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      Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

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          Abstract

          Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric ( Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants ( e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

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          Resveratrol Inhibits Invasion and Metastasis of Colorectal Cancer Cells via MALAT1 Mediated Wnt/β-Catenin Signal Pathway

          Resveratrol, extracted from Chinese herbal medicine Polygonum cuspidatum, is known to inhibit invasion and metastasis of human colorectal cancer (CRC), in which long non-coding Metastasis Associated Lung Adenocarcinoma Transcript 1 (RNA-MALAT1) also plays an important role. Using MALAT1 lentiviral shRNA and over-expression constructs in CRC derived cell lines, LoVo and HCT116, we demonstrated that the anti-tumor effects of resveratrol on CRC are through inhibiting Wnt/β-catenin signaling, thus the expression of its target genes such as c-Myc, MMP-7, as well as the expression of MALAT1. In detail, resveratrol down-regulates MALAT1, resulting in decreased nuclear localization of β-catenin thus attenuated Wnt/β-catenin signaling, which leads to the inhibition of CRC invasion and metastasis. This finding of ours surely provides important pre-clinical evidence supporting future use of resveratrol in prevention and treatment of CRC.
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            Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway.

            Metformin activates both PRKA and SIRT1. Furthermore, autophagy is induced by either the PRKA-MTOR-ULK1 or SIRT1-FOXO signaling pathways. We aimed to elucidate the mechanism by which metformin alleviates hepatosteatosis by examining the molecular interplay between SIRT1, PRKA, and autophagy. ob/ob mice were divided into 3 groups: one with ad libitum feeding of a standard chow diet, one with 300 mg/kg intraperitoneal metformin injections, and one with 3 g/d caloric restriction (CR) for a period of 4 wk. Primary hepatocytes or HepG2 cells were treated with oleic acid (OA) plus high glucose in the absence or presence of metformin. Both CR and metformin significantly improved body weight and glucose homeostasis, along with hepatic steatosis, in ob/ob mice. Furthermore, CR and metformin both upregulated SIRT1 expression and also stimulated autophagy induction and flux in vivo. Metformin also prevented OA with high glucose-induced suppression of both SIRT1 expression and SIRT1-dependent activation of autophagy machinery, thereby alleviating intracellular lipid accumulation in vitro. Interestingly, metformin treatment upregulated SIRT1 expression and activated PRKA even after siRNA-mediated knockdown of PRKAA1/2 and SIRT1, respectively. Taken together, these results suggest that metformin alleviates hepatic steatosis through PRKA-independent, SIRT1-mediated effects on the autophagy machinery.
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              Berberine: new perspectives for old remedies.

              Chemical compounds derived from plants have been used since the origin of human beings to counteract a number of diseases. Among them, the natural isoquinoline alkaloid berberine has been employed in Ayurvedic and Chinese Medicine for hundreds of years with a wide range of pharmacological and biochemical effects. More recently, a growing body of reports supports the evidence that berberine has anticancer effects, being able to block the proliferation of and to kill cancer cells. This review addresses the properties and therapeutic use of berberine and focuses on the recent advances as promising anticancer drug lead. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                ImpactJ
                Aging (Albany NY)
                Impact Journals LLC
                1945-4589
                June 2017
                12 February 2017
                : 9
                : 6
                : 1477-1536
                Affiliations
                1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
                2 Department of Comparative Medicine, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
                3 Department of Internal Medicine, Hematology/Oncology Section, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA
                4 Department of Foundational Sciences, School of Dental Medicine, East Carolina University, Greenville, NC 27834, USA
                5 Department of Physiological Sciences, Piracicaba Dental School, State University of Campinas, Piracicaba, Brazil
                6 Unit of Oncologic Diseases, ASP-Catania, Catania 95100, Italy
                7 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
                8 Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
                9 Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland
                10 Department of Molecular Physiology and Neurobiology, Wroclaw University, Wroclaw, Poland
                11 Naxospharma, Novate Milanese 20026, Italy
                12 Department of Biomedical and Biotechnological Sciences, Oncological, Clinical and General Pathology Section, University of Catania, Catania, Italy
                13 Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy
                14 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy
                Author notes
                Correspondence to: James A. McCubrey, mccubreyj@ 123456ecu.edu
                Article
                101250
                10.18632/aging.101250
                5509453
                28611316
                83320246-f925-4e58-b543-ee71f0f66937
                Copyright: © 2017 McCubrey et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 19 May 2017
                : 4 June 2017
                Categories
                Review

                Cell biology
                mirs,sirt,gene methylation,cscs,natural products,resveratrol,curcumin
                Cell biology
                mirs, sirt, gene methylation, cscs, natural products, resveratrol, curcumin

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