Integrated metabolomic and transcriptome analyses reveal the regulatory mechanisms of partridge tea phenolics-rich extracts on type 2 diabetes mice

Partridge tea (Mallotus oblongifolius Muell-Arg), an important and widely consumed substitute tea in Hainan, China, possessed multi-biological activities. This study investigated the composition and content of phenolics-rich extracts purified from partridge tea, and then explored the effect of partridge tea polyphenol extract (PTE) on glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) mice. The results showed that the dominant components in PTE included rutin ((63.78 ± 1.86) mg/g), 3-chlorogenic acid ((85.81 ± 3.48) mg/g), caffeic acid ((152.78 ± 2.93) mg/g), catechin ((12.10 ± 1.41) mg/g), gallic acid ((5.24 ± 0.12) mg/g), kaempferitrin, ellagic acid, ferulic acid, caffeic acid methylester, and geraniin. After 6 weeks of PTE intervention, glucose tolerance, insulin resistance, and pancreatic β-cell function in T2DM mice had significantly improved. This improvement was corroborated by an increase in glucagon-like peptide-1 (GLP-1) to homeostasis model assessment of β-cell function (HOMA-β), glycogen, insulin protein expression, and reduction in insulin levels, glycosylated serum protein (GSP), homeostasis model assessment-insulin resistance index (HOMA-IR), glucagon protein expression. The supplementation of PTE also seems to alleviate the inflammatory response, as evidenced by a decrease in endotoxin and inflammatory cytokine levels. Hyperglycemia-induced mitochondrial damage is alleviated by PTE intervention. Hematoxylin-eosin staining (H&E staining) and lipid profile analysis indicate that PTE intervention can help regulate lipid metabolism disorders. In addition, the integration of metabolomics and transcriptomic analysis indicates that PTE intervention could regulate glycolipid metabolism pathways related to T2DM, including insulin, AMPK, bile acid metabolism and glutathione metabolism signaling pathways. More importantly, the validation results from reverse transcription-polymerase chain reaction (RT-PCR) confirmed that the expressions of Scd1, Fasn, Hmgcr, and Slc2a4 (related to glycolipid metabolism) were consistent with the transcriptomics data. In conclusion, these results suggested that PTE may exhibit significant health promoting effects for T2DM mice.