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

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. <i>Berberis vulgaris</i> L. (<i>B. vulgaris</i>) has a proven role in several therapeutic applications in...

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Main Authors: Sarfraz Ahmad, Amina Hussain, Aroosha Hussain, Iskandar Abdullah, Muhammad Sajjad Ali, Matheus Froeyen, Muhammad Usman Mirza
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/8/6/185
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author Sarfraz Ahmad
Amina Hussain
Aroosha Hussain
Iskandar Abdullah
Muhammad Sajjad Ali
Matheus Froeyen
Muhammad Usman Mirza
author_facet Sarfraz Ahmad
Amina Hussain
Aroosha Hussain
Iskandar Abdullah
Muhammad Sajjad Ali
Matheus Froeyen
Muhammad Usman Mirza
author_sort Sarfraz Ahmad
collection DOAJ
description 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. <i>Berberis vulgaris</i> L. (<i>B. vulgaris</i>) 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 <i>B. vulgaris</i> (<i>Bv</i>RE). Berberine chloride in <i>Bv</i>RE was found to be 10.29% <i>w/w</i>. To assess the prophylactic and curative protective effects of <i>Bv</i>RE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130&#8722;180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of <i>Bv</i>RE (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 (<i>p</i> &lt; 0.05) variations were observed in various parameters. Moreover, histological studies of liver and kidney tissues revealed that the protective effect of <i>Bv</i>RE 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, <i>Bv</i>RE, 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 <i>Bv</i>RE as a protective agent in combination therapy with cisplatin.
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spelling doaj.art-ed3cd4a65853443aab04a97ce782d5812023-09-02T19:27:48ZengMDPI AGAntioxidants2076-39212019-06-018618510.3390/antiox8060185antiox8060185Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro CytotoxicitySarfraz Ahmad0Amina Hussain1Aroosha Hussain2Iskandar Abdullah3Muhammad Sajjad Ali4Matheus Froeyen5Muhammad Usman Mirza6Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Biochemistry, Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore 54000, PakistanDepartment of Biochemistry, Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore 54000, PakistanDepartment of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Biochemistry, Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore 54000, PakistanDepartment of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, B-3000 Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, B-3000 Leuven, BelgiumCisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of cancer treatments, but dose-dependent side effects limit its usefulness. <i>Berberis vulgaris</i> L. (<i>B. vulgaris</i>) 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 <i>B. vulgaris</i> (<i>Bv</i>RE). Berberine chloride in <i>Bv</i>RE was found to be 10.29% <i>w/w</i>. To assess the prophylactic and curative protective effects of <i>Bv</i>RE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130&#8722;180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of <i>Bv</i>RE (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 (<i>p</i> &lt; 0.05) variations were observed in various parameters. Moreover, histological studies of liver and kidney tissues revealed that the protective effect of <i>Bv</i>RE 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, <i>Bv</i>RE, 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 <i>Bv</i>RE as a protective agent in combination therapy with cisplatin.https://www.mdpi.com/2076-3921/8/6/185cisplatin<i>Berberis vulgaris</i>high-performance liquid chromatographynephrotoxicityhepatotoxicityhyperlipidemia
spellingShingle Sarfraz Ahmad
Amina Hussain
Aroosha Hussain
Iskandar Abdullah
Muhammad Sajjad Ali
Matheus Froeyen
Muhammad Usman Mirza
Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity
Antioxidants
cisplatin
<i>Berberis vulgaris</i>
high-performance liquid chromatography
nephrotoxicity
hepatotoxicity
hyperlipidemia
title Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity
title_full Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity
title_fullStr Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity
title_full_unstemmed Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity
title_short Quantification of Berberine in <i>Berberis vulgaris</i> L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity
title_sort quantification of berberine in i berberis vulgaris i l root extract and its curative and prophylactic role in cisplatin induced in vivo toxicity and in vitro cytotoxicity
topic cisplatin
<i>Berberis vulgaris</i>
high-performance liquid chromatography
nephrotoxicity
hepatotoxicity
hyperlipidemia
url https://www.mdpi.com/2076-3921/8/6/185
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