# Anti-Inflammatory Effect of Finger Citron Extract on RAW264.7 Macrophages via NF-κB and MAPK Signaling Pathways

**Authors:** Jiateng Hu, Yuanshan Yu, Ying Tang, Zhibin Bu, Yujuan Xu, Jijun Wu, Gengsheng Xiao, Bo Zou

PMC · DOI: 10.3390/foods15040688 · 2026-02-13

## TL;DR

Finger Citron extract reduces inflammation in macrophages by affecting key signaling pathways, suggesting its potential as a natural anti-inflammatory agent.

## Contribution

The study identifies the anti-inflammatory mechanisms of Finger Citron extract through NF-κB and MAPK pathways in macrophages.

## Key findings

- Finger Citron extract suppresses production of TNF-α, IL-6, and NO in LPS-stimulated macrophages.
- The extract inhibits phosphorylation in MAPK and NF-κB signaling pathways.
- Polyphenols like hesperidin and hesperetin are major components contributing to anti-inflammatory effects.

## Abstract

Finger Citron (Citrus medica L. var. sarcodactylis Swingle) holds significant potential as both a culinary ingredient and a traditional medicinal remedy; however, its precise molecular mechanisms of action remain largely unexplored. This study investigates the anti-inflammatory properties of Finger Citron extract (FCE) in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). Using UPLC-ESI-QTF-MS, we analyzed the extract’s composition, revealing a rich presence of polyphenols and polysaccharides, with hesperidin, melitidin, and hesperetin as the predominant polyphenolic compounds. Additionally, the study elucidated the monosaccharide composition profile of polysaccharides in the extract. Furthermore, Finger Citron extract markedly suppressed the production of key inflammatory mediators, including TNF-α, IL-6, and NO. The inhibition of protein phosphorylation levels of inhibiting the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling was also observed, indicating that the anti-inflammatory effects of Finger Citron extract may involve the NF-κB and MAPK signaling pathway. Given these findings, Finger Citron extract has the potential to act as a natural product with anti-inflammatory activity.

## Linked entities

- **Proteins:** NFKB1 (nuclear factor kappa B subunit 1), MAPK (mitogen activated kinase-like protein)
- **Chemicals:** IL-6 (PubChem CID 165368475), NO (PubChem CID 24822), hesperidin (PubChem CID 10621), melitidin (PubChem CID 101485562), hesperetin (PubChem CID 3593)

## Full-text entities

- **Genes:** Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, Zfp2 (zinc finger protein 2) [NCBI Gene 22678] {aka 9930007F06Rik, Fnp-2, Zfp-2, mKR2, mkr-2, mszf87}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}
- **Diseases:** cancer (MESH:D009369), Inflammation (MESH:D007249), injury to (MESH:D014947), psoriasis (MESH:D011565), psoriatic arthritis (MESH:D015535), osteoarthritis (MESH:D010003), neurological-related disorders (MESH:D009461), fatty liver (MESH:D005234), immune-mediated inflammatory disorders (MESH:C567355), uveitis (MESH:D014605), chronic obstructive pulmonary disease (MESH:D029424), infection (MESH:D007239), hay fever (MESH:D006255), Cytotoxicity (MESH:D064420), rheumatoid arthritis (MESH:D001172), abnormalities of lipid metabolism (MESH:D052439), periodontal disease (MESH:D010510), tissue injury (MESH:D017695), ulcerative colitis (MESH:D003093), inflammatory bowel disease (MESH:D015212), inflammatory cytokines (MESH:D000080424), type II diabetes mellitus (MESH:D003924), allergic reactions (MESH:D004342)
- **Chemicals:** nitrogen (MESH:D009584), Hesperidin (MESH:D006569), coumaric acid (MESH:D003373), Polysaccharide (MESH:D011134), Rutin (MESH:D012431), streptomycin (MESH:D013307), Monosaccharide (MESH:D009005), acetonitrile (MESH:C032159), COO (MESH:C041069), NaCl (MESH:D012965), mannose (MESH:D008358), methanol (MESH:D000432), Gallic acid (MESH:D005707), formazan (MESH:D005562), formic acid (MESH:C030544), sugars (MESH:D000073893), alkaloids (MESH:D000470), B (MESH:D001895), galactose (MESH:D005690), NO (MESH:D009569), ethanol (MESH:D000431), phenol (MESH:D019800), water (MESH:D014867), neohesperidin (MESH:C546526), Hesperetin (MESH:C013015), Trizol (MESH:C411644), essential oils (MESH:D009822), 1-phenyl-3-methyl-5-pyrazolone (MESH:D000077553), phenolic acids (MESH:C017616), MTT (MESH:C070243), RNS (MESH:D026361), rhamnose (MESH:D012210), Saccharide (MESH:D002241), TFA (MESH:D014269), bergapten (MESH:D000078223), NO (MESH:D009614), Naringin (MESH:C005274), DMEM (-), superoxide (MESH:D013481), penicillin (MESH:D010406), oligosaccharides (MESH:D009844), coumarins (MESH:D003374), Melitidin (MESH:C543780), sulfuric acid (MESH:C033158), ROS (MESH:D017382), flavonoids (MESH:D005419), DMSO (MESH:D004121), D-glucose (MESH:D005947), glucosamine (MESH:D005944), BCA (MESH:C047117), CO2 (MESH:D002245), polyphenol (MESH:D059808), agarose (MESH:D012685), p-Coumaric acid (MESH:C495469), lipid (MESH:D008055), LPS (MESH:D008070), Rhoifolin (MESH:C089378)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Citrus medica (citron, species) [taxon 171251]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939456/full.md

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Source: https://tomesphere.com/paper/PMC12939456