INTRODUCTION:

It is been recorded in history that Medicinal herbs have been used as form of therapy for the relief of pain. The exploration of the chemical constituents from plants, pharmacological and phytochemical screening would provide the basis for developing the new lead molecules in strategic favour of natural product drug discovery. The aim and subject of many researchers is the discovery and development of isolating a new efficient, active and less toxic molecule for systemic activities. The biologically active agents from natural sources have always been of great interest to working on various diseases ¹.

Received on 16.03.2015 Modified on 25.03.2015

Research J. Pharm. and Tech. 8(4): April, 2015; Page 496-502

DOI: 10.5958/0974-360X.2015.00083.9

The traditional knowledge of these herbal recipes is popular among the indigenous and local communities. Even today the Tribal communities are solely dependent on plants for their medication; hence they are using them against different. They have preserved the wealth of traditional knowledge as a part of their belief and customs. They are practicing these methods generation after generation successfully. Apart from medicinal uses phytochemical components which are environment friendly, economical and effectively shows anti corrosive properties^2,3 and also phyto-compounds are used as biofuels^4-6.

Boerhaavia diffusa has long history of uses in different traditional medicine system. It is an effective natural remedy, specially for the liver and kidneys. Seveal research groups studying various biological activities of Boerhaavia diffusa have shown the safety of the plant.

Boerhaavia diffusa L. (Nyctaginaceae), figure-1 commonly known as 'Punarnava' in the Indian system of medicine, is a perennial creeping herb found throughout the waste land of India. The roots are reputed to be diuretic and laxative and are given for the treatment of anasarca, ascites and jaundice ⁷. The Boerhaavia sp. has ancient medicinal use in different societies from the times of the B.C. The herbal medicine has evolved and changed through the years. A number of plant products have been identified through phyto-chemistry and the extract of their different plant parts are useful in various diseases without side effects⁸.

Pharmacognosy:

Scientific Name: Boerhaavia diffusa Linn. Syn. B. repens; B. repens Family: Nyctaginaceae, Family Name: Hog weed, Horse Purslane, Common Indian Names Gujarati: Dholia-saturdo, Moto-satoda, Hindi: Snathikari Kannada: Kommegida Marathi: Tambadivasu Sanskrit: Punarnava, Raktakanda, Shothaghni,Varshabhu Bengali: Punurnava Tamil: Mukaratee-Kirei Telugu: Punernava, Habitat: Grows as common weed, useful Parts: Root, leaves and seeds ⁹.

(Root of B.diffusa)

(Leaves of B.diffusa)

Geographical Distribution and Habitat:

Genus Boerhaavia, consisting of 40 species is distributed in tropical and sub- tropical regions and warm climate. It is found in Ceylon, Australia, Sudan and Malay Peninsula, extending to China, Africa, America and Islands of the Pacific. Among 40 species of Boerhaavia, 6 species are found in India, namely B. diffusa, B. erecta, B. rependa, B. chinensis, B. hirsute and B. rubicunda. Boerhaavia diffusa in India is found in warmer parts of the country and throughout up to 2,000 m altitude in the Himalayan region. It is a perennial, spreading hogweed, commonly occurring abundantly in waste places, ditches and marshy places during rains. The plant is also cultivated to some extent in West Bengal.

Phytochemistry:

The Boerhaavia diffusa plant contains a large number of such compounds as flavonoids, alkaloids, steroids, triterpenoids, lipids, lignins, carbohydrates, proteins, and glycoproteins. Punarnavine C₁₇H₂₂N₂O m.p. 236–237°C 12,13. Boeravinone A-F14, 15, hypoxanthine 9-Larabinofuranoside, ursolic acid, punarnavoside, lirodendrin, and a glycoprotein having a molecular weight of 16– 20 kDa have been isolated and studied in detail for their biological activity. Punarnava also contains arachidic acid, β-Sitosterol, α-2-sitosterol, palmitic acid, ester of β-sitosterol, tetracosanoic, hexacosonoic, stearic, urosilic acid, Hentriacontane, β-Ecdysone, triacontanol etc. Phytochemical screening of the roots from garden-grown in vivo plants of B. diffusa of different ages revealed that the maximum alkaloid content (2%) accumulated in the roots of 3- year old mature plants. The herb and roots are rich in proteins and fats. The herb contains 15 amino acids, including 6 essential amino acids, while the root contains 14 amino acids, including 7 essential amino acids. Plant contained large quantities of potassium nitrate, besides punarnavine ¹⁰. Previous studies reported the presence of flavonoids, alkaloids, steroids, triterpenoids, lipids, lignins, carbohydrates, proteins and glycoproteins in B. diffusa^11-13. It contains about 0.04 % of alkaloids known as punarnavine and punernavoside, an antifibrinolytic agent. It also contains about 6 % of potassium nitrate, an oily substance, and ursolic acid¹⁴.The seeds of this plant contain fatty acids and allantoin and the roots contain alkaloids ¹⁵.The green stalk of the plant has also been reported to contain boerhavin and boerhaavic acid¹⁶.

Pharmacological and Biological Activity:

Antioxidant Activity:

The evaluation of the antioxidant potential of ethanolic extract of Andrographis echioides and Boerhaavia diffusa was carried out by determining the levels of enzymatic and non-enzymatic antioxidants. The results showed that both the plant extracts possessed significant levels of enzymatic and non-enzymatic antioxidants. The results of the enzymatic and non-enzymatic antioxidants in Andrographis echioides and Boerhaavia diffusa exhibits that they possess preventive and productive role to maintain the cell survival, cellular interaction and maintenance of cell membrane architecture. Andrographis echioides and Boerhaavia diffusa have effective and therapeutic antioxidant potential against various inflammatory diseases¹⁷.

The study was undertaken to evaluate antioxidant activity of Chloroform, Ethanol, and Ethyl acetate fraction of Boerhaavia diffusa L. roots which might have improved its hepatoprotective action. Invitro nitric oxide scavenging activity, the percentage inhibition was 71.35%, 33.74%, 23.85% in ethanol, chloroform and ethyl acetate extracts at 250mcg/ml when compared with Curcumin at 62 mcg/ml showed only 84.7% inhibition respectively. The ethanol extract and ethyl acetate showed a biphasic response whereas the chloroform extract showed a dose dependent increase. In DPPH radial scavenging activity, the ethanol extract showed 81.94% inhibition and the chloroform extract showed 42.58% inhibition at 1000mcg/ml compared with 88.02 % inhibition by Quercetin. The above results suggest that roots of Boerhaavia diffusa were found to reveal antioxidant potential which supports the use of this plant in traditional medicine.¹⁸

Antidiabetic Activity:

The study indicates that Boerhaavia diffusa and ethanolic extracts exhibit significant anti- hyperglycemic activities in alloxan induced as well as streptazotocin induced hyperglycemic rats. They can also improve the condition of diabetes as indicated by parameters like body weight along with serum cholesterol and triglyceride levels. The number of functionally intact β-cells in the islet organ is of decisive importance for the development course and outcome of diabetes. The renewal of β-cells in diabetes has been studied in several animal models. The total β-cell mass reflects the balance between the renewal and loss of these cells. It was also suggested that regeneration of islet β-cells following destruction by alloxan may be the primary cause of the recovery of alloxan-injected guinea pigs from the effects of the drug. In alloxan-induced diabetes, (-)Epicatechin and Vinca rosea extracts has also been shown to act by β- cells regeneration. Similar effects in streptozotocin-treated diabetic animals were reported by pancreas tonic, ephedrine, and Gymnema sylvestre leaf extracts. In the current studies, the damage of pancreas in streptazotoc in treated diabetic control rats and regeneration of β- cells by glibenclamide was observed. The comparable regeneration was also shown by methanolic extracts of Boerhaavia diffusa¹⁹.

A study was carried out to investigate the effects of daily oral administration of aqueous solution of Boerhaavia diffusa L. leaf extract (BLEt) (200 mg/kg) for 4 weeks on blood glucose concentration and hepatic enzymes in normal and alloxan induced diabetic rats. A significant decrease in blood glucose and significant increase in plasma insulin levels were observed in normal and diabetic rats treated with BLEt ^[20].

Antibacterial Activity:

A Potent antibacterial activity against gram positive and gram negative bacteria shown by the leaves of B. diffusa might be due to the phytochemicals present in the leaves. Ethanol extract showed inhibitory an effect on grampositive bacteria like S. aureus, B. subtilis, S. faecalis, M. luteus and all gram-negative bacteria selected for the present study. Methanol extract showed inhibitory effect against all gram-positive bacteria selected for the present study except M. luteus and gram-negative bacteria like K. pneumoniae, P. vulgaris, S. marcescens and S. flexneri²¹ .

The aqueous and ethanolic extracts of B. diffusa leaves had activity on E. coli, S. aureus and P. aeruginosa. This activity occurred at varying concentrations, indicating that the plant extracts contained active principle with broad antibacterial spectrum. E. coli displayed the highest susceptibility in ethanolic extract, followed by S. aureus and the least susceptible was P. aeruginosa. In aqueous extract, P. aeruginosa showed the highest susceptibility, followed by S. aureus and E. coli exhibited the least susceptibility. The antimicrobial activity of the different extracts increased with increase in concentration. The results of the investigations support the ethnomedicinal use of this plant by local practitioners. Results from this study showed that the aqueous and ethanolic extracts of B. diffusa had antibacterial activity on E. coli, S. aureus and P. aeruginosa.

Antiviral Activity:

Boerhaavia diffusa has many ethno- botanical uses (the leaves are used as vegetable; the root juice is used to cure asthma, urinary disorders, leucorrhoea, rheumatism, and encephalitis), and is medicinally used in the traditional, Ayurvedic system. Besides, the Boerhaavia diffusa plant is reported to possess many pharmacological, clinical, and antimicrobial properties. Recently, the authors observed potent antiviral efficacy of this plant against phyto- pathogenic viruses. The antiviral agent isolated from this plant was found to be a glycoprotein with a molecular weight of 16– 20 kDa. Administered by foliar spraying in the field, this antiviral agent could protect some economically important crops against natural infection by plant viruses.

The aqueous extracts of plant material were prepared and tested in vitro as well as in vivo against phytopathogenic viruses on their hypersensitive and systemic hosts. The botanical identity of each plant was established before the extracts were prepared. of the large number of plants screened, Boerhaavia diffusa root extracts were found to have a broad spectrum and very high antiviral activity. The aqueous extracts of plant material were prepared and tested in vitro as well as in vivo against phyto-pathogenic viruses on their hypersensitive and systemic hosts. The botanical identity of each plant was established before the extracts were prepared. The large number of plants screened, Boerhaavia diffusa root extracts were found to have a broad spectrum and very high antiviral activity²².

Antistress / Adaptogenic / Immunomodulatory Activity: Hydroethanolic extract (80%) of Boerhaavia diffusa (HEBD) and a polyherbal formulation (Punarnava mandur) PHF-09 containing Boerhaavia diffusa were compared for their antistress activity using cold restraint stress model. Stress was induced by subjecting animals to cold restraint. Due to cold restraint stress there was an imbalance in the levels of biochemical parameters like glucose, triglycerides, cholesterol, SGOT, SGPT which were near normalized following the administration of HEBD and PHF-09. HEBD and PHF-09 were found to have comparable anti-stress activity²³.

The ethanol extracts of roots of B. diffusa was evaluated for antistress, adoptogenic activity in albino mice, by swim endurance test and cold restrains stress and the extract showed improved stress tolerance in immunomodulatory activity was shown by increased carbon clearance, indicating stimulation of the reticuloendothelial system. There was an increase in DTH response to SRBC in mice, corresponding to cell mediated immunity and indicating stimulatory effects on lymphocytes and accessory cell types²⁴.

Adaptogens is useful in both adrenal hyperstress as well as adrenal hypofatigue. By definition, an adaptogen implies the capability for bi directional or normalizing effects. The most important adaptogens for the adrenals include Panax Ginseng, Siberian Ginseng, Ashwagandha, Rhodiolia, Boerhaavia diffusa, and Holybasil Leaf Extract. Boerhaavia diffusa (Punarnava) has the ability to support both adrenal over and under activation. In stressful conditions it has demonstrated the ability to buffer the elevations of serum cortisol and prevent the suppression of the immune system that takes place with elevated cortisol. On the other hand, Boerhaavia diffusa has also demonstrated the ability to improve cortisol levels with end stage adrenal exhaustion ²⁵.

Hepatoprotective Activity:

The hepatoprotective activity of roots of different diameters were collected in three seasons, rainy, summer and winter, and examined in thioacetamide intoxicated rats. The results showed that an aqueous extract (2 ml/kg) of roots of diameter 1-3 cm, collected in the month of May (summer), exhibited marked protection of a majority of serum parameters, i.e., GOT, GPT, ACP and ALP, but not GLDH and bilirubin, thereby suggesting the proper size and time of collection of B. diffusa L. roots for the most desirable results. Further, the studies also proved that the aqueous form of drug (2 ml/kg) administration has more hepatoprotective activity than the powder form; this is probably due to the better absorption of the liquid form through the intestinal tract. The hepatoprotective activity of Boerhaavia diffusa L. roots showed marked protection of serum parameters in thioacetamide toxicity in rats. Furthermore, the aqueous extract of thin roots collected in the summer has more activity suggesting the proper time and type of root collection for the most desirable result. The investigation also validates the use of B. diffusa L. roots in hepatic ailments by the several tribes in India²⁶.

An alcoholic extract of whole plant Boerhaavia diffusa given orally exhibited hepatoprotective activity against experimentally induced carbon tetrachloride hepatotoxicity in rats and mice. The extract also produced an increase in normal bile flow in rats suggesting a strong choleretic activity. The extract does not show any signs of toxicity up to an oral dose of 2 g/kg in mice²⁷.

Analgesic/Anti-Inflammatory Activity:

The Decoction (DE) or Juice (JE) of the leaves of Boerhaavia diffusa were used to study the antinociceptive effect in chemical (acetic acid) and thermal (hot Plate) models of hyperalgesia in Mice. The DE, raised the pain thresholds during the first period (30 min) of observation. In the acetic acid-induced abdominal writhing in mice, pre-treatment of the animals with naloxone (5 g/kg, i.p.) significantly reversed the analgesic effect of morphine and JE but not that of DE. The study proves that the active antinociceptive principle of B. diffusa is present mainly in the juice of fresh leaves and has a significant antinociceptive effect when assessed in these pain models²⁸.

Ethanol extract of leaves at dose of 400mg/kg exhibited maximum anti-inflammatory effect with 30.4, 32.2, 33.9 and 32% with carrageenin, serotonin, histamine and dextran induced rat paw edema models, respectively. Ethanol extract of stem bark also exhibited COX-1 and IC50 value of 100ng/ml proving the drug use in the treatment of inflammatory condition. Anti-inflammatory activity was assessed using extract of latex of plant by using a carragenan induced inflammatory model²⁹.

Antitumor Activity:

Cancer chemo preventive property of B. diffusa was evaluated on 7,12-dimethyl benz(a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice (6-7 weeks old). The cancer chemopreventive efficacy was assessed by its ability to modulate the activities of enzymes associated with drug metabolism and bifunctional modulators reduced the availability of ultimate carcinogen metabolites in the epithelial stage. A significant increase in the activities of hepatic phase I, phase II system enzymes and antioxidant enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and glutathione level) were observed when mice were fed by oral gavage with Boerhaavia diffusa extract at a dose level of 125 mg and 250 mg/kg body weight for a period of 14 days in our laboratory. This lead to an assumption that the inhibition of tumorigenesis by the plant extract might have been executed either by preventing the formation of active carcinogens from their precursors or by augmenting detoxification process, preventing promotional events in the mouse skin through free radical scavenging mechanism ³⁰.

Anti-Convulsant Activity:

The study was carrired out to investigate the methanolic root extract of B. diffusa and its different fractions including liriodendrin-rich fraction for exploring the possible role of liriodendrin in its anti-convulsant activity. Air-dried roots of B. diffusa were extracted with methanol by cold maceration. The methanol soluble fraction of extract thus obtained was successively extracted to obtain liriodendrin rich fraction and two side fractions, that is, chloroform fraction and phenolic compound fraction. Anti-convulsant activity of methanolic extract and its different fractions, that is, liriodendrin-rich fraction and phenolic compound fraction were studied in pentylenetetrazol (PTZ)- induced seizures. The crude methanolic extract of B. diffusa and only its liriodendrin-rich fraction showed a dose-dependent protection against PTZ-induced convulsions. The liriodendrin- rich fraction showed significant protection against seizures induced by BAY k-8644. These findings reiterated the anti-convulsant activity of methanolic extract of B. diffusa roots and also it can be concluded that the observed anticonvulsant activity was due to its calcium channel antagonistic action as this activity was retained only in the liodendrin-rich fraction, which has additionally been confirmed by significant anti- convulsant activity of liriodendrin-rich fraction in BAY k-8644- induced seizures³¹.

Study showed the crude methanolic extract of B. diffusa and its liriodendrin-rich fraction showed a dose-dependent protection against PTZ-induced convulsions ³².

Antiproliferative and Antiestrogenic Activity:

Antiproliferative and antiestrogenic properties of methanol extract of Boerhaavia diffusa (BME) in MCF-7 breast cancer cell lines.

Boerhaavia diffusa extracts exhibited a strong inhibitory effect on the proliferation of human breast cancer cells in vitro and the antiestrogenic effects are mediated by ER. Phytochemical studies have revealed the presence of alkaloids, flavonoids, phenols and saponins in BME. The antiestrogenic activity shown by the extract may be attributed to these diverse compounds³³.

Cytological Activity:

The extract of B. diffusa exhibited a strong depressive effect on the mitosis of C. jagus roots. The study was conducted using B. diffusa extract, the mitotic index of the control experiment was found to be 5.27. There was a negative correlation between the concentrations of the treatment extracts and the mitotic indices obtained from their action. This points to an inhibition of mitosis by this extract. Inhibition of the mitotic index increased significantly with an increase in the concentration of treatment solution of B. diffusa. This again shows a very negative correlation between the concentration of the extract and the mitotic indices produced by the observed action. Owing to the ability of the root extracts of B. diffusa to accumulate metaphase and hence inhibit mitosis, it is possible to use these extracts as an alternative to the rather expensive colchicine for cytological studies³⁴.

Bronchial Asthma:

Dried leaves of Punerneva can be used in dhoomapana in treatment of bronchial asthma. The leaf decoction is said to be an excellent expectorant when decocted with punarnava (Boerhaavia diffusa) and then combined with ginger juice and black pepper.

Anti Fibrinolytic Activity:

A study evaluated the effect of anti-fibrinolytic agents; α aminocaproic acid (α-ACA), tranexamic acid (AMCA); anti-inflammatory drugs (indomethacin, ibuprofen, naproxen); and plant extract (root extract of Boerhaavia diffusa) on endometrial histology of IUD-fitted menstruating monkeys. It is effective in reducing stromal edema, inflammation, and tortuosity of glands, and in increasing the degree of deposition of fibrin and platelets in the vessel lumen³⁵.

Anti-Arthritic activity:

The extract of the root of the plant Boerhaavia diffusa was studied for their Anti rheumatoid activity in Freunds Adjuvant induced Arthritis rats with the dose of 500 and 1000 mg/kg p.o. The administration of extract reported significant reduction in paw swelling on 4^th,8^th,14^th and 21^st day after sub-plenter administration of complete Freunds adjuvant. The paw swelling was measured as a volume displacement using digital plethysmometer. From the results observed in the investigation, it may be concluded that the extract of Boerhaavia diffusa possesses potentially useful anti-arthritic activity in complete Freunds Adjuvant model³⁶.

Antiurolithic activity:

Evaluated the antiurolithic activity of Boerhaavia diffusa root aqueous extract(BDE) as prophylaxis for renal stones.In vitro calcium oxalate (caOx) crystallization inhibitory effect of BDE was determined by measuring chande in turbidity at 620nm on addition of sodium oxalate in the synthetic urine. In a rat model of urolithiasis, induced by adding 0.75% ethylene glycol(EG) in drinking water and effect of simultaneous treatment of BDE(100-200mg/kg) was observed for 28 days.BDE inhibited CaOx nucleation, aggregation and crystal formation in the synthetic urine in vitro on addition of NaOx. The litogenic treatment caused polyuria, weight loss, hyperoxaluria and impairment of renal function which was prevented by BDE. Hyperoxaluria and CaOx crystal deposition in the renal tubules caused by EG intake was prevented by BDE treatment. The study indicates that the antiurolithic activity of Boerhaavia diffusa extract possibly mediated through inhibition of CaOx crystallization, diuresis and hypo-oxaluria may justify its prophylactic use in urolithiasis³⁷.

CONCLUSION:

From the above review we can conclude that the plant Boerhaavia diffusa which is having a wide range of medicinal value due to their variety of chemical constituents can be further investigated on toxicological and other parameters to obtain a valuable marketed products. Apart from the chemical constituents, Boerhaavia diffusa having a various pharmacological activities.

REFERENCES

1. Rajavel R., Mallika P, Rajesh V., Pavan Kumar K., Krishna Moorthy S. and Sivakumar T., Antinociceptive and Anti-inflammatory Effects of the Methanolic extract of Oscillatoria annae, Res. J. Chem. Sci., 2(7); 2012: 53-6.

2. Sulaiman S, Nor-Anuar A, Abd-Razak A.S. and Chelliapan S., A Study of Using Allium cepa (Onion) as Natural Corrosion Inhibitor in Industrial Chill Wastewater System, Res. J. Chem. Sci., 2(5);2012: 10-16.

3. Nutan Kumpawat, Alok Chaturvedi and R.K. Upadhyay., Corrosion Inhibition of Mild Steel by Alkaloid Extract of Ocimum sanctum in HCl and HNO₃ Solution., Res. J. Chem. Sci., 2(5); 2012: 51-56.

4. Bobade S.N. and Khyade V.B., Preparation of Methyl Ester (Biodiesel) from Karanja (Pongamia pinnata) Oil., Res. J. Chem. Sci., 2(8); 2012: 43-50.

5. Deshpande D.P, Urunkar Y.D. and Thakare P.D., Production of Biodiesel from Castor Oil using acid and Base catalysts., Res. J. Chem. Sci., 2(8); 2012: 51-56.

6. Mishra S.R, Mohanty M.K, Das S.P. and Pattanaik A.K., Production of Bio-diesel (Methyl Ester) from Simarouba glauca Oil., Res. J. Chem. Sci., 2(5); 2012: 66-71.

7. Rawat AKS, Mehrotra S, Tripathi SC and Shome U., Hepatoprotective activity of Boerhaavia diffusa L. roots a popular Indian ethnomedicine., Journal of Ethnopharmacology, 56; 1997: 61-66.

8. Ahmad Najam, Akhilesh K. Singh and Verma H.N, Ancient and modern medicinal potential of Boerhaavia diffusa and Clerodendrum aculeatum. Research in Environment and Life Sciences, 1(1); 2008: 1-4.

9. Pankaj Oudhia., Traditional medicinal knowledge about useful herb Punarnava (Boerhaavia diffusa, family Nyctaginaceae) in Chhattisgarh Plains, India, Available at: http://botanical.com/site/column_poudhia/138_punarnava. html (2011)

10. Chopra R.N., Ghosh S., Dey P. and Ghosh B.N., Pharmacology and therapeutics of Boerhaavia diffusa (Punarnava), Indian Medical Gazette . 68; 1923: 203-08.

11. Agarwal R.R., Dutt S.S., Chemical examination of punarnava or Boerhaavia diffusa Linn, Isolation of an alkaloid punarnavine, Chem Abstr,30(2);1936:3585.

12. Basu N.K., Lal S.B., Sharma S.N., Investigations on Indian medicinal plants, Q J Pharmacology,20;1947:38-42.

13. Surange S.R. and Pendse G.S., Pharmacognostic study of roots of Boerhaavia diffusa Wild. (Punarnava). J Res Indian Med, 7; 1972:1.

14. Kokate C.K., Purohit A.P. and Gokhale S.B., Pharmacognosy. Edn 38, Nirali Prakashan, Pune, 2005:537-538.

15. Aslam M., Asian Medicine and its practice in Britain. In: Evans, W.C. (Ed.), Pharmacognosy, Saunders Company Ltd, London., 1996:499–500.

16. Liogier A., Plants Medicinal de Puerto Rico y del Caribe, Iberoamerican de Ediciones Inc (1990 )

17. Premkumar P., Priya J. and Suriyavathana M., Evaluation of Antioxidant Potential of Andrographis echioides and Boerhaavia diffusa, International Journal of Current Research , 3; 2010:59-62.

18. Gopal T.K., Harish G., Chamundeeswari D. and Umamaheswara Reddy C., In -vitro Anti-Oxidant Activity of Roots of Boerhaavia diffusa Linn. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 1(4); 2010: 782-788.

19. Bhatia V., Kinja K. and Bishnoi H., Antidiabetic Activity of the Alcoholic Extract of the Arial Part of Boerhaavia diffusa in Rats. In and Gnaneshwari D editors. Recent Research in Science and Technology, 3(7); 2001: 04-07.

20. Pari L. and Satheesh M.A., Antidiabetic activity of Boerhaavia diffusa L.: Effect on Hepatic key Enzymes in Experimental Diabetes, Journal of Ethnopharmacology, 91; 2004:109–113.

21. Sharma M., Vohra S., Arnason J.T. and Hudson J.B., Echinacea extracts contain significant and selective activities against human pathogenic bacteria, Pharm. Bio. 46; 2008: 111-116.

22. Awasthi L.P. and Verma H.N., Boerhaavia diffusa – A Wild Herb with Potent Biological and Antimicrobial Properties Cold Restraint Stress model, Asian Agri- History, 10(1); 2006: 55-68.

23. Akinnibosun F.I., Akinnibosun H.A., and Ogedegbe D., Investigation On the Antibacterial Activity Of The Aqueous And Ethanolic Extracts Of the Leaves Of Boerhavia diffusa L, Science World Journal., 4(2);2009: 25-28.

24. Meera Sumanth, Mustafa S.S., Anistress, Adoptogenic and Immunopotentiating Activity of Roots of Boerhaavia diffusa in Mice, International Journal of Pharmacology, 3(5); 2007: 416-420.

25. Mungantiwar A.A., Nair A.M., Shinde U.A. and Saraf M.N., Effect of stress on plasma and adrenal cortisol levels and immune responsiveness in rats: modulation by alkaoidal fraction of Boerhaavia diffusa, Fitoterapia ,6;1997: 498-500.

26. Rawat A.K.S., Mehrotra S., Tripathi S.C. and Shome U., Hepatoprotective activity of Boerhaavia diffusa L. roots a popular Indian ethnomedicine, Journal of Ethnopharmacology,56; 1997: 61-66.

27. Chandan B.K., Sharma A.K. and Anand K.K., Boerhaavia diffusa - A Study of its Hepatoprotective activity, Journal of Ethnopharmacology,31;1991: 299-307.

28. Hiruma Lima C.A., Gracioso J.S., Bighetti E.J.B., Germonse´n Robineou L. and Souza Brito A.R.M., The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in mice, Journal of Ethnopharmacology,2000: 267-274.

29. Krishna Murthi, Mayank AP and Vijay Lambole. Pharmacological properties of Boerhaavia diffusa-A Review, In editor, Indian Journal of Experimental Biology,5(2);2010:107-110.

30. Rupjyoti Bharali, Mohammed R.H. Azad and Jawahira Tabassum, Chemopreventive Action of Boerhaavia diffusa On DMBA-Induced Skin Carcinogenesis in Mice. Indian J Physiol Pharmacol, 47(4); 2003: 459-464.

31. Mandeep Kaur and Rajesh Kumar Goel, Anti-Convulsant Activity of Boerhaavia diffusa: Plausible Role of Calcium Channel Antagonism. Evidence-Based Complementary and Alternative Medicine, 4; 2011: 1-7.

32. Adesina S.K., Anticonvulsant properties of the roots of Boerhaavia diffusa. Quarterly Journal of Crude Drug Research, 17; 1979: 84-86.

33. Sreeja S. and Sreeja S., An in vitro study on antiproliferative and antiestrogenic effects of Boerhaavia diffusa L. extracts, Journal of Ethnopharmacology,126; 1923: 221-225.

34. Ndubuisi Moses Chikere Nwakanma, Bosa Ebenezer Okoli, Cytological effects of the root extracts of Boerhaavia diffusa on root tips of Crinum jagus, European Asian Journal of BioSciences, 4; 2010: 105-111.

35. Sasi kala M., Vijay S.K., Gauthaman K., Relevance of the use of Alternative Medicine for Bronchial Asthma: A review, J young pharm,1(2); 2009: 184-189.

36. Barthwal M. and Srivastava K., Histological studies on endometrium of menstruating monkeys wearing IUDs: comparative evaluation of drugs, Advances in contraception, 6; 1990:113-124.

37. Premkumar P., Priya J. and Suriyavathana M., Evaluation of Antioxidant Potential of Andrographis Echioides and Boerhaavia diffusa, International Journal of Current Research,3;2010: 59-62.