Gentiopicroside targets PAQR3 to activate the PI3K/AKT signaling pathway and ameliorate disordered glucose and lipid metabolism

The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.

Cost-effectiveness analysis of three kinds of schemes in the treatment of acute exacerbation of chronic bronchitis / 中国基层医药

Objective From the point of view of pharmaceutical economics,to analyze and compare the clinical efficacy,safety,compliance and economic effect of three kinds of scheme:1.moxifloxacin,2.moxifioxacin combined with ambroxol,3.azithromycin combined with levofloxacin in the treatment of acute exacerbation of chronic bronchitis (AECB).Methods Retrieval Chinese joumal full-text database,Wanfang medical database and Chinese science and technology periodical full-text database,included three options for the treatment of AECB randomized controlled trial (RCT) literature,through the analysis of the data to make drug economics evaluation.Results The total effective rates of three programs were 94.92％,95.08％,94.90％,the difference was not statistically significant (P ＞ 0.05).The cost-effectiveness ratios were 213.34,536.40,61.22.Conclusion The efficacy of three treatment options is similar,azithromycin combined with levofloxacin has economic advantages.