Park Sun Young, Jin Mei Ling, Kang Nam Jun, Park Geuntae, Choi Young-Whan
Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
Center for Diabetes, Obesity and Metabolism, Department of Physiology, Shenzhen University Health Science Center, Shenzhen, Guangdong province, China.
Neurosci Lett. 2017 Jun 9;651:43-51. doi: 10.1016/j.neulet.2017.04.057. Epub 2017 Apr 27.
The incorporation of Polygonum multiflorum into the diet can result in anti-aging effects owing to its wide range of biological and pharmaceutical properties. We investigated the anti-neuroinflammatory properties of CRPE56IGIH isolated from P. multiflorum by focusing on its role in the induction of phase II antioxidant enzymes and the modulation of upstream signaling pathways. In microglia, CRPE56IGIH significantly inhibited lipopolysaccharide (LPS)-stimulated nitric oxide and prostaglandin E production with nonspecific cytotoxicity. CRPE56IGIH also markedly inhibited LPS-inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein and mRNA expression in the same manner as it inhibited nitric oxide and prostaglandin E production. In the control cells, NF-κB transactivation and nuclear translocation occurred at a baseline level, which was significantly increased in response to LPS. However, pretreatment with CRPE56IGIH concentration-dependently inhibited the LPS-induced NF-κB transactivation and nuclear translocation. The phosphorylation of Janus kinase-signal transducers and activators of transcription and mitogen-activated protein kinases was markedly upregulated by LPS, but considerably and dose-dependently inhibited by pretreatment with CRPE56IGIH. Furthermore, CRPE56IGIH induced the expression of phase II antioxidant enzymes, including heme oxygenase-1 (HO-1) and NADPH dehydrogenase quinone-1 (NQO-1). The activation of upstream signaling pathways, such as the Nrf2 pathway, was significantly increased following CRPE56IGIH treatment. Furthermore, the anti-neuroinflammatory effect of CRPE56IGIH was reversed by transfection of Nrf2, HO-1, and NQO-1 siRNA. Our results indicated that CRPE56IGIH isolated from P. multiflorum could be used as a natural anti-neuroinflammatory agent that induces phase II antioxidant enzymes via Nrf2 signaling.
由于何首乌具有广泛的生物学和药学特性，将其纳入饮食中可产生抗衰老作用。我们通过关注其在诱导II期抗氧化酶中的作用以及对上游信号通路的调节，研究了从何首乌中分离出的CRPE56IGIH的抗神经炎症特性。在小胶质细胞中，CRPE56IGIH显著抑制脂多糖（LPS）刺激的一氧化氮和前列腺素E的产生，且无特异性细胞毒性。CRPE56IGIH还以与抑制一氧化氮和前列腺素E产生相同的方式，显著抑制LPS诱导的一氧化氮合酶（iNOS）和环氧化酶-2蛋白及mRNA表达。在对照细胞中，NF-κB反式激活和核转位在基线水平发生，LPS刺激后显著增加。然而，用CRPE56IGIH预处理可浓度依赖性地抑制LPS诱导的NF-κB反式激活和核转位。Janus激酶-信号转导子和转录激活子以及丝裂原活化蛋白激酶的磷酸化在LPS刺激下显著上调，但CRPE56IGIH预处理可显著且剂量依赖性地抑制。此外，CRPE56IGIH诱导II期抗氧化酶的表达，包括血红素加氧酶-1（HO-1）和NADPH脱氢酶醌-1（NQO-1）。CRPE56IGIH处理后，Nrf2通路等上游信号通路的激活显著增加。此外，转染Nrf2、HO-1和NQO-1 siRNA可逆转CRPE56IGIH的抗神经炎症作用。我们的结果表明，从何首乌中分离出的CRPE56IGIH可作为一种天然抗神经炎症剂，通过Nrf2信号诱导II期抗氧化酶。
