BuShen HuoXue decoction improves fertility through intestinal hsp-16.2-mediated heat-shock signaling pathway in Caenorhabditis elegans

Frontiers in Pharmacology

Pharmacology

Xudong Zhao¹  Lei Li¹  Jing Jin²  Miao Chen³  Jun Guo³  Xian Xiao³  Qinli Ruan³  Kanglu Wu³  Chao Jiang³  Liang Wu⁴ 

[1] Department of General Practice, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China;Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China;School of Medicine, Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China;School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China;

关键词: Bushen Huoxue decoction;    fertility;    HSP-16.2;    intestinal barrier;    C. elegans;   

DOI  :  10.3389/fphar.2023.1210701

 received in 2023-04-23, accepted in 2023-05-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: BuShen HuoXue (BSHX) decoction is commonly used in the clinical treatment of premature ovarian failure because it can increase estradiol level and decrease follicle-stimulating hormone level. In this study, we determined the potential therapeutic effects of BSHX decoction via anti-stress pathway and the underlying mechanism by using the nematode Caenorhabditis elegans as an assay system.Methods: Bisphenol A (BPA, 175 μg/mL) was used to establish a fertility-defective C. elegans model. Nematodes were cultivated according to standard methods. Brood size, DTC, the number of apoptotic cells and oocytes were used to evaluate the fertility of nematodes. Nematodes were cultivated at 35°C as heat stress. RNA isolation and RT-qPCR were used to detect the mRNA expression level of genes. Intestinal ROS and intestinal permeability were used to evaluate the function of intestinal barrier. BSHX decoction was extracted with water and analyzed by LC/Q-TOF.Results and Discussion: In BPA-treated N2 nematodes, 62.5 mg/mL BSHX decoction significantly improved the brood size and the oocytes quality at different developmental stages. BSHX decoction improved resistance to heat stress through the hsf-1-mediated heat-shock signaling pathway. Further analysis showed that the decoction significantly improved the transcriptional levels of hsf-1 downstream target genes, such as hsp-16.1, hsp-16.2, hsp-16.41, and hsp-16.48. Other than hsp-16.2 expression in the gonad, the decoction also affected intestinal hsp-16.2 expression and significantly reversed the adverse effects induced by BPA. Moreover, the decoction ameliorated intestinal ROS and permeability. Thus, BSHX decoction can improve fertility by increasing intestinal barrier function via hsp-16.2-mediated heat-shock signaling pathway in C. elegans. These findings reveal the underlying regulatory mechanisms of hsp-16.2-mediated heat resistance against fertility defect.

【 授权许可】

Unknown   
Copyright © 2023 Wu, Zhao, Xiao, Chen, Wu, Jiang, Jin, Li, Ruan and Guo.