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Open Access 01-01-2019 | Original Paper

Identification of β-carboline and canthinone alkaloids as anti-inflammatory agents but with different inhibitory profile on the expression of iNOS and COX-2 in lipopolysaccharide-activated RAW 264.7 macrophages

Authors: Pan Liu, Huixiang Li, Ruiling Luan, Guiyan Huang, Yanan Liu, Mengdi Wang, Qiuli Chao, Liying Wang, Danna Li, Huaying Fan, Daquan Chen, Linyu Li, Keiichi Matsuzaki, Wei Li, Kazuo Koike, Feng Zhao

Published in: Journal of Natural Medicines | Issue 1/2019

Abstract

A compound library, which consists of 75 natural β-carboline-type or canthinone-type alkaloids from Simaroubaceae plants and their chemical synthetic analogues, was screened for the anti-inflammatory activity by inhibition of the overproduction of inflammatory mediator nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Six compounds, namely, benzalharman (23), kumujian (27), 1-ethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (37), 1-acetophenone-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (42), cathin-6-one (46), and 9-methoxy-cathin-6-one (57), exhibited significant inhibitory activity on the overproduction of NO with good dose dependency. Further investigation demonstrated that all of the six compounds down-regulated the high expression of inducible nitric oxide synthase (iNOS) protein. Among them, two canthinone-type alkaloids (46 and 57) potently down-regulated cyclooxygenase-2 (COX-2) protein expression in a dose-dependent manner and also inhibited the overproduction of inflammatory mediator prostaglandin E₂ (PGE₂). However, the β-carboline-type alkaloids (23, 27, 37, and 42) exhibited no obvious inhibition on the overproduction of PGE₂ and the expression of COX-2 protein. The results suggested that β-carboline-type alkaloids and canthinone-type alkaloids may exert an anti-inflammatory effect through different mechanism.

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Chesrown SE, Monnier J, Visner G, Nick HS (1994) Regulation of inducible nitric oxide synthase mRNA levels by lipopolysaccharide, interferon-γ, TGF-β and IL-10 in murine macrophage cell lines and rat peritoneal macrophages. Biochem Biophys Res Commun 200:126–134CrossRef

Bos CL, Richel DJ, Ritsema T, Peppelenbosch MP, Versteeg HH (2004) Prostanoids and prostanoid receptors in signal transduction. Int J Biochem Cell B 36:1187–1205CrossRef

Pairet M, Engelhardt G (1996) Distinct isoforms (COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications. Fund Clin Pharmacol 10:1–15CrossRef

Lee JK, Sayers BC, Chun KS, Lao HC, Shipley-Phillips JK, Bonner JC, Langenbach R (2012) Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP Kinase-dependent and-independent mechanisms in mouse RAW 264.7 macrophages. Part Fibre Toxi 9:14CrossRef

Kim YS, Ahn CB, Je JY (2016) Anti-inflammatory action of high molecular weight Mytilus edulis hydrolysates fraction in LPS-induced RAW 264.7 macrophage via NF-κB and MAPK pathways. Food Chem 202:9–14CrossRef

Liu JX, Tang JS, Zuo YH, Yu Y, Luo P, Yao XS, Dong Y, Wang PX, Liu L, Zhou H (2016) Stauntoside B inhibits macrophage activation by inhibiting NF-κB and ERK MAPK signaling. Pharmacol Res 111:303–315CrossRef

Zhao F, Chen L, Bi CC, Zhang ML, Jiao HW, Yao XS (2013) In vitro anti-inflammatory effect of picrasmalignan A by the inhibition of iNOS and COX-2 expression in LPS-activated macrophage RAW 264.7 cells. Mol Med Rep 8:1575–1579CrossRef

Schuster R, Zeindl L, Holzer W, Khumpirapang N, Okonogi S, Viernstein H, Mueller M (2017) Eulophia macrobulbon-an orchid with significant anti-inflammatory and antioxidant effect and anticancerogenic potential exerted by its root extract. Phytomedicine 24:157–165CrossRef

Kalinski P (2012) Regulation of immune responses by prostaglandin E₂. J Immunol 188:21–28CrossRef

10.

Zimmer AR, Leonardi B, Miron D, Schapoval E, Oliveira JR, Gosmann G (2012) Antioxidant and anti-inflammatory properties of Capsicum baccatum: from traditional use to scientific approach. J Ethnopharmacol 139:228–233CrossRef

11.

Fynn PM, Opoku-Boahen Y, Adukpo GE, Armah FA (2016) Anti-inflammatory and antioxidant activities of canthinone alkaloids from Anthostema aubryanum (Baill). Nat Prod Plant Resour 6:13–24

12.

Ohmoto T, Koike K (1984) Studies on the constituents of Picrasma quassioides Bennet. III. Chem Pharm Bull 32:3579–3583CrossRef

13.

Ohmoto T, Koike K (1984) Studies on the constituents of Ailanthus altissima Swingle. III. The alkaloidal constituents. Chem Pharm Bull 29:390–395CrossRef

14.

Jiao WH, Gao H, Li CY, Zhou GX, Kitanaka S, Ohmurae A, Yao XS (2010) β-Carboline alkaloids from the stems of Picrasma quassioides. Magn Reson Chem 48:490–495PubMed

15.

Zhu CC, Deng GH, Lin CZ (2012) Chemical constituents of Picrasma quassioides (D. Don) Benn. Nat Prod Res Dev 24:476–478

16.

Zhao W, Chen ZW, Sun JH, He Y, Liu W, Hu S, Guan ZY, Chen FL (2012) Alkaloid extraction from Picramia quassioides (D. Don) Benn. and safety of its compound injection. J South Agric 43:865–868

17.

Sung YI, Koike K, Nikaido T, Ohmoto T, Sankawa U (1984) Inhibitors of cyclic AMP phosphodiesterase in Picrasma quassioides Bennet, and inhibitor activities of related β-carboline alkaloids. Chem Pharm Bull 32:1872–1877CrossRef

18.

Jiang MX, Zhou YJ (2008) Canthin-6-one alkaloids from Picrasma quassioides and their cytotoxic activity. J Asian Nat Prod Res 10:1009–1012CrossRef

19.

Sasaki T, Li W, Higai K, Koike K (2015) Canthinone alkaloids are novel protein tyrosine phosphatase 1B inhibitors. Bioorg Med Chem Lett 25:1979–1981CrossRef

20.

Sasaki T, Li W, Ohmoto T, Koike K (2016) Evaluation of canthinone alkaloids as cerebral protective agents. Bioorg Med Chem Lett 26:4992–4995CrossRef

21.

Zhao F, Gao Z, Jiao W, Chen L, Chen L, Yao X (2012) In vitro anti-inflammatory effects of beta-carboline alkaloids, isolated from Picrasma quassioides, through inhibition of the iNOS pathway. Planta Med 78:1906–1911CrossRef

22.

Cho SK, Jeong M, Jang DS, Choi JH (2018) Anti-inflammatory effects of canthin-6-one alkaloids from Ailanthus altissima. Planta Med 84:527–535CrossRef

23.

Ngoc PB, Pham TB, Nguyen HD, Tran TT, Chu HH, Chau VM, Lee JH, Nguyen TD (2016) A new anti-inflammatory β-carboline alkaloid from the hairy-root cultures of Eurycoma longifolia. Nat Prod Res 30:1360–1365CrossRef

24.

Ohmoto T, Koike K (1983) Studies on the constituents of Picrasma quassioides Bennet. II. On the alkaloidal constituents. Chem Pharm Bull 31:3198–3204CrossRef

25.

Dejos C, Voisin P, Bernard M, Regnacq M, Berges T (2014) Canthin-6-one displays antiproliferative activity and causes accumulation of cancer cells in the G2/M phase. J Nat Prod 77:2481–2487CrossRef

26.

Jin X, Song SQ, Wang J, Zhang QZ, Qiu F, Zhao F (2016) Tiliroside, the major component of Agrimonia pilosa Ledeb ethanol extract, inhibits MAPK/JNK/p38-mediated inflammation in lipopolysaccharide-activated RAW 264.7 macrophages. Exp Ther Med 12:499–505CrossRef

Title: Identification of β-carboline and canthinone alkaloids as anti-inflammatory agents but with different inhibitory profile on the expression of iNOS and COX-2 in lipopolysaccharide-activated RAW 264.7 macrophages
Authors: Pan Liu
Huixiang Li
Ruiling Luan
Guiyan Huang
Yanan Liu
Mengdi Wang
Qiuli Chao
Liying Wang
Danna Li
Huaying Fan
Daquan Chen
Linyu Li
Keiichi Matsuzaki
Wei Li
Kazuo Koike
Feng Zhao
Publication date: 01-01-2019
Publisher: Springer Singapore
Published in: Journal of Natural Medicines / Issue 1/2019
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-018-1251-5

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Identification of β-carboline and canthinone alkaloids as anti-inflammatory agents but with different inhibitory profile on the expression of iNOS and COX-2 in lipopolysaccharide-activated RAW 264.7 macrophages

Abstract

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Abstract

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