A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury.

Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.

Structural elucidation and hypoglycemic effect of an inulin-type fructan extracted from Stevia rebaudiana roots.

Diabetes mellitus (DM) is a common chronic medical condition characterized by hyperglycemia resulting from abnormal insulin functionality, of which type 2 DM (T2DM) is the predominant form. An inulin-type fructan, denoted as SRRP, was obtained from Stevia rebaudiana roots via hot-water extraction and alcoholic precipitation, which was subsequently purified by column chromatography. The extracted SRRP sample had a molecular weight of 5.4 × 103 Da. Structural analyses indicated that SRRP was composed of 2,1-linked-ß-D-fructofuranosyl and α-D-glucopyranosyl residues in a ratio of approximately 29 : 1. In vivo assays revealed that SRRP significantly reduced fasting blood glucose levels, improved insulin resistance, decreased oxidative stress, and regulated lipid metabolism in T2DM mouse models. In addition, SRRP altered the diversity of the gut microbiota and its metabolites in T2DM mice; it increased probiotic bacteria and the concentration of short-chain fatty acids and decreased harmful bacteria. The findings demonstrate the potential of SRRP in the treatment of T2DM.

Structural elucidation and anti-nonalcoholic fatty liver disease activity of Polygonatum cyrtonema Hua polysaccharide.

The chemical structure and pharmacological activity of Polygonatum cyrtonema Hua polysaccharides have garnered significant attention in recent years. In this study, a homogeneous polysaccharide, PCP1, was extracted from P. cyrtonema Hua rhizomes and purified. Monosaccharide composition analysis showed that PCP1 is primarily composed of fructose, glucose, and mannose. Chemical structure analysis showed that the main chain of PCP1 is composed mainly of →1)-ß-D-Fruf-(2→ and →1,6)-ß-D-Fruf-(2→, with small amounts of →6)-α-D-Glcp-(1→, →4)-ß-D-Manp-(1→, and ß-D-Glcp-(1→. The side chain is ß-D-Fruf-(2→ linked at C-6 of →1,6)-ß-D-Fruf-(2→. In vivo experiments showed that PCP1 mitigates liver pathological damage, improves abnormal lipid metabolism and oxidative stress, promotes the production of short-chain fatty acids, and balances the composition of the intestinal microbiota in non-alcoholic fatty liver disease (NAFLD) mice. Thus, PCP1 can be used as a natural ingredient in functional foods for the treatment of NAFLD.