Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Jinhua Institute of Zhejiang University, Jinhua, 321016, China.
J Ethnopharmacol. 2022 Jun 28;292:115205. doi: 10.1016/j.jep.2022.115205. Epub 2022 Mar 17.
BBD is a well-known traditional Chinese medicine widely used in clinic to treat viral hepatitis, cholecystitis, angiocholitis and urinary tract infection. According to traditional medicinal theory, BBD exerts the effects of "clearing and humid heat, activating blood and removing toxicity, curing jaundice and relieving pain", the signs of which are recognized as common symptoms of inflammation during infectious diseases in modern medicine.
To determine the therapeutic effect of BBD on bacterial endotoxin lipopolysaccharide (LPS) induced sepsis and to investigate the relevant pharmacological and molecular mechanisms of action whereby BBD mitigates inflammation.
In vivo, a mouse sepsis model was induced by intraperitoneally injection of LPS; the BBD were formulated as drug suspension for intragastric administration. The survival rate, secretion of pro-inflammatory cytokines of IL-1β and TNF-α, and multiple organ injury of lung, liver and spleen were examined. In vitro, peritoneal macrophages (PMs) were stimulated with LPS plus ATP for NLRP3 inflammasome activation; polar gradient extractions of BBD from ultrapure water (sample 1) followed by 70% ethanol (sample 2) were added as interventions. In addition to detect the secretion of IL-1β and TNF-α, the activation of NF-κB, ASC-speck formation and ASC oligomerization were examined by western blotting and immunofluorescent stainning. Eventually, the extractions of BBD were applied for UPLC-QTOF-MS analyses; refer to the identified chemicals, the bioactive compounds in BBD with anti-NLRP3 inflammasome activities were discussed.
BBD improved the survival of sepsis mice accomplished with diminished inflammatory cytokines production and multiple organ injury. Mechanistically, BBD inhibited both the NF-κB pathway and the assembly of NLRP3 complex in PMs. There were 29 chemical compounds identified from sample 1 and 20 from sample 2. Both samples contained bile acids and saponins and sample 2 contained 2 extra chemicals in the category of bile acids.
BBD presents therapeutic role of endotoxin induced sepsis by inhibiting NLRP3-medaited inflammasome activation, which supports its traditional use for the treatment of infectious diseases. The bile acids and saponins are most likely related to the anti-NLRP3 inflammasome activation effect of BBD.
BBD 是一种广为人知的中药，临床上常用于治疗病毒性肝炎、胆囊炎、胆管炎和尿路感染。根据传统医学理论，BBD 具有“清热利湿、活血解毒、退黄止痛”的功效，这些症状被认为是现代医学传染病炎症的常见症状。
确定 BBD 对内毒素脂多糖（LPS）诱导的败血症的治疗作用，并探讨 BBD 减轻炎症的相关药理和分子作用机制。
体内，通过腹腔注射 LPS 诱导小鼠败血症模型；BBD 制成混悬液灌胃给药。检测生存率、促炎细胞因子 IL-1β和 TNF-α的分泌以及肺、肝和脾的多器官损伤。体外，用 LPS 加 ATP 刺激腹腔巨噬细胞（PMs）激活 NLRP3 炎性体；从超纯水（样品 1）和 70%乙醇（样品 2）中对 BBD 进行极性梯度提取作为干预措施。除检测 IL-1β和 TNF-α的分泌外，还通过 Western blot 和免疫荧光染色检测 NF-κB 的激活、ASC 斑点形成和 ASC 寡聚化。最后，对 BBD 提取物进行 UPLC-QTOF-MS 分析；参考鉴定的化学物质，讨论 BBD 中具有抗 NLRP3 炎性体活性的生物活性化合物。
BBD 通过减少炎症细胞因子的产生和多器官损伤，改善了败血症小鼠的生存率。在机制上，BBD 抑制了 PMs 中的 NF-κB 途径和 NLRP3 复合物的组装。从样品 1 中鉴定出 29 种化学物质，从样品 2 中鉴定出 20 种化学物质。两个样品都含有胆汁酸和皂苷，样品 2 中胆汁酸类多了 2 种化学物质。
BBD 通过抑制 NLRP3 介导的炎性体激活，对内毒素诱导的败血症具有治疗作用，支持其传统用于治疗传染病的用途。胆汁酸和皂苷很可能与 BBD 抗 NLRP3 炎性体激活作用有关。
