The combination of catechin, baicalin and β‑caryophyllene potentially suppresses the production of inflammatory cytokines in mouse macrophages in vitro

Yamaguchi,Masayoshi; Levy,Robert  M.

doi:10.3892/etm.2019.7452

The combination of catechin, baicalin and β‑caryophyllene potentially suppresses the production of inflammatory cytokines in mouse macrophages in vitro

Authors:
- Masayoshi Yamaguchi
- Robert M. Levy
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Affiliations: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095‑1732, USA, Department of Clinical Development, Primus Pharmaceuticals, Inc., Scottsdale, AZ 85251, USA
Published online on: March 29, 2019 https://doi.org/10.3892/etm.2019.7452
Pages: 4312-4318

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Abstract

It has been demonstrated that the combination of three botanical factors of (+)‑catechin, baicalin and β‑caryophyllene, which exhibit anti‑inflammatory effects, with comparatively lower concentrations of each factor, demonstrating a potent synergistic‑suppressive effect on the growth of mouse macrophage RAW264.7 cells in vitro, and suggesting it may function as a pharmacologic tool for managing inflammatory diseases. The present study was undertaken to determine the suppressive effects of (+)‑catechin, baicalin or β‑caryophyllene on the production of inflammatory cytokines, including TNF‑α, IL‑6 and IL‑1β, which was enhanced by lipopolysaccharide (LPS) in RAW264.7 cells in vitro. The cells were cultured for 3 days without botanical factors, followed by incubation for 5 h in the presence of either vehicle, (+)‑catechin [1 µg/ml (3.45 µM)], baicalin [1 µg/ml (2.24 µM)], or β‑caryophyllene [1 µg/ml (5 µM)] with or without LPS (100 ng/ml); this did not have significant effects on the number of RAW264.7 cells. The production of TNF‑α, IL‑6 and IL‑1β was not altered by the addition of (+)‑catechin, baicalin, β‑caryophyllene, or the three combined factors in RAW264.7 cells without LPS. LPS treatment caused a marked production of TNF‑α, IL‑6, and IL‑1β. This enhancement was suppressed by the addition of (+)‑catechin, baicalin or β‑caryophyllene. Of note, the production of these cytokines was additively suppressed by the combination of the three factors in macrophages. Thus, the combination of (+)‑catechin, baicalin and β‑caryophyllene was found to reveal a potent suppressive effect on cytokine production in macrophages in vitro. This composition may be a useful tool as a potent anti‑inflammatory agent.

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1	Villanueva-Romero R, Gutiérrez-Cañas I, Carrión M, Pérez García S, Seoane IV, Martínez C, Gomariz RP and Juarranz Y: The anti-inflammatory mediator, vasoactive intestinal peptide, modulates the differentiation and function of Th subsets in rheumatoid arthritis. J Immunol Res. 2018:60437102018. View Article : Google Scholar : PubMed/NCBI
2	Kalaiselvi P, Rajashree K, Bharathi Priya L and Padma VV: Cytoprotective effect of epigallocatechin-3-gallate against deoxynivalenol-induced toxicity through anti-oxidative and anti-inflammatory mechanisms in HT-29 cells. Food Chem Toxicol. 56:110–118. 2013. View Article : Google Scholar : PubMed/NCBI
3	Morrison M, van der Heijden R, Heeringa P, Kaijzel E, Verschuren L, Blomhoff R, Kooistra T and Kleemann R: Epicatechin attenuates atherosclerosis and exerts anti-inflammatory effects on diet-induced human-CRP and NFκB in vivo. Atherosclerosis. 233:149–156. 2014. View Article : Google Scholar : PubMed/NCBI
4	Qian Y, Chen Y, Wang L and Tou J: Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis1. Acta Cir Bras. 33:556–564. 2018. View Article : Google Scholar : PubMed/NCBI
5	Bitto A, Squadrito F, Irrera N, Pizzino G, Pallio G, Mecchio A, Galfo F and Altavilla D: Flavocoxid, a nutraceutical approach to blunt inflammatory conditions. Mediators Inflamm. 2014:7908512014. View Article : Google Scholar : PubMed/NCBI
6	Sharma C, Al Kaabi JM, Nurulain SM, Goyal SN, Kamal MA and Ojha S: Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Curr Pharm Des. 22:3237–3264. 2016. View Article : Google Scholar : PubMed/NCBI
7	Klauke AL, Racz I, Pradier B, Markert A, Zimmer AM, Gertsch J and Zimmer A: The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol. 24:608–620. 2014. View Article : Google Scholar : PubMed/NCBI
8	Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, Altmann KH, Karsak M and Zimmer A and Zimmer A: Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci USA. 105:9099–9104. 2008. View Article : Google Scholar : PubMed/NCBI
9	Ormeño E, Baldy V, Ballini C and Fernandez C: Production and diversity of volatile terpenes from plants on calcareous and siliceous soils: effect of soil nutrients. J Chem Ecol. 34:1219–1229. 2008. View Article : Google Scholar : PubMed/NCBI
10	Katsuyama S, Mizoguchi H, Kuwahata H, Komatsu T, Nagaoka K, Nakamura H, Bagetta G, Sakurada T and Sakurada S: Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. Eur J Pain. 17:664–675. 2013. View Article : Google Scholar : PubMed/NCBI
11	Paula-Freire LI, Andersen ML, Gama VS, Molska GR and Carlini EL: The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice. Phytomedicine. 21:356–362. 2014. View Article : Google Scholar : PubMed/NCBI
12	Chavan MJ, Wakte PS and Shinde DB: Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona squamosa L. bark. Phytomedicine. 17:149–151. 2010. View Article : Google Scholar : PubMed/NCBI
13	Ghelardini C, Galeotti N, Di Cesare Mannelli L, Mazzanti G and Bartolini A: Local anaesthetic activity of beta-caryophyllene. Farmaco. 56:387–389. 2001. View Article : Google Scholar : PubMed/NCBI
14	Martinez RM, Zarpelon AC, Cardoso RD, Vicentini FT, Georgetti SR, Baracat MM, Andrei CC, Moreira IC, Verri WA Jr and Casagrande R: Tephrosia sinapou ethyl acetate extract inhibits inflammatory pain in mice: Opioid receptor dependent inhibition of TNFα and IL-1β production. Pharm Biol. 51:1262–1271. 2013. View Article : Google Scholar : PubMed/NCBI
15	Yamaguchi M and Levy RM: The combination of β-caryophyllene, baicalin and catechin synergistically suppresses the proliferation and promotes the death of RAW267.4 macrophages in vitro. Int J Mol Med. 38:1940–1946. 2016. View Article : Google Scholar : PubMed/NCBI
16	Pomari E, Stefanon B and Colitti M: Effect of plant extracts on H2O2-induced inflammatory gene expression in macrophages. J Inflamm Res. 7:103–112. 2014.PubMed/NCBI
17	Yamaguchi M, Vikulina T, Arbiser JL and Weitzmann MN: Suppression of NF-κB activation by gentian violet promotes osteoblastogenesis and suppresses osteoclastogenesis. Curr Mol Med. 14:783–792. 2014. View Article : Google Scholar : PubMed/NCBI
18	Yamaguchi M and Weitzmann MN: The bone anabolic carotenoid p-hydroxycinnamic acid promotes osteoblast mineralization and suppresses osteoclast differentiation by antagonizing NF-κB activation. Int J Mol Med. 30:708–712. 2012. View Article : Google Scholar : PubMed/NCBI
19	Yamaguchi M and Daimon Y: Overexpression of regucalcin suppresses cell proliferation in cloned rat hepatoma H4-II-E cells: involvement of intracellular signaling factors and cell cycle-related genes. J Cell Biochem. 95:1169–1177. 2005. View Article : Google Scholar : PubMed/NCBI
20	Izumi T and Yamaguchi M: Overexpression of regucalcin suppresses cell death in cloned rat hepatoma H4-II-E cells induced by tumor necrosis factor-alpha or thapsigargin. J Cell Biochem. 92:296–306. 2004. View Article : Google Scholar : PubMed/NCBI
21	Okuno T, Gijón MA, Zarini S, Martin SA, Barkley RM, Johnson CA, Ohba M, Yokomizo T and Murphy RC: Altered eicosanoid production and phospholipid remodeling during cell culture. J Lipid Res. 59:542–549. 2018. View Article : Google Scholar : PubMed/NCBI
22	Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG and Moulinoux JP: Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 243:527–536. 1997. View Article : Google Scholar : PubMed/NCBI
23	Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R, Brown KD, Zhang L and Baskaran R: Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J Biol Chem. 279:25813–25822. 2004. View Article : Google Scholar : PubMed/NCBI
24	Serrano-Nascimento C, da Silva Teixeira S, Nicola JP, Nachbar RT, Masini-Repiso AM and Nunes MT: The acute inhibitory effect of iodide excess on sodium/iodide symporter expression and activity involves the PI3K/Akt signaling pathway. Endocrinology. 155:1145–1156. 2014. View Article : Google Scholar : PubMed/NCBI
25	Chen S, Wang Y, Ruan W, Wang X and Pan C: Reversing multidrug resistance in hepatocellular carcinoma cells by inhibiting extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway activity. Oncol Lett. 8:2333–2339. 2014. View Article : Google Scholar : PubMed/NCBI
26	Zhao Y, Jing Z, Li Y and Mao W: Berberine in combination with cisplatin suppresses breast cancer cell growth through induction of DNA breaks and caspase-3-dependent apoptosis. Oncol Rep. 36:567–572. 2016. View Article : Google Scholar : PubMed/NCBI
27	Echizen K, Hirose O, Maeda Y and Oshima M: Inflammation in gastric cancer: interplay of the COX-2/prostaglandin E2 and Toll-like receptor/MyD88 pathways. Cancer Sci. 107:391–397. 2016. View Article : Google Scholar : PubMed/NCBI
28	Lin CC, Chan CM, Huang YP, Hsu SH, Huang CL and Tsai SJ: Methylglyoxal activates NF-κB nuclear translocation and induces COX-2 expression via a p38-dependent pathway in synovial cells. Life Sci. 149:25–33. 2016. View Article : Google Scholar : PubMed/NCBI
29	Li N, Liu BW, Ren WZ, Liu JX, Li SN, Fu SP, Zeng YL, Xu SY, Yan X, Gao YJ, et al: GLP-2 attenuates LPS-induced inflammation in BV-2 cells by inhibiting ERK1/2, JNK1/2 and NF-κB signaling pathway. Int J Mol Sci. 17:1902016. View Article : Google Scholar : PubMed/NCBI
30	Cha SM, Cha JD, Jang EJ, Kim GU and Lee KY: Sophoraflavanone G prevents Streptococcus mutans surface antigen I/II-induced production of NO and PGE2 by inhibiting MAPK-mediated pathways in RAW 264.7 macrophages. Arch Oral Biol. 68:97–104. 2016. View Article : Google Scholar : PubMed/NCBI
31	Xu X, Yin P, Wan C, Chong X, Liu M, Cheng P, Chen J, Liu F and Xu J: Punicalagin inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-κB activation. Inflammation. 37:956–965. 2014. View Article : Google Scholar : PubMed/NCBI
32	Cho BO, So Y, Jin CH, Nam BM, Yee ST and Jeong IY: 3-deoxysilybin exerts anti-inflammatory effects by suppressing NF-κB activation in lipopolysaccharide-stimulated RAW264.7 macrophages. Biosci Biotechnol Biochem. 78:2051–2058. 2014. View Article : Google Scholar : PubMed/NCBI
33	Zhao G, Zhang T, Ma X, Jiang K, Wu H, Qiu C, Guo M and Deng G: Oridonin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-induced RAW264.7 cells and acute lung injury. Oncotarget. 8:68153–68164. 2017.PubMed/NCBI