title: Corynoline Isolated from Corydalis bungeana Turcz. Exhibits Anti-Inflammatory Effects via Modulation of Nfr2 and MAPKs.
abstract: Corydalis bungeana Turcz. is an anti-inflammatory medicinal herb used widely in traditional Chinese medicine for upper respiratory tract infections. It is demonstrated that corynoline is its active anti-inflammatory component. The nuclear factor-erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and the mitogen-activated protein kinase (MAPK) pathway play important roles in the regulation of inflammation. In this study, we investigated the potential anti-inflammatory mechanism of corynoline through modulation of Nfr2 and MAPKs. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore modulatory role of NO production and the activation of signaling proteins and transcription factors using nitrite assay, Western bloting and qPCR. Treatment with corynoline reduced production of nitric oxide (NO) and the protein and mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) Treatment also significantly increased the expression of Nrf2, quinone oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1) at the mRNA and protein levels, which demonstrated that corynoline may protect cells from inflammation through the Nrf2/ARE pathway In addition, corynoline suppressed the expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), at the mRNA and protein levels. Furthermore, molecular data revealed that corynoline inhibited lipopolysaccharide-stimulated phosphorylation of c-jun NH2-terminal kinase (JNK) and p38. Taken together, these results suggest that corynoline reduces the levels of pro-inflammatory mediators, such as iNOS, COX-2, TNF-α and IL-1β, by suppressing extracellular signal-regulated kinase 1/2 (ERK) and p38 phosphorylation in RAW264.7 cells, which is regulated by the Nrf2/ARE pathway. These findings reveal part of the molecular basis for the anti-inflammatory properties of corynoline.
authors.affiliation: Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, China. chunjuanyang@126.com.|Center for Phytochemical Epigenome Studies, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. chunjuanyang@126.com.
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: Center for Phytochemical Epigenome Studies, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. chengyue.zhang@gamil.com.
authors.forename: Chengyue
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Phytochemical Epigenome Studies, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. wzbmailbox@126.com.|Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, China. wzbmailbox@126.com.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, China. 13199472861@163.com.
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, China. hxkuang@yahoo.com.
authors.forename: Haixue
authors.initials: H
authors.lastname: Kuang
authors.affiliation: Center for Phytochemical Epigenome Studies, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. KongT@pharmacy.rutgers.edu.
authors.forename: Ah-Ng Tony
authors.initials: AN
authors.lastname: Kong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D031311:Corydalis / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D001600:Berberine Alkaloids; D016207:Cytokines; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; C487644:corynoline; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: MAPKs; Nrf2; anti-inflammation; corynoline