, Multiple Sclerosis, Juvenile Arthritis, Gouty arthritis, Rheumatic fever, etc. Wedelia chinensis leaves extracts are a natural alternative to commonly used anti-inflammatory drugs like Dolonex (Piroxicam), Brufen (Ibuprofen) and Voveran etc. Wedelia chinensis leaves extract can be used with confidence for treating Rheumatic fever⁸.

The plant is reported to contain six new acylated eudesmanoids, germacrene, a-humulene, caryophyllene, squalene, phellandrene, p-cymene, sitosterol and wedelia-seco-kaurenolide ^[9]; leaves contain isoflavonoids and wedelolactone. This plant is considered to have different pharmacological properties such as antihepatotoxicity^10-12; leaves are used in cough, cephalagia, alopecia and skin diseases ; dyeing hair and for promoting hair growth; roots yield a black dye, ethanolic extract of the herb has been shown to inhibit the growth of Ehrlich ascities carcinoma ¹³; decoction of the plant is used as deobstruent and given in uterine hemorrhage and menorrhagia. The compounds of this herb have been reported to have synergistically suppression activity on androgen and growth in prostate cancer cells¹⁴. This herb can be propagated by seeds and vegetative stem cuttings. Due to cross-pollination the germinated seedlings are not true to type and propagation through this way is not reliable due to low span of viability. Habitat destruction and use in large quantities has endangered this species. Although, in vitro propagation of W. chinensis has been published previously^15,16.

The hepatoprotective activity of ethanolic extract of Wedelia calendulacea L. was studied against CCl₄ induced, acute hepatotoxicity in rats. Hepatoprotective activity of the ethanolic-leaf extract of W.calendulacea (EEWC) was studied by estimating serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), protein and bilirubin. The treatment with EEWC showed a dose-dependent reduction of CCl₄ induced elevated serum levels of enzyme activities with parallel increase in total protein and bilirubin, indicating the extract could preserve the normal functional status of the liver. The weight of the organs such as liver, heart, lung, spleen and kidney in CCl₄ induced experimental animals administered with EEWC showed an increase over CCl₄ control group^17,18. Investigating the anti-inflammatory and analgesic activity of leaves of wedelia chinensis. The ethanolic extract of Wedelia chinensis was evaluated by hot plate and acetic acid induced writhing methods to assess its analgesic activity. The results indicate the potent analgesic and anti-inflammatory effects and therapeutic efficacy of Wedelia chinensis extract on animal models which are comparable with those of standard drugs such as Aspirin, Morphine and Indomethacin respectively¹⁹.

Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells. Four anti-proliferative phytocompounds in Wedelia chinensis, an oriental herbal medicine, identified through their ability to modulate the androgen receptor (AR) activation of transcription from prostate-specific antigen promoter in PCa cells. The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 mM, respectively. Study had identified synergistic effects of active compounds in W. chinensis and demonstrated their potential in prostate cancer prevention and therapy²⁰. The ethanolic extract was found to possess significant wound healing activity, which was evidenced by decrease in the period of epithelialization, increase in the rate of wound contraction, skin breaking strength, granulation tissue dry weight, and its breaking strength²¹. Ethanolic extract of the Wedelia chinensis was studied on cold immobilization induced lipid peroxidation in albino rats. The results of the study suggest the potential use of the plant for decreasing anxiety and stress in many emotional and physical disorders. Study shows that Wedelia chinensis extract exhibit significant analgesic and anti-inflammatory activity against early phase (acute paw edema), late phase (cotton pellet granuloma) of inflammation models. This plant which contains natural products such as flavonoids, terpenoids and steroids etc. have received considerable attention in recent years due to its diverse pharmacological properties including antioxidant activity. We propose that the additive and synergistic antioxidant activity of phytochemicals such as flavonoids, triterpenoids, steroids, etc, present in Wedelia chinensis are responsible for the analgesic and anti-inflammatory activity²².

The subject invention relates to extracts of tissues of certain plant species from the genera Wedelia. Eclipta and AsDilia which are effective as gastrointestinal mucosal- protective agents. Various species from the genera Wedelia. Eclipta and Asoilia have been disclosed to have a variety of different biological or pharmacological activities. Two frequently studied species of these genera are Wedelia caiendulaceae and Eclipta alba. The most common medicinal use of extracts from these plants is for treatment of liver ailments. For this use, the active compounds found in these species are beleved to be coumestans, especially wedelolactone and related compounds. Extracts from these plants have also been used to mm treat a number of other ailments such as catarrh, skin diseases, elephantiasis, toothaches and headaches, as well as being used as emetic and purgative materials, and as external antiseptics. Shoot extracts have been shown to have antibiotic activity against certain species²³.

Wedelia calendulacea Less., containing isoflavanoids, is used in liver disorders, uterine hemorrhage and menorrhagia. Osteoporosis in women occurs mainly due to estrogen deficiency following menopause. Studies indicate that isoflavones are estrogenic enough to promote bone formation. Study was aimed to investigate the antiosteoporotic effect of the ethanol extract of W. calendulacea in the ovariectomized rat model of osteoporosis, at two different dose levels of 500 and 750 mg/kg/body wt. day. The findings, assessed on the basis of biomechanical and biochemical parameters, showed that the ethanol extract of the plant had a definite protective effect. Phytochemical investigation revealed the presence of isoflavones and wedelolactone, which are known to act as phytoestrogens and may be responsible for the antiosteoporotic activity²⁴. The neuropharmacological activities of the methanolic and aqueous extract of Wedelia calendulacea stem were screened in rats and mice. The extracts effect on pentobarbital-induced sleeping time, pentylenetetrazole- and styrychnine-induced seizure, spontaneous motor activity, exploratory behaviour, and rota-rod performance (motor coordination) were evaluated. These results suggest that the extract contained an agent with neuropharmacological activity that may be sedative in nature²⁵. The cytotoxicity and antibacterial activity of petroleum ether, chloroform and methanol extracts of Wedelia calendulacea were assayed by brine shrimp lethality bioassay and standardized disk diffusion method against 19 bacterial strains. Among the crude extracts and pure compounds tested, (-)-kaur-16-en-19-oic acid isolated from the chloroform extract showed the highest inhibitory activity against most of the bacterial strains with mean zone of inhibition of 10-21 mm at 200 microg/disc²⁶.

Hepatoprotective effect of coumestans isolated from the leaves of W. calendulacea was evaluated in paracetamol induced liver damage. The increased serum enzyme levels (lactate dehydrogenase, alanine and aspartate transaminase and alkaline phophatase) by paracetamol induction were significantly lowered due to coumestans treatment. Results of study revealed that coumestans of W. calendulacea afforded a significant protective action in the alleviation of paracetamol induced hepatocellular injury²⁷.

There is some confusion between the Sanskrit and vernacular names of Wedelia calendulacea, and Eclipta prostrata. Both these plants are called kesarάj or kesuria in Bengali, and the two Sanskrit names of bhringaraja and kesaraja are used as synonyms. The Hindustani term bhangra, derived from the Sanskrit bhrin-gardja is however generally applied to Wedelia calendulacea, and this is the plant used in medicine at present. The leaves, which have a slight camphoraceous taste, are considered tonic, alterative, and useful in cough, cephalalgia, skin diseases and alopecia. The juice of the leaves is much used as a snuff in cephalalgia, and in soaking various sorts of powders for the preparation of pills.1 "In tattooing the natives after puncturing the skin, rub the juicy green leaves of Eclipta prostrata over the part; which gives the desired indelible colour, namely a deep bluish black." The leaves of both these plants are used in various ways for the purpose of dyeing grey hair and for promoting the growth of hair.

2. Wedelia trilobata Linn:

Wedelia trilobata is a very attractive plant because of its nearly constant and prolific blooming. It is fairly salt resistant and grows well at the seashore. Wedelia trilobata is a soil creeper and forms a thick carpet. It is especially good for soil retention and erosion control. The plant can also be used in hanging baskets. It may be best used as a container plant where it will cascade over the side forming a weeping mound of yellow flowers. Wedelia trilobata now known officially by the scientific name, Sphagneticola trilobata (L.) Pruski, but still widely known by its previously accepted name, Wedelia trilobata (L.) Hitch.), is a member of the family Asteraceae (formerly Compositae), the sunflower or daisy family. The most widely used common name in the Pacific is “Wedelia” (after its former genus), although in Australia it is known as “Singapore daisy”, in spite of its tropical American origin. Other common names include trailing or creeping daisy, water zinnia, rabbit’s paw and creeping. Wedelia has a vine-like habit and will grow up into shrubs and trees planted in the bed. When used as a groundcover in and among shrubs, this will make it a high maintenance plant. It looks best planted in a mass over large areas. Like ivy and other creepers, it will require regular trimming along the edge of the groundcover bed to control its spread. It may be best used as a container plant where it will cascade over the side forming a weeping mound of yellow flowers. It has escaped cultivation in certain regions of south Florida where it proliferates, especially in wet areas. Propagation is easily accomplished by setting enrooted tip cuttings in the landscape soil where new plants are wanted, or by layering, the stems rooting quickly²⁸.

Low-growing mat about 10" with deeply lobed leaves. Blooms profusely with 1" yellow-orange flowers resembling marigolds or zinnias, which are borne singly on the end of each stem. Plant creeps and roots at nodes, making a dense ground cover. West Indies, Hawaii, south Florida, Central America, West Africa, especially at low elevations. Excellent ground cover in warm climates. Especially good for soil retention and erosion control. Very attractive because of nearly constant and prolific blooming. It may be mowed to keep low and manicured. The plant has use in traditional medicine: crushed leaves are used as a poultice; tea is given to alleviate symptoms of colds and flu; and it is used to treat hepatitis, infections and to clear the placent after birth. Abortion, fever, sores, colds Used for reproductive problems, amenorrhea, dysmenorrhea. In South America, used to treat symptoms of colds and flu; for fevers and inflammations²⁹.

Main bioactive sesquiterpene lactones, trilobolid-6-O-isobutyrates A and B. From the flower, the structure of trilobolide-6-O-isobytyrate shows a eudesmanolide sesquiterpene skeleton ³⁰. Leaves and stems contains the diterpene (kaurenoic acid), eudesmanolide lactones and luteolin. The structure of trilobolide-6-O-isobutyrate, C₂₃H₃₂O₉, isolated from the flower of Wedelia trilobata, shows an eudesmanolide sesquiterpene skeleton constructed from the fusion of two cyclohexane rings and a lactone ring ^[31]. Two new sesquiterpene lactones, wedelolides A and B, were isolated by bioassay-guided fractionation from the leaves of Wedelia trilobata, together with known trilobolides 6-O-isobutyrate and 6-O-methacrylate.

An investigation of four herbal drugs, including Sphagneticola trilobata, on the anti-inflammatory activity of Central American plants used in traditional medicine, showed all the extracts reduced croton oil-induced ear dermatitis. Results suggest the lipophilic extracts to be potential sources of antiinflammatory activity. A study of the n-hexane extract of Wedelia trilobata showed antibacterial activity against Bacilus subtilis, Mycobacterium smegmatis, Pseudomonas aeruginosa, Salmonella group C, S paratyphi and Shigella sonnei. Study in mice on the analgesic activity of the ethanol extracts of W trilobata, W bilofra and E alba showed dose-dependent blocking of writhing response.^32-34. Wedelia trilobata has been historically used for amenorrhea in Trinidad³⁵. Kaurenoic acid and luteolin in Wedelia paludosa showed antinociceptive action more potent than the standard analgesic drugs (acetyl salicylic acid, acetaminophen, dipyrone and indomethacin). Wedelia paludosa and Wedelia trilobata contain the diterpene (kaurenoic acid), eudesmanolide lactones and luteolin (in leaves and stems). Kaurenoic acid has antibacterial, larvicidal and tripanocidal activity; it is also a potent stimulator of uterine contractions. Luteolin exerts antitumoural, mutagenic and antioxidant effects, has depressant action on smooth muscles and a stimulant action on isolated guinea pig heart³⁶.

A biological screening of activity against Gram-positive and Gram-negative bacteria, yeasts, and fungi of crude extracts from Wedelia trilobata is reported. The n-hexane extract showed antibacterial activity against Bacillus subtilis, Mycobacterium smegmatis, Staphylococcus aureus, and Staphylococcus epidermidis (Gram-positive bacteria); along with Proteus vulgaris, Pseudomonas aeruginosa, Salmonella group C, Salmonella paratyphi, and Shigella sonnei (Gram-negative bacteria). The ethyl acetate extract was active only against Salmonella group C; and the aqueous extract was inactive against the tested bacteria. None of the tested extracts showed biological activity against the yeasts (Candida albicans, Candida tropicalis, Rhodotorula rubra) or the fungi (Aspergillus flavus, Aspergillus niger, Mucor sp., Trichophyton rubrum)³⁷.

The liver plays an astonishing array of vital functions in the maintenance, performance and regulating homeostasis of the body. It is involved with almost all the biochemical pathways to growth, fight against disease, nutrient supply, energy provision and reproduction³⁸. Some of these major functions include carbohydrate, protein and fat metabolism, detoxification and secretion of bile. Therefore, the maintenance of a healthy liver is vital to overall health and well being. Unfortunately, the liver is often abused by environmental toxins, poor eating habits, alcohol and prescription and over-the-counter drug use, which can damage and weaken the liver and eventually lead to hepatitis, cirrhosis and alcoholic liver disease ^[39]. Conventional medicine is now pursuing the use of natural products such as herbs to provide the support that the liver needs on a daily basis⁴⁰. Many Ayurvedic herbs, such as Wedelia calendulacea have a long history of traditional use in revitalizing the liver and treating liver dysfunction and disease ⁴¹.

Wedelia trilobata contain the diterpene (kaurenoic acid), eudesmanolide lactones and luteolin with a variety of biological activities

3. Wedelia biflora:

This plant is a climbing, somewhat rough, herbaceous vine. The leaves are opposite, ovate, and 6 to 8 centimeters long, with pointed tip and rounded base, rather coarsely toothed margins, and stalks 2 to 6 centimeters long. The heads are 3 centimeters in diameter or less, and number 1 to 3, sometimes more, in the upper axils, with stalks 7 to 10 centimeters long. The involucral bracts are narrowly oblong, somewhat recurved, hairy, and equalling or exceeding the disk. The ray flowers are 6 to 15, the ligule being oblong, yellow, 3-toothed, and 6 to 12 millimeters long. The disk flowers are numerous, yellow, or yellowish-brown.

According to Ridley the leaves are used for dressing ulcers; the juice of the leaves is given internally with cow’s milk, after childbirth, as a tonic. Dalgado, states that the leaves, with ginger, are prescribed for flatulence. Burkill says that the same preparation is used for venereal diseases in Singapore. A decoction of the leaves is recommended as an antiperiodic in malaria and in haematuria. The flowers are said to be a violent purgative. Burkill quotes Rumpf, who says that the roots are used to check vaginal discharges. He also inform us, on the authority of Sir Arthur Keith, that the plant is used in Lower Thailand for headache and fever.

Decoction of roots is slightly purgative, Used with Blumea balsamifera for baths. Leaves in decoction are antiscabious, Decoction of roots and leaves for stomach aches and fevers. Leaves used for cleaning and dressing ulcers, Juice of leaves, with cow's milk, taken as tonic after childbirth. Decoction of leaves with ginger for flatulence, Flowers are known to be a violent , purgative.

Four compounds, veratrylidenehydrazide, 3,3′-di-O-methylquercetin, 2,7-dihydroxy-3(3t'-methoxy-4′- hydroxy)-5-methoxyisoflavone and 3′,7-di-O-methylquercetin were isolated from the methylene chloride extract of dried leaves of Wedelia biflora. The structures were elucidated from spectroscopic evidence. The third compound possessed antifungal and boll weevil antifeedant activity while the fourth showed antifungal activity.

Cotton boll weevil antifeedant activity and antifungal activity (Rhizoctonia solani and Pythium ultimum) of extracts of the stems of Wedelia biflora: Extracts showed antifeedant activity which led to an investigation of antifungal properties. Comparative study on analgesic activity of ethanol extracts of Wedelia biflora, W trilobata and E alba showed significant antinociceptive activity in a dose-dependent manner in mice comparable with standard drugs such as aspirin. Phytochemical screening yielded alkaloids, steroids, sugars, tannins, terpenes, proteins, carbohydrates, coumarins, anthraquinone, glucosides and cardiac glycosides.

Helminthic parasites infesting man belongs to varied zoological species. In man they may be located in intestinal tract or other tissues. There are three categories of worm. The worms are responsible for malnutrition, anaemia, and ill health of the host^42,43

The alcoholic and aqueous extracts of roots of Wedelia biflora (Linn) D.C were screened for anthelmintic and antimicrobial activities. The anthelmintic activity was investigated against adult Indian earthworm, Pheretima posthuma, using Piperazine citrate as a reference standard. Both the extracts exhibited significant anthelmintic activity at higher concentration of 100mg/ml and moreover the ethanolic extract was found to be more potent than the reference control piperazine citrate.

The results of Antimicrobial activity revealed that the ethanolic extract exhibited maximum activity against the tested organisms when compared to aqueous extract. Comparative study on analgesic activity was carried using ethanol extracts in animal models. Wedelia trilobata (EEWT), Wedelia biflora (EEWB) and Eclipta alba (EEEA) was evaluated by acetic acid induced writhing method and hot plate assay to assess analgesic activity in mice. It was found that the extract caused an inhibition on the writhing response induced by acetic acid in a dose dependent manner. Dose of 500 mg/kg EEWT, EEWB, EEEA and Aspirin could block the writhing response by 49.17 %, 49.45, %, 55.23 % and 68.68 %( p<0.001) respectively. It was also indicated that the EEEA showed significant antinociceptive action in hot plate reaction time method in mice. This effect was comparable to that of standard drug morphine treated controls. The results reflects that analgesic effects and therapeutic efficacy of the extract on animal models which are comparable with those of standard drugs such as Aspirin and Morphine⁴⁴.

CONCLUSION:

The above collected information regarding the use of genus Wedelia in world is matched with available literature. Recent years, ethno-botanical and traditional uses of natural compounds, especially of plant origin received much attention as they are well tested for their efficacy and generally believed to be safe for human use. It is best classical approach in the search of new molecules for management of various diseases. Thorough screening of literature available on genus Wedelia depicted the fact that it is a popular remedy among the various ethnic groups, Ayurvedic and traditional practitioners for treatment of ailments. Researchers are exploring the therapeutic potential of this plant as it has more therapeutic properties which are not known.

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Received on 03.02.2011 Accepted on 21.02.2011

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