School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China.
Food Funct. 2023 Jul 31;14(15):7011-7023. doi: 10.1039/d1fo04377c.
Murr. (LR) has long been used as a unique nutritional and medicinal food to treat various diseases such as gouty arthritis. However, although recently the literature has focused on the protective roles of LR anthocyanins on gouty arthritis, there is no relevant research from a holistic perspective of lipid metabolism to study their anti-gout effects. In this study, a combined tissue lipidomics, network pharmacology, and molecular docking approach was performed to investigate the intervention mechanism of LR anthocyanins against a monosodium urate (MSU)-induced gout mouse model. 54 gout-related lipid markers were identified lipidomic profiling of the mouse knee joint, including glycerophospholipids, sphingolipids, glycerolipids, and plasmalogens. Integrating with pathway analysis, network pharmacology, and molecular docking, the potential targets of LR anthocyanins for treating gouty arthritis were predicted, while pathways in cancer, prostate cancer, sphingolipid signaling, choline metabolism in cancer, arachidonic acid metabolism, and ovarian steroidogenesis were involved as shared critical pathways of lipidomic analysis and network pharmacology. Furthermore, the binding sites and patterns of 3 active components and 4 core targets with the lowest binding energies were explored. Western blotting was finally used to verify the expression levels of 4 core proteins: MMP2, MMP9, MAP2K1, and MAPK14. These results provide new insights into our understanding of gouty arthritis and the anti-gout mechanism of LR anthocyanins.
Murr. (LR) 长期以来一直被用作一种独特的营养和药用食品，用于治疗各种疾病，如痛风性关节炎。然而，尽管最近文献集中于 LR 花青素对痛风性关节炎的保护作用，但从脂质代谢的整体角度研究其抗痛风作用的相关研究尚未见报道。在这项研究中，采用组织脂质组学、网络药理学和分子对接方法，研究了 LR 花青素对尿酸单钠（MSU）诱导的痛风小鼠模型的干预机制。通过对小鼠膝关节的脂质组学分析，鉴定出 54 种与痛风相关的脂质标志物，包括甘油磷脂、鞘脂、甘油酯和脑苷脂。结合通路分析、网络药理学和分子对接，预测了 LR 花青素治疗痛风性关节炎的潜在靶点，而癌症、前列腺癌、鞘脂信号、癌症中的胆碱代谢、花生四烯酸代谢和卵巢类固醇生成等途径则作为脂质组学分析和网络药理学的共同关键途径。此外，还探讨了 3 种活性成分和 4 个核心靶标与最低结合能的结合位点和结合模式。最后，采用 Western blot 验证了 4 个核心蛋白（MMP2、MMP9、MAP2K1 和 MAPK14）的表达水平。这些结果为我们理解痛风性关节炎和 LR 花青素的抗痛风机制提供了新的见解。
