Astragalus and Paeoniae radix rubra extract inhibits liver fibrosis by modulating the transforming growth factor‑β/Smad pathway in rats.
It has been previously demonstrated that Astragalus and Paeoniae radix rubra extract (APE) had a protective effect against liver fibrosis in mice. The present study aimed to investigate the hepatoprotective effect of APE on CCl4‑induced hepatic fibrosis in rats. Liver fibrosis was induced in male Sprague‑Dawley rats by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. Organ coefficients, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), procollagen type III (PCIII), hydroxyproline (Hyp), glutathione (GSH‑Px), malondialdehyde (MDA), superoxide dismutase (SOD) and transforming growth factor β1 (TGF‑β1) levels were measured in rats with hepatic fibrosis. Histopathological changes in affected livers were studied using hematoxylin‑eosin and Masson's trichrome staining. The expression of transforming growth factor‑β/Smad pathway proteins, α‑smooth muscle actin (α‑SMA), collagen I and collagen III was observed in fibrotic livers using western blot analysis. The present study observed significant reductions in serum levels of AST, ALT, HA, LN, PCIII and Hyp in APE‑treated (2.6 and 5.2 g/kg) rats, indicating the significant hepatoprotective effects of APE. Furthermore, the depletion of GSH‑Px and SOD, in addition to the accumulation of MDA in liver tissue was suppressed by APE (2.6 and 5.2 g/kg). Pathological assessment of CCl4‑induced fibrotic livers revealed a significant reduction of liver injury and development of hepatic fibrosis in rats treated with APE (2.6 and 5.2 g/kg). Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGF‑β1, α‑SMA, collagen I and collagen III expression, inhibited Smad2/3 phosphorylation as well as elevated the expression of the TGF‑β1 inhibitor Smad7. These results suggested that APE may protect against liver damage and inhibit the progression of CCl4‑induced hepatic fibrosis. The mechanism of action of APE is hypothesized to proceed via scavenging free radicals, decreasing TGF‑β1 levels and blocking of the TGF‑β/Smad signaling pathway.
Department of Scientific Research, Xi'an Medical College, Xi'an, Shaanxi 710061, P.R. China.
Weijuan
W
Huang
Department of Scientific Research, Xi'an Medical College, Xi'an, Shaanxi 710061, P.R. China.
Lin
L
Li
State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
Xiaopeng
X
Tian
Department of Pharmacology, Xi'an Medical College, Xi'an, Shanxi 710061, P.R. China.
Jinjin
J
Yan
Department of Pharmacology, Xi'an Medical College, Xi'an, Shanxi 710061, P.R. China.
Xinzheng
X
Yang
Department of Scientific Research, Xi'an Medical College, Xi'an, Shaanxi 710061, P.R. China.
Xinlong
X
Wang
Department of Scientific Research, Xi'an Medical College, Xi'an, Shaanxi 710061, P.R. China.
Guozhen
G
Liao
Department of Traditional Chinese Medicine, First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi 710061, P.R. China.
Genquan
G
Qiu
D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D027883:Astragalus Plant / Q000737:chemistry* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D029596:Paeonia / Q000737:chemistry* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism*
D000199:Actins; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D008315:Malondialdehyde; D010936:Plant Extracts; D020011:Protective Agents; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat