Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

• Published in: Antioxidants Vol. 11; no. 9; p. 1705
• Main Authors: Li, Yiqi, Li, Yeli, Chen, Nana, Feng, Linying, Gao, Jianmei, Zeng, Nan, He, Zhixu, Gong, Qihai
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30.08.2022; MDPI
• Subjects: AKT protein; Beta cells; Cell viability; CRISPR; Cytokines; Diabetes; Diabetes mellitus (non-insulin dependent); Drug dosages; Dyslipidemia; Fatty liver; Gene expression; Glucose; Hyperglycemia; Icariside II; Inflammation; Insulin; Insulin resistance; Laboratory animals; Medical research; Metabolic disorders; NF-κB protein; Oxidative stress; Palmitic acid; Pancreas; peroxisome proliferator-activated receptors α and γ; Phosphorylation; Prevention; Signal transduction; Steatosis; Tumor necrosis factor-TNF; Type 2 diabetes; Type 2 diabetes mellitus; China; United States > US
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox11091705

Type 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic β-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exerts potent anti-inflammatory and anti-oxidative properties. In this study, we investigated whether ICS II exerted anti-T2DM profile and further explored its possible underlying mechanism both in vivo and in vitro. db/db mice were administered ICS II (10, 20, 40 mg·kg−1) for 7 weeks. We found that ICS II dose-dependently attenuated hyperglycemia and dyslipidemia, as well as inhibited hepatic steatosis and islet architecture damage in db/db mice. Moreover, ICS II not only dramatically reduced inflammatory cytokines and oxidative stress, but also up-regulated PPARα/γ protein expressions, phosphorylation of Akt, GSK3β and IR, meanwhile, down-regulated phosphorylation of NF-κB(p65) and IRS1 in db/db mice. In palmitic acid (PA)-treated HepG2 or MIN6 cells, ICS II (5−20 μM) concentration-dependently promoted the cell viability via mediating PPARα/γ/NF-κB signaling pathway. PPARα/γ knockout by CRISPR-Cas9 system partly abolished the protective effects of ICS II on HepG2 or MIN6 cells following PA insults. These findings reveal that ICS II effectively confer anti-T2DM property by targeting PPARα/γ through mediation of ROS/NF-κB/IRS1 signaling pathway.