Flavonoid compound from Agrimonia Pilosa Ledeb improves adipose insulin resistance by alleviating oxidative stress and inflammation

Background: Researches and practice of Chinese medicine indicated that Agrimonia Pilosa Ledeb could improve insulin resistance (IR) and treat type 2 diabetes (T2DM). Flavonoid component (FC) was collected from Agrimonia Pilosa Ledeb . The aim of this study was to elucidate the effects of FC on glucose metabolism to improve IR by suppressing oxidative stress and inflammation. Methods By overdosed glucose and insulin or high-fat diet to establish adipocytes or mice IR model. The uptake of 2-NBDG and glucose consumption were measured to verify insulin sensitivity in vitro and vivo. Reactive oxidative species (ROS) were detected by flow cytometry, activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were also measured. Meanwhile, factors related to insulin signal pathway such as PPARγ, insulin receptor substrate-1 (IRS-1) and GLUT4, factors related to oxidative stress such as NF-E2-related factor 2 (Nrf2), and expression and secretion of inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α were tested. Furthermore, the JNK/PI3K/Akt signal pathway were also explored. Results FC ameliorated the impaired glucose metabolism significantly. Further study indicated that FC could promote the expression related to insulin signal pathway to improve insulin resistance. What’s more, it could not only upregulated PPARγ with the similar efficacy as pioglitazone (Piog) straightway. But FC also decreased the endogenous ROS, lowered the content of MDA, increased the activity of SOD and expression of Nrf2 to facilitate oxidative homeostasis. It also attenuated expression and secretion of inflammatory cytokines obviously. At last, the underling mechanism JNK/PI3K/Akt pathway was improved in adipocytes and adipose tissue. Conclusion FC could ameliorate glucose metabolism and improve IR. It exerted these effects by suppressing oxidative stress and inflammation. FC from Agrimonia Pilosa Ledeb has a good prospect to be drugs or functional foods for IR and T2DM.