Pentagalloylglucose reduces AGE-induced inflammation by activating Nrf2/HO-1 and inhibiting the JAK2/STAT3 pathway in mesangial cells.

Pentagalloylglucose (PGG), a gallotannin polyphenolic compound, has been found to possess a host of beneficial pharmacologic activities, such as anti-inflammatory and antioxidative activities. We previously demonstrated that PGG is capable of binding to the cell membrane of renal mesangial cells, but the pharmacological effect of PGG on diabetic renal injury and the underlying mechanisms are still not yet clear. In this study, the effects of PGG on Nrf2/HO-1 and JAK2/STAT3 signaling were explored in AGE-stimulated mesangial cells. Furthermore, the Nrf2 transcriptional inhibitor ML385 was used to verify the involvement of Nrf2 in the PGG-mediated inhibition of the JAK2/STAT3 cascade. Our results showed that PGG significantly inhibited AGE-induced ROS generation and activated AGE-inhibited Nrf2/HO-1 signaling. Moreover, AGE-induced inflammatory cytokines (IL-1ß and TNF-α) and their signaling through JAK2/STAT3 were blocked by PGG. Furthermore, ML385 suppressed Nrf2/HO-1 signaling, elevated ROS and cytokine production, and activated JAK2/STAT3 cascade were reversed by PGG. These findings indicate that PGG inhibits the JAK2/STAT3 cascade by activating Nrf2/HO-1 signaling.

Screening active components from Rubus amabilis for pancreatic ß-cells protection.

CONTEXT: Rubus species (Rosaceae) have been used in folk medicine to treat diabetes due to their hypoglycaemic activity. OBJECTIVE: To screen the active components that act as hypoglycaemic agents in Rubus amabilis Focke and the underlying mechanisms. MATERIALS AND METHODS: Aqueous stem extract of R. amabilis was incubated with MIN6 ß-cells, PBS was used as the blank control. Then the cells were washed, cell membrane-bound components were dissociated and identified by UPLC/MS. Total procyanidins (PCs) in R. amabilis was enriched and the cytotoxicity and anti-proliferation on ß-cell were evaluated by MTT assay. PCs at 25, 50, and 75 µg/mL was applied for 24 h to determine its effects on palmitate (PA)-induced apoptosis and GSIS. Western blotting was employed to detect the protein expression of PI3K/Akt/FoxO1 signalling. The antioxidant indices were also measured. RESULTS: ß-Cell membrane-bound components were identified as three procyanidin B dimers and a C trimer. PCs showed no significant cytotoxicity up to a concentrations of 100 µg/mL. PCs treatment reversed the elevated apoptosis rate and impaired GSIS induced by PA. PCs markedly decreased the intracellular ROS and MDA production and increased the SOD activity. Moreover, PCs promoted the phosphorylation of Akt and FoxO1, and regulated Pdx-1 and Bax expression in MIN6 cells. Discussion and conclusion: The active components that act as hypoglycaemic agents in R. amabilis are procyanidins, which protected MIN6 cells against PA-induced apoptosis by activating PI3K/Akt/FoxO1 signalling. These results indicate that ß-cell extraction, combined with UPLC/MS, is a valid method for screening antidiabetic components from herbal medicines.