Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu, PR China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, Jiangsu, PR China; Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, 210008, Jiangsu, PR China; Nanjing Neuropsychiatry Clinic Medical Center, Nanjing 210008, Jiangsu, PR China.
Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu, PR China; Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, Jiangsu, PR China; Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, 210008, Jiangsu, PR China; Nanjing Neuropsychiatry Clinic Medical Center, Nanjing 210008, Jiangsu, PR China.
Int Immunopharmacol. 2017 Oct;51:148-157. doi: 10.1016/j.intimp.2017.08.014. Epub 2017 Aug 30.
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-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-a (TNF-α) in both BV2 microglia and primary microglia cells. Moreover, EsA markedly suppressed nuclear factor-κB p65 (NF-κB p65) translocation by blocking IκB-α 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 β-amyloid (Aβ)-induced production of TNF-α, IL-1β and IL-6 in primary microglia. Thus, EsA might be a promising therapeutic agent for alleviating neuroinflammatory diseases.
Esculentoside A（EsA）是从商陆根部分离得到的一种皂苷。本研究旨在评估 EsA 对脂多糖（LPS）刺激的 BV2 小胶质细胞和原代小胶质细胞的药理作用。我们的结果表明，EsA 预处理可显著降低 LPS 诱导的一氧化氮（NO）和前列腺素 E2（PGE2）的产生，并抑制 LPS 介导的促炎介质表达的上调，如一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-12（IL-12）和肿瘤坏死因子-α（TNF-α）在 BV2 小胶质细胞和原代小胶质细胞中。此外，EsA 通过抑制 LPS 处理的 BV2 细胞中 IκB-α 的磷酸化和降解，显著抑制核因子-κB p65（NF-κB p65）易位。EsA 还降低了丝裂原活化蛋白激酶（MAPKs）的磷酸化水平，并抑制了 LPS 刺激的 BV2 细胞中 NOD 样受体吡喃结构域包含蛋白 3（NLRP3）炎性小体介导的半胱天冬酶-1 的激活。此外，EsA 降低了原代小胶质细胞中β-淀粉样蛋白（Aβ）诱导的 TNF-α、IL-1β 和 IL-6 的产生。因此，EsA 可能是一种有前途的治疗神经炎症性疾病的药物。
