Sophflarines B−E, four distinctive matrine alkaloids from Sophora flavescens with potential neuroprotective activities

• DOI: 10.1016/j.phytochem.2024.114310
• Publication Date: 2024-10-25T00:25:04Z
• Authors: Ding Luo; Qian Xie; He Tian; Xin-Kai Zheng; Jia-Wen Zou; Yue-Hao Huang; Yan-Jun Chen; Chun-Lin Fan; Li-Jun Hu; Jian-Xin Chen; Hao Wang; Guo-Cai Wang; Yu-Bo Zhang
• Keywords: Sophora flavescens; Sophora; Oxymatrine

The four matrine-derived alkaloids, namely sophflarines B-E (1-4), with distinct skeleton types, were isolated from Sophora flavescens. Compounds 1 and 2 possess rare 1-aza-11-oxatricyclo[5.3.1.02,6] undecane cores, featuring unprecedented N,O-heterocyclic systems of 5/5/6/6/6 and 6/5/5/6/6, respectively. Compounds 3 and 4 exhibit two novel C15 units with tetracyclic skeletons of 5/6/6/6 and 6/5/6/6, respectively. The structures were elucidated through spectroscopic analyses, quantum chemical calculations, and X-ray diffraction data. A plausible biosynthetic pathway for these newly discovered compounds was proposed. Furthermore, compounds 1 and 2 showed anti-neuroinflammatory activity against the cytokines NO, TNF-α, and IL-6. Compound 2 exhibited a neuroprotective effect potentially mediated by activating the Keap1-Nrf2/HO-1 pathway to reduce inflammation and oxidative stress.