Quantification of Berberine in Berberis vulgaris L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity

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 validated the use of BvRE as a protective agent in combination therapy with cisplatin.

Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis

“…Cisplatin can induce activation of the pro-apoptotic proteins, which form pores in the outer membrane of mitochondria, resulting in induction of cytochrome c release into cytosol and resultant activation of executioner caspases such as caspase-3. Previous studies have shown that in addition to its anti-oxidant and radical-scavenging properties, melatonin exerts an anti-apoptotic effect on various types of cells [13,25]. In this study, we found that melatonin greatly inhibited caspase-3 activation and subsequent cleavage of PARP-1 in kidneys after cisplatin injection.…”

Pharmacological Activation of Sirt1 Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing Apoptosis, Oxidative Stress, and Inflammation in Mice

“…In this study, we found that administration of SRT1720 ameliorates acute renal failure in cisplatin-treated mice, as represented by decreased levels of creatinine and BUN. Because cisplatin treatment induces structural damages in kidneys, especially tubular injuries [25,26,27], we further examined the effect of SRT1720 on levels of NGAL and Kim-1. We found that tubular injuries in kidneys of cisplatin-treated mice were also markedly prevented by SRT1720, as evidenced by reduced expression of NGAL and Kim-1.…”

Integrated Analysis of m6A Methylome in Cisplatin-Induced Acute Kidney Injury and Berberine Alleviation in Mouse

“…As a promising drug, various pharmacological activities of berberine have been reported, including antimicrobial, antiemetic, antipyretic, anti-pruritic, antioxidant, anti-inflammatory, hypotensive, anti-arrhythmic, and sedative activities (Shamsa et al, 1999;Chen et al, 2012;Caliceti et al, 2016). Several reports have mentioned that berberine shows nephroprotective effects against cisplatin-induced kidney damage (Domitrović et al, 2013;Teng et al, 2015;Ojha et al, 2016;Ahmad et al, 2019). However, the mechanism of alleviating CI-AKI is still unclear.…”