Antinociceptive effect of gelsenicine, principal toxic alkaloids of gelsemium, on prostaglandin E2-induced hyperalgesia in mice: Comparison with gelsemine and koumine

• Published in: Biochemical and biophysical research communications Vol. 681; pp. 55 - 61
• Main Authors: Xu, Wen-Bo, Tang, Mo-Huan, Long, Jiang-Yu, Wang, Wei-Wei, Qin, Jiao-Yan, Qi, Xue-Jia, Liu, Zhao-Ying
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 12.11.2023
• Subjects: Gelsemine; Gelsenicine; Glycine receptor; Koumine; Pain; Gelsemine; Pain; Gelsenicine; Koumine; Glycine receptor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2023.09.037

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 ED50 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 (LD50 = 0.185 mg/kg). The study also investigated the mechanism of action by analyzing the expression levels of GlyRα3 and Gephyrin. The PGE2 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 PGE2-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 PGE2.•Gelsenicine did not cause pathological damage to the mouse's spinal cord.•Gelsenicine has the best analgesic effect among the G.elegans alkaloids.