Protective effect of sinomenine against inflammation and oxidative stress in gestational diabetes mellitus in female rats via TLR4/MyD88/NF‐κB signaling pathway

Abstract

Gestational diabetes mellitus (GDM) is a dangerous complication of pregnancy which is induced via dysfunction in glucose metabolism during pregnancy. Sinomenine (SM) has already proved an antidiabetic effect against streptozotocin (STZ)-induced diabetes mellitus (DM) in rats. In this protocol, we examined the protective effect of SM against STZ-induced GDM in rats. Wistar rats were divided into three groups and STZ (40 mg/kg) was used to induce GDM. At the end of the experimental protocol, bodyweight, pub weight, and survival rate were estimated. Blood glucose level (BGL), fasting insulin (FINS), free fatty acid (FFA), Hemoglobin A1C (HbA1c), and C-peptide were measured. Lipid, antioxidant, inflammatory cytokines, and inflammatory mediators were also determined. RT-PCR was used for estimation of the role of TLR4/ MyD88/NF-κB signaling pathway. SM treatment significantly (p < .001) reduced BGL, hepatic glycogen, and improved the levels of FINS, C-peptide, FFA, and HbA1c. SM significantly (p < .001) suppressed the levels of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), coronary artery index (CAI), very low-density lipoprotein (VLDL), atherogenic index (AI), and boosted high-density lipoprotein (HDL) levels. SM significantly (p < .001) decreased the lipid peroxidation (LPO) level and enhanced glutathione peroxidase (GPx), total antioxidant capacity (TAC), glutathione S-transferase (GST), superoxide dismutase (SOD), respectively. It reduced the levels of inflammatory cytokines including interleukin-1β (IL-1β), tumor necrosis factorα (TNFα), interleukin-6 (IL-6), and inflammatory mediators viz., nuclear kappa B factors (NF-κB). SM significantly (p < .001) reduced the mRNA expression of Myd88, NLRP3, TLR4, and NF-κB, which were boosted in the GDM group rats. These findings suggest that SM could be a probable drug to be used for treating GDM via inhibition of the TLR4 signaling pathway.

Beneficial Effects of lncRNA-UC.360+ shRNA on Diabetic Cardiac Sympathetic Damage via NLRP3 Inflammasome-Induced Pyroptosis in Stellate Ganglion

“…Under physiological conditions, the level of NLRP3 in the body is extremely low, NLRP3 mRNA needs to be transcribed first. At this time, NF-κB activation is required, and then translation and posttranslational modifications ensue . Studies have shown that increasing the content of ROS in the cytoplasm can activate NLRP3 inflammasomes. , The high glucose in diabetes promotes the production of a large amount of ROS in the cell, which in turn can activate the NLRP3 inflammasome.…”

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

“…Recently years, sinomenine has gained more popularity for improving cardiac qualities. Sinomenine suppressed inflammatory mediators, resulting in an anti-inflammatory action against STZ-induced diabetes ( Li et al, 2021 ). Additionally, sinomenine demonstrated an anti-oxidative and hypo-lipidemic effect on the high fet diet induced atherosclerosis ( Feng et al 2019 ).…”

“…Last few decades, sinomenine widely used for the treatment of chronic glomerulonephritis, allograft rejection, autoimmune nephritis condition and mesangial proliferative nephritis ( Zhou et al, 2020 , Zhang et al, 2012 , Lin et al, 2008 , Li et al, 2021 ). Recent investigation showed that sinomenine suppress the synovial and lymphocyte fibroblast proliferation, macrophage infiltration and the production of inflammatory cytokines ( Geng et al, 2021 , Yang et al, 2017 , Li et al, 2021 ). As my best knowledge, the myocardial protective effect of sinomenine against the I/R induced ventricular arrhythmias not explored.…”

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease

“…[ 103 ]. Sinomenine has an anti-diabetes effect on gestational diabetes rats and STZ-induced diabetes rats, reducing fasting blood glucose and inflammation levels in animals [ 104 ]. Studies found that sinomenine has a protective effect on human renal glomerular endothelial cells (HRGEs) induced by HG.…”