RESUMO
Withania somnifera commonly known as Ashwagandha in India is used in many herbal formulations to treat various cardiovascular diseases. The key metabolite of this plant, Withaferin A was analyzed for its molecular mechanism through docking studies on different targets of cardiovascular disease. Six receptor proteins associated with cardiovascular disease were selected and interaction studies were performed with Withaferin A using AutoDock Vina. CORINA was used to model the small molecules and HBAT to compute the hydrogen bonding. Among the six targets, ß1- adrenergic receptors, HMG-CoA and Angiotensinogen-converting enzyme showed significant interaction with Withaferin A. Pharmacophore modeling was done using PharmaGist to understand the pharmacophoric potential of Withaferin A. Clustering of Withaferin A with different existing drug molecules for cardiovascular disease was performed with ChemMine based on structural similarity and physicochemical properties. The ability of natural active component, Withaferin A to interact with different receptors associated with cardiovascular disease was elucidated with various modeling techniques. These studies conclusively revealed Withaferin A as a potent lead compound against multiple targets associated with cardiovascular disease.
Assuntos
Acil Coenzima A/metabolismo , Doenças Cardiovasculares/metabolismo , Simulação de Acoplamento Molecular , Receptores Adrenérgicos beta 1/metabolismo , Withania , Vitanolídeos/farmacologia , Proteína C-Reativa/metabolismo , Ligantes , Receptores de Estrogênio/metabolismo , Xantina Desidrogenase/metabolismoRESUMO
Present study deals with the hepatoprotective activity of polyherbal formulation Hepatoplus (HP) as an oral supplement to the INH and RIF induced hepatitis in experimental rats. Rats treated with INH and RIF show abnormal liver function with significant increase in serum transaminases, bilirubin and clotting time (CT) and significant decrease in total protein and Albumin, which is brings to near normal levels by HP and LIV 52 treatments. Rats treated with INH and RIF suffer from oxidative stress in the hepatocytes, due to the decrease in Glutathione (GSH), Glutathione peroxidase (GPX), Catalase (CAT), Super oxide dismutase (SOD) and significant increase in Lipid Per oxidation (LPO). HP decreases the oxidative stress and protects the liver cells membrane from LPO. 85% of DNA damage (comet tail) seen with RIF and INH treatment is reduced to 34.1% on HP application. A decrease of hepatocytes mitochondrial dehydrogenase activity is observed in INH and RIF treatment is restored by HP supplementation. Hepatic apoptotic and CYP2E1 gene expressions were also studied, BAX, p53, Caspase 3 and CYP2E1 were significantly up regulated and Bcl2 was down- regulated in INH and RIF treated rats. Concomitant application of HP prevents the modulation of these gene expressions. It is concluded that high dose of HP (100mg/kg) supplemented along with INH and RIF effectively prevents the toxicity induced by INH and RIF, as effective as 100mg/kg of LIV52.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , Expressão Gênica/efeitos dos fármacos , Isoniazida/toxicidade , Fígado/efeitos dos fármacos , Preparações de Plantas/farmacologia , Substâncias Protetoras/farmacologia , Rifampina/toxicidade , Animais , Caspase 3/efeitos dos fármacos , Caspase 3/genética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Curcuma , Cycas , Citocromo P-450 CYP2E1/efeitos dos fármacos , Citocromo P-450 CYP2E1/genética , Eclipta , Genes p53/efeitos dos fármacos , Fígado/metabolismo , Ayurveda , Orchidaceae , Phyllanthus , Picrorhiza , Pinus , Pistacia , Ratos , Tephrosia , Withania , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/genéticaRESUMO
Cardiovascular and related disorders are one of the most common disease prevailing all over the world. Hyperlipidemic condition have been largely considered in the treatment of cardiovascular diseases. The present study was carried out to investigate the effect of Ambrex on hematological factors in hyperlipidemic rats and untreated hyperlipidemic rats. In this study, eighteen rats were randomly divided into three groups of six animals each. The groups received normal diet (Control Group A) high fat diet (HFD group B) and Ambrex treatment (Group C). After the study period, White Blood Cell (WBC), Red Blood Cell (RBC), hematocrit (HCT), Hemoglobin, platelet (PLT), lymphocytes, monocytes, granulocytes, Mean Corpuscular Hemoglobin Concentration (MCHC), plateletcrit (PCT), Mean Corpuscular Volume (MCV), Platelet Distribution Width (PDW), red cell distribution-standard deviation (RDW-SD), red cell distribution-correlation variance (RDW-CV), micro red blood cell (pRBC), macroRBC were measured using digital cell counter (MS9-3s). Hyperlipidemia increases markedly the PLT count. Administration of Ambrex appeared to significantly increase WBC, Lymphocytes, granulocytes. However, erythrocyte indices does not show statistically significant variations among the test groups and control groups. The findings demonstrated that Ambrex does not cause any significant undesirable alterations in hematological factors in male rats. Ambrex also enhances white blood cell concentration and lymphocytes which probably stimulate the immune defense mechanism.
