Anti-inflammatory Activity of Sorghum bicolor (L.) Moench var. Hwanggeumchal Grains in Lipopolysaccharide-stimulated RAW264.7 Murine Macrophage Cell Line

다국어 초록 (Multilingual Abstract)

To investigate the anti-inflammatory activity of the grains of sorghum, three Sorghum bicolor (L.) Moench variants (Hwanggeumchal, Huinchal, and Chal) being cultivated in Korea, the 80% ethanol (EtOH) extracts of individual sorghum grains were compared for their inhibitory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cell line. Among them, the EtOH extract of sorghum Hwanggeumchal grains could exert the highest inhibitory effect on the LPS-induced NO production. However, under these conditions, the viability of RAW264.7 cells was not affected. When the EtOH extract of sorghum Hwanggeumchal grains was sequentially fractionated with n-hexane, methylene chloride (MC), ethyl acetate (EtOAc), and n-butanol, the anti-NO production activity was predominantly detected in both MC and EtOAc fractions. In particular, treatment with the MC fraction reduced dose-dependently the expression levels of iNOS, COX-2 and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-stimulated RAW264.7 cells. Simultaneously, the MC fraction could prevent LPS-induced activating phosphorylation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). HPLC analysis of the MC fraction showed gentisic acid and naringenin as the major phenolic components. Both gentisic acid and naringenin commonly exhibited a potent inhibitory activity against LPS-induced NO production in RAW264.7 cells. Together, these results provide the evidence of the inhibitory activity of Hwanggeumchal grains on LPS-induce inflammatory responses in RAW264.7 murine macrophage cells and also suggest that sorghum grains possess beneficial health effects which can be applicable in development of the grain-based functional foods.

참고문헌 (Reference)

1 Slavin, J., "Why whole grains are protective : biological mechanisms" 62 : 129-134, 2003

2 Hajihashemi, P., "Whole-grain intake favorably affects markers of systemic inflammation in obese children : a randomized controlled crossover clinical trial" 58 : 1301-1308, 2014

3 Roberts, R. A., "Toxicological and pathophysiological roles of reactive oxygen and nitrogen species" 276 : 85-94, 2010

4 Sharma, S., "Study on prevention of two-stage skin carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical constituent, gentisic acid, in the inhibition of tumour promotion response and oxidative stress in mice" 13 : 53-63, 2004

5 Yang, L., "Sorghum 3-deoxyanthocyanins possess strong phase II enzyme inducer activity and cancer cell growth inhibition properties" 57 : 1797-1804, 2009

6 Hinz, B., "Salicylate metabolites inhibit cyclooxygenase-2-dependent prostaglandin E2 synthesis in murine macrophages" 274 : 197-202, 2000

7 Watson, W. H., "S-adenosylmethionine attenuates the lipopolysaccharide-induced expression of the gene for tumor necrosis factor alpha" 342 : 21-25, 1999

8 Dykes, L., "Phenolic compounds in cereal grains and their health benefits" 52 : 105-111, 2007

9 Aslan, M., "Oxidative and nitrative stress markers in glaucoma" 45 : 367-376, 2008

10 Nathan, C., "Nitric oxide synthases : roles, tolls, and controls" 78 : 915-918, 1994

11 Kubes, P., "Nitric oxide and intestinal inflammation" 109 : 150-158, 2000

12 Fardet, A., "New hypotheses for the health-protective mechanisms of whole-grain cereals : what is beyond fibre?" 23 : 65-134, 2010

13 Park, H. Y., "Naringenin attenuates the release of pro-inflammatory mediators from lipopolysaccharide-stimulated BV2 microglia by inactivating nuclear factor-κB and inhibiting mitogen-activated protein kinases" 30 : 204-210, 2012

14 Goyal, A., "Naringenin : A prospective therapeutic agent for Alzheimer's and Parkinson's disease" e14415-, 2022

15 Rhee, S. H., "Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NFκB and expression of the inducible cyclooxygenase" 275 : 34035-34040, 2000

16 Fujihara, M., "Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide : roles of the receptor complex" 100 : 171-194, 2003

17 Lu, Y. C., "LPS/TLR4signal transduction pathway" 42 : 145-151, 2008

18 Nguyen, P. H., "Isolation of benzoic and cinnamic acid derivatives from the grains of Sorghum bicolor and their inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells" 168 : 512-519, 2015

19 Libby, P., "Inflammatory mechanisms : the molecular basis of inflammation and disease" 65 : S140-S146, 2007

20 Conforti, F., "In vivo anti-inflammatory and in vitro antioxidant activities of Mediterranean dietary plants" 116 : 144-151, 2008

21 Guo, W., "Imperatorin attenuates LPSinduced inflammation by suppressing NF-κB and MAPKs activation in RAW 264.7 macrophages" 35 : 1764-1772, 2012

22 Fernandez, I. S., "Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors" 285 : 11714-11729, 2010

23 Dicko, M. H., "Evaluation of the effect of germination on phenolic compounds and antioxidant activities in sorghum varieties" 53 : 2581-2588, 2005

24 Gomez-Cordoves, C., "Effects of wine phenolics and sorghum tannins on tyrosinase activity and growth of melanoma cells" 49 : 1620-1624, 2001

25 박동화 ; 김영호 ; 전도연 ; 이지영 ; 우미희 ; 김기영 ; 서명철 ; 고지연 ; 우관식 ; 정태욱 ; 곽도연 ; 남민희 ; 이승태, "Comparative Evaluation of Antioxidant Activities of Ethanol Extracts and Their Solvent Fractions Obtained from Selected Miscellaneous Cereal Grains" 한국생명과학회 24 (24): 26-38, 2014

26 Gao, J. J., "Autocrine/paracrine IFN-αβ mediates the lipopolysaccharide-induced activation of transcription factor Stat1α in mouse macrophages : pivotal role of Stat1α in induction of the inducible nitric oxide synthase gene" 161 : 4803-4810, 1998

27 Phi-Hung Nguyen ; Vu Viet Dung ; Bing Tian Zhao ; 김영호 ; 민병선 ; 우미희, "Antithrombotic and antidiabetic flavonoid glycosides from the grains of Sorghum bicolor (L.) Moench var. hwanggeumchal" 대한약학회 37 (37): 1394-1402, 2014

28 Zbasnik, R., "Antiproliferation properties of grain sorghum dry distiller’s grain lipid in Caco-2cells" 57 : 10435-10441, 2009

29 Kil, H. Y., "Antioxidant and antimicrobial activities of crude sorghum extract" 115 : 1234-1239, 2009

30 Anson, N. M., "Antioxidant and anti-inflammatory capacity of bioaccessible compounds from wheat fractions after gastrointestinal digestion" 51 : 110-114, 2010

31 Choi, Y. M., "Antioxidant activity of methanolic extracts from some grains consumed in Korea" 103 : 130-138, 2006

32 Jung, Y. S., "Anti-inflammatory effect of tricin 4′-O-(threo-β-guaiacylglyceryl) ether, a novel flavonolignan compound isolated from Njavara on in RAW264.7cells and in ear mice edema" 277 : 67-76, 2014

33 Woo, H. J., "Anti-inflammatory action of 2-carbomethoxy-2,3-epoxy-3-prenyl-1,4-naphthoquinone (CMEP-NQ) suppresses both the MyD88-dependent and TRIF-dependent pathways of TLR4 signaling in LPS-stimulated RAW264.7cells" 205 : 103-115, 2017

34 이지영 ; 전도연 ; 윤영호 ; 고지연 ; 우관식 ; 우미희 ; 김영호, "Anti-inflammatory Effect of Flavonoids Kaempferol and Biochanin A-enriched Extract of Barnyard Millet (Echinochloa crus-galli var. frumentacea) Grains in LPS-stimulated RAW264.7 Cells" 한국생명과학회 24 (24): 1157-1167, 2014

35 Green, L. C., "Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids" 126 : 131-138, 1982

36 Cargnello, M., "Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases" 75 : 50-83, 2011