Bin Lu,Kun Zhang,Qingrong Dong,Lan Wei,Jia Shi,Fang Liu,Taigang Liang,Jiangfeng Du
Sepsis is a heterogeneous disease with high morbidity and mortality due to the limited therapeutic. Calycosin (CA), one of the main active ingredients of Astragalus, can potentially treat sepsis, but its therapeutic effect is limited by low blood circulation concentration and poor bioavailability. To address this challenge, we have successfully prepared BSA@Se-CA nanocomposite system （BSC） through self-assembly loading calycosin (CA) onto BSA@Se nanoparticles (BS). Compared to CA, BSC enhances the scavenging of ROS more effectively than CA alone by enhancing the activity of glutathione peroxidase (GPX). Notably, BSC reducing the expression level of inflammatory factors (NO, IL-6, IL-1β, and TNF-α) in inflammatory macrophages by synergistically inhibit the NF-κB signaling pathway. Moreover, the in vitro experiments demonstrated that BSC can also effectively alleviate RAW264.7 cells and HUVEC cells damage caused by oxidative stress, which can maintain the normal cells physiological function. In vivo, BSC exhibit significantly improve the therapeutic effect of sepsis by intraperitoneal injection, such as increase the survival rate of sepsis mice, and alleviate normal organ damage. Thus, this study provides a new strategy for improving the utilization efficiency of natural products with poor treatment effect and provides a reference for improving the therapeutic effect of sepsis.
Junling Zhu,Rilian Lai,Qin Zheng,Shuying Huang,Shenghua Hu,Zhangfei Xu,Huixia Sun
1. To study the effects of calycosin on palmitic acid-induced HepG2 cells, as well as the potential mechanisms of action.2. Potential targets of calycosin for the alleviation of insulin resistance were predicted by network pharmacology. Glucose concentration in the culture medium was determined by the GOD-POD method. The model of insulin resistance was established by palmitic acid-induced HepG2 cells. Effects of palmitic acid and calycosin on HepG2 cell activity were determined using an MTT assay kit. The expression levels of AKT1 and FOXO3a were detected by western blot.The expression level of hsa-miR-324-3p was detected by RT-qPCR. Dual luciferase reporter assay to detect targeting of AKT1 by hsa-miR-324-3p.3. AKT1 was predicted and validated as a potential target of calycosin for treatment of insulin resistance. The model of insulin resistance was successfully established by palmitic acid-induced HepG2 cells. Up-regulation of AKT1 expression inhibits FOXO3a entry into the nucleus. Calycosian was demonstrated to concentration-dependently increase the sensitivity of insulin resistance cells to insulin. The hsa-miR-324-3p was proven to exist in insulin-resistant cells. Hsa-miR-324-3p was found to target AKT1 involved in the alleviation of insulin resistance.4. Calycosin inhibits FOXO3a nuclear translocation by regulating the hsa-miR-324-3p/AKT pathway, thus alleviating insulin resistance.
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