Unigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USA.
College of Pharmacy and Health Sciences, St John's University, Queens, NY 11439, USA.
Molecules. 2023 Sep 11;28(18):6560. doi: 10.3390/molecules28186560.
HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from and was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.
高迁移率族蛋白 B1（HMGB1）是一种关键的晚期炎症介质，在空气污染诱导的氧化应激中上调。细胞外 HMGB1 在气道和肺部的积累在炎症性肺损伤的发病机制中起着重要作用。降低细胞外 HMBG1 水平可能会恢复固有免疫细胞的功能，从而保护肺部免受有害损伤。目前针对空气污染引起的呼吸问题的治疗方法还不够完善。天然来源的膳食抗氧化剂可以作为对抗空气污染诱导的氧化应激和肺损伤的第一道防线。在这里，评估了一种标准化的来自和的植物抗氧化剂组合物在减轻急性炎症性肺损伤和败血症中的功效。利用包括高氧暴露、细菌挑战性急性肺损伤、LPS 诱导的败血症和 LPS 诱导的急性炎症性肺损伤模型在内的几种疾病的小鼠模型来评估植物组合物对吞噬活性和 HMGB1 释放的影响。使用高氧应激培养的巨噬细胞来评估植物组合物对吞噬活性和 HMGB1 释放的影响。进行了苏木精-伊红（HE）染色评估肺组织损伤、ELISA 检测炎症细胞因子和趋化因子、Western blot 分析包括细胞外 HMGB1 在内的蛋白质、肺和气道中的细菌计数等分析。在体内研究中观察到死亡率（50%）、血清和支气管肺泡灌洗液（BALF）中的促炎细胞因子（TNF-α、IL-1β、IL-6）和趋化因子（CINC-3）显著降低，气道和肺部的细菌清除率增加，气道总蛋白减少，细胞外 HMGB1 减少。在培养的巨噬细胞中观察到细胞外 HMGB1 水平降低 75.9%，吞噬作用增强。本报告中的数据综合表明，该植物组合物可用于氧化应激诱导的肺损伤保护，可能通过减轻细胞外 HMGB1 积累增加来实现。
