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Citri Reticulatae Pericarpium extract and flavonoids reduce inflammation in RAW 264.7 macrophages by inactivation of MAPK and NF-kappa B pathways

文献类型： 外文期刊

作者： Zhang, Xutao 1 ; Zhou, Yan 1 ; Cheong, Meng Sam 1 ; Khan, Haroon 2 ; Ruan, Cheng-Chao 3 ; Fu, Manqin 4 ; Xiao, Jianbo 5 ; Cheang, Wai San 2 ;

作者机构： 1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China

2.Abdul Wali Khan Univ Mardan, Dept Pharm, Mardan, Khyber Pakhtunk, Pakistan

3.Fudan Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Shanghai Key Lab Bioact Small Mol, Shanghai, Peoples R China

4.Minist Agr & Rural Affairs, Guangdong Acad Agr Sci, Sericultural & Agrifood Res Inst, Key Lab Funct Foods,Guangdong Key Lab Agr Prod Pro, Guangzhou, Peoples R China

5.Jinan Univ, Inst Food Safety & Nutr, Guangzhou, Peoples R China

6.Univ Vigo, Fac Sci, Dept Analyt & Food Chem, Nutr & Bromatol Grp, Orense, Spain

7.Univ Vigo, Fac Food Sci & Technol, Dept Analyt Chem & Food Sci, Vigo 36310, Spain

8.Univ Macau, Room 5008a, Bldg N22,Ave Univ, Taipa, Macao, Peoples R China

关键词： Criti reticulata; inflammation; lipopolysaccharide; macrophage; MAPK; NF-kappa B

期刊名称：FOOD FRONTIERS （ 影响因子：9.9； 五年影响因子：10.0 ）

ISSN：

年卷期： 2022 年 3 卷 4 期

页码：

收录情况： SCI

摘要： Citri reticulatae Pericarpium (CRP) is widely consumed as a food and herbal medicine in various countries and has many biological activities, including anti-inflammatory effects, but the molecular mechanism is not completely known. This study aims to investigate whether CRP extract and its major flavonoids hesperidin (Hsd) and hesperetin (Hst) can reduce inflammation in macrophages and the underlying mechanism. The chemical composition of CRP was detected by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. The inflammatory cell model was induced by stimulating RAW 264.7 cells with lipopolysaccharide (LPS, 1 mu g/ml). Levels of nitric oxide (NO) and cytokines were determined by Griess assay and enzyme-linked immunosorbent assay kits, respectively. Protein expressions were examined by western blotting. CRP extract dose-dependently suppressed LPS-induced production of NO, interleukin-6 (IL-6), and tumor necrosis factor-alpha. Elevated expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) and phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p65 in LPS-stimulated cells were prevented by CRP extract. Hsd and Hst are flavonoids present in CRP, as confirmed by UPLC-MS analysis. Both Hsd and Hst ameliorated LPS-triggered inflammation to reduce NO release, IL-6 generation, and protein expressions of iNOS and COX-2. These results reveal that CRP extract possesses anti-inflammatory activity by inactivating the mitogen-activated protein kinase and nuclear factor kappa-light chain-enhancer of activated B cells pathways, where Hsd and Hst are bioactive constituents, implying the potential application of CRP as dietary supplements against inflammatory diseases.

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