title: Antifibrotic effect of total flavonoids of Astmgali Radix on dimethylnitrosamine-induced liver cirrhosis in rats.
abstract: OBJECTIVE
  To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR).
  
  
  METHODS
  Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen I, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen I, α-SMA, PPARγ, UCP2 and FXR.
  
  
  RESULTS
  Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen I and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01).
  
  
  CONCLUSIONS
  TFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.
authors: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. drchengyang@126.com.
authors: Yang
authors: Y
authors: Cheng
authors: Shanghai Pudong New Area Hospital of Traditional Chinese Medicine, Shanghai, 201299, China.
authors: Jing-Yin
authors: JY
authors: Mai
authors: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors: Mei-Feng
authors: MF
authors: Wang
authors: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors: Gao-Feng
authors: GF
authors: Chen
authors: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors: Jian
authors: J
authors: Ping
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000199:Actins; D024042:Collagen Type I; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D006909:Hydroxyproline; D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000071246:Uncoupling Protein 2; D000099150:Receptor, Farnesoid X-Activated; C000604391:Ucp2 protein, rat
keywords: dimethylnitrosamine; farnesoid X receptor; liver cirrhosis; peroxisome proliferatoractivated receptor γ; rat; total flavonoids of Astmgali Radix; uncoupling protein 2