Bavachalcone

The number of acute liver failure cases is rising worldwide as a result of both external and internal factors. This demonstrates a significant risk to global human health and well‐being. The excessive use of synthetic drugs mostly causes the occurrence of liver failure. The present study aims to investigate the therapeutic efficacy of bavachalcone in preventing acetaminophen (APAP)‐induced liver damage in mice. To develop liver toxicity, the animals were administered 300 mg/kg of APAP via the intraperitoneal route for 3 days. The mice were pretreated with 10 and 20 mg/kg of bavachalcone by oral route 1 h before the APAP administration. The silymarin (50 mg/kg) was utilized as a standard hepatoprotective drug to compare the results of bavachalcone treatment. After the completion of the treatments, the body weight and relative liver weight of the mice were assessed. The levels of liver marker enzymes, oxidative stress markers, antioxidant levels, and inflammatory cytokines were evaluated using kits. The hepatic tissues obtained from the experimental mice were utilized for the histological methods. The treatment of bavachalcone at concentrations of 10 and 20 mg/kg effectively lowered body weight and slightly decreased liver mass in the APAP‐induced mice. The bavachalcone treatment also led to elevated antioxidant levels and effectively reduced oxidative stress markers. Bavachalcone treatment also decreased the levels of inflammatory cytokines and liver marker enzymes in the APAP‐induced mice. The histopathological examination of liver tissues further validated the therapeutic potential of bavachalcone. The findings of the current study highlight the beneficial properties of bavachalcone in protecting against APAP‐induced liver injury in mice. Therefore, it possesses the potential to serve as an effective therapeutic choice for treating liver toxicity.

Gemcitabine resistance drives bladder cancer recurrence and progression. Using high‐throughput drug screening in bladder cancer cells, we identified Bavachalcone (Bava) as a potent gemcitabine sensitizer. Mechanistically, Bava simultaneously targets transferrin receptor (TFRC) and epidermal growth factor receptor (EGFR). It competes with transferrin (Tf) for TFRC binding, reducing cellular iron influx, and inhibits EGFR‐mediated phosphorylation of TFRC at tyrosine 20 (Y20). These actions disrupt mitochondria iron utilization and impairs respiration. The combination of Bava and gemcitabine synergistically inhibits the repair of gemcitabine‐induced DNA damage, while suppressing the iron‐dependent ATR‐CHEK1‐E2F1 pathway and downregulating RRM1 expression. Patient‐derived xenograft models confirmed the superior antitumor efficacy of the Bava‐gemcitabine co‐treatment compared to monotherapies. Clinically, elevated TFRC and RRM1 expression correlates with poor prognosis, supporting their utility as biomarkers of bladder cancer. Our study identified Bava as the first small‐molecule TFRC inhibitor that overcomes gemcitabine resistance through iron modulation, providing both mechanistic insights and a promising therapeutic strategy for bladder cancer.