Kaempferol 7-O-β-D-glucoside (KPG), a natural flavonol isolated from Cudrania tricuspidata, has been reported to exert anti-cancer effects; however, its anti-inflammatory effects have not yet been reported. In this study, we demonstrate the suppressive effect of KPG on the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and mouse bone marrow-derived macrophages. KPG downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level and iNOS, COX-2, TNF-α, IL-1β, and IL-6 at the mRNA level in LPS-treated RAW 264.7 macrophages. Moreover, we elucidated the underlying molecular mechanism, demonstrating that KPG attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 nuclear translocation, inhibiting κBα (IκBα) phosphorylation/degradation and IκB kinaseα/β (IKKα/β) phosphorylation. KPG additionally reduced LPS-induced activator protein-1 (AP-1) activity by inhibiting c-Fos expression in the nucleus, though c-Jun was not affected. Furthermore, we revealed that KPG significantly abrogated the LPS-induced phosphorylation of signal transducer and activator of transcription (STAT) 1 (Ser 727, Tyr 701) and STAT3 (Tyr 705) through inhibiting the phosphorylation of Janus kinase (JAK) 1 and JAK2, its upstream activating proteins. Taken together, our data suggest that KPG induces anti-inflammatory activity by blocking NF-κB, AP-1, and JAK-STAT signaling pathways in LPS-treated RAW 264.7 macrophages, thus suppressing inflammatory mediators.

据报道，山茱emp酚7 - O - β -D-葡萄糖苷（KPG）是一种从Cu木（Cudrania tricuspidata）分离得到的天然黄酮醇，具有抗癌作用。但是，其抗炎作用尚未见报道。在这项研究中，我们证明了KPG对一氧化氮（NO），前列腺素E ₂（PGE ₂），脂多糖（LPS）诱导的RAW 264.7巨噬细胞和小鼠骨髓来源的巨噬细胞中的肿瘤坏死因子-α（TNF-α），白介素-1β（IL-1β）和白介素6（IL-6）。KPG在蛋白水平下调了诱导型一氧化氮合酶（iNOS）和环氧合酶2（COX-2）的表达，并在LPS的mRNA水平下调了iNOS，COX-2，TNF-α，IL-1β和IL-6的表达。处理的RAW 264.7巨噬细胞。此外，我们阐明了潜在的分子机制，证明KPG通过降低p65核易位，抑制κBα（IκBα）磷酸化/降解和IκB激酶α/β（IKKα/β）来减弱LPS诱导的核因子κB（NF-κB）活化。磷酸化。KPG还通过抑制细胞核中c-Fos的表达来降低LPS诱导的激活蛋白1（AP-1）活性，尽管c-Jun不受影响。此外，我们发现KPG通过抑制Janus激酶（JAK）1和JAK2的磷酸化显着消除了LPS诱导的信号转导和转录激活（STAT）1（Ser 727，Tyr 701）和STAT3（Tyr 705）的磷酸化。上游激活蛋白。两者合计，我们的数据表明KPG通过阻断LPS处理的RAW 264.7巨噬细胞中的NF-κB，AP-1和JAK-STAT信号传导途径来诱导抗炎活性，从而抑制炎症介质。