In vitro assesment of anti-inflammatory activities of coumarin and Indonesian cassia extract in RAW264.7 murine macrophage cell line

Document Type: Short Communication

Authors

1 Faculty of Pharmacy, University of Pancasila, Jl. Srenseng Sawah, Jagakarsa, Jakarta 12640, Indonesia

2 Bimolecular and Biomedical Research Center, Aretha Medika Utama,Jl. Babakan Jeruk 2 no 9, Bandung 40163, Indonesia

3 Medical Research Center, Faculty of Medicine, Maranatha Christian University, Jl. Prof. drg. Suria Sumantri no 65 Bandung 40164, Indonesia

Abstract

Objective(s): Inflammation is an immune response toward injuries. Although inflammation is healing response, but in some condition it will lead to chronic disease such as rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, Alzheimer’s and various cancer. Indonesian cassia (Cinnamomum burmanni C. Nees & T. Ness) known to contain coumarin, is widely used for alternative medicine especially as an antiinflammator.This study was conducted to determine the anti-inflammatory properties of coumarin and Indonesian cassia extract (ICE) in LPS-induced RAW264.7 cell line.
Materials and Methods: The cytotoxic assay of coumarin and ICE against RAW264.7 cells was conducted using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium). The anti-inflammatory potential was determined using LPS-induced RAW 267.4 macrophages cells to measure inhibitory activity of both compounds on production of nitric oxide (NO), prostaglandin E2 (PGE2), and also cytokines such as interleukin-6 (IL-6), interleukin-1β  (IL-1β)  and TNF-α.
Results: Coumarin 10 µM and ICE 10 µg/ml were nontoxic to the RAW264.7 cells. Both of coumarin and ICE were capable to reduce the PGE2, TNF-α, NO, IL-6, and IL-β level in LPS-induced RAW264.7 cells. Coumarin had higher activity to decrease PGE2 and TNF-α, whilst ICE had higher activity to inhibit NO, IL-6, and IL-β levels.
Conclusion: Coumarin and ICE possess anti-inflammatory properties through inhibition of PGE2 and NO along with pro-inflammatory cytokines TNF-α, IL-6, IL-1β production.

Keywords


1.Huang SS, Chiu CS, Chen HJ, Hou WC, Sheu MJ, Lin YC, et al. Antinociceptive activities and the mechanisms of anti-inflammation of asiatic acid in mice. J Evid Based Complementary Altern Med 2011;2011:1-10.

2.Fang SC, Hsu CL, Yen GC. Anti-inflammatory effects of phenolic compounds isolated from the fruits of Artocarpus heterophyllus. J Agr Food Chem 2008; 56:4463-4468.

3.Kim KM, Kwon YG, Chung HT, Yun YG, Pae HO, Han JA, et al. Methanol extract of Cordyceps pruinosa inhibits in vitro and in vivo inflammatory mediators by suppressing NF-kappaB activation. Toxicol Appl Pharmacol 2003;190:1-8.

4.Kim AR, Cho JY, Zou Y, Choi JS, Chung HY. Flavonoids differentially modulate nitricoxide production pathways in lipopolysaccharide-activated RAW264.7 cells. Arch Pharm Res 2005; 28:297-304.

5.Chang HY, Sheu MJ, Yang CH, Lu TC, Chang YS, Peng WH, et al. Analgesic effects and the mechanisms of anti-inflammation of hispolon in mice. J Evid Based Complementary Altern Med 2011;2011:1-8.

6.Depress JP, Moorjani S, Tremblay A, Ferland M, Lupien PJ, Nadeau A, et al. Relation of high plasma triglyceride level associated with obesity and regional adipose tissue distribution to plasma lipoprotein-lipid composition in premenopausal women. Clin Invest Med 1989;12;6:374-380.

7.Tohda C, Nakayama N, Hatanaka F, Komatsu K. Comparison of anti-inflammatory activities of six Curcuma rhizomes: a possible curcuminoid-independent pathway mediated by Curcuma phaeocaulis extract. J Evid Based Complementary Altern Med 2006;3;2:255-260.

8.Yoon S, Lee Y, Park SK, Kim H, Bae H, Kim HM et al. Anti-inflammatory effects of Scutellariabaicalensis water extract on LPS-activated RAW264.7 macrophages. J Ethnopharmacol 2009;125:286-290.

9.Krenn L, Paper DH. Inhibition of angiogenesis and inflammation by an extract of red clover (Trifolium pretense L.). Phytomed 2009;16:1083-1088.

10.Rita C, Andrade LN, Dos RBOR, de Sousa DP. A review on anti-inflammatory activity of phenylpropanoids founds in esssential oils. Mol 2014;19:459-480.

11.Sung YY, T Yoon, JY Jang, SJ Park, GH Jeong, HK Kim. Inhibitory effects of Cinnamomum cassia extract on atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice. J Ethnopharmacol 2011;133;2:621-628.

12.Kwon HK, Hwang JS, So JS, Lee CG, Sahoo A, Ryu JH, et al. Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1. BMC Cancer 2010;10;392;1-10.

13.Iranshahi M, Kalategi F, Rezaee R, Shahverdi AR, Ito C, Furukawa H, Tokuda H, Itogawa M. Cancer chemopreventive activity of terpenoid coumarins from Ferula species. Plants Med 2008;74:147- 150.

14.Hadjipavlou-Litina DJ, Litinas KE, Kontorgiorgis C. The anti-inflammatory effect of coumarin and its derivates. Antiinflamm Antiallergy Agents Med Chem 2007;6;14:293-306.

15.Widowati W, Mozef T, Risdian C, Yelliantty Y. Anticancer and free radical scavenging potency of Catharanthusroseus, Dendrophthoepetandra, Piper betle and Curcuma mangga extracts in breast cancer cell lines. Oxidant Antioxid Med Sci 2013;2;2:137-142.

16.Widowati W, Wijaya L, Wargasetia TL, Bachtiar I, Yellianty, Laksmitawati DR. Antioxidant, anticancer, and apoptosis-inducing effects of Piper extracts in HeLa cells. J Exp Integr Med 2013;3;3:225-230.

17.Dewi K, Widyarto B, Erawijantari PP, Widowati W. In vitro study of Myristica fragrans seed (Nutmeg) ethanolic extract and quercetin compound as anti-inflammatory agent. Int J Res Med Sci 2015;3;9:2303-2310.

18.Rusmana D, Elisabeth M, Widowati W, Fauziah N, Maesaroh M. inhibition of inflammatory agent production by ethanol extract and eugenol of Syzigium aromaticum flower bud (clove) in LPS-stimulated RAW264.7 cells. Res J Med Plants 2015;9;6:264-274.

19.Widowati W, Darsono L, Suherman J, Fauziah N, Maesaroh M, Erawijantari PP. Anti-inflammatory Effect of Mangosteen (Garcinia mangostana L.) Peel Extract and its Compounds in LPS-induced RAW264. 7 Cells. Nat Prod Sci 2016;22:147-153.

20.Zhu XX, L Yang, YJ Li, D Zhang, Y Chen, P Kostecka et al. Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisisa annua L. on production of mediators of angiogenesis. Pharmacol Rep 2013;65;2;410-20.

21.Kuroishi T, Bando K, Endo Y, Sugawara S. Metal allergens induce nitric oxide production by mouse dermal fibroblast via the hypoxia-inducible factor-2alpha-dependent pathway. Toxicol Sci 2013;135;1:119-228.

22.Kawamura K, Kawamura N, Kumagai J, Fukuda J, Tanaka T. Tumor necrosis factor regulation of apoptosis in mouse preimplantation embryos and its antagonism by transforming growth factor alpha/ phospatidylionsitol 3-kinase signaling system. Biol Reprod 2007;76;4:611-618.

23.Musa AM, Cooperwood SJ, Khan MOF. A review of coumarin derivatives in pharmacotherapy of breast cancer. Curr Med Chem 2008;15;26:2664-2679.

24.Dinarello CA. Anti-inflammatory agents present and future. National Institute of Health 2010;140;6:935-950.

25.Blonska M, Czuba ZP, Krol W. Effect of flavone derivatives on interleukin-1beta (IL-1beta) mRNA expression and IL-1beta protein synthesis in stimulated RAW264.7 macrophages. Scan J Immunol 2003;52:162-166.

26.Venugopala KN, Rashmi V, Odhav B. Review on natural coumarin lead compounds for their pharmacological activity. BioMed Res Int 2013:1-14.

27.Arora RK, Kaur N, Bansal Y, Bansal G. Novel coumarin-benzimidazole derivatives as antioxidants and safer anti-inflammatory agents. Acta Pharmaceutica Sinica B 2014;4;5:368-375.

28.Simpson RJ, Hammacher A, Smith KD, Matthews MJ, Ward DL. Interleukin-6: structure-function relationships. Protein Sci 1997;6:929-955.

29.Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 2002;13;4-5:357-368.

30.Brochner A, Toft P. Pathophysiology of the systemic inflammatory response after major accidental trauma. Scand J Trauma Resusc Emerg Med 2009;17;1:1-43.

31.Kim, EY, Moudgil KD. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunol Lett 2008;120:1-5.

32.Shin EM, Zhou HY, Guo LY, Kim JA, Lee SH, Merfort I et al. Anti-inflammatory effects of glycyrol isolated from Glychirhiza uralensis in LPS-stimulated RAW264.7 macrophages. Int Immunopharmacol, 2008; 8:1524-1532.

33.Sahu, D. 8-methoxy chromen-2-one alleviates collagen induced arthritis by down regulating nitric oxide, NFκB and proinflammatory cytokines. ScienceDirect 2015;29; 2:891-900.

34.He ZD, Qiao CF, Han QB, Cheng CL, Xu HX, Jiang RW, 

et al. Authentication and quantitative analysis on the chemical profile of cassia bark (Cortex Cinnamomi) by high-pressure liquid chromatography. J Agric Food Chem 2005;53:2424–2428.

35.Szliszka E, Skaba D, Czuba ZP, Krol W. Inhibition of inflammatory mediators by neobaisoflavone in activated RAW264.7 macrophages. Mol 2011;16:3701-3712.

36.Hsieh IN, Chang AS, Teng CM, Chen CC, Yang CR. Aciculatin inhibits lipopolysaccharide-mediated inducible nitric oxide synthase and cyclooxygenase-2 expression via suppressing NF-κB and JNK/p38 MAPK activation pathways. J Biomed Sci 2011;18;1:1-28.

37.Handy RL, Moore PK. A comparison of the effects of L-NAME, 7-NI and L-NIL on caurageenan-induced hindpawoedema and NOS activity. British J Pharmacol 1998; 123;6:1119-1126.

38.Liao JC, Deng JS, Chiu CS, Hou WC, Huang SS, Shie PH, et al. Anti-inflammatory activities of Cinnamomum cassia constituent in vivo and in vitro. J Evid Based Complementary Altern Med 2012;2012:1-12.

39.Chunmei W, Xingxu D, He L. Anti-inflammatory effects of coumarin of Angelicae dahuricae. InHuman Health and Biomedical Engineering (HHBE), 2011 International Conference 2011: 164-167.

40.de Sousa DP. A review on anti-inflammatory activity of phenylpropanoids found in essential oils. Mol 2014;19:1459-1480.

41.Tak P, Firestein G. NF-kappaB: a key role in inflammatory disease. J Clin Investig  2001;107:7-11.

42.Libby P. Inflammation in atherosclerosis. Nature 2002;420:868-874.

43.Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR. In vitro and ex vivo anti-infammatory activity of quercetin in healthy volunteers. Nutrition  2008;24;7-8:703-710.