Caffeic Acid Phenethyl Ester (Propolis Extract) Ameliorates Insulin Resistance by Inhibiting JNK and NF-κB Inflammatory Pathways in Diabetic Mice and HepG2 Cells Models.
J Agric Food Chem. 2017 Aug 11. Epub 2017 Aug 11. PMID: 28799756
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated the ameliorative effects on insulin resistance and identified the mechanisms, using noninsulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5-week of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Pro-inflammatory cytokines in serum and the expressions of tumour necrosis factor- alpha (TNF-α) mRNA in tissues were markedly down-regulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536) and nuclear translocation ofp-NF-κB p65 (Ser536). In summary, CAPE can ameliorate on insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.