title: Salvianolic Acid a prevents the pathological progression of hepatic fibrosis in high-fat diet-fed and streptozotocin-induced diabetic rats.
abstract: Type 2 diabetes patients have an increased risk of developing hepatic fibrosis. Salvianolic acid A (SalA) has been reported to be a strong polyphenolic anti-oxidant and free radical scavenger. The aim of the present study was to evaluate the effect of SalA on the pathological progression of hepatic fibrosis in high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Type 2 diabetic animal model with hepatic fibrosis was developed by a high-sucrose, HFD and low-dose STZ injection (i.p.). Diabetic rats were randomly divided into SalA group (0.3 mg/kg/day) and diabetic control groups fed with a HFD. After administration for four months, SalA reversed the hyperlipidemia and reduced hepatic triglyceride (TG). Hematoxylin-Eosin (HE) and Picro acid-Sirius red staining results indicated that SalA significantly alleviated the lesions of hepatic steatosis and fibrosis, with the reduction of type I and III collagens. The expression of α-smooth-muscle-actin (α-SMA) and transforming growth factor β1 (TGF-β1) in the liver were markedly down-regulated by SalA treatment. TUNEL staining showed that SalA reduced apoptosis in hepatocytes. In addition, SalA improved hepatic mitochondrial respiratory function in diabetic rats. Taken together, these findings demonstrated that SalA could prevent the pathological progression of hepatic fibrosis in HFD-fed and STZ-induced diabetic rats. The underlying mechanisms may be involved in reducing oxidative stress, suppressing α-SMA and TGF-β1 expression, as well as exerting anti-apoptotic and mitochondria-protective effects.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Guifen
authors.initials: G
authors.lastname: Qiang
authors.forename: Xiuying
authors.initials: X
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xuan
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.forename: Hengai
authors.initials: H
authors.lastname: Zhang
authors.forename: Bainian
authors.initials: B
authors.lastname: Chen
authors.forename: Xiaoxiu
authors.initials: X
authors.lastname: Li
authors.forename: Mian
authors.initials: M
authors.lastname: Zu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Haiguang
authors.initials: H
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000199:Actins / Q000378:metabolism; D000475:Alkenes / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D059305:Diet, High-Fat / Q000009:adverse effects*; D018450:Disease Progression; D007773:Lactates / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008517:Phytotherapy; D059808:Polyphenols / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D000475:Alkenes; D002109:Caffeic Acids; D007773:Lactates; D059808:Polyphenols; D013311:Streptozocin; D053773:Transforming Growth Factor beta1; C568740:salvianolic acid; C498862:Acta2 protein, rat; C066201:salvianolic acid A
keywords: Apoptosis; Hepatic Fibrosis; Salvianolic Acid A; TGF-β1; Type 2 Diabetes; α-SMA