Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways
Abstract
Abstract: Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 μg/mL) and capsaicin (25, 50, 75, or 100 μg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 μg/mL, tumor necrosis factor (TNF)-α level was 860 μg/mL, and nitric oxide (NO) level was 19.8 μg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.
References
1 . Anti-inflammatory activity of Ternstroemia gymnanthera stem bark extracts in bacterial lipopolysaccharide-stimulated RAW264. 7 murine macrophage cells. Pharm Biol. 2017;55:837–46.
2 . Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1β generation. Clin Exp Immunol. 2007;147:227–35.
3 . Anti-inflammatory effect of dandelion sterol on MAPKs signaling pathway in vitro [doctoral dissertation]. Yabian: Yanbian University; 2014.
4 Anti-inflammatory activity of edible brown alga Saccharina japonica and its constituents pheophorbide a and pheophytin a in LPS-stimulated RAW 264.7 macrophage cells. Food Chem Toxicol. 2013;55:541–8.
5 . Recent advances in the study on capsaicinoids and capsinoids. Eur J Pharmacol. 2011;650:1–7.
6 Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1, 2-dimethylhydrazine in rats. Toxicol Appl Pharmacol. 2018;338:93–102.
7 . Capsaicin, a tasty free radical scavenger: mechanism of action and kinetics. J Phys Chem B. 2012;116:1200–8.
8 . Targeting TRP channels for pain relief. Eur J Pharmacol. 2013;716:61–76.
9 . Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;6:1101–8.
10 . Effects of Coptis chinensis alkaloids on peritoneal macrophages cultured in vitro in mice. Chin J Trad Chin Med. 2015;23:4660–6.
11 Cytokine network in chronic perianal Crohn’s disease and indeterminate colitis after colectomy. J Gastrointest Surg. 2007;11:16–21.
12 . Effect of Shiga toxin and its subunits on cytokine induction in different cell lines. Int J Mol Cell Med. 2014;3:108.
13 . Inflammatory mediator profiling reveals immune properties of chemotactic gradients and macrophage mediator production inhibition during thioglycollate elicited peritoneal inflammation. Mediators Inflamm. 2013;2013.
14 . MAP3K-related kinase involved in NF-kB induction by TNF, CD95 and IL-1. Nature. 1997;385:540–4.
15 . Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages. J Pharmacol Exp Ther. 2002;302:138–44.
16 . IKKalpha controls formation of the epidermis independently of NF-kappa B. Nature. 2001;410:710–14.
17 . A signal transducer and activator of transcription 3 nuclear factor κB (Stat3 NFκB) complex is necessary for the expression of fascin in metastatic breast cancer cells in response to interleukin (IL)-6 and tumor necrosis factor (TNF)-α. J Biol Chem. 2014;289:30082–9.
18 . Control of NF-kappa B activity by proteolysis. Curr Top Microbiol Immunol. 2011;349:97–114.
19 . IKKalpha limits macrophage NF-kappa B activation and contributes to the resolution of inflammation. Nature. 2005;434:1138–43.
20 Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: Involvement of calcitonin gen-related peptide. Peptides. 2018;105:1–6.
21 Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages. Eur J Pharmacol. 2013;708:21–9.
22 , Interleukin-1 family cytokines and mast cells: activation and inhibition. J Biol Regul Homeost Agents. 2019;33:1–6.
23 . Impact of mast cells in systemic lupus erythematosus: can inflammation be inhibited? J Biol Regul Homeost Agents. 2019;33:669–73.
24 . Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34:9–14.
25 Interleukin-1 family cytokines and mast cells: activation and inhibition. J Biol Regul Homeost Agents. 2019;33:1–6.
26 . Impact of mast cells in systemic lupus erythematosus: can inflammation be inhibited? J Biol Regul Homeost Agents. 2019;33:669–73.
27 . Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34:9–14.
