TITLE OF THE TOPIC:
PRECLINICAL INVESTIGATION OF TRICHOSANTHES LOBATA ROXB. EXTRACTS FOR HEPATOPROTECTIVE AND ANTIOXIDANT ACTIVITY IN ALBINO RATS
6.
BRIEF RESUME OF THE INTENDED WORK: 6.1 Need for the study: Liver is an organ of paramount importance, which plays an essential role in metabolism of foreign compound entering into the body. Human beings are exposed to these compounds through environmental exposure, consumption of contaminated food or during exposure to the chemical substances in the occupational environment. In addition human being consumes a lot of synthetic drugs during disease condition which are alien to the body organs. All the compounds produce a variety of toxic manifestation1. Conventional drugs used in treatment of liver diseases are often inadequate. It is therefore necessary to search for alternative drugs for the treatment of liver disease to replace the currently used drugs of doubtful efficacy and safety.
Liver diseases are a serious health problem. In the absence of reliable liver protective drug in allopathic medical practices, herbs play an important role in management of various liver disorders like jaundice and liver cirrhosis. Numerous medicinal plants and their formulations are used for liver disorders in ethno-medicinal practices and in traditional system of medicine in India2. Traditional plants like Glycyrrhiza glabra1, Aerva lanata3,Leucas lavendulaefolia4, Phyllanthus amarus5,Nyctanthes arbor-tristis6, Calotropis procera7, Acacia catechu8, Phyllanthus rheedii9, Bacopa monniera10, have already been reported to have hepatoprotective activity. Since, most of the herbal drugs speed up the natural healing process of the liver by their antioxidant and free radical scavenging properties, in this protocol we propose to evaluate the hepatoprotective activity of Trichosantheslobata11by its antioxidant and free radical scavenging properties.
6.2 Review of literature: Literature review suggested that Trichosanthes lobata Roxb.[family: Cucurbitaceae] is a slender, annual, monoecious climber with furrowed stems distributed through out India.
No adequate phytochemical studies has been carried out on the given plant.
According to the uses mentioned in traditional medicine the whole plant can be used for laxative, thermogenic, emollient, depurative, alexeteric, anthelmintic, appetizer, carminative, digestive, cholagogue, stomachic, anodyne, expectorant, cardiotonic, suppurative, vulnerary, anti-inflammatory, antipyretic and tonic. It is also used in case of vitiated condition of tridosa, leprosy12, leucoderma, pruritus, anorexia, dyspepsia, flatulence, colic dipsia, hyperacidity, helminthiasis, hepatopathy and jaundice11.
Since after through literature search no data regarding the hepatoprotective activity of the given plant is available. We therefore have taken this project with the following objectives.
6.3 Objective of the study:
To carry out acute toxicity study of Trichosanthes lobata by staircase method in mice13.
To investigate the dose dependant hepatoprotective activity of different extracts (aqueous and alcoholic) of Trichosanthes lobata in CCl4 and D-galactosamine induced hepatotoxicity model in rats.
To carry out histopathological investigation of the rat liver tissue.
To evaluate and establish the antioxidant activity of Trichosanthes lobata by In-vivo methods.
7.
MATERIALS AND METHODS : 7.1 Sources and collection of data: Data is generated using laboratory experimental techniques. In-vivo evaluations such as hepatoprotective and antioxidant activities will be carried out on either sex of albino rats. The result and data obtained from present study will be analyzed by statistical methods.
7.2 Pharmacological studies: 1. Hepatoprotective activity
D-galactosamine induced hepatotoxicity4:
Wistar rats either sex, weighing 150-200 g, will be maintained in standard environmental condition and fed with standard laboratory diet and water ad libitum will be used for the experiment. D-galactosamine(800mg/kg, i.p single dose) will be use to induce hepatotoxicity in rats. Different extracts of Trichosanthes lobata will be administered orally for 7 days at different dosage level to study the efficacy against D-galactosamine induced intoxicated rats. SGOT, SGPT, ALP and Total Bilirubin level will be estimated 24 hrs after administration of hepatotoxicity inducing agents. Animals will be sacrificed and liver samples are collected for histopathological investigation.
CCl4 induced peroxidative damage in liver6:
Wistar rats either sex, weighing 150-200 g, will be maintained in standard environmental condition and fed with standard laboratory diet and water ad libitum will be used for the experiment. CCl4 (0.7ml, 3rd, 6th & 10th day) will used to induce hepatotoxicity in rats. Different extracts of Trichosanthes lobata will be administered orally for 10 days at different dosage level to study the efficacy against CCl4 induced peroxidative damage in liver of rats. SGOT, SGPT, ALP and Total Bilirubin level will be estimated.
c) Endogenous antioxidant level will be determined by estimating different parameters (GSH, LPO, SOD etc.) from excised liver homogenate14.
7.3 Does the study require any investigation or intervention to be conducted on patients or other human / animals? If so please describe briefly. The above study requires investigation to be done on mice for toxicity study and on albino rats of wistar strain for determination of hepatoprotective and antioxidant activity. These studies are planned according with the procedure reported in the literature.
7.4 Has ethical clearance been obtained from your institution in case of above 7.3? The copy of the ethical clearance certificate is enclosed.
8.
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Rajesh MG, Latha MS. Protective effect of Glycyrrhiza glabra Linn. On carbon tetrachloride-induced peroxidative damage. Indian J pharmacol 2004;36(5):284-87
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Nevin KG, Vijayammal PL. Effect of Aerva lanata against hepatotoxicity of carbon tetrachloride in rats. Environ toxicology pharmacol 2005;20:471-77
Kotoky J, Dasgupta B, Sarma GK. Protective properties of Leucas lavendulaefolia extracts against D-galactosamine induced hepatotoxicity in rat. Fitoterapia 2008;79:290-92
Pramyothin P et al. Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: In vitro and in vivo studies. J Ethnopharmacol 2007;114:169-73
Hukkeri VI et al. Hepatoprotective activity of the leaves of Nyctanthes arbor-tristis Linn. Indian J Pharm Sci 2006;68(4):542-43
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Naik SR, Panda VS. Hepatoprotective effect of Ginkgoselect Phytosome in rifampicin induced liver injury in rats: Evidence of antioxidant activity. Fitoterapia 2008;79:439-45
Shilova IV et al. Hepatoprotective and Antioxidant Activity of Meadowsweet Extract during Experimental Toxic Hepatitis. Bull Experimental Biol Med 2006;142(8):181-84
Visweswaram D, Rao PR, Satyanarayan S. A Non-Invasivemethod for screening hepatoprotective drugs against carbon tetrachloride induced hepatotoxicity. Indian J Pharmacol 1994;26:301-03
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