Abstract

The present study attempts to investigate the cytotoxic activity of ethanol and ethyl acetate extracts of the Moroccan Berberis vulgaris and its major component berberine, together with exploring their antioxidant properties. It also consists of studying the combination effect of berberine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, against the human breast adenocarcinoma cell line (MCF-7). Using the MTT assay, we report a differential cytotoxic effect of ethanol and ethyl acetate extracts since the ethanol extract is more cytotoxic than the ethyl acetate one, with IC50 = 3.54 μg/mL and 596.71 μg/mL, respectively. Interestingly, no cytotoxic effect was observed against normal cells. Furthermore, these extracts showed a remarkable antioxidant activity as measured by the DPPH free radicals scavenging assay. In fact, the IC50 values are 69.65 μg/mL and 77.75 μg/mL for the ethanol and ethyl acetate extracts, respectively. In addition, several concentrations of berberine, when combined with the NO donor used at IC30, induced a synergistic cytotoxic activity at concentrations ranging from 8.40 μM to 33.60 μM, as revealed by the combination index values, using the Chou–Talalay method. However, at the other concentrations tested, an antagonistic effect was observed. The observed cytotoxicity was related to apoptosis induction as demonstrated by the annexin-V-streptavidin FITC-staining analysis.

Highlights

  • Our knowledge of plants and their benefits is as old as mankind

  • In Vitro Cytotoxic Effect of Berberis vulgaris Extracts. e in vitro cytotoxic activity of Berberis vulgaris extracts was measured by the methyl tetrazolium (MTT) assay against the MCF-7 tumour cell line at various concentrations. is activity was evaluated for the ethyl acetate and ethanol extracts of root barks

  • E results are summarised in Figure 1. e cells were incubated for 48 h with increasing concentrations of extracts of Berberis vulgaris, and the cytotoxic activity was measured by the MTT test as described in the Materials and Methods section

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Summary

Introduction

Our knowledge of plants and their benefits is as old as mankind. Man discovered very early the therapeutic properties of certain plants to overcome his suffering and improve his health. us, we chose to work on Berberis vulgaris from Oujda, east of Morocco, a plant of the Berberidaceae family locally named “Aghriss,” “Izergui,” and “Bou-Semmane” and used in traditional medicine for its antipyretic, hepatoprotective, and anti-inflammatory properties [1]. Us, we chose to work on Berberis vulgaris from Oujda, east of Morocco, a plant of the Berberidaceae family locally named “Aghriss,” “Izergui,” and “Bou-Semmane” and used in traditional medicine for its antipyretic, hepatoprotective, and anti-inflammatory properties [1]. Erefore, the first part of this work consists of comparing the cytotoxic activity of Berberis vulgaris extracts against breast cancer cells and normal human cells, as the nonselectivity of chemotherapy treatment is what causes the systemic toxicity. We investigated the molecular mechanisms of the cytotoxicity, as recent knowledge on molecular carcinogenesis has provided the potential for therapeutic intervention in cancer by targeting and sensitising cancer cells to apoptosis [9]. This work aims to explore the combination effect of berberine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, against breast cancer cells. Knowing that NO is a free radical synthesised from L-arginine by NO synthase (NOS), three isoforms of NOS (neuronal (nNOS), endothelial NOS (eNOS), and inducible

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