National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China.
NMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, Changchun 130117, China.
Int J Mol Sci. 2021 Nov 9;22(22):12128. doi: 10.3390/ijms222212128.
It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from (), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.
似乎有必要从天然产物中获得针对炎症反应 (IR) 的有效物质，因为目前存在伴随副作用和生活质量下降的临床问题。本工作旨在研究从 ( ) 中分离得到的新型酚糖苷 hyssoside (HY) 对脂多糖 (LPS) 诱导的 RAW 264.7 细胞和小鼠腹腔巨噬细胞中 IR 的作用。结果表明，HY 可降低一氧化氮 (NO) 的产生，并抑制 LPS 刺激的巨噬细胞中促炎介质包括肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6) 和白细胞介素-1β (IL-1β) 的产生和分泌。此外，免疫荧光研究数据表明，HY 抑制 LPS 诱导的核因子-κB (NF-κB) 核转位。Western blot 结果表明，HY 逆转了 LPS 诱导的 IκB (NF-κB 抑制剂) 的降解，这是 NF-κB 激活所必需的。同时，HY 的存在显著减少了 LPS 刺激时诱导型一氧化氮合酶 (iNOS) 和环氧化酶-2 (COX-2) 的过表达。另一方面，HY 对丝裂原活化蛋白激酶 (MAPK) 途径的激活几乎没有影响。此外，对 HY 针对四种必需蛋白/酶的计算机模拟研究表明，COX-2 是相互作用效率最高的酶，而与 HY 结合的残基 Phe179、Asn351 和 Ser424 发挥了重要作用。结构分析表明，具有苯乙醇苷特征的典型特征有助于 HY 的抗炎作用。这些结果表明，HY 主要通过阻断 NF-κB 信号转导途径来发挥其抗炎作用。总之，我们认为 HY 可能是缓解许多炎症相关疾病中过度炎症的潜在替代酚类药物。
