Schisandrin B

This study investigates the therapeutic effects of Schisandrin B (Sch B) combined with vitamin D (VD) on cognitive dysfunction and Alzheimer's disease (AD)-like pathology in aged rats induced by a high-fat and high-sugar (HFHS) diet, with a focus on the inhibition of NLRP3 inflammasome activation as a potential mechanism.

Eighteen-week-old male Sprague-Dawley rats were randomly assigned to five groups: Control, HFHS, HFHS + Sch B, HFHS + VD, and HFHS + Sch B + VD. After 20 weeks of treatment, metabolic parameters (body weight, fasting blood glucose, insulin resistance, lipid profiles), inflammatory markers, and hippocampal protein expression were assessed. Cognitive function was evaluated using the Morris water maze, novel object recognition, open field, and elevated plus maze tests.

Combined Sch B and VD markedly attenuated body weight gain, fasting blood glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), while improving lipid profiles (TG, TC, LDL-C). Behavioral tests revealed significant improvements in spatial learning, memory, and object recognition (p < 0.01), with combined therapy outperforming monotherapy. Additionally, the combination downregulated hippocampal NLRP3 inflammasome components (ASC, cleaved caspase-1, IL-1β, IL-18) and reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).

In this HFHS diet-induced aging rat model, Sch B combined with VD improved cognitive performance and reduced AD-like lesions, likely via inhibition of NLRP3 inflammasome-mediated neuroinflammation. These findings provide mechanistic insights and support further preclinical evaluation of this combination as a potential strategy for AD prevention and intervention.

Schisandrin B (SchB), a natural lignan with reported organ-protective effects, was hypothesized to ameliorate severe acute pancreatitis (SAP). We investigated the effects of SchB (30 and 60 mg/kg) in a caerulein-induced mouse model of SAP using histological, biochemical, and transcriptomic analyses. Contrary to our hypothesis, SchB administration significantly exacerbated pancreatitis, evidenced by more severe pancreatic edema, necrosis, inflammatory infiltration, and significantly higher serum α-amylase levels compared to vehicle-treated controls. Global RNA sequencing (RNA-seq) of pancreatic tissue identified "Pancreatic Secretion" as a key upregulated pathway. SchB induced a massive transcriptional upregulation of genes encoding digestive enzymes, including trypsinogens, lipases, and amylase. Concurrently, the gene for the calcium efflux pump Atp2a3 was downregulated, suggesting a mechanism for intracellular calcium overload. In conclusion, SchB exacerbates acute pancreatitis, likely by transcriptionally promoting the overproduction of digestive enzymes, leading to enhanced auto-digestion. These findings reveal a novel, context-specific harmful effect of SchB, challenging its perception as a universally protective agent and urging caution in its use for patients with or at risk for pancreatic diseases.