title: Pharmacological safety evaluation of a traditional herbal medicine "Zereshk-e-Saghir" and assessment of its hepatoprotective effects on carbon tetrachloride induced hepatic damage in rats.
abstract: BACKGROUND
  "Zereshk-e-Saghir" (ZES), one of the traditional herbal medicines in old manuscripts of Persian hakims, has been used for the treatment of liver disorders. This current study is aimed to evaluate ZES effects on animal model to investigate its safety and hepatoprotective activity.
  
  
  METHODS
  ZES was prepared according to a traditional method by blending aqueous extracts of Berberis vulgaris L., with fine particles of other plants including Rosa damascene Mill, Cichorium intybus L., Cucumis sativus L., Portulaca oleracea L., Rheum palmatum L., and Nardostachys jatamansi DC.. The lethality of ZES was determined in male NMRI mice. Acute organ toxicity of ZES (750 and 1500mg/kg for 15 days, orally) was evaluated by measuring the cell blood count, liver marker enzymes, creatinine, antioxidant status and histopathological examinations in rats. CCl4-induced liver toxicity was used to examine the hepatoprotective effects of the preparation. The rats were pretreated with 250, 500, 750 and 1500mg/kg ZES by gavage for 15 days. At day 16, the rats were intraperitoneally injected 1ml/kg CCl4 in olive oil. Forty-eight hours after CCl4 injection, the animals were sacrificed and their liver samples and blood were collected for determination of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (ALT, AST, and ALP), histopathological examinations and antioxidant status.
  
  
  RESULTS
  Treatment of the mice with a single dose of ZES up to 2g/kg did not cause mortality. Treatment of the rats with doses of 750 and 1500mg/kg for 15 days showed no significant hematotoxicity and hepatotoxicity. Treatment of the rats with ZES reduced the increased serum levels of ALT, AST, and ALP induced by CCl4 at the doses of 250, 500, and 750mg/kg. This was almost confirmed by histopathological examinations. Pretreatment with ZES also decreased lipid peroxidation and maintained the levels of glutathione and total antioxidant capacity.
  
  
  CONCLUSIONS
  The present in vivo study revealed that the long term usage of ZES was safe for organs in laboratory animals. Meanwhile, prescribing the traditionally-recommended dose of ZES can be probably used against the liver injuries induced by xenobiotics. Further studies in other models of liver injuries are recommended for finding the exact hepatoprotective mechanism of ZES.
authors.affiliation: Department of Pharmacognosy and Herbal and Traditional Medicines Research Center, School of Pharmacy, Haft-Bagh Blvd., P.O. Box 7616911319, Kerman, Iran. Electronic address: zarrinsarhady@yahoo.com.
authors.forename: Zarrin
authors.initials: Z
authors.lastname: Sarhadynejad
authors.affiliation: Department of Pharmacognosy and Herbal and Traditional Medicines Research Center, School of Pharmacy, Haft-Bagh Blvd., P.O. Box 7616911319, Kerman, Iran. Electronic address: fsharififar@kmu.ac.ir.
authors.forename: Fariba
authors.initials: F
authors.lastname: Sharififar
authors.affiliation: Department of Pharmaceutics and Pharmaceutics Research Center, Neuropharmacology Institute, School of Pharmacy, Haft-Bagh Blvd., P.O. Box 7616911319, Kerman, Iran. Electronic address: abpardakhty@kmu.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Pardakhty
authors.affiliation: Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, P.O. Box 7616914111, Kerman, Iran. Electronic address: mh.nematollahi@yahoo.com.
authors.forename: Mohammad-Hadi
authors.initials: MH
authors.lastname: Nematollahi
authors.affiliation: Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman, Iran. Electronic address: saeedehmokhtari@gmail.com.
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Sattaie-Mokhtari
authors.affiliation: Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, P.O. Box 7616911319, Kerman, Iran; Gastroenterology and Hepatology Research Center, Afzalipour"s Hospital, Imam Highway, P.O. Box 7616913911, Kerman, Iran. Electronic address: alimandegary@kmu.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Mandegary
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D028142:Berberis / Q000187:drug effects* / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D028321:Plant Preparations; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione
keywords: CCl(4)-induced liver damage; Emodin (PubChem CID: 3220); Gallic acid (PubChem CID: 370); Hepatoprotective effect; Kaempferol (PubChem CID: 5280863); Oxidative stress; Quercetin (PubChem CID: 5280343); Rutin (PubChem CID: 5280805); Traditional herbal medicine