Rapid Characterization of the Potential Active of Sinomenine in Rats by Ultra-High-Performance Liquid Chromatography-Quadrupole-Exactive Orbitrap Mass Spectrometry and Molecular Docking
Haixia Li, KaiLin Li, Wenhui Cheng, Mingjuan Liu, Linwen Wen, Zexu Zhang, Wendan Zhang, Jin Su, Wei Cai
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引用次数: 0
Abstract
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.
Sinomenium acutum (Thunb.) Rehd. et Wils 被广泛用于治疗类风湿性关节炎,其生物碱化合物 sinomenine(SIN)以显著的抗炎特性而闻名。然而,尽管其应用广泛,但人们对 SIN 的体内抗炎机制和代谢途径仍不完全了解。本研究采用超高效液相色谱法结合四极杆-极性轨道阱质谱法和分子对接法,建立了一种快速可靠的方法,对大鼠血浆、尿液和粪便中的 SIN 和 69 种代谢物进行了鉴定和表征,揭示了羟基化、去甲基化、硫酸化和葡萄糖醛酸化等主要代谢途径。分子对接结果显示,第一阶段反应,包括脱甲基化、脱甲基化、脱氢和二羟基化,以及它们的复合反应,是影响 SIN 体内抗炎活性的关键。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,有助于深入了解其生物过程,并提出了一种探索药物活性成分的新方法。这些发现为进一步了解 SIN 的抗炎机制铺平了道路,对开发新的治疗策略大有裨益。
期刊介绍:
The Journal of Separation Science (JSS) is the most comprehensive source in separation science, since it covers all areas of chromatographic and electrophoretic separation methods in theory and practice, both in the analytical and in the preparative mode, solid phase extraction, sample preparation, and related techniques. Manuscripts on methodological or instrumental developments, including detection aspects, in particular mass spectrometry, as well as on innovative applications will also be published. Manuscripts on hyphenation, automation, and miniaturization are particularly welcome. Pre- and post-separation facets of a total analysis may be covered as well as the underlying logic of the development or application of a method.