title: 'Ashvagandharishta' prepared using yeast consortium from Woodfordia fruticosa flowers exhibit hepatoprotective effect on CCl4 induced liver damage in Wistar rats.
abstract: BACKGROUND
  [corrected] Consortium of yeasts sourced from traditionally used Woodfordia fruticosa flowers proved to be beneficial for fermenting Ashvagandharishta. It resulted in faster fermentation, acceptable organoleptic properties and demonstrable hepatoprotective potential in CCl4 induced hepatotoxicity. To formulate Ashvagandharishta using consortium of yeasts and to investigate its physiochemical parameters. Standardize the formulation with the help of standard withaferin-A and withanolide-A and to evaluate its hepatoprotective potential in CCl4 induced hepatotoxicity in the rat model.
  
  
  METHODS
  Ashvagandharishta was prepared using a 5% consortium of yeasts and ascertained its quality through physiochemical and phytochemical investigation. Withaferin-A and withanolide-A was simultaneously estimated by HPLC for standardization. Hepatoprotective potential was evaluated by administering 2.31 and 1.15 ml/kg doses while considering biochemical parameters like serum AST, ALT, ALP and lipid profile. Gene expression study was carried out for the expression of antioxidant and inflammatory genes such as CAT, GPx and proinflammatory gene IL-6. Histopathology of liver was also studied with the help of H&E staining.
  
  
  RESULTS
  Ashvagandharishta was found organolepticaly acceptable with optimized physiochemical parameters. Withaferin-A and withanolide-A in Ashvagandharishta estimated as 0.3711, 0.7426 (%w/v), respectively. In the CCl4 induced hepato-toxicity model, Ashvagandharishta-2.31ml/kg dose showed significant decrease in elevated hepatic level of AST(p<0.001), ALT(p<0.01) and ALP(p<0.001). Both doses of Ashvagandharishta showed significant reduction of TG, Cholesterol, VLDL and LDL in serum, with corresponding reduction of (p<0.001) serum-HDL. Ashvagandharishta also showed increased serum protein (p<0.05) and albumin (p<0.01) with decrease in bilirubin (p<0.01). Additionally, Ashvagandharishta administration revealed up-regulation in antioxidant genes such as CAT and GPx in liver with concomitant down-regulation in proinflammatory IL-6gene (p<0.01). Histopathological parameters revealed restoration of normal tissue architecture by both doses of Ashvagandharishta.
  
  
  CONCLUSIONS
  Consortium of yeasts from Woodfordia fruticosa flowers showed better fermentation pattern for Ashvagandharishta produced with acceptable organoleptic properties. Hepatoprotection shown by Ashvagandharishta was mainly through prevention of oxidative damage. Up-regulation of CAT and GPx genes and corresponding down regulation of proinflammatory IL6 gene was revealed as possible mechanism of its action.
authors.affiliation: Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra, India. Electronic address: prashantbhondave@gmail.com.
authors.forename: Prashant D
authors.initials: PD
authors.lastname: Bhondave
authors.affiliation: Cell and Molecular Biology, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune 411043, India. Electronic address: prasad.devarshi@gmail.com.
authors.forename: Prasad P
authors.initials: PP
authors.lastname: Devarshi
authors.affiliation: Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra, India. Electronic address: krmahadik@rediffmail.com.
authors.forename: Kakasaheb R
authors.initials: KR
authors.lastname: Mahadik
authors.affiliation: Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune 411038, Maharashtra, India. Electronic address: aharsulkar@yahoo.com.
authors.forename: Abhay M
authors.initials: AM
authors.lastname: Harsulkar
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D005285:Fermentation; D035264:Flowers / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008515:Medicine, Ayurvedic; D051381:Rats; D017208:Rats, Wistar; D031565:Woodfordia / Q000382:microbiology*; D015003:Yeasts / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008055:Lipids; D002251:Carbon Tetrachloride; D002374:Catalase
keywords: (0)Brix; 1(0)Brix; Ashvagandharishta; Gene expression; HPLC; Hepatoprotection; Woodfordia fruticosa; Yeast; approximately equal to 0.996% (w/v) dissolved sugar; represents the amount of dissolved sugar present in aqueous solution