College Pharmacy, Jiamusi University, Jiamusi, China.
Sino-Pakistan Center on Traditional Chinese Medicine, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua, China.
J Sep Sci. 2024 Oct;47(19):e202400486. doi: 10.1002/jssc.202400486.
Sinomenium acutum (Thunb.) Rehd. et Wils is widely used in the treatment of rheumatoid arthritis, with its alkaloid compound sinomenine (SIN) being renowned for its significant anti-inflammatory properties. However, despite its widespread application, the in vivo anti-inflammatory mechanisms and metabolic pathways of SIN remain incompletely understood. This study established a rapid and reliable method based on an ultra-high-performance liquid chromatography method coupled with Quadrupole-Exactive Orbitrap mass spectrometry and molecular docking to identify and characterize SIN and 69 metabolites in rat plasma, urine, and feces, revealing primary metabolic pathways of hydroxylation, demethylation, sulfation, and glucuronidation. Molecular docking results revealed that phase I reactions, including dedimethylation, demethylation, dehydrogenation, and dihydroxylation, along with their composite reactions, were pivotal in influencing SIN's in vivo anti-inflammatory activity. M28, M36, and M59 are potentially the most anti-inflammatory active metabolites of SIN in vivo. This comprehensive analysis unveils SIN's metabolic pathways, offering insights into its biological processes and suggesting a novel approach for exploring active drug constituents. These findings pave the way for further understanding SIN's anti-inflammatory mechanisms, contributing significantly to the development of new therapeutic strategies.
青风藤（Sinomenium acutum (Thunb.) Rehd. et Wils）广泛用于治疗类风湿关节炎，其生物碱化合物青藤碱（SIN）以显著的抗炎特性而闻名。然而，尽管其应用广泛，但 SIN 的体内抗炎机制和代谢途径仍不完全清楚。本研究建立了一种快速可靠的方法，基于超高效液相色谱法结合四极杆-静电轨道阱质谱法和分子对接，以鉴定和表征大鼠血浆、尿液和粪便中的 SIN 和 69 种代谢物，揭示了羟化、去甲基化、硫酸化和葡萄糖醛酸化等主要代谢途径。分子对接结果表明，包括去二甲基化、去甲基化、脱氢和二羟基化在内的 I 相反应及其复合反应，对影响 SIN 体内抗炎活性至关重要。M28、M36 和 M59 可能是 SIN 在体内最具抗炎活性的代谢物。这项全面的分析揭示了 SIN 的代谢途径，深入了解其生物学过程，并为探索活性药物成分提供了一种新方法。这些发现为进一步了解 SIN 的抗炎机制铺平了道路，为新的治疗策略的发展做出了重要贡献。
