Liquiritigenin protects against cadmium-induced testis damage in mice by inhibiting apoptosis and activating androgen receptor

Cadmium (Cd) is a prevalent contaminant in both dietary and drinking water sources, posing harm to multiple tissues and disrupting reproductive function. Recent evidence indicates that natural products derived from plants may offer a mitigating Cd-induced tissue damage. However, the protective role of Liquiritigenin (LQ) and its underlying mechanism remain unclear. The present study was to investigate the protective effect of LQ against short-term, low-dose Cd-induced multi-organ damage. Notably, Cd exposure had no significant impact on body or tissue weight but did induce damage to the heart, liver, lungs, kidneys and testes of mice, while also reducing sperm quality. These adverse effects were reversed by LQ treatment, suggesting that LQ alleviates Cd toxicity. Mechanistically, LQ inhibited testicular apoptosis by modulating the protein levels of Bad, Caspase-3, Bax, Bcl-2, and NF-κB. Furthermore, molecular docking and molecular dynamics simulations provided insights into the interaction between LQ and the androgen receptor (AR). Further studies indicate that LQ increases AR level and further prevent testicular damage. Collectively, these findings support the potential of LQ in preventing Cd-induced tissue damage, particularly in the context of reproductive toxicity.