To discover novel anti-inflammatory agents, a series of nitrogen-containing derivatives of aloe-emodin were designed and synthesized. The anti-inflammatory activities of all synthesized derivatives were screened by evaluating their inhibitory effects on LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was determined. Among them, 2i exhibited the best nitric oxide inhibitory activity (IC₅₀ = 3.15 μM), with no obvious toxicity. Further evaluation of the inhibitory effect of 2i on inflammatory cytokines showed that 2i significantly reduced the levels of TNF-α, IL-1β, IL-6 and PGE2. In addition, 2i markedly downregulated the expression levels of iNOS and COX-2. Preliminary mechanistic studies indicated that the anti-inflammatory effect of 2i might be related to the inhibition of the Akt, NF-κB and JNK signaling pathways. Overall, our findings suggested that 2i might be a promising anti-inflammatory agent, or might serve as a new lead compound for the further development of anti-inflammatory agents.

为发现新型抗炎药，设计合成了一系列芦荟大黄素的含氮衍生物。通过评估它们对 LPS 诱导的 RAW264.7 巨噬细胞中一氧化氮产生的抑制作用来筛选所有合成衍生物的抗炎活性。初步确定了构效关系。其中，2i表现出最好的一氧化氮抑制活性（IC ₅₀  = 3.15 μM），无明显毒性。进一步评估2i对炎性细胞因子的抑制作用表明，2i显着降低了 TNF-α、IL-1β、IL-6 和 PGE2 的水平。此外，2i显着下调 iNOS 和 COX-2 的表达水平。初步机制研究表明， 2i的抗炎作用可能与抑制 Akt、NF-κB 和 JNK 信号通路有关。总体而言，我们的研究结果表明，2i可能是一种有前途的抗炎剂，或者可能作为进一步开发抗炎剂的新先导化合物。