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.

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 Ca2+ 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 Ca2+ 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.

Alpinia officinarum Hance extract ameliorates diabetic gastroparesis by regulating SCF/c-kit signaling pathway and rebalancing gut microbiota.

Diabetic gastroparesis (DGP) is a common complication of type 2 diabetes mellitus (T2DM). Alpinia officinarum Hance (AOH) is one of the most commonly used both as a food and folk medicines, which is rich in diarylheptanoids and flavonoids. The gastroprotection and hypoglycemic effect make AOH has great potential in developing of anti-DGP complementary medicine. However, the molecular mechanisms of AOH that act against DGP are yet to be elucidated. In this study, we evaluated the therapeutic effects, the potential molecular mechanism, and the changes of gut microbiota of AOH in DGP. The 5 components of the AOH were analyzed, and the potential signaling pathway of AOH improving DGP was predicted by molecular docking. Subsequently, DGP rat model was constructed using high-fat-irregular-diet, AOH intervention significantly reduced blood glucose levels, increased gastrointestinal propulsion rate, and improved gastric histological morphology in DGP rats. Meanwhile, AOH has been shown to regulate the SCF/c-kit signaling pathway and rebalance the gut microbiota, which may be closely related to its role in improving DGP. Taken together, AOH may play a protective role on DGP through multiple mechanisms, which might pave the road for development and utilization of AOH.