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      A Comparative Study on Phytochemical Profiles and Biological Activities of Sclerocarya birrea (A.Rich.) Hochst Leaf and Bark Extracts

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          Abstract

          Sclerocarya birrea (A.Rich.) Hochst (Anacardiaceae) is a savannah tree that has long been used in sub-Saharan Africa as a medicinal remedy for numerous ailments. The purpose of this study was to increase the scientific knowledge about this plant by evaluating the total content of polyphenols, flavonoids, and tannins in the methanol extracts of the leaves and bark (MLE and MBE, respectively), as well as the in vitro antioxidant activity and biological activities of these extracts. Reported results show that MLE is rich in flavonoids (132.7 ± 10.4 mg of quercetin equivalents/g), whereas MBE has the highest content of tannins (949.5 ± 29.7 mg of tannic acid equivalents/g). The antioxidant activity was measured using four different in vitro tests: β-carotene bleaching (BCB), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), O 2 −•, and nitric oxide (NO ) assays. In all cases, MBE was the most active compared to MLE and the standards used (Trolox and ascorbic acid). Furthermore, MBE and MLE were tested to evaluate their activity in HepG2 and fibroblast cell lines. A higher cytotoxic activity of MBE was evidenced and confirmed by more pronounced alterations in cell morphology. MBE induced cell death, triggering the intrinsic apoptotic pathway by reactive oxygen species (ROS) generation, which led to a loss of mitochondrial membrane potential with subsequent cytochrome c release from the mitochondria into the cytosol. Moreover, MBE showed lower cytotoxicity in normal human dermal fibroblasts, suggesting its potential as a selective anticancer agent.

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          Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy.

          Reactive oxygen species (ROS) play a major role in carcinogenesis: pro-oxidant agents like tobacco smoke, asbestos or N-nitrosamines, are known as mutagenic and carcinogenic, and cancer cells show increased levels of ROS and redox deregulation. However, pro-oxidant molecules can also act as selective cytotoxic agents against cancer cells by achieving toxic levels of ROS. Although polyphenols are well-known as potent antioxidants, a pro-oxidant effect has been associated with their pro-apoptotic effect in various types of tumor cells. The aim of the present review is to present the main evidences of the pro-oxidant-related cytotoxic activity of naturally occurring polyphenols and their underlying mechanisms.
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            Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies

            Cancer onset and progression have been linked to oxidative stress by increasing DNA mutations or inducing DNA damage, genome instability, and cell proliferation and therefore antioxidant agents could interfere with carcinogenesis. It is well known that conventional radio-/chemotherapies influence tumour outcome through ROS modulation. Since these antitumour treatments have important side effects, the challenge is to develop new anticancer therapeutic strategies more effective and less toxic for patients. To this purpose, many natural polyphenols have emerged as very promising anticancer bioactive compounds. Beside their well-known antioxidant activities, several polyphenols target epigenetic processes involved in cancer development through the modulation of oxidative stress. An alternative strategy to the cytotoxic treatment is an approach leading to cytostasis through the induction of therapy-induced senescence. Many anticancer polyphenols cause cellular growth arrest through the induction of a ROS-dependent premature senescence and are considered promising antitumour therapeutic tools. Furthermore, one of the most innovative and interesting topics is the evaluation of efficacy of prooxidant therapies on cancer stem cells (CSCs). Several ROS inducers-polyphenols can impact CSCs metabolisms and self-renewal related pathways. Natural polyphenol roles, mainly in chemoprevention and cancer therapies, are described and discussed in the light of the current literature data.
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              Calcium and regulation of the mitochondrial permeability transition.

              Recent years have seen renewed interest in the permeability transition pore, a high conductance channel responsible for permeabilization of the inner mitochondrial membrane, a process that leads to depolarization and Ca(2+) release. Transient openings may be involved in physiological Ca(2+) homeostasis while long-lasting openings may trigger and/or execute cell death. In this review we specifically focus (i) on the hypothesis that the PTP forms from the F-ATP synthase and (ii) on the mechanisms through which Ca(2+) can reversibly switch this energy-conserving nanomachine into an energy-dissipating device.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                08 January 2018
                January 2018
                : 19
                : 1
                : 186
                Affiliations
                [1 ]University of Basilicata, Department of Science, V.le dell’AteneoLucano, 85100 Potenza, Italy; daniela.russo@ 123456unibas.it (D.R.); rocchina.miglionico@ 123456virgilio.it (R.M.); monica.carmosino@ 123456unibas.it (M.C.); faustino.bisaccia@ 123456unibas.it (F.B.); mariafrancesca.armentano@ 123456unibas.it (M.F.A.)
                [2 ]REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; pandrade@ 123456ff.up.pt (P.B.A.); valentao@ 123456ff.up.pt (P.V.)
                Author notes
                [* ]Correspondence: luigi.milella@ 123456unibas.it ; Tel.: +39-0971-205-525; Fax: +39-0971-205-501
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-9764-3920
                https://orcid.org/0000-0002-0740-4396
                https://orcid.org/0000-0002-5874-1237
                Article
                ijms-19-00186
                10.3390/ijms19010186
                5796135
                29316691
                5ffe47c5-2427-4af7-858d-3ee87b989290
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 December 2017
                : 02 January 2018
                Categories
                Article

                Molecular biology
                polyphenols,cytotoxic effect,ros,apoptosis,mitochondrial membrane potential,hepg2 cell line

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