<p>Sinomenine Attenuates Acetaminophen-Induced Acute Liver Injury by Decreasing Oxidative Stress and Inflammatory Response via Regulating TGF-β/Smad Pathway in vitro and in vivo</p>

Abstract

Introduction: Liver disease is common and often life-threatening. Sinomenine (SIN) is an active ingredient extracted from Sinomenium acutum. This study investigated the protective effect and mechanism of sinomenine (SIN) on acetaminophen (APAP)-induced liver injury from in vitro and in vivo. Methods: In vivo experiments, mice were randomly divided into six groups (n=10): control group, model group, SIN (25 mg/kg) group, SIN (50 mg/kg) group, SIN (100 mg/kg) group and SIN (100 mg/kg) + SRI-011381 group. Alanine transaminases (ALT), aspartate transaminases (AST) and alkaline phosphatase (ALP) were detected. The pathological lesion was measured by HE staining. Apoptosis was measured by TUNEL staining. In vitro experiments, BRL-3A cells were treated with APAP (7.5 mM) and then subjected to various doses of SIN (10, 50 and 100 μg/mL) at 37°C for 24 h. Inflammatory factors and oxidative stress index were measured by ELISA. The expression of proteins was detected by Western blot. Results: The results showed that compared with the control group, the levels of ALT, AST and ALP in the serum of APAP-induced mice were significantly increased, followed by liver histological damage and hepatocyte apoptosis. Besides, APAP reduced the activity of SOD and GSH-Px, while increasing the content of MDA and LDH. Notably, APAP also promoted the expression of NLRP3, ASC, caspase-1 and IL-1β. Interestingly, SIN treatment dose-dependently reduced APAP-induced liver injury and oxidative stress, inhibited the activation of NLRP3 inflammasomes, and reduced the levels of inflammatory cytokines. In vitro studies have shown that SIN treatment significantly reduced the viability of BRL-3A cells and oxidative stress and inflammation. In addition, the Western blotting analysis showed that SIN inhibited the activation of TGF-β/Smad pathway in a dose-dependent manner in vitro and in vivo. These effects were significantly reversed by TGF-β/Smad activator SRI-011381 or TGF-β overexpression. Discussion: The study indicates that SIN attenuates APAP-induced acute liver injury by decreasing oxidative stress and inflammatory response via TGF-β/Smad pathway in vitro and in vivo.

Fermentation of Panax notoginseng root extract polysaccharides attenuates oxidative stress and promotes type I procollagen synthesis in human dermal fibroblast cells

“…Smad protein is the downstream transmembrane receptor of TGF-β and is an important regulatory molecule of TGF-β superfamily signaling [48]. Oxidative stress can induce MMPs and pro-inflammatory cytokines in cells.…”

Sinomenine hydrochloride ameliorates dextran sulfate sodium‑induced colitis in mice by modulating the gut microbiota composition whilst suppressing the activation of the NLRP3 inflammasome

“…Sinomenine (CAS: 115-53-7) is a pure alkaloid that was originally extracted from the Chinese herb, Sinomenium acutum (Rehder and Wilson) of the Menispermaceae family ( 12 ). Sinomenine hydrochloride (SIN) is a hydrochloride form of sinomenine that has attracted the interest of researchers due to its reported safety and potent anti-inflammatory and immunoregulatory effects both in vitro and in vivo ( 13 , 14 ). It has been reported that SIN demonstrated notable therapeutic efficacy for treating collagen-induced arthritis in a rat model ( 15 ).…”

In vitro and Ex vivo Antioxidant Activity and Sustained Release Properties of Sinomenine-Loaded Liposomes-in-Hydrogel Biomaterials Simulating Cells-in-Extracellular Matrix

“…In vivo, SIN can increase the levels of GSH-Px and SOD, reduce the production of MDA, enhance the resistance to oxidative stress and the defense function of cell membranes. 43,44 According to the experimental results, SIN had a good scavenging rate on DPPH radicals in the concentration range of 0.025 to 0.125 mg/mL, and with an IC 50 of 0.084 mg/mL; 0.2 to 0.6 mg/mL of SIN had a good scavenging rate for H 2 O 2 , and the IC 50 was 0.3771 mg/mL. The ability of antioxidants to scavenge radicals depends on the ability of hydroxyl groups to provide hydrogen ions (H + ).…”

“…In vivo , SIN can increase the levels of GSH-Px and SOD, reduce the production of MDA, enhance the resistance to oxidative stress and the defense function of cell membranes. 43,44…”