Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake

喀麦隆香料提取物对 HepG2 细胞氧化应激的调节:Nrf2 的参与和葡萄糖摄取的改善

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作者:Achille Parfait Atchan Nwakiban, Stefania Cicolari, Stefano Piazza, Fabrizio Gelmini, Enrico Sangiovanni, Giulia Martinelli, Lorenzo Bossi, Eugénie Carpentier-Maguire, Armelle Deutou Tchamgoue, Gabriel Agbor, Jules-Roger Kuiaté, Giangiacomo Beretta, Mario Dell'Agli, Paolo Magni

Abstract

Oxidative stress plays a relevant role in the progression of chronic conditions, including cardiometabolic diseases. Several Cameroonian plants, including spices, are traditionally used as herbal medicines for the treatment of diseases where oxidative stress contributes to insulin resistance, like type 2 diabetes mellitus. This study evaluated the antioxidant capacity and the effects on oxidative-stress-induced impairment of glucose uptake of 11 Cameroonian spice extracts. H2O2-induced reactive oxygen species (ROS) production by human HepG2 cells was significantly reduced by 8/11 extracts. The most effective extracts, Xylopia parviflora, Echinops giganteus, and Dichrostachys glomerata, showed a concentration-dependent ROS-scavenging activity, which involved Nrf2 translocation into the nucleus. Xylopia parviflora, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum extracts showed the highest antioxidant capacity, according to oxygen radical absorbance capacity (ORAC) (2.52-88 μM Trolox Eq/g of extract), ferric-reducing antioxidant power (FRAP) (40.23-233.84 mg gallic acid Eq/g of extract), and total phenol (8.96-32.96% mg gallic acid Eq/g of extract) assays. In HepG2 cells, glucose uptake was stimulated by 4/11 extracts, similarly to insulin and metformin. H2O2-induced oxidative stress reduced glucose uptake, which was rescued by pretreatment with Xylopia aethiopica, Xylopia parviflora, Scorodophloeus zenkeri, Monodora myristica, and Dichrostachys glomerata extracts. The ROS-scavenging ability of the spice extracts may reside in some secondary metabolites observed by phytochemical profiling (reverse-phase high-performance liquid chromatography coupled to a diode array detector (HPLC-UV-DAD)). Further studies are needed to better clarify their biological activities and potential use to control oxidative stress and promote insulin sensitivity.

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