Diabetic nephropathy (DN) is a worldwide health problem with increasing incidence. Diosgenin (DIO) is a natural active ingredient extracted from Chinese yams (Rhizoma dioscoreae) with potential antioxidant, anti-inflammatory, and antidiabetic effects. However, the protective effect of DIO on DN is still unclear. The present study explored the mitigating effects and underlying mechanisms of DIO on DN in vivo and in vitro. In the current study, the DN rats were induced by a high-fat diet and streptozotocin and then treated with DIO and metformin (Mef, a positive control) for 8 weeks. The high-glucose (HG)-induced HK-2 cells were treated with DIO for 24 h. The results showed that DIO decreased blood glucose, biomarkers of renal damage, and renal pathological changes with an effect comparable to that of Mef, indicating that DIO is potential active substance to relieve DN. Thus, the protective mechanism of DIO on DN was further explored. Mechanistically, DIO improved autophagy and mitophagy via the regulation of the AMPK-mTOR and PINK1-MFN2-Parkin pathways, respectively. Knockdown of CaMKK2 abolished AMPK-mTOR and PINK1-MFN2-Parkin pathways-mediated autophagy and mitophagy. Mitophagy and mitochondrial dynamics are closely linked physiological processes. DIO also improved mitochondrial dynamics through inhibiting fission-associated proteins (DRP1 and p-DRP1) and increasing fusion proteins (MFN1/2 and OPA1). The effects were abolished by CaMKK2 and PINK1 knockdown. In conclusion, DIO ameliorated DN by enhancing autophagy and mitophagy and by improving mitochondrial dynamics in a CaMKK2-dependent manner. PINK1 and MFN2 are proteins that concurrently regulated mitophagy and mitochondrial dynamics.

Heat-inactivated microorganisms are a typical class of postbiotics with promising potential health effects, as they contain various physiologically active components. Dietary supplementation with Companilactobacillus crustorum MN047 (CC) has been shown to have the potential to alleviate ulcerative colitis (UC). However, it is unclear whether the UC-relieving effect of this strain is partly attributed to its bacterial composition. Therefore, the interventional effects of heat-inactivated CC (HICC) on UC mice were explored. The results showed that the administration of HICC significantly ameliorated the UC-related pathological parameters by (1) alleviating the pathologic lesions of UC (e.g., preventing the increase in disease activity index and the shortening of colon length); (2) ameliorating the colonic inflammation (e.g., inhibiting the expressions of chemokines and pro-inflammatory cytokines, such as Cxcl1, Cxcl5, Ccl7, TNF-α, IL-1β, IL-6, and MCP-1; (3) attenuating the oxidative damage (e.g., suppressing the increase in myeloperoxidase and malondialdehyde); (4) mitigating the damage of gut barrier (e.g., promoting colonic occludin, ZO-1, and claudin levels); and (5) modulating gut microbiota structure (e.g., increasing the relative abundance of potential probiotics, such as Akkermansia and Lactobacillus). In conclusion, our study suggested that HICC can be effective in preventing UC and has the potential as a dietary supplement to intervene in UC.

Rambutan peel polyphenols effectively improve the lifespan and health of Drosophila . It may exert the life-extending effect through the preservation of balanced redox status and gut barrier integrity, as well as the attenuation of Toll/Imd pathway.