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Neurosci Lett. 2017 Jun 9;651:43-51. doi: 10.1016/j.neulet.2017.04.057. Epub 2017 Apr 27.

Anti-inflammatory effects of novel polygonum multiflorum compound via inhibiting NF-κB/MAPK and upregulating the Nrf2 pathways in LPS-stimulated microglia.

Author information

1
Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
2
Center for Diabetes, Obesity and Metabolism, Department of Physiology, Shenzhen University Health Science Center, Shenzhen, Guangdong province, China.
3
Department of Nanomaterials Engineering, Pusan National University, Busan 609-735, Republic of Korea.
4
Department of Nanomaterials Engineering, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: gtpark@pusan.ac.kr.
5
Department of Horticultural Bioscience, Pusan National University, Myrang 627-706, Republic of Korea. Electronic address: ywchoi@pusan.ac.kr.

Abstract

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 E2 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 E2 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.

KEYWORDS:

Anti-neuroinflammation; Lipopolysaccharide; Microglia; Nrf2; Polygonum multiflorum

PMID:
28458018
DOI:
10.1016/j.neulet.2017.04.057
[Indexed for MEDLINE]

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