Abstract：
Inflammation plays a critical role in the development of numerous diseases. Cannabidiol (CBD), found in hemp, exhibits significant pharmacological activities. Accumulating evidence suggests that CBD has anti-inflammatory and cardiovascular protection effects, but the potential mechanisms require further exploration. In this study, we aimed to reveal the mechanisms of CBD against high-fat, high-cholesterol (HFC) diet-induced inflammation combining metabolomics with network pharmacology. First, plasma lipidomics results indicated that oxidized lipids could serve as potential biomarkers for HFC diet-induced inflammation, and CBD reversed the elevated levels of oxidized lipids. The HFC diet was also found to enhance intestinal permeability, facilitating the entry of lipopolysaccharides (LPSs) into the circulatory system and subsequently increasing systemic inflammation. Additionally, cell metabolomic results indicated that CBD could reverse 10 important differential metabolites in LPS-induced RAW 264.7 cells. Using network pharmacology, we identified 49 core targets, and enrichment analysis revealed that arachidonic acid was the most significantly affected by CBD, which was closely associated with inflammation. Further integrated analysis focused on three key targets, including PTGS2, ALOX5, and ALOX15. Molecular docking showed high affinities between key targets and CBD, and qPCR further demonstrated that CBD could reverse the mRNA expression of these key targets in RAW 264.7 cells. Collectively, this finding integrates lipidomics and metabolomics with network pharmacology to elucidate the anti-inflammatory effects of CBD and validates key therapeutic targets.
摘要：
炎症在许多疾病的发展中起关键作用。大麻二酚（CBD），在大麻中发现，具有显著的药理活性。越来越多的证据表明，CBD具有抗炎和心血管保护作用，但是潜在的机制需要进一步探索。在这项研究中,我们旨在揭示CBD对抗高脂肪的机制，结合代谢组学和网络药理学的高胆固醇（HFC）饮食诱导的炎症。首先,血浆脂质组学结果表明，氧化脂质可以作为HFC饮食诱导的炎症的潜在生物标志物，和CBD逆转了氧化脂质水平的升高。还发现HFC饮食可以增强肠道通透性，促进脂多糖（LPS）进入循环系统并随后增加全身性炎症。此外,细胞代谢组学结果表明，CBD可以逆转LPS诱导的RAW264.7细胞中的10种重要差异代谢产物。使用网络药理学，我们确定了49个核心目标,和富集分析表明，花生四烯酸受CBD影响最大，与炎症密切相关。进一步的综合分析侧重于三个关键目标，包括PTGS2、ALOX5和ALOX15。分子对接显示关键靶标和CBD之间的高度亲和力，qPCR进一步证明CBD可以逆转RAW264.7细胞中这些关键靶标的mRNA表达。总的来说，这一发现将脂质组学和代谢组学与网络药理学相结合,以阐明CBD的抗炎作用并验证关键治疗靶点.
