A plasma metabolomic analysis revealed the metabolic regulatory mechanism of the water extract of Dendrobium huoshanense in improving streptozotocin-induced type 1 diabetes model rats.

Abstract

D. huoshanense is a traditional Chinese medicine with antidiabetes effects, but the underlying metabolic regulatory mechanism remains unknown. Plasma metabolomic analysis was applied to assess the metabolic regulatory mechanism underlying the alleviation of streptozotocin-induced type 1 diabetes (STZ-T1D) by D. huoshanense. The successfully STZ-T1D model rats were assigned to the model group, the model + water extract of D. huoshanense (DHWE) group, and the model + metformin (MET) group. They were administered the corresponding medication by gavage. After 28 days, the plasma levels of glucose, malondialdehyde (MDA), C-reactive protein (CRP), and total antioxidant capacity (T-AOC) were determined. Morphological changes in the pancreatic islet tissue were analyzed via hematoxylin and eosin (H&E) staining. The expression of occludin-1, zonula occludens protein 1 (ZO-1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) in the ileum tissue was determined via western blotting. Nontargeted metabolome analysis of the plasma was performed via ultrahigh-performance liquid chromatography. The results revealed that DHWE reduced blood glucose, C-reactive protein, and MDA levels; increased plasma T-AOC; improved intestinal mucous integrity and pancreatic islet morphological structure; and alleviated intestinal endoplasmic reticulum stress. Plasma metabolomics revealed that DHWE significantly increased the levels of ascorbic acid 2-sulfate, L-thyroxine, phosphatidylcholine (PC) (14:0e/5:0), and PC (16:1e/4:0); decreased the levels of D-(-)-fructose and indole-3-lactic acid; and significantly affected ascorbate and aldarate metabolism and glyoxylate and dicarboxylate metabolism in STZ-T1D rats (p < 0.05), and the effects on the citric acid cycle and pyruvate metabolism tended to be significant (p < 0.1). This study confirmed that DHWE alleviated STZ-T1D by reducing oxidative stress and the inflammatory response, enhancing intestinal mucosa integrity and affecting mainly the energy metabolism and vitamin C metabolism of STZ-T1D rats.