Discretamine is a tetrahydroprotoberberine alkaloid isolated from Duguetia moricandiana (Annonaceae). In the present study, anti-inflammatory ability of discretamine in a lipopolysaccharide (LPS) stimulated macrophages model was investigated. LPS-induced NO production was reduced by discretamine treatment (100 and 200 μg/mL) around 50%. Furthermore, discretamine (50, 100, and 200 μg/mL) treatment down-regulated pivotal inflammatory cytokines levels, such as IL-6 (74.1, 76.6, and 75.1%, respectively), IL1-β (89.4, 87.4, and 71.8%, respectively), and TNF-α (61, 45.2, and 52.6%, respectively) levels. Also, discretamine did not reduce peritoneal macrophage viability. Besides that, in vivo carrageenan-induced paw edema experiments were also carried out. Discretamine treatment (5, 10, and 20 mg/kg) reduced paw edema up to 6h. Taken together, these data demonstrated that discretamine exerted its anti-inflammatory effect by down-regulation the levels of TNF-α, IL-6, and IL1-β, and by inhibition of NO release.
CraggGM, NewmanDJ. (2013). Natural products: a continuing source of novel drug leads. Biochimica et Biophysica Acta, 1830, 3670–3695.
2.
SoutoAL, TavaresJF, da SilvaMS, DinizMFFM, de Athayde-FilhoPF, Barbosa FilhoJM. (2011). Anti-inflammatory activity of alkaloids: an update from 2000 to 2010. Molecules, 16, 8515–8534.
3.
FechineIM, LimaMA, NavarroVR, Cunha EVLda, SilvaMS, Barbosa-FilhoJM, MaiaJGS. (2002) Alcalóides de Duguetia trunciflora Maas (Annonaceae). Revista Brasileira de Farmacognosia, 12, 17–19.
4.
KoFN, YuSM, SuMJ, WuYC, TengCM. (1993) Pharmacological activity of (-)-discretamine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens. British Journal of Pharmacology, 110, 882–888.
5.
AlmeidaJRGS, de LimaJT, de OliveiraHR, de OliveiraMR, MeiraPRM, LúcioASSC, Barbosa FilhoJM, Quintans JúniorLJ. (2011) Antinociceptive activity of discretamine isolated from Duguetia moricandiana. Natural Product Research, 25, 1908–1915.
6.
ChiaYC, ChangFR, WuCC, TengCM, ChenKS, WuYC. (2006) Effect of isoquinoline alkaloids of different structural types on antiplatelet aggregation in vitro. Planta Medica, 72, 1238–1241.
7.
SilvaDF, PortoDL, AraújoIG, DiasKLG, CavalcanteKVM, VerasRC, TavaresJF, CorreiaNA, GuedesDN, SilvaMS, MedeirosIA. (2009) Endothelium-derived nitric oxide is involved in the hypotensive and vasorelaxant effects induced by discretamine in rats. Pharmazie, 64, 327–331.
8.
Barbosa-FilhoJM, PiuvezamMR, MouraMD, SilvaMS, LimaKV, Batista da-CunhaEVL, FechineIM, TakemuraOS. (2006) Anti-inflammatory activity of alkaloids: a twenty-century review. Revista Brasileira de Farmacognosia, 16, 109–139.
9.
ChenS. (2011) Natural products triggering biological targets–a review of the anti-inflammatory phytochemicals targeting the arachidonic acid pathway in allergy asthma and rheumatoid arthritis. Current Drug Targets, 12, 288–301.
10.
VarolC, MildnerA, JungS. (2015) Macrophages: development and tissue specialization. Annual Review of Immunology, 33, 643–675.
11.
Liaunardy-JopeaceA, GayNJ. (2014) Molecular and cellular regulation of toll-like receptor-4 activity induced by lipopolysaccharide ligands. Frontiers in Immunology, 5, 1–5.
12.
MacMickingJ, XieQW, NathanC. (1997) Nitric oxide and macrophage function. Annual Review of Immunology, 15, 323–350.
13.
NohEJ, AhnKS, ShinEM, JungSH, KimYS. (2006) Inhibition of lipopolysaccharide-induced iNOS and COX-2 expression by dehydroevodiamine through suppression of NF-kappaB activation in RAW 264.7 macrophages. Life Science, 79, 695–701.
14.
ZhaoF, ChenL, ZhangM, BiC, LiL, ZhangQ, ShiC, LiM, ZhouS, KongL. (2013) Inhibition of lipopolysaccharide-induced iNOS and COX-2 expression by indole alkaloid, 3-(hydroxymethyl)-6,7-dihydroindolo[2,3-a]quinolizin-(12H)-one, via NF-κB inactivation in RAW 264.7 macrophages. Planta Medica, 79, 782–787.
15.
YunKJ, ShinJS, ChoiJH, BackNI, ChungHG, LeeKT. (2009) Quaternary alkaloid, pseudocoptisine isolated from tubers of Corydalis turtschaninovi inhibits LPS-induced nitric oxide, PGE(2), and pro-inflammatory cytokines production via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells. International Immunopharmacology, 9, 1323–1331.
16.
ZhangY, YanR, HuY. (2015) Oxymatrine inhibits lipopolysaccharide-induced inflammation by down-regulating Toll-like receptor 4/nuclear factor-kappa B in macrophages. Canadian Journal of Physiology and Pharmacology, 93, 253–260.
17.
PosadasI, BucciM, RoviezzoF, RossiA, ParenteL, SautebinL, CirinoG. (2004) Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression. British Journal of Pharmacology, 142, 331–338.
