文献类型：期刊文献

英文题名：Chikusetsusaponin IVa ameliorates paroxetine-induced Leydig cells (TM3 cells) injury via the Nrf2/HO-1 signaling pathway

作者：Huang, Qianqian[1];Wu, Haiying[3];Xiao, Xiangxin[1];Lu, Zhen[1];Fan, Xiuping[1];Cao, Wenhong[1];Liu, Suqing[2];Qin, Xiaoming[1]

机构：[1]Guangdong Ocean Univ, Coll Food Sci & Technol, Guangdong Prov Sci & Technol Innovat Ctr Subtrop F, Guangdong Prov Key Lab Aquat Prod Proc & Safety, Zhanjiang 524088, Peoples R China;[2]Guangdong Ocean Univ, Coll Coastal Agr Sci, Zhanjiang 524088, Peoples R China;[3]Chinese Acad Trop Agr Sci, Agr Prod Proc Res Inst, Lab Qual & Safety Risk Assessment Agroprod Zhanjia, Minist Agr & Rural Affairs PRC, Zhanjiang 524001, Peoples R China

年份：2025

卷号：137

外文期刊名：REPRODUCTIVE TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:001566692600001)、、Scopus(收录号：2-s2.0-105014334449)、WOS

基金：This research was financially supported by the Study on Introduction, Cultivation and Demonstration of Brazil Ginseng under Forest (2022KJCX002).

语种：英文

外文关键词：Chikusetsusaponin IVa; Leydig cells; Reproductive toxicity; Androgen synthesis; Oxidative stress; Nrf2/HO-1 pathway

外文摘要：Paroxetine (PRX) exhibits significant toxic effects on the male reproductive system. Previous animal studies have demonstrated that Pfaffia glomerata extract can ameliorate PRX-induced sexual dysfunction in male mice, but its active components and underlying mechanisms remain unclear. Chikusetsusaponin IVa (CHS-IVa), a major saponin component of Pfaffia glomerata with well-documented antioxidant and anti-apoptotic activities, has become a research focus. This study aimed to investigate whether CHS-IVa could mitigate PRX-induced injury in mouse Leydig cells (TM3 cells) by regulating oxidative stress, apoptosis, and androgen synthesis pathways. To achieve this, a PRX-induced injury model in TM3 cells was established and subjected to comprehensive evaluation using CCK-8 assay for cell viability, ELISA for sex hormone levels, DCFH-DA fluorescent probe for reactive oxygen species (ROS) detection, and RT-qPCR/Western blot for mRNA and protein expression analysis. Results showed that compared to PRX group, CHS-IVa (6.25 mu g/mL) significantly increased cell viability by 12.9 % (p < 0.05); activated Nrf2/HO1 signaling pathway, reducing intracellular ROS levels by at least 21.9 % (p < 0.05), thereby alleviating oxidative stress injury; upregulated mRNA expression of androgen synthesis-related genes (StAR, CYP11a1, CYP17a1, LHr) by over 2-fold (p < 0.05), with maximal increases in testosterone, dihydrotestosterone and luteinizing hormone levels by 8.4 %, 50.4 % and 13.0 % respectively (p < 0.05); enhanced anti-apoptotic factor Bcl-2 mRNA and protein expression by up to 3.4-fold and 1.6-fold (p < 0.05), while reducing pro-apoptotic factor Bax mRNA and protein expression by 40.5 % and 44.6 % (p < 0.05), and decreasing Caspase-3 mRNA expression by 61.5 % (p < 0.05), ultimately reducing PRX-induced abnormal apoptosis in TM3 cells. In conclusion, CHS-IVa serves as the key active component in Pfaffia glomerata that protects against PRX-induced reproductive toxicity by ameliorating injury in TM3 cells through multiple mechanisms.