Astragalus and Paeoniae radix rubra extract inhibits liver fibrosis by modulating the transforming growth factor-β/Smad pathway in rats

Abstract

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.

Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers

“…The accumulation of oxygen free radicals in the body results in evident damage to cells, while peptic ulcers have also been associated with the damage induced by oxygen free radicals (19). The activity of SOD and GSH-Px is known to significantly decrease in high altitude areas, while the content of MDA significantly increases (20). As a result, the morbidity of peptic ulcers in high altitude areas is significantly higher compared with that in plain areas (21).…”

Astragalus and Paeoniae Radix Rubra extract (APE) inhibits hepatic stellate cell activation by modulating transforming growth factor-β/smad pathway

“…Astragalus and Paeoniae Radix Rubra extract (APE) is produced from a variety of herbs ( Astragali Radix, Paeoniae Radix Rubra, Curcumae Rhizoma, Bupleuri Radix and Eupolyphaga ) with a standard ratio of 30:30:15:12:10 by crude herb weight and contains the active components paeoniflorin, astragalosides and curzenone ( 16 ). Astragali Radix is thought to have restorative properties in Chinese Medicine, and studies have demonstrated that it is a hepatoprotective agent ( 17 , 18 ).…”

Free Radicals, the Natural Antioxidant Buyang Huanwu Decoction and Ischemic Stroke

“…The extract of red peony root (Radix Paeoniae Rubra) is also a component of BYHWD and acts an effective natural antioxidant [36][37] . Radix Paeoniae Rubra extract can suppress the depletion of antioxidant enzymes, glutathione and SOD [38] . Pu Tian et al studied and demonstrated the total glycosides (TG) activity in Radix Paeoniae Rubra extract, as well as its anticoagulant activity and ability to scavenge free radicals in vitro.…”