Cytotoxicity of Saikosaponin A targets HEKa cell through apoptosis induction by ROS accumulation and inflammation suppression via NF-κB pathway
Cytotoxicity of Saikosaponin A targets HEKa cell through apoptosis induction by ROS accumulation and inflammation suppression via NF-κB pathway
复制标题
柴胡皂苷 A 通过 ROS 积累诱导细胞凋亡和通过 NF-kappa B 途径抑制炎症来靶向 HEKa 细胞
DOI：
10.1016/j.intimp.2020.106751
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Zheng, Yan
中科院分区：
文献类型：
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作者：
Liu, Meng;Zhang, Guanfei;Zheng, Yan
柴胡皂苷A（Saikosaponin A，SSA）是从东方药用植物柴胡中提取的一种三萜皂苷类化合物，具有抗炎、免疫调节、抗病毒等多种生物学功能。本研究旨在探讨SSA在体内外对银屑病的治疗作用。我们的研究结果表明，SSA增加活性氧（ROS）的产生，降低线粒体膜电位（MMP）和M5诱导的炎症细胞因子水平在HEKa细胞中以剂量依赖性的方式。此外，SSA在体外促进细胞凋亡和抑制NF-κ B B的磷酸化，这是由ROS清除剂N-乙酰半胱氨酸（NAC）恢复。在咪喹莫特（imiquimod，IMQ）诱导的小鼠中，灌胃SSA可通过抑制NF-κ B和NLRP 3信号通路，显著降低银屑病面积和严重程度指数（PASI）评分，并改善表皮增生。总之，我们的研究表明，SSA诱导细胞凋亡，抑制HEKa细胞的炎症，并改善IMQ诱导的小鼠银屑病，使其成为银屑病的治疗候选药物。
Saikosaponin A (SSA) is a triterpenoid saponin extracted from oriental medicinal plant Radix bupleuri, possessing various biological functions such as anti-inflammatory, immune regulation and anti-virus. This study aimed to explore therapeutic effects of SSA on psoriasis in both vitro and vivo. Our results showed that SSA increased reactive oxygen species (ROS) generation, and decreased mitochondrial membrane potential (MMP) and M5-induced inflammatory cytokines levels in HEKa cells in a dose-dependent manner. In addition, SSA promoted apoptosis and suppressed phosphorylation of NF-kappa B in vitro, which were restored by the ROS scavenger N-acetylcysteine (NAC). In imiquimod (IMQ)-induced mice, gavage with SSA markedly decreased Psoriasis Area and Severity Index (PASI) score and ameliorated epidermal hyperplasia through inhibition of NF-kappa B and NLRP3 signaling pathway. In conclusion, our studies demonstrate that SSA induces apoptosis and suppresses inflammation in HEKa cells and ameliorates IMQ-induced psoriasis in mice, making it a therapeutic candidate for psoriasis.