Multi-Target Synergy of Coridius chinensis in Testicular Aging via Network Pharmacology-Metabolomics Integration

Aging is among the major risk factors for male infertility. Coridius chinensis is a traditional Chinese insect medicine that has been utilized to improve male reproduction in China for hundreds of years, but elucidation of the underlying mechanisms involved remains challenging.

An aging male mouse model was administered Coridius chinensis extract (CcE) over four weeks. Sperm parameters, such as total count and viability, were assessed, and serum testosterone levels were measured via enzyme-linked immunosorbent assay (ELISA). To explore the underlying mechanisms, the metabolics and network pharmacology were conducted.

The serum testosterone concentration, total sperm count, and sperm survival rate significantly improved. Network pharmacology analysis revealed that the improvement in testicular aging mediated by Coridius chinensis extract was related mainly to TLR9, PTGS2, and ALPL. The molecular docking results revealed that 3,4-dihydroxybenzalacetone tightly binds to ALPL, PTGS2, and TLR9. Metabolomics analysis revealed that Coridius chinensis extract regulated biomarkers such as 5-hydroxyindoleacetaldehyde, glycerol 3-phosphate, coproporphyrin I, inosine, PE (22:5 (4Z, 7z, 10z, 13z, 16Z)/24:1 (15z)), and 5-oxo-delta-bilirubin, the main pathways of which are associated with metabolic pathways and choline metabolism in cancer and Kaposi sarcoma-associated herpes infection.

This integrated study elucidates the multi-target mechanism of CcE against testicular aging, substantiating its traditional use. CcE improved testosterone synthesis and spermatogenesis by modulating key targets (TLR9, ALPL, PTGS2) and metabolic pathways, presenting a promising therapeutic strategy for male reproductive aging. Future work requires target validation and long-term safety studies.