Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, China.
Department of Pathophysiology, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, China.
Phytother Res. 2023 Oct;37(10):4690-4705. doi: 10.1002/ptr.7938. Epub 2023 Jul 9.
Ulcerative colitis (UC) has emerged as a global healthcare issue due to high prevalence and unsatisfying therapeutic measures. 20(S)- Protopanaxadiol saponins (PDS) from Panax notoginseng with anti-inflammatory properties is a potential anti-colitis agent. Herein, we explored the effects and mechanisms of PDS administration on experimental murine UC. Dextran sulfate sodium-induced murine UC model was employed to investigate anti-colitis effects of PDS, and associated mechanisms were further verified in HMGB1-exposed THP-1 macrophages. Results indicated that PDS administration exerted ameliorative effects against experimental UC. Moreover, PDS administration remarkably downregulated mRNA expressions and productions of related pro-inflammatory mediators, and reversed elevated expressions of proteins related to NLRP3 inflammasome after colitis induction. Furthermore, administration with PDS also suppressed the expression and translocation of HMGB1, interrupting the downstream TLR4/NF-κB pathway. In vitro, ginsenoside CK and 20(S)-protopanaxadiol, the metabolites of PDS, exhibited greater potential in anti-inflammation, and intervened with the TLR4-binding domain of HMGB1 predictably. Expectedly, ginsenoside CK and 20(S)-protopanaxadiol administrations inhibited the activation of TLR4/NF-κB/NLRP3 inflammasome pathway in HMGB1-exposed THP-1 macrophages. Summarily, PDS administration attenuated inflammatory injury in experimental colitis by blocking the binding of HMGB1 to TLR4, majorly attributed to the antagonistic efficacies of ginsenoside CK and 20(S)-protopanaxadiol.
溃疡性结肠炎（UC）由于其高患病率和不理想的治疗措施，已成为全球医疗保健问题。具有抗炎作用的三七总皂苷（PDS）是一种潜在的抗结肠炎药物。在此，我们研究了 PDS 给药对实验性 UC 小鼠的作用和机制。采用葡聚糖硫酸钠诱导的 UC 小鼠模型来研究 PDS 的抗结肠炎作用，并在 HMGB1 暴露的 THP-1 巨噬细胞中进一步验证相关机制。结果表明，PDS 给药对实验性 UC 具有改善作用。此外，PDS 给药可显著下调相关促炎介质的 mRNA 表达和产生，并在结肠炎诱导后逆转 NLRP3 炎性体相关蛋白的升高表达。此外，PDS 给药还抑制了 HMGB1 的表达和易位，阻断了下游 TLR4/NF-κB 通路。在体外，PDS 的代谢产物人参皂苷 CK 和 20(S)-原人参二醇在抗炎方面表现出更大的潜力，并可预测性地干预 HMGB1 的 TLR4 结合域。如预期的那样，人参皂苷 CK 和 20(S)-原人参二醇给药抑制了 HMGB1 暴露的 THP-1 巨噬细胞中 TLR4/NF-κB/NLRP3 炎性小体途径的激活。总之，PDS 给药通过阻断 HMGB1 与 TLR4 的结合减轻实验性结肠炎的炎症损伤，主要归因于人参皂苷 CK 和 20(S)-原人参二醇的拮抗作用。
