Zhuling Yanzong formula ameliorates obesity-induced oligoasthenozoospermia via regulating HSL/StAR and HSL/TIMP-1
Min Pan1, Hongsu Zhao2, Fengqing Xu2
1Pharmacological Department of the College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
Ethnopharmacological Relevance:
Zhuling Yanzong Formula (ZLYZF) is composed of Jiawei Buzhong Yiqi Decoction (Fuqingzhu Nvke) and Wuzi Yanzong Pill (Shesheng Zhongmiao Fang). Jiawei Buzhong Yiqi Decoction has been utilized in medical practice for thousands of years in China for treating obesity-related infertility. Wuzi Yanzong Pill is a famous prescription for male infertility. ZLYZF is effective in obesity-induced oligoasthenozoospermia, with the pharmacological mechanism remaining unclear.
Aim Of The Study:
To investigate the potential mechanistic insights of ZLYZF in treating obesity-induced oligoasthenozoospermia by exploring their effect on the HSL/StAR and HSL/TIMP-1.
Materials And Methods:
Mice were divided into six groups: control group, model group, ZLYZF low-/medium-/high-dose groups, and Huanshao Jiaonang (HSJN) group (n = 16 per group). The control group was fed normal diet (ND), and the other groups were fed high-fat-diet (HFD) for 12 weeks. Serum lipid and hormone profiles, sperm quality and apoptosis assay, and fertility test were performed to assess treatment effect. H&E/Oil Red O/Nile Red staining as measures of testicular lipid, Immunofluorescence assay, measurement of testosterone, testosterone synthesis and blood-testis barrier (BTB) integrity protein expression were performed to assess testicular function. The compound of ZLYZF was analyzed by UPLC-HRMS, followed by molecular docking to predict the binding affinity between identified components and HSL. HSL/StAR and HSL/TIMP-1 expression were measured. Furthermore, HSL-targeted adeno-associated virus (AAV) were used to explore the related molecular mechanisms.
Results:
ZLYZF alleviated body weight, serum lipid and hormone levels, sperm quality and fertility. Additionally, ZLYZF reduced testicular damage and lipid accumulation by activating HSL expression. ZLYZF activated HSL and upregulated StAR expression, and inhibited TIMP-1, thereby improving testosterone synthesis and BTB integrity. In addition, HSL knockdown in obese mice abolished ZLYZF-generated efficacy.
Conclusion:
Our study demonstrated that ZLYZF improve testicular lipid accumulation and function via HSL/StAR and HSL/TIMP-1. providing a potential therapeutic agent forobesity-induced oligoasthenozoospermia.
