Treatment effects of the traditional Chinese medicine Shenks in bleomycin-induced lung fibrosis through regulation of TGF-beta/Smad3 signaling and oxidative stress

Abstract

Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production. The aberrantly high Smad3 phosphorylation levels and SBE activity in TGF-β-induced fibroblasts were dramatically decreased as a result of Shenks treatment. At the same time, Shenks was able to increase the expression of antioxidant-related genes, including Gclc and Ec-sod, while reduce the transcription levels of oxidative-related genes, such as Rac1 and Nox4 demonstrated by both in vivo and in vitro studies. Further investigations found that Shenks could decrease the oxidative productions of protein (3-nitrotyrosine) and lipid (malondialdehyde) and increase GSH content both in bleomycin treated mouse lungs and TGF-β stimulated fibroblasts, as well as inhibit the production of ROS stimulated by TGF-β to fight against oxidative stress. Overall, Shenks inhibited fibrosis by blocking TGF-β pathway and modulating the oxidant/antioxidant balance.

New insights into TGF-β/Smad signaling in tissue fibrosis

“…Polysaccharide (ESP-B4) from Ephedra sinica Stapf against airway and pulmonary inflammation revealed that ESP-B4 could downregulate the production of TGF-β1, p-Smad2 and p-Smad3, upregulate the expression of Smad7, which indicated that ESP-B4 reduced airway and pulmonary inflammation by regulating the TGF-β1/Smad2 pathway [118]. Shen-mai-kai-fei-san (Shenks) has been shown to be effective in the treatment of pulmonary fibrosis [119]. In vivo and in vitro studies demonstrated that Shenks inhibited fibrosis by blocking TGF-β pathway.…”

Aloperine Protects Mice against Bleomycin-induced Pulmonary Fibrosis by Attenuating Fibroblast Proliferation and Differentiation

“…The pathology of IPF is characterized by migration, proliferation and differentiation of fibroblast and remodeling of the extracellular matrix (ECM) 3 . Fibroblasts have been noted to play a central role in the fibrotic processes regulated by transforming growth factor-β (TGF-β) 4 , 5 or other profibrotic mediators, such as platelet-derived growth factor (PDGF) 6 , 7 and connective tissue growth factor (CTGF) 8 . These fibroblasts characterized by abnormal α-SMA and fibrillar collagens expression are called myofibroblasts 9 .…”

Electroacupuncture Ameliorates Motor Dysfunction via Inhibiting p66Shc-Associated Oxidative Stress and Endoplasmic Reticulum Stress in Rats with Spinal Cord Injury

“…Several lines of evidence suggests that excessive ROS may directly interact with cellular biomolecules, such as lipids, proteins and nucleic acids, and cause damage to cellular constituents [45]. Within cells, there exists an antioxidant system capable of scavenging ROS, which comprises enzymatic antioxidants such as catalase, superoxide dismutase (SOD), guaiacol peroxidase (GPX), as well as non-enzymatic scavengers including GSH, vitamin C and vitamin E [46]. Studies have revealed that GSH is a predominant antioxidant that scavenges cellular ROS and other reactive nitrogen species through non-enzymatically reacts with radicals in a direct manner or indirectly enzymatic reaction [47,48].…”