Liangliang He,Jinjin Xu,Qi Wang,Yezi Zhang,Zifei Qin,Yang Yu,Zhengming Qian,Zhihong Yao,Xinsheng Yao
Shogaols, mainly [6]-shogaol (6S), [8]-shogaol (8S) and [10]-shogaol (10S), the predominant and characteristic pungent phytochemicals in ginger, are responsible for most of its beneficial effects. However, poor oral bioavailability owing to extensive glucuronidation limits their application. The present study aimed to characterize the glucuronidation pathways of 6S, 8S and 10S by using pooled human liver microsomes (HLM), human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). The rates of glucuronidation were determined by incubating shogaols with uridine diphosphate glucuronic acid-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Reaction phenotyping assays, activity correlation analyses and relative activity factors were performed to identify the main UGT isoforms. As a result, one mono-4′-O-glucuronide was detected after incubating each shogaol with HLM and HIM. Enzymes kinetic analysis demonstrated that glucuronidation of shogaols consistently displayed the substrate inhibition profile, and the liver showed higher metabolic activity for shogaols (CLint = 1.37–2.87 mL min−1 mg−1) than the intestine (CLint = 0.67–0.85 mL min−1 mg−1). Besides, reaction phenotyping assays revealed that UGT2B7 displayed the highest catalytic ability (CLint = 0.47–1.17 mL min−1 mg−1) among all tested UGTs. In addition, glucuronidation of shogaols was strongly correlated with AZT glucuronidation (r = 0.886, 0.803 and 0.871 for glucuronidation of 6S, 8S and 10S, respectively; p < 0.01) in a bank of individual HLMs (n = 9). Furthermore, UGT2B7 contributed to 40.8%, 34.2% and 36.0% for the glucuronidation of 6S, 8S and 10S in HLM, respectively. Taken altogether, shogaols were efficiently metabolized through the glucuronidation pathway, and UGT2B7 was the main contributor to their glucuronidation.
Zeng Xin,Wang Shang,Peng Ze,Wang Meng,Zhao Kui,Xu Ben Bin,Yin Xiongwei,Ibrahim Mohamed M.,Mersal Gaber A. M.,El-Bahy Zeinhom M.,Guo Zhanhu,Xiang Wei,Wang Jianwei
Non-alcoholic fatty liver disease is a prevalent chronic metabolic condition, for which no approved medications are available. As a condiment and traditional Chinese medicine, ginger can be useful in reducing the symptoms of non-alcoholic fatty liver disease. Although its active ingredients and mechanisms of action are unknown, there is a lack of research on them. The purpose of this study is to prepare magnetite (Fe 3 O 4 )@Stearoyl-CoA desaturase 1 (SCD1) materials and analyze them using ultra-high performance liquid-chromatography-mass spectrometry (UPLC-MS) for rapid screening of potential inhibitors of SCD1 in ginger. Based on this analysis, it has been shown that the primary components in ginger that bind SCD1 directly are gingerols, with 10-gingerol having a greater affinity for binding to SCD1 than 8-gingerol and 6-gingerol. Moreover, further studies indicated that free fatty acids (FFA)-induced lipid accumulation is improved by this class of compounds in normal human hepatocytes (THLE-3), with 10-gingerol being the most effective compound. This study provides a new insight into the mechanism, by which ginger contributes to the improvement of non-alcoholic fatty liver disease (NAFLD) and provide support for the effective use of 10-gingerol for the treatment of NAFLD.
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