Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation

Abstract

Cynanchum acutum L. is a climbing vine that belongs to the family Apocynaceae. Using different chromatographic techniques, seven compounds were isolated from the methanolic extract of the plant. The isolated compounds include six flavonoid compounds identified as rutin (1), quercetin-3-O-neohesperidoside (2), quercetin-3-O-β-galactoside (3), isoquercitrin (4), quercetin (5), and kaempferol 3-O-β-glucoside (6), in addition to a coumarin, scopoletin (7). The structures of the compounds were elucidated based on 1D NMR spectroscopy and high-resolution mass spectrometry (HR-MS), and by comparison with data reported in the literature. The first five compounds were selected for in vivo investigation of their anti-inflammatory and antioxidant properties in a rat model of type 2 diabetes. All tested compounds significantly reduced oxidative stress and increased erythrocyte lysate levels of antioxidant enzymes, along with the amelioration of the serum levels of inflammatory markers. Upregulation of miR-146a expression and downregulation of nuclear factor kappa B (NF-κB) expression were detected in the liver and adipose tissue of rats treated with the isolated flavonoids. Results from the biological investigation and those from the validated molecular modeling approach on two biological targets of the NF-κB pathway managed to highlight the superior anti-inflammatory activity of quercetin-3-O-galactoside (3) and quercetin (5), as compared to other bioactive metabolites.

Glycine Betaine Relieves Lead-Induced Hepatic and Renal Toxicity in Albino Rats

“…Several studies demonstrated that Pb-induced oxidative injury could be the main reason for Pb-induced renal and hepatic toxicity [ 8 , 10 , 11 , 13 , 42 ]. The oxidative stress marker, MDA, in liver and kidney homogenates are dramatically increased in Pb-intoxicated rats [ 43 ].…”

“…In vivo studies also confirmed that Pb treatments increased the production of ROS and caused remarkable changes in the activities of antioxidant defense systems in experimental animals [ 9 , 10 , 11 , 12 ]. Furthermore, Pb exposure causes alterations in antioxidant activities by inhibiting functional SH groups in several enzymes such as δ-aminolevulinic dehydrogenase (ALAD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) [ 10 , 13 , 14 ]. Glutathione plays a vital role in the scavenging of reactive oxygen radicals.…”

Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases

“…The hepatoprotective efficacy of Hyp has also been evaluated in experimental models of various diseases, including heart failure, pneumonia, hepatitis B, hepatic ischemia, and diabetes [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Hyp administration resulted in a significant reduction in serum AST and ALT levels and ameliorated the severity of hepatocellular necrosis and vacuolation.…”

“…Although previous studies on the antisteatotic effects of Hyp are scarce, this compound has been reported to reduce hepatic fat accumulation in rodents fed a high-fat diet and alcohol and in diabetes-induced rats [ 39 , 60 , 61 , 74 , 75 , 76 ]. The antisteatotic activity of Hyp in high-fat diet-induced C57BL/6 mice and diabetes-induced rats occurred with liver weight loss and reduced hepatic lipid contents, such as TG, TC, and NEFA [ 60 , 74 ].…”

“…The hepatic expression of several key inflammatory cytokines and chemokines, such as TNF-α, interleukin (IL)-1β, IL-6, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)2, C-C motif chemokine ligand (CCL)2, and CCL5, was downregulated by the administration of Hyp during the inflammatory pathogenesis induced by CCl 4 and a high-fat diet [ 34 , 38 , 53 , 60 , 76 ].…”