Unraveling the Mystery in Search of Nephroprotective Therapeutics from Sri Lankan Flora.

Abstract

Drug-induced nephrotoxic1ty has become a serious ! iealth problem worldwide due to the wide use of pharmaceutical agents with potential toxicities. Doxorubicin i1: one such anthracycline drug in which the use in cancer chemc,therapy has been largely limited due to its dose-dependent organ toxicities including n phrotoxicity (Heravi et al., 2018). Doxorubicin-induced nephrotoxicity is well explair,ed via the mechanisms of oxidative stress, inflammation, and apoptosis in previous repo,ts (Ibrahim et al., 2020). Despite the fact that doxorubicin chemotherapy has been in practice for almost six decades and associated toxicities are well recognized, no specific antidote has been developed to eliminate its toxic effect>. Although the antidote; d1 xrazoxane has been commonly used to reduce doxorubicin-induced cardiotoxicity, the m.e of the same drug in alleviating free radical pathologies related to nephrotoxicity is quite challenging due to marked heterogeneity in cell populations (Lahoti et al., W 12). These limitations of current therapeutic approaches kd scientists to pay attentio 1 to alternative therapeutic strategies, particularly the conventional system of medicine, to prevent disease progression and improving kidney functi,m in doxorubicin-induced 1 tephrotoxicity. The multifactorial nature of the effects of drug-induced nephrotoxicity often demands therapeutic approaches with multiple protective ,:ffects to alleviate associated risks (Sharma et al., 2020). In this context, polyherbal fon nulations offer an invaluable resource for the development ofr.ew pharmaceuticals due to their potential bio-interactions within and between the constitJcnts (Caesar and Cech, 2()19). On some occasions, the desired pharmacological effect!, of the medicinal herbs are generated only when they are potentiated by other plants, rather than using them aione (Sharma et al., 2020). Due to this comparable efficacy and the fewer side effects reported, a revival of interest is being observed worldwide for polyherbal formulations at Jresent. Hence, the present study is based on a polyherbal :ombination of Sri Lankan medicinal plants that will be safe and therapeutically benefici, las potential therapeutic agents in the management of kidney-related diseases, pa ticularly for doxorubidn-induccd nephrotoxicity. The polyhcrbal combination was de ived based on initial investigations on Abelmoschus moschatuc; Medikus. (leaves), Asp<. ragus falcatus L. (leaves), Barleria prionitis L. (whole plant), Gme/ina arborea Roxb. stem bark), and Vetiveria zizanioides (L,) Nash (root). These medicinal plants were initially selected with refer, nee to pharmacopeias and other monographs related to traditional medicine (A urveda Pharmacopoeia, 1985; Amarasiri, et al., 2020a).