Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm) via reducing NOX2 expression and inhibiting JNK–caspase 3 apoptotic cascade subsequently to protect β-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in β-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving β-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on β-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on β-cells were AMPK activation dependent. Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing β-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

Diabetes is characterized by a loss and dysfunction of the β-cell. Glucagon-like peptide 1 receptor (GLP-1R) signaling plays an important role in β-cell survival and function. It is meaningful to identify promising agents from natural products which might activate GLP-1R signaling. In this study, puerarin, a diet isoflavone, was evaluated its beneficial effects on β-cell survival and GLP-1R pathway. We showed that puerarin reduced the body weight gain, normalized blood glucose, and improved glucose tolerance in high-fat diet-induced and db/db diabetic mice. Most importantly, increased β-cell mass and β-cell proliferation but decreased β-cell apoptosis were observed in puerarin-treated diabetic mice as examined by immunostaining of mice pancreatic sections. The protective effect of puerarin on β-cell survival was confirmed in isolated mouse islets treated with high glucose. Further mechanism studies showed that the circulating level of GLP-1 in mice was unaffected by puerarin. However, puerarin enhanced GLP-1R signaling by up-regulating expressions of GLP-1R and pancreatic and duodenal homeobox 1, which subsequently led to protein kinase B (Akt) activation but forkhead box O1 inactivation, and promoted β-cell survival. The protective effect of puerarin was remarkably suppressed by Exendin(9–39), an antagonist of GLP-1R. Our study demonstrated puerarin improved glucose homeostasis in obese diabetic mice and identified a novel role of puerarin in protecting β-cell survival by mechanisms involving activation of GLP-1R signaling and downstream targets.

T-cell factor 7-like 2 (TCF7L2) is an important transcription factor of Wnt/β-catenin signaling, which has critical roles in β-cell survival and regeneration. In preliminary screening assay, we found geniposide, a naturally occurring compound, was able to increase TCF7L2 mRNA level in Min6 cells. Here we aimed to investigate the role of geniposide in β-cell and underlying mechanism involved. Geniposide was found to promote β-cell survival by increasing β-cell proliferation and decreasing β-cell apoptosis in cultured mouse islets after challenge with diabetic stimuli. Geniposide protected β-cell through activating Wnt signaling, enhanced expressions of TCF7L2 and GLP-1R, activated AKT, inhibited GSK3β activity, and promoted β-catenin nuclear translocation. The protective effect of geniposide was remarkably suppressed by siRNAs against β-catenin, or by ICG001 (β-catenin/TCF-mediated transcription inhibitor). Moreover, geniposide promoted β-cell regeneration in vivo to normalize blood glucose in high-fat diet and db/db mice. Increased β-cell proliferation was observed in pancreatic sections of geniposide-treated diabetic mice. Most importantly, geniposide triggered small islet-like cell clusters formation as a result of β-cell neogenesis from ductal epithelium, which was well correlated with the increase in TCF7L2 expression. In exocrine cells isolated from mouse pancreas, geniposide could induce duct cell differentiation through upregulating TCF7L2 expression and activating JAK2/STAT3 pathway. Taken together, we identified a novel role of geniposide in promoting β-cell survival and regeneration by mechanisms involving the activation of β-catenin/TCF7L2 signaling. Our finding highlights the potential value of geniposide as a possible treatment for type 2 diabetes.

Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.

Depression is one of the most common complications in patients with diabetes. Our previous study demonstrated puerarin, a dietary isoflavone, improved glucose homeostasis and β-cell regeneration in...