Preclinical efficacy and cellular mechanisms of a polyherbal formulation in doxorubicin nephrotoxicity

Abstract

The study aimed to evaluate the efficacy and cellular mechanisms of a standardised polyherbal formulation (PHF) derived from Asparagus falcatus L., Abelmoschus moschatus Medik. and Barleria prionitis L. of Sri Lankan origin in an animal model of doxorubicin nephrotoxicity. In vitro studies were carried out for chemical standardisation and determination of shelf life. The efficacy and nephroprotective mechanisms of the standardised PHF were investigated after repeated oral administration of the aqueous PHF at low (200 mg/kg body weight), therapeutic (400 mg/kg body weight), and high (600 mg/kg body weight) doses in the doxorubicin-induced (5 mg/kg body weight) nephrotoxicity model in Wistar rats. Fosinopril (0.09 mg/kg body weight) was used as the standard drug. The PHF derived from the selected medicinal herbs showed satisfactory purity and quality. Treatment of the standardised PHF for 28 days in nephrotoxic rats caused a significant reduction in serum creatinine, blood urea nitrogen, β₂-microglobulin, cystatin C, and urine total protein compared to the doxorubicin model group (p<0.05). The biochemical findings on markers of oxidative stress, inflammatory cytokines, and immunohistochemical evaluation of COX-2, BCL-2, and Bax further demonstrated the anti-inflammatory and anti-apoptotic activities of the novel PHF. The findings revealed that PHF was efficacious at the selected doses and its’ nephroprotective mechanisms were mediated by mitigating doxorubicin-induced oxidative stress, inflammation, and apoptosis in experimental rats.