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Acute lung injury (ALI) caused by sepsis is one of the most common critical diseases, which is difficult to treat and has a high fatality rate. Koumine is one of the main active components of Gelsemium plants and has been confirmed to have potential for drug development; however, its therapeutic effects on ALI have not yet been studied. This study established ALI due to sepsis using cecal ligation and puncture (CLP) and assessed the therapeutic effects of koumine by measuring mouse survival rates, lung tissue pathological damage, inflammatory factors, and oxidative stress levels. Additionally, network pharmacology was utilized to explore the underlying mechanisms. The results showed that koumine inhibited the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), thereby inhibiting inflammatory response, reducing lung injury score and lung wet to dry ratio. In addition, koumine reduced oxidative stress in mice by reducing myeloperoxidase (MPO) and malondialdehyde (MDA) and increasing superoxide dismutase (SOD) content. Network pharmacology analysis showed that 52 putative targets were relevant, and SLC6A4, HTR3A, JAK2 and JAK3 were the key targets. GO and KEGG pathway enrichment analysis showed that the related mechanisms involved neuroactive ligand-receptor interaction, calcium signaling pathway, serotonergic synapses, cholinergic synapses, etc. In summary, this study confirmed the potential therapeutic effect of koumine in sepsis induced ALI, suggesting its development prospect as a novel candidate drug for ALI, and providing data support. [Display omitted] • To study for the first time the effect of active components of Gelsemium plant on pulmonary diseases. • Analyzed the role and mechanism of koumine in acute lung injury through inflammation, oxidative stress, and network pharmacology. • Koumine is a potential treatment for sepsis-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Gelsemium elegans (G.elegans) is a plant of the Loganiaceae family, known for its indole alkaloids, including gelsemine, koumine, and gelsenicine. Gelsemine and koumine are well-studied active alkaloids with low toxicity, valued for their anti-anxiety and analgesic properties. However, gelsenicine, another important alkaloid, remains underexplored due to its high toxicity. This study focuses on evaluating the analgesic properties of gelsenicine and comparing them with gelsemine and koumine. The results indicate that all three alkaloids exhibit robust analgesic properties, with gelsemine, koumine, and gelsenicine showing ED 50 values of 0.82 mg/kg, 0.60 mg/kg, and 8.43 μg/kg, respectively, as assessed by the hot plate method. Notably, the therapeutic dose of gelsenicine was significantly lower than its toxic dose (LD 50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyRα3 and Gephyrin. The PGE 2 model group showed decreased expression levels of GlyRα3 and Gephyrin, while groups treated with gelsemine, koumine, and gelsenicine were able to reverse this decrease. These results suggest that gelsenicine effectively alleviates PGE 2 -induced hyperalgesia by upregulating the expression of GlyRα3 and Gephyrin, which are key targets of the Gly receptor pathway. • This study explored the analgesic mechanism of gelsenicine for the first time. • Gelsenicine can significantly relieve the hypersensitivity pain caused by PGE 2. • Gelsenicine did not cause pathological damage to the mouse's spinal cord. • Gelsenicine has the best analgesic effect among the G.elegans alkaloids. [ABSTRACT FROM AUTHOR]