title: Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.
abstract: In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50values of 6.8, 14.5, 30.2, 23.7, and 38.5 μM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50value of 9.5 μM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: College of Pharmacy, Drug Research, and Development Center, Catholic University of Daegu, Gyeongbuk, 38430, Korea.
authors.forename: Quynh Mai Thi
authors.initials: QM
authors.lastname: Ngo
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do, 24341, Korea.
authors.forename: Phuong Thao
authors.initials: PT
authors.lastname: Tran
authors.affiliation: College of Pharmacy, Drug Research, and Development Center, Catholic University of Daegu, Gyeongbuk, 38430, Korea.
authors.forename: Manh Hung
authors.initials: MH
authors.lastname: Tran
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Korea.
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Korean Medicine of College, DaeguHaany University, Daegu, 42158, Korea.
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Rho
authors.affiliation: Department of Bio Environmental Chemistry, Chungnam National University, Deajeon, 34134, Korea.
authors.forename: Chi-Hwan
authors.initials: CH
authors.lastname: Lim
authors.affiliation: College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Korea.
authors.forename: Jin-Cheol
authors.initials: JC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Drug Research, and Development Center, Catholic University of Daegu, Gyeongbuk, 38430, Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Woo
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 48513, Korea.
authors.forename: Jae Sui
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do, 24341, Korea.
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Drug Research, and Development Center, Catholic University of Daegu, Gyeongbuk, 38430, Korea.
authors.forename: Byung Sun
authors.identifier: http://orcid.org/0000-0002-8501-4289
authors.initials: BS
authors.lastname: Min
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D029222:Piper nigrum / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D051267:NF-E2-Related Factor 2
keywords: Nrf2; Piper nigrum; alkaloid; antiinflammation; chabamide; heme oxygenase-1