Xia Zhaobin, Zhao Xing, Wang Lu, Huang Lin, Yang Yanwen, Yin Xiangyu, He Luyu, Aga Yuebumo, Kahaer Ankaer, Yang Shiyu, Hao Lili, Chen Chaoxi
College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China.
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Southwest Minzu University, Chengdu 610041, China.
Int J Mol Sci. 2024 Dec 28;26(1):165. doi: 10.3390/ijms26010165.
Asthma is a chronic inflammatory respiratory disease that affects millions globally and poses a serious public health challenge. Current therapeutic strategies, including corticosteroids, are constrained by variable patient responses and adverse effects. In this study, a polyphenolic extract derived from the Tibetan medicinal plant Trimen (SRT) was employed and shown to improve experimentally (ovalbumin + cigarette smoke, OVA + CS) induced asthma in rats. Initially, the potential therapeutic mechanism of the polyphenolic components in SRT on OVA + CS-induced asthma was predicated by network pharmacology analysis. Subsequently, in vivo experiments identified that SRT polyphenols exhibit significant anti-asthmatic activities, primarily mediated by lowering inflammatory cell counts such as the WBC (white blood cell), eosinophils, and neutrophils, decreasing the expression of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α), alleviating lung histological damage (reduced inflammation, collagen deposition, and mucus secretion), and enhancing the epithelial barrier integrity (upregulation of ZO-1, occludin, and claudin-1). Additionally, SRT polyphenols downregulated the PI3K/Akt (Phosphoinositide 3-kinase/protein kinase B) signaling pathway, improved gut microbiota disruption, and regulated fecal metabolites (glucose-6-glutamate, PS (16:0/0:0), 8-aminocaprylic acid, galactonic acid, Ascr#10, 2,3,4,5,6,7-hexahydroxyheptanoic acid, phosphodimethylethanolamine, muramic acid, 9-oxohexadeca-10e-enoic acid, and sedoheptulose) in asthmatic rats. In conclusion, SRT polyphenols exerted multifaceted protective effects against OVA + CS-induced asthma in rats, highlighting their potential value in preventing asthma via the PI3K/Akt signaling pathway.
哮喘是一种慢性炎症性呼吸道疾病，全球数百万人受其影响，对公共卫生构成严重挑战。目前的治疗策略，包括使用皮质类固醇，受到患者反应多变和不良反应的限制。在本研究中，使用了一种从藏药植物Trimen中提取的多酚提取物（SRT），结果表明其可改善实验性（卵清蛋白+香烟烟雾，OVA+CS）诱导的大鼠哮喘。最初，通过网络药理学分析预测了SRT中多酚成分对OVA+CS诱导哮喘的潜在治疗机制。随后，体内实验确定SRT多酚具有显著的抗哮喘活性，主要通过降低炎症细胞计数，如白细胞（WBC）、嗜酸性粒细胞和中性粒细胞，减少炎症细胞因子（IL-4、IL-5、IL-13和TNF-α）的表达，减轻肺部组织学损伤（减少炎症、胶原沉积和黏液分泌），以及增强上皮屏障完整性（上调紧密连接蛋白1、闭合蛋白和Claudin-1）来介导。此外，SRT多酚下调PI3K/Akt（磷脂酰肌醇3激酶/蛋白激酶B）信号通路，改善肠道微生物群紊乱，并调节哮喘大鼠的粪便代谢物（葡萄糖-6-谷氨酸、PS（16:0/0:0）、8-氨基辛酸、半乳糖酸、Ascr#10、2,3,4,5,6,7-六羟基庚酸、磷酸二甲基乙醇胺、胞壁酸、9-氧代十六碳-10E-烯酸和景天庚酮糖）。总之，SRT多酚对OVA+CS诱导的大鼠哮喘发挥了多方面的保护作用，突出了其通过PI3K/Akt信号通路预防哮喘的潜在价值。
