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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 Spenceria ramalana 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-\u03b1), 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.<\/jats:p>","DOI":"10.3390\/ijms26010165","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:34:19Z","timestamp":1735630459000},"page":"165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Amelioration of Inflammation in Rats with Experimentally Induced Asthma by Spenceria ramalana Trimen Polyphenols via the PI3K\/Akt Signaling Pathway"],"prefix":"10.3390","volume":"26","author":[{"given":"Zhaobin","family":"Xia","sequence":"first","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"},{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"},{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"},{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyu","family":"He","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebumo","family":"Aga","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankaer","family":"Kahaer","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Hao","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"},{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoxi","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China"},{"name":"Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Southwest Minzu University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,28]]},"reference":[{"key":"ref_1","unstructured":"GBD Chronic Respiratory Disease Collaborators (2020). 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