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A. officinarum Hance – P. cablin (Blanco) Benth drug pair improves oxidative stress, intracellular Ca2+ concentrations and apoptosis by inhibiting the AGE/RAGE axis to ameliorate diabetic gastroparesis: In vitro and in vivo studies

Xiuwen Zheng,Qianrong Xue,Yinghuan Wang,Lu Lu,Yipeng Pan,Jian Xu,Junqing Zhang

Ethnopharmacological relevance Alpinia officinarum Hance is a perennial natural medicine herbivorous plant, has been used in the management of treat stomach pain and diabetes, it is abundantly cultivated in Qiongzhong, Baisha and other places. P. cablin (Blanco) Benth, one of the most important traditional Chinese plants, which plays functions in antioxidant and gastrointestinal regulation, has been extensively planted in Hainan, Guangdong and other regions. Aim of the study In this study, we investigated the role and underlying molecular mechanism of AP on diabetic gastroparesis (DGP) in vitro and in vivo . Materials and methods In this study, using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum Hance– P. cablin (Blanco) Benth drug pair (AP). Molecular docking were utilized to explore the potential mechanism of AP treatment of DGP. In in vitro assays, gastric smooth muscle cells (GSMCs) were treated with 35 mM glucose to promote apoptosis and construct the DGP model, which was treated with different concentrations of AP. Furthermore, transfection technology was used to overexpress RAGE in GSMCs and elucidate the underlying mechanisms of alleviation of DGP by AP. Results Using UPLC-MS/MS analysis, nine components of AP were identified. We found that AP effectively blocked the increase in apoptosis, oxidative stress, and intracellular Ca 2+ concentrations. For in vivo experiments, mice were fed with a high-fat irregular diet to construct DGP model, and AP was co-administered via oral gavage daily to prevent the development of DGP. Compared with DGP mice, AP significantly decreased fasting blood glucose levels and increased gastric emptying levels. Consistent with in vitro experiments, AP also considerably decreased the increase in oxidative stress in DGP mice. Mechanistically, AP alleviates apoptosis and DGP by decreasing oxidative stress and intracellular Ca 2+ concentrations via the inhibition of the AGE/RAGE axis. Conclusions Collectively, this study has established that AP can improve DGP, and the mechanism may be related to the inhibition the AGE/RAGE axis to mitigate apoptosis and DGP. To summarize, this study provides a novel supplementary strategy for DGP treatment.