Schisandrin B

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.

Ochratoxin A (OTA), a mycotoxin produced by Aspergillus and Penicillium species, exerts toxic effects on reproduction and embryonic development through oxidative stress. Although OTA contamination in animal feed is a well-recognized threat, effective protective strategies remain limited. Schisandrin B (Sch-B), a bioactive lignan derived from Schisandra chinensis, is known for its potent antioxidant activity. This study investigated whether Sch-B could alleviate OTA-induced oxidative damage in porcine preimplantation embryos. Porcine zygotes were cultured in vitro with OTA (0.5 mg/L) and/or Sch-B (1 mg/L), and developmental competence, oxidative stress, mitochondrial function, apoptosis, and NRF2/KEAP1 signaling were assessed. OTA exposure significantly reduced cleavage and blastocyst formation rates, increased ROS and MDA levels, and impaired mitochondrial membrane potential. In contrast, Sch-B treatment restored embryonic development, decreased ROS accumulation, increased glutathione (GSH) levels, and improved mitochondrial function. Moreover, Sch-B upregulated NRF2 expression and downregulated KEAP1, indicating activation of the NRF2-mediated antioxidant pathway. Apoptosis assays and mRNA analysis revealed that Sch-B attenuated OTA-induced cell death by modulating the expression of pro- and anti-apoptotic genes. Co-treatment, however, did not fully restore all parameters to control levels, suggesting that higher Sch-B concentrations or additional interventions may be needed. These results demonstrate that Sch-B mitigates OTA-induced oxidative stress and supports early embryonic development via NRF2 pathway activation. Sch-B represents a promising candidate for improving in vitro embryo culture conditions and counteracting mycotoxin-induced reproductive toxicity.