LAUSR

Abstract Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. This study was designed to evaluate the pharmacological effects of EsA on lipopolysaccharide (LPS)‐stimulated BV2 microglia and primary microglia cells. Our results indicated that EsA pretreatment significantly decreased LPS‐induced production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) and impeded LPS‐mediated upregulation of pro‐inflammatory mediators’ expression such as nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), interleukin‐1&bgr; (IL‐1&bgr;), interleukin‐6 (IL‐6), interleukin‐12 (IL‐12) and tumor necrosis factor‐a (TNF‐&agr;) in both BV2 microglia and primary microglia cells. Moreover, EsA markedly suppressed nuclear factor‐&kgr;B p65 (NF‐&kgr;B p65) translocation by blocking I&kgr;B‐&agr; phosphorylation and degradation in LPS‐treated BV2 cells. EsA also decreased phosphorylation level of mitogen‐activated protein kinases (MAPKs) and inhibited NOD‐like receptor pyrin domain‐containing protein 3 (NLRP3) inflammasome mediated caspase‐1 activation in LPS‐stimulated BV2 cells. Additionally, EsA decreased &bgr;‐amyloid1–42 (A&bgr;1–42)‐induced production of TNF‐&agr;, IL‐1&bgr; and IL‐6 in primary microglia. Thus, EsA might be a promising therapeutic agent for alleviating neuroinflammatory diseases. HighlightsEsA attenuated LPS‐induced inflammatory mediators’ production in activated microglia.The anti‐inflammatory effects of EsA was associated with the inactivation of NF‐&kgr;B, MAPKs and NLRP3 pathways.EsA suppressed mRNA levels of cytokines in A&bgr;1–42‐induced primary microglia cells.