Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province Yunnan Characteristic Plant Extraction Laboratory, School of Chemical Science and Technology, Yunnan University, Kunmina 650500, PR China.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province Yunnan Characteristic Plant Extraction Laboratory, School of Chemical Science and Technology, Yunnan University, Kunmina 650500, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.
Fitoterapia. 2022 Oct;162:105283. doi: 10.1016/j.fitote.2022.105283. Epub 2022 Aug 23.
Acute lung injury (ALI), a severe respiratory disorder, frequently develops into acute respiratory distress syndrome (ARDS) without timely treatment and scores highly in terms of morbidity and mortality rates. Fritillaria hupehensis is a famous traditional Chinese medicine with antitussive, expectorant and anti-asthmatic effect. Here, the effects of F. hupehensis extracts on lipopolysaccharide (LPS)-induced ALI mice were evaluated for the first time. We showed ethyl acetate fraction (EAF) significantly reduced the leukocytes and neutrophils of bronchoalveolar lavage fluid (BALF) and the lung index as well as pro-inflammatory cytokines (TNF-α and IL-6) of lung homogenates but increasing the anti-inflammatory cytokines (IL-4 and IL-10). Additionally, the alleviation of EAF treatment on lung injury was verified through histopathological observations. Subsequent phytochemical investigation on bioactive fraction led to isolation of 17 compounds including two new, in which compounds 2, 5 and 6 exhibited better anti-inflammatory effect on LPS-induced 16 human airway epithelial (16HBE) cells model by inhibiting the production of CRP and PCT. Furthermore, compound 2 suppressed the LPS-induced upregulation of proteins containing p-p65, COX-2, Caspase-1 and IL-18. In summary, F. hupehensis alleviating LPS-induced ALI in mice may be associated with the anti-inflammatory activity of steroidal alkaloids by suppressing the NF-κB-regulated pro-inflammatory proteins.
急性肺损伤 (ALI) 是一种严重的呼吸系统疾病，如果不及时治疗，通常会发展成急性呼吸窘迫综合征 (ARDS)，其发病率和死亡率都很高。浙贝母是一种具有镇咳、祛痰和平喘作用的著名中药。本研究首次评价了浙贝母提取物对脂多糖 (LPS) 诱导的 ALI 小鼠的作用。结果表明，乙酸乙酯部分 (EAF) 可显著降低支气管肺泡灌洗液 (BALF) 中的白细胞和中性粒细胞以及肺匀浆中的促炎细胞因子 (TNF-α 和 IL-6)，同时增加抗炎细胞因子 (IL-4 和 IL-10)。此外，通过组织病理学观察证实了 EAF 治疗对肺损伤的缓解作用。对生物活性部分进行后续的植物化学研究，分离得到 17 种化合物，其中化合物 2、5 和 6 通过抑制 CRP 和 PCT 的产生，对 LPS 诱导的 16 人气道上皮 (16HBE) 细胞模型表现出更好的抗炎作用。此外，化合物 2 抑制了 LPS 诱导的 p-p65、COX-2、Caspase-1 和 IL-18 蛋白的上调。综上所述，浙贝母缓解 LPS 诱导的 ALI 小鼠的作用可能与甾体生物碱的抗炎活性有关，通过抑制 NF-κB 调节的促炎蛋白。
