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Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane

Journal of Chinese Pharmaceutical Sciences 2016年第8期25卷 559-569页

作者： Francisco Fuentes Yury Gomez Ximena Paredes-Gonzalez Avantika Barve Sujit Nair Siwang Yu Constance Lay Lay Saw Ah-Ng Tony Kong Facultad de Agronomia e Ingenieria Forestal Pontificia Universidad Cato1ica de Chile Casilla 306-22 Santiago Chile Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers The State University of New Jersey New Jersey 08854 USA Novartis Institutes for Biomedical Research East Hanover NJ-07470 USA Amrita Cancer Discovery Biology Laboratory Amrita Vishwa Vidyapeetham University Amritapuri Clappana P.O. Kollam Kerala-690525 India School of Pharmaceutical Sciences Peking University Health Science Center Beo'ing 100191 China

The dietary phytochemicals curcumin （CUR） and sulforaphane （SFN） have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE （antioxidant response element） response in HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes-heme oxygenase-1 （HO-I） and UDP-glucuronosyltransferase-1A （UGT1A）-was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR （10 ~tM） and SFN （12.5 ~tM） significantly induced the expression of HO-1 and UGT 1 A1 proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in HepG2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.

关键词： Antioxidant response element, curcumin, HepG2-C8 cell-s, HO-1, Nrf2, Sulforaphane, UGT 1A1

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Antimicrobial Efficacy of curcumin Formulations byPhotodynamic Therapy

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Journal of Pharmacy and Pharmacology 2017年第8期5卷 506-511页

作者： Kate C. Blanco Natalia M. Inada Fernanda M. Carbinatto Vanderlei S. Bagnato University of S6o Paulo Sao Carlos Institute of Physics Sao Paulo 13566-590 Brazil

URTI （upper respiratory tract infections） are caused by acute, chronic or recurrent infections including pharyngitis andtonsillitis. The etiologic agents involved are bacteria, virus, and fungi. The standard treatment for bacterial infections is the use ofantibiotics. The antibiotic resistance, side effects of drugs and URTI complications indicate the importance of new therapies. PDT（photodynamic therapy） is a treatment option with a fast onset of action, low side effects, and easy administration of PS（photosensitizer） based on this study. The main aim of this study was to develop a new modality for the treatment of infectiouspharyngotonsillitis by photodynamic therapy. In addition, this study aims to evaluate components of the therapy as the PS, curcumin,in two formulations and irradiation conditions in the effectiveness of treatment. The procedure consists of two steps： oraladministration of CFs （curcumin formulations） containing a PS and illumination （450 nm and 0-60 J/cm2）. Bacterial isolates wereobtained from patients in a routine clinical pratice. The new methodology has been developed from the principle ofPI （photodynamicinactivation）. The strain identification number of colony forming units determined the efficacy of PI using each component, lightingand PS. The use of curcumin formulations in PI presented microbial reduction of 5 log.

关键词： Upper respiratory tract infections, pharyngitis, tonsillitis, curcumin, photodynamic therapy, clinical isolates, syrup, gum.

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