Antioxidants

Cadmium (Cd) is a recognized environmental contaminant, present in soil, water, and food, which has been reported to cause male reproductive damage in vivo and vitro. Selenium-enriched rapeseed flowering stalks exhibit protective effects against Cd-induced reproductive damage, yet the bioactive components and underlying mechanisms remain unclear. We optimized the process of obtaining the crude extract (CE) via single-factor experiments. Subsequent bioassay-guided fractionation identified the water extract (WE) as significantly more effective in alleviating Cd-induced cytotoxicity compared to the petroleum ether extract, ethyl acetate extract, and n-butanol extract. High-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS) analysis revealed that WE contained the highest contents of methylselenocysteine (MeSeCys) and selenocystine (SeCys₂) among four fractions. Both MeSeCys and SeCys₂ exhibited protective effects against Cd-induced cytotoxicity. To further elucidate the underlying mechanisms, network pharmacology, RNA-Seq, qPCR, and Western blotting analysis were employed. The results revealed that WE exhibited good free radical scavenging capabilities, and the protective mechanisms of WE, MeSeCys, and SeCys₂ against Cd-induced cytotoxicity were related to a reduction in oxidative damage, the inhibition of the ERK/p38 MAPK signaling pathway, and the suppression of cell cycle arrest, inflammation, and apoptosis triggered by Cd exposure. Collectively, these findings suggest that selenium-enriched rapeseed flowering stalks may serve as a promising dietary supplement in the prevention of Cd-induced reproductive toxicity.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders.

Background: Diabetes mellitus adversely affects female reproductive health by inducing oxidative stress, impairing autophagy, and promoting fibrotic remodeling in ovarian and uterine tissues. Spermidine, a natural polyamine, has gained attention as an antioxidant and autophagy enhancer. This study aimed to investigate the potential protective role of spermidine against diabetes-induced reproductive injury in rats. Methods: Thirty adult female Wistar rats were randomly divided into three groups (n = 10 each): Control, Diabetes, and Diabetes + Spermidine. Diabetes was induced with streptozotocin (60 mg/kg, i.p.). After confirmation of hyperglycemia (≥250 mg/dL), rats received either saline or spermidine (40 mg/kg/day, oral gavage) for four weeks. At sacrifice, plasma anti-Müllerian hormone (AMH) levels were determined, and ovarian and uterine tissues were assessed histologically and biochemically for oxidative stress markers (GSH, MDA, Nrf2), autophagy proteins (LC3, Beclin-1), and fibrosis indicators (TGF-β, histological scoring). Results: Diabetic rats exhibited severe hyperglycemia, pronounced follicular and endometrial degeneration, increased fibrosis, reduced plasma AMH, depleted GSH, SOD, CAT, GPx and Nrf2, and elevated MDA (p < 0.001). Spermidine treatment significantly mitigated these alterations, lowering glucose levels, alleviating histopathological injury, elevating the antioxidant defense (GSH, SOD, CAT, GPx) and the Nrf2 and decreasing MDA and TGF-β concentrations (p < 0.05 vs. Diabetes). Moreover, spermidine supplementation enhanced LC3 and Beclin-1 expression, suggesting improved autophagic activity. Conclusions: Spermidine counteracts diabetes-induced ovarian and uterine damage by reinforcing antioxidant defense, stimulating autophagy, and limiting fibrosis. These findings highlight spermidine as a promising adjunctive agent to support female reproductive health under diabetic conditions.