Modulation of serum transient receptor potential ankyrin 1 (TRPA1) levels by Phyllanthus emblica fruit extract in doxorubicin-treated rats

Abstract

Doxorubicin is widely used as an anticancer agent, but its clinical use is limited by cardiovascular toxicity associated with oxidative stress and inflammatory responses. Transient receptor potential ankyrin 1 (TRPA1) has been implicated in cardiovascular regulation and may contribute to doxorubicin-related cardiovascular alterations. Balakka fruit (Phyllanthus emblica) contains bioactive compounds with antioxidant potential; however, its effect on TRPA1 expression in doxorubicin-induced cardiovascular injury remains unclear. The aim of this study was to evaluate the effect of ethanol extract of balakka fruit (EEBF) on TRPA1 levels in doxorubicin-induced experimental animals. Balakka fruit extract was prepared using 70% ethanol maceration, followed by simplicia and extract characterization and phytochemical screening. An in vivo experiment was conducted using six groups: normal control, doxorubicin control, doxorubicin plus quercetin, and doxorubicin plus EEBF at doses of 100, 300, and 500 mg/kg BW. TRPA1 levels were measured using enzyme-linked immunosorbent assay. Phytochemical screening showed that balakka fruit simplicia and extract contained alkaloids, flavonoids, glycosides, saponins, and tannins. Doxorubicin administration increased TRPA1 levels compared with the normal group, while EEBF reduced TRPA1 levels in a dose-related pattern. The EEBF 500 mg/kg BW dose showed the strongest reduction in TRPA1 levels compared with the doxorubicin control group. These findings suggest that EEBF may modulate TRPA1 expression in doxorubicin-induced cardiovascular injury, potentially through its antioxidant-related bioactive compounds. Further studies are needed to evaluate its active compounds, antioxidant and inflammatory pathways, toxicity, and direct cardiovascular effects.