Abstract
Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of cancer treatments, but dose-dependent side effects limit its usefulness. Berberis vulgaris L. (B. vulgaris) has a proven role in several therapeutic applications in the traditional medicinal system. High-performance liquid chromatography was used to quantify berberine, a potent alkaloid in the methanolic root extract of B. vulgaris (BvRE). Berberine chloride in BvRE was found to be 10.29% w/w. To assess the prophylactic and curative protective effects of BvRE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130–180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of BvRE (500 mg/kg/day, orally). An array of marked toxicity effects appeared in response to cisplatin dosage evident by morphological condition, biochemical analysis of serum (urea, creatinine, total protein, alanine transaminase, aspartate transaminase, total cholesterol, and triglyceride), and organ tissue homogenates (malondialdehyde and catalase). Statistically-significant (p < 0.05) variations were observed in various parameters. Moreover, histological studies of liver and kidney tissues revealed that the protective effect of BvRE effectively minimized and reversed nephrotoxic, hepatotoxic, and hyperlipidemic effects caused by cisplatin in both prophylactic and curative groups with relatively promising ameliorative effects in the prophylactic regimen. The in vitro cell viability effect of cisplatin, BvRE, and their combination was determined on HeLa cells using the tetrazolium (MTT) assay. MTT clearly corroborated that HeLa cells appeared to be less sensitive to cisplatin and berberine individually, while the combination of both at the same concentrations resulted in growth inhibition of HeLa cells in a remarkable synergistic way. The present study validated the use of BvRE as a protective agent in combination therapy with cisplatin.
Highlights
Cancer is known to be a major cause of human morbidity and mortality
The present study focuses on the synergic effect of a toxic agent in combination with a non-toxic cancer inhibitor accompanying the efficacy of the treatment and combination decreasing tumor growth significantly compared to single-agent administration
The present study endorsed and substantiated the historical use of B. vulgaris as a curative agent for the treatment of kidney, liver, and heart disorders. It was concluded from the consequences of the present study that both prophylactic and curative regimens of Berberis vulgaris vulgaris root root extract extract (BvRE) had a marked protective activity against cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia in rats
Summary
Cisplatin (Cis-diamminedichloroplatinum (II)), an alkylating chemotherapeutic drug, has been in clinical practice for over 30 years It is among the most common frontline medicines for the treatment of some of the most devastating types of solid-organ cancers such as lung, esophagus, head, neck, stomach, testis, and ovary, as well as lymphoma and osteosarcoma [1]. The etiology concomitant with cisplatin-induced toxicities comprise inflammation, apoptosis, and the generation of reactive oxygen species [1]. These facts suggest that there is an urgent need for therapeutic agents that reduce/ameliorate cisplatin-induced side effects and synergistically improve its chemotherapeutic activity [2,3]. Plants are performing the role of a major health care resource all over the world, and the potential of plant-based remedies has progressively become well known due to their preventive actions and treating human diseases
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