Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK/NF-κB pathway

• Published in: Food and chemical toxicology 2019-09, Vol.131, p.110583-110583, Article 110583
• Main Authors: Alam, Md Badrul, Ju, Mi-Kyoung, Kwon, Yoon-Gyung, Lee, Sang Han
• Format: Article
• Language: English
• Subjects: Anti-inflammatory effect; Mitogen-activated protein kinase; Neuro-inflammation; Nuclear factor-kappa B signaling; Protopine
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2019.110583

We investigated the anti-inflammatory activity of protopine (PTP) and sought to determine its mechanism of action in LPS-stimulated BV2 cells and a carrageenan (CA)-induced mouse model. Treatment with PTP (5, 10, and 20 μM) significantly suppresses the secretion of NO and PGE2 in a concentration-dependent manner without affecting cell viability by downregulating iNOS and COX-2 expression in LPS-induced BV2 cells. PTP also attenuates the production of pro-inflammatory chemokines, such as MCP-1, and cytokines, including TNF-α, IL-1β and IL-6, and augments the expression of the anti-inflammatory cytokine IL-10. In addition, PTP suppresses the nuclear translocation of NF-κB by hindering the degradation of IκB and downregulating the expression of mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK protein. Furthermore, PTP treatment significantly suppresses CA-induced paw oedema in mice compared to that seen in untreated mice. Expression of iNOS and COX-2 proteins is also abrogated by PTP (50 mg/kg) treatment in CA-induced mice. PTP treatment also abolishes IκB phosphorylation, which hinders the activation of NF-κB. Collectively, these results suggest PTP has potential for attenuating CA- and LPS-induced inflammatory symptoms through modulation of MAPKs/NF-κB signaling cascades. [Display omitted] •Protopine suppressed the secretion of NO and PGE2 in LPS-induced BV2 cells.•Protopine attenuated the production of pro-inflammatory chemokine and cytokines in microglia.•Protopine inhibited the NF-κB by hindering the degradation of IκB.•Protopine mitigated the inflammatory symptoms in carrageenan induced mice.