ReferenceID 1211

Arctigenin mitigates insulin resistance by modulating the IRS2/GLUT4 pathway via TLR4 in type 2 diabetes mellitus mice

Int Immunopharmacol

Arctigenin (AR), extracted from Arctium lappa L. (Burdock), is a folk herbal medicine used to treat diabetes. However, its mechanism of action has remained elusive. In this study, type 2 diabetes mellitus (T2DM) mice rec

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Reference Id
1211
Evidence Id
17801
Core Evidence Id
17801
Source Reference Id
2409
Herb2 Reference Id
HBREF003206
Subject Paper Key
HBIN016609_36481528
Pubmed Id
36481528
Doi
10.1016/j.intimp.2022.109529
Paper Title
Arctigenin mitigates insulin resistance by modulating the IRS2/GLUT4 pathway via TLR4 in type 2 diabetes mellitus mice
Paper Abstract
Arctigenin (AR), extracted from Arctium lappa L. (Burdock), is a folk herbal medicine used to treat diabetes. However, its mechanism of action has remained elusive. In this study, type 2 diabetes mellitus (T2DM) mice received AR orally for 10 weeks to evaluate its therapeutic effect based on changes in glucose and lipid metabolism, histological examination of target tissues, and liver immunohistochemistry. Furthermore, HepG2 insulin-resistant cells were established to verify the mechanism of AR against diabetes. The results showed that AR treatment reduced blood glucose and lipid levels, reversing liver as well as pancreas tissue damage in T2DM mice. AR reduced the levels of pro-inflammatory cytokines in the serum of T2DM mice, as well as those in insulin-resistant HepG2 cell supernatants, while increasing interleukin-10 (IL-10) levels. The levels of p-p65, phospho-c-Jun N-terminal kinase (p-JNK), induced nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were reduced in the liver tissue of T2DM mice, accompanied by an upregulation of glucose transporter 4 (GLUT4) and insulin receptor substrate 2 (IRS-2). In vitro studies further showed that AR downregulated toll-like receptor 4-mediated inflammation, while upregulating insulin pathway-related proteins and ultimately improving glucose uptake in insulin-resistant HepG2 cells. In conclusion, AR protected mice from insulin resistance, and its therapeutic effect was likely associated with inhibition of toll-like receptor 4 inflammatory signaling to reactivate IRS-2/GLUT4.
Journal
Int Immunopharmacol
Publish Year
2022
Experiment Subject
mouse; hepg2 insulin-resistant cells; insulin-resistant hepg2 cells
Experiment Type
Animal Experiment
Phenotype Related
Type 2 Diabetes Mellitus; Diabetes
Paper Title Cn
Paper Title En
Arctigenin mitigates insulin resistance by modulating the IRS2/GLUT4 pathway via TLR4 in type 2 diabetes mellitus mice
Bilingual Status
semi_complete