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Pathway and Genomics of Immunomodulator Natural Products

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Plants and Phytomolecules for Immunomodulation

Abstract

Immune dysfunction has become a major public health problem, so the search for natural products with efficacy, safety, and therapeutic effects on the host immune functions has attracted extensive attention. Several in vitro and in vivo models have been used to outline the immunomodulation effects of natural products due to their anti-inflammatory property, induction of phagocytosis, and immune cells stimulation activity. The updated research progress of immunomodulatory mechanisms of natural products was reviewed. Furthermore, several immune-related pathways, including NF-𝜅B, IL-6/JAK/STAT, MAPK, and PI3K pathways, were elucidated. It is hoped that by analyzing and summarizing the research progress of the immunomodulatory activity of phytochemicals (mainly flavonoids, isoflavones, saponins, catechins, anthocyanins, and alkaloids), a more comprehensive understanding of the immunomodulatory activity of NPs can be provided.

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References

  • Afaq F, Adhami VM, Ahmad N, Mukhtar H (2003) Inhibition of ultraviolet B-mediated activation of nuclear factor κ B in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate. Oncogene 22(7):1035–1044

    Article  CAS  PubMed  Google Scholar 

  • Ahn SI, Lee JK, Youn HS (2009) Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol. Mol Cells 27(2):211–215

    Article  CAS  PubMed  Google Scholar 

  • Ali SA, Singh G, Datusalia AK (2021) Potential therapeutic applications of phytoconstituents as immunomodulators: preclinical and clinical evidences. Phytother Res 35(7):3702–3731

    Article  PubMed  Google Scholar 

  • Allan SM et al (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2(10):734–744

    Article  CAS  PubMed  Google Scholar 

  • Balagopalan L, Coussens NP, Sherman E et al (2010) The LAT story: a tale of cooperativity, coordination, and choreography. Cold Spring Harb Perspect Biol 2(8):a005512

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barioni ED et al (2013) Achyrocline satureioides (Lam.) D.C. hydroalcoholic extract inhibits neutrophil functions related to innate host defense. Evid Based Complement Alternat Med 2013:787916

    Article  PubMed  PubMed Central  Google Scholar 

  • Bhaskar S, Shalini V, Helen A (2011) Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-κB signaling pathway. Immunobiology 216(3):367–373

    Article  CAS  PubMed  Google Scholar 

  • Bilanges B, Posor Y, Vanhaesebroeck B (2019) PI3K isoforms in cell signalling and vesicle trafficking. Nat Rev Mol Cell Biol 20(9):515–534

    Article  CAS  PubMed  Google Scholar 

  • Call ME, Wucherpfermig KW (2005) The T cell receptor: critical role of the membrane environment in receptor assembly and function. Annu Rev Immunol 23:101–125

    Article  CAS  PubMed  Google Scholar 

  • Cespedes CL, Alarcon J, Avila JG, Nieto A (2010) Anti-inflammatory Activity of Aristotelia chilensis Mol. (Stuntz)(Elaeocarpaceae). Boletin Latinoamericano y del Caribe de Plantas Medicinales y Aromaticas 9(2):127–135

    CAS  Google Scholar 

  • Chanet A, Milenkovic D, Claude S, Maier JA, Khan MK, Rakotomanomana N, Shinkaruk S, Bérard AM, Bennetau-Pelissero C, Mazur A (2013) Flavanone metabolites decrease monocyte adhesion to TNF-α-activated endothelial cells by modulating expression of atherosclerosis-related genes. Br J Nutr 110(4):587–598

    Article  CAS  PubMed  Google Scholar 

  • Chen RJ, Lee YH, Yeh YL, Wu WS, Ho CT, Li CY, Wang YJ (2017) Autophagy-inducing effect of pterostilbene: a prospective therapeutic/preventive option for skin diseases. J Food Drug Anal 25(1):125–133

    Article  CAS  PubMed  Google Scholar 

  • Cheng W-E et al (2015) Berberine reduces Toll-like receptor-mediated macrophage migration by suppression of Src enhancement. Eur J Pharmacol 757:1–10

    Article  CAS  PubMed  Google Scholar 

  • Cho JW, Lee KS, Kim CW (2007) Curcumin attenuates the expression of IL-1β, IL-6, and TNF-α as well as cyclin E in TNF-α-treated HaCaT cells; NF-κB and MAPKs as potential upstream targets. Int J Mol Med 19(3):469–474

    CAS  PubMed  Google Scholar 

  • Cho M, Choi G, Shim I et al (2019) Enhanced Rg3 negatively regulates Th1 cell responses. J Ginseng Res 43(1):49–57

    Article  PubMed  Google Scholar 

  • Choy EH, De Benedetti F, Takeuchi T, Hashizume M, John MR, Kishimoto T (2020) Translating IL-6 biology into effective treatments. Nat Rev Rheumatol 16(6):335–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chtourou Y, Aouey B, Kebieche M, Fetoui H (2015) Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways. Chem Biol Interact 239:76–86

    Article  CAS  PubMed  Google Scholar 

  • Chung JY, Park JO, Phyu H, Dong Z, Yang CS (2001) Mechanisms of inhibition of the Ras-MAP kinase signaling pathway in 30.7 b Ras 12 cells by tea polyphenols (−)-epigallocatechin-3-gallate and theaflavin-3, 3′-digallate1. FASEB J 15(11):2022–2024

    Article  CAS  PubMed  Google Scholar 

  • Chung S, Kim HJ, Choi HK, Park JH, Hwang JT (2020) Comparative study of the effects of diosmin and diosmetin on fat accumulation, dyslipidemia, and glucose intolerance in mice fed a high-fat high-sucrose diet. Food Sci Nutr 8(11):5976–5984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung-Yi C, Chiu-Li K, Chi-Ming L (2018) The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the TLR4 signaling pathway. Int J Mol Sci 19(9):2729

    Article  CAS  Google Scholar 

  • Clara JA, Monge C, Yang Y, Takebe N (2019) Targeting signalling pathways and the immune microenvironment of cancer stem cells—a clinical update. Nat Rev Clin Oncol 17(Suppl. 5):204–232

    PubMed  Google Scholar 

  • Crespo I, García-Mediavilla MV, Gutiérrez B, Sánchez-Campos S, Tuñón MJ, González-Gallego J (2008) A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells. Br J Nutr 100(5):968–976

    Article  CAS  PubMed  Google Scholar 

  • Cui C, Zong J, Sun Y, Zhang L, Ho CT, Wan X, Hou R (2018) Triterpenoid saponins from the genus Camellia: structures, biological activities, and molecular simulation for structure-activity relationship. Food Funct 9(6):3069–3091

    Article  CAS  PubMed  Google Scholar 

  • Darnell JE Jr, Kerr IM, Stark GR (1994) Jak-STAT Pathways and Transcriptional Activation in response to IFNs and other extracellular signaling proteins. Science 264(5164):1415–1421

    Article  CAS  PubMed  Google Scholar 

  • de Oliveira Ferreira E, Fernandes MYSD, de Lima NMR, Neves KRT, do Carmo MRS, Lima FAV, de Andrade GM (2016) Neuroinflammatory response to experimental stroke is inhibited by eriodictyol. Behav Brain Res 312:321–332

    Article  CAS  Google Scholar 

  • Deguine J, Barton GM (2014) MyD88: a central player in innate immune signaling. F1000prime Rep 6:97

    Article  PubMed  PubMed Central  Google Scholar 

  • Deng Y et al (2014) The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling. J Immunol 193(6):2994

    Article  CAS  PubMed  Google Scholar 

  • Deng L, Qi M, Li N, Lei Y, Zhang D, Chen J (2020) Natural products and their derivatives: promising modulators of tumor immunotherapy. J Leukoc Biol 108(2):493–508

    Article  CAS  PubMed  Google Scholar 

  • Deopurkar R et al (2010) Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care 33(5):991–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diomede F, Zingariello M, Cavalcanti MF, Merciaro I, Pizzicannella J, de Isla N, Trubiani O (2017) MyD88/ERK/NFkB pathways and pro-inflammatory cytokines release in periodontal ligament stem cells stimulated by Porphyromonas gingivalis. Eur J Histochem EJH 61(2)

    Google Scholar 

  • Dou W, Zhang J, Sun A, Zhang E, Ding L, Mukherjee S et al (2013) Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Br J Nutr 110(4):599–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doyle SL, O’Neill LAJ (2006) Toll-like receptors: from the discovery of NFkB to new insights into transcriptional regulations in innate immunity. Biochem Pharmacol 72(9):1102–1113

    Article  CAS  PubMed  Google Scholar 

  • Duodu KG, Awika JM (2019) Phytochemical-related health-promoting attributes of sorghum and millets. In: Sorghum and millets. AACC International Press, pp 225–258

    Chapter  Google Scholar 

  • Ehteshamfar SM, Akhbari M, Afshari JT et al (2020) Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation. J Cell Mol Med 24(23):13573–13588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fallah AA, Sarmast E, Fatehi P, Jafari T (2020) Impact of dietary anthocyanins on systemic and vascular inflammation: systematic review and meta-analysis on randomised clinical trials. Food Chem Toxicol 135:110922

    Article  CAS  PubMed  Google Scholar 

  • Fu Y et al (2014) Curcumin attenuates inflammatory responses by suppressing TLR4-mediated NF-κB signaling pathway in lipopolysaccharide-induced mastitis in mice. Int Immunopharmacol 20(1):54–58

    Article  CAS  PubMed  Google Scholar 

  • Gadina M, Chisolm DA, Philips RL, McInness IB, Changelian PS, O’Shea JJ (2020) Translating JAKs to Jakinibs. J Immunol 204(8):2011–2020

    Article  CAS  PubMed  Google Scholar 

  • Galleggiante V, De Santis S, Cavalcanti E, Scarano A, De Benedictis M, Serino G, Kunde D (2017) Dendritic cells modulate iron homeostasis and inflammatory abilities following quercetin exposure. Curr Pharm Des 23(14):2139–2146

    Article  CAS  PubMed  Google Scholar 

  • Galon J, Bruni D (2020) Tumor immunology and tumor evolution: intertwined histories. Immunity 52(1):55–81

    Article  CAS  PubMed  Google Scholar 

  • Gao X, Kuo J, Jiang H, Deeb D, Liu Y, Divine G, Gautam SC (2004) Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem Pharmacol 68(1):51–61

    Article  CAS  PubMed  Google Scholar 

  • Garbers C, Aparicio-Siegmund S, Rose-John S (2015) The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition. Curr Opin Immunol 34:75–82

    Article  CAS  PubMed  Google Scholar 

  • Garcia KC, Adams JJ, Feng D et al (2009) The molecular basis of TCR germline bias for MHC is surprisingly simple. Nat Immunol 10(2):143–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germain RN, Stefanova I (1999) The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Annu Rev Immunol 17:467–522

    Article  CAS  PubMed  Google Scholar 

  • Ghanim H et al (2010) Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr 91(4):940–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gholami A, Baradaran HR, Hariri M (2020) Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials. Phytother Res 35(3):1147–1162

    Article  PubMed  CAS  Google Scholar 

  • Gómez-Zorita S, González-Arceo M, Trepiana J, Aguirre L, Crujeiras AB, Irles E, Portillo MP (2020) Comparative effects of pterostilbene and its parent compound resveratrol on oxidative stress and inflammation in steatohepatitis induced by high-fat high-fructose feeding. Antioxidants 9(11):1042

    Article  PubMed Central  CAS  Google Scholar 

  • Grudzien M, Rapak A (2018) Effect of natural compounds on NK cell activation. J Immunol Res 2018:1–11

    Article  CAS  Google Scholar 

  • Guillermo García-Laínez MS, García-Bayarri V, Orzáez M (2017) Identification and validation of uterine stimulant methylergometrine as a potential inhibitor of caspase-1 activation. Apoptosis 22(10):1310–1318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo S, Wang Y, Li Y, Li Y, Feng C, Li Z (2020) Daidzein-rich isoflavones aglycone inhibits lung cancer growth through inhibition of NF-κB signaling pathway. Immunol Lett 222:67–72

    Article  CAS  PubMed  Google Scholar 

  • Haghighatdoost F, Hariri M (2019) Can resveratrol supplement change inflammatory mediators? A systematic review and meta-analysis on randomized clinical trials. Eur J Clin Nutr 73(3):345–355

    Article  CAS  PubMed  Google Scholar 

  • Haque A et al (2011) Flavopiridol inhibits lipopolysaccharide-induced TNF-α production through inactivation of nuclear factor-κB and mitogen-activated protein kinases in the MyD88-dependent pathway. Microbiol Immunol 55(3):160–167

    Article  CAS  PubMed  Google Scholar 

  • Harvey AL, Edrada-Ebel RA, Quinn RJ (2015) The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 14(2):111–129

    Article  CAS  PubMed  Google Scholar 

  • Hasnat MA, Pervin M, Cha KM, Kim SK, Lim BO (2015) Anti-inflammatory activity on mice of extract of Ganoderma lucidum grown on rice via modulation of MAPK and NF-κB pathways. Phytochemistry 114:125–136

    Article  CAS  PubMed  Google Scholar 

  • Heine M, Fischer AW, Schlein C, Jung C, Straub LG, Gottschling K et al (2018) Lipolysis triggers a systemic insulin response essential for efficient energy replenishment of activated brown adipose tissue in mice. Cell Metab 28(4):644–655.e4

    Article  CAS  PubMed  Google Scholar 

  • Hostetler G, Riedl K, Cardenas H, Diosa-Toro M, Arango D, Schwartz S, Doseff AI (2012) Flavone deglycosylation increases their anti-inflammatory activity and absorption. Mol Nutr Food Res 56(4):558–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou D-X, Kai K, Li J-J, Lin S, Terahara N, Wakamatsu M, Fujii M, Young MR, Colburn N (2004) Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure–activity relationship and molecular mechanisms. Carcinogenesis 25(1):29–36

    Article  CAS  PubMed  Google Scholar 

  • Hou D-X, Yanagita T, Uto T, Masuzaki S, Fujii M (2005) Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure–activity relationship and molecular mechanisms involved. Biochem Pharmacol 70(3):417–425

    Article  CAS  PubMed  Google Scholar 

  • Huang TC, Tseng KY, Tsai SS, Liu HJ, Ho CT, Lin HY et al (2010) Eriodictyol decreases very late antigen-4 (VLA-4) expression, cellular adhesion, and migration through an NFκB-dependent pathway in monocytes. J Funct Foods 2(4):263–270

    Article  CAS  Google Scholar 

  • Huang H et al (2011) Isolation and characterization of two flavonoids, engeletin and astilbin, from the leaves of engelhardia roxburghiana and their potential anti-inflammatory properties. J Agri Food Chem 59(9):4562–4569

    Article  CAS  Google Scholar 

  • Hyun KH, Gil KC, Kim SG et al (2019) Delphinidin chloride and its hydrolytic metabolite gallic acid promote differentiation of regulatory T cells and have an anti-inflammatory effect on the allograft model. J Food Sci 84(4):920–930

    Article  CAS  PubMed  Google Scholar 

  • Ivashkiv LB (2018) IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nat Rev Immunol 18(9):545–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jara E, Hidalgo MA, Hancke JL et al (2014) Delphinidin activates NFAT and induces IL-2 production through SOCE in T cells. Cell Biochem Biophys 68(3):497–509

    Article  CAS  PubMed  Google Scholar 

  • Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, Jiang Z (2012) Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages. PLoS One 7(12):e53101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiao A, Yang Z, Fu X et al (2020) Phloretin modulates human Th17/Treg cell differentiation in vitro via AMPK signaling. Biomed Res Int 2020:1–12

    Google Scholar 

  • Johnson DE, O’Keefe RA, Grandis JR (2018) Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 15(4):234–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato M, Pu MY, Isobe KI et al (1994) Characterization of the immunoregulatory action of saikosaponin-d. Cell Immunol 159(1):15–25

    Article  CAS  PubMed  Google Scholar 

  • Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:461

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Keating SE et al (2007) IRAK-2 participates in multiple toll-like receptor signaling pathways to NFκB via activation of TRAF6 ubiquitination. J Biol Chem 282(46):33435–33443

    Article  CAS  PubMed  Google Scholar 

  • Keyhanmehr N, Motedayyen H, Eskandari N (2019) The effects of silymarin and cyclosporine A on the proliferation and cytokine production of regulatory T cells. Immunol Investig 48(5):533–548

    Article  CAS  Google Scholar 

  • Khan H, Ullah H, Castilho PCMF, Gomila AS, D’Onofrio G, Filosa R et al (2020) Targeting NF-κB signaling pathway in cancer by dietary polyphenols. Crit Rev Food Sci Nutr 60(16):2790–2800

    Article  CAS  PubMed  Google Scholar 

  • Kim JM, Uehara Y, Choi YJ, Ha YM, Ye BH, Yu BP, Chung HY (2011) Mechanism of attenuation of pro-inflammatory Ang II-induced NF-κB activation by genistein in the kidneys of male rats during aging. Biogerontology 12(6):537–550

    Article  CAS  PubMed  Google Scholar 

  • Kim TH, Ku SK, Bae JS (2012) Inhibitory effects of kaempferol-3-O-sophoroside on HMGB1-mediated proinflammatory responses. Food Chem Toxicol 50(3–4):1118–1123

    Article  CAS  PubMed  Google Scholar 

  • Kim MH, Kim HH, Jeong JM et al (2020) Ginsenoside F2 attenuates chronic binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells. J Ginseng Res 44:815–822

    Article  PubMed  PubMed Central  Google Scholar 

  • Kishimoto TI (1973) Regulation of antibody response in vitro VII. Enhancing soluble factors for IgG and IgE antibody response. J Immunol 111:1194–1205

    CAS  PubMed  Google Scholar 

  • Krishnan G, Subramaniyan J, Subramani PC, Muralidharan B, Thiruvengadam D (2017) Hesperetin conjugated PEGylated gold nanoparticles exploring the potential role in anti-inflammation and anti-proliferation during diethylnitrosamine-induced hepatocarcinogenesis in rats. Asian J Pharmaceut Sci 12(5):442–455

    Google Scholar 

  • Kumar A, Rimando AM, Levenson AS (2017) Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer. Ann N Y Acad Sci 1403(1):15–26

    Article  CAS  PubMed  Google Scholar 

  • Kumari N, Dwarakanath BS, Das A, Bhatt AN (2016) Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol 37(9):11553–11572

    Article  CAS  PubMed  Google Scholar 

  • Kurosaki T, Wienands J (2016) B cell receptor signaling. In: Current topics in microbiology and immunology, 1st edn. Springer International Publishing: Imprint: Springer, Cham. (pp. 1 online resource (X, 231 pages))

    Google Scholar 

  • Lai X, Cao M, Song X, Jia R, Zou Y, Li L, Ye G (2017) Resveratrol promotes recovery of immune function of immunosuppressive mice by activating JNK/NF-κB pathway in splenic lymphocytes. Can J Physiol Pharmacol 95(6):763–767

    Article  CAS  PubMed  Google Scholar 

  • Lakshmi SP, Reddy AT, Kodidhela LD, Varadacharyulu NC (2020) The tea catechin epigallocatechin gallate inhibits NF-κB-mediated transcriptional activation by covalent modification. Arch Biochem Biophys 695:108620

    Article  CAS  PubMed  Google Scholar 

  • Lee EJ, Ko E, Lee J et al (2004) Ginsenoside Rg1 enhances CD4+ T-cell activities and modulates Th1/Th2 differentiation. Int Immunopharmacol 4(2):235–244

    Article  CAS  PubMed  Google Scholar 

  • Lee KW, Bode AM, Dong Z (2011) Molecular targets of phytochemicals for cancer prevention. Nat Rev Cancer 11(3):211–218

    Article  CAS  PubMed  Google Scholar 

  • Lee WH et al (2014) Specific oligopeptides in fermented soybean extract inhibit NF-κB-dependent iNOS and cytokine induction by toll-like receptor ligands. J Med Food 17(11):1239–1246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee HS, Kim EN, Jeong GS (2020a) Oral administration of liquiritigenin confers protection from atopic dermatitis through the inhibition of T cell activation. Biomolecules 10(5)

    Google Scholar 

  • Lee H, Sung J, Kim Y, Jeong HS, Lee J (2020b) Inhibitory effect of diosmetin on inflammation and lipolysis in coculture of adipocytes and macrophages. J Food Biochem 2020:e13261

    Google Scholar 

  • Lemaitre B et al (1996) The dorsoventral regulatory gene cassette spatzle/toll/cactus controls the potent antifungal response in drosophila adults. Cell 86(6):973–983

    Article  CAS  PubMed  Google Scholar 

  • Leonard WJ, O’Shea JJ (1998) Jaks and STATs: biological implications. Annu Rev Immunol 16:293–322

    Article  CAS  PubMed  Google Scholar 

  • Leung CY, Liu L, Wong RNS et al (2005) Saikosaponin-d inhibits T cell activation through the modulation of PKC0, JNK, and NF-κB transcription factor. Biochem Biophys Res Commun 338(4):1920–1927

    Article  CAS  PubMed  Google Scholar 

  • Li HY et al (2012) Role of baicalin in regulating Toll-like receptor 2/4 after ischemic neuronal injury. Chin Med J 9:1586–1593

    Google Scholar 

  • Li J, Deng R, Hua X, Zhang L, Lu F, Coursey TG, Li DQ (2016) Blueberry component pterostilbene protects corneal epithelial cells from inflammation via anti-oxidative pathway. Sci Rep 6:19408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G et al (2017) Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 5:14. 

    Article  PubMed  PubMed Central  Google Scholar 

  • Li HJ, Wu NL, Lee GA, Hung CF (2018) The therapeutic potential and molecular mechanism of isoflavone extract against psoriasis. Sci Rep 8(1):6335

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lingappan K (2018) NF-κB in oxidative stress. Curr Opin Toxicol 7:81–86

    Article  PubMed  Google Scholar 

  • Liu J, Huang H, Huang Z, Ma Y, Zhang L, He Y, Zheng X (2019) Eriocitrin in combination with resveratrol ameliorates LPS-induced inflammation in RAW264. 7 cells and relieves TPA-induced mouse ear edema. J Funct Foods 56:321–332

    Article  CAS  Google Scholar 

  • Luo W et al (2012) Baicalin downregulates porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling. PLoS One 7(12):e51008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv S, Yi PF, Shen HQ et al (2014) Ginsenoside Rh2-B1 stimulates cell proliferation and IFN-γ production by activating the p38 MAPK and ERK-dependent signaling pathways in CTLL-2 cells. Immunopharmacol Immunotoxicol 36(1):43–51

    Article  CAS  PubMed  Google Scholar 

  • Ma J, Chan CC, Huang WC, Kuo ML (2020) Berberine Inhibits Pro-inflammatory Cytokine-induced IL-6 and CCL11 Production via Modulation of STAT6 Pathway in Human Bronchial Epithelial Cells. Int J Med Sci 17(10):1464–1473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Machova Urdzikova L, Karova K, Ruzicka J, Kloudova A, Shannon C, Dubisova J, Jendelova P (2016) The anti-inflammatory compound curcumin enhances locomotor and sensory recovery after spinal cord injury in rats by immunomodulation. Int J Mol Sci 17(1):49

    Article  CAS  Google Scholar 

  • Mao X, Ren Z, Parker GN, Sondermann H, Pastorello MA, Wang W, McMurray JS, Demeler B, Darnell JE Jr, Chen X (2005) Structural bases of unphosphorylated STAT1 association and receptor binding. Mol Cell 17(6):761–771

    Article  CAS  PubMed  Google Scholar 

  • Mcgettrick AF, O’Neill LA (2010) Localisation and trafficking of Toll-like receptors: an important mode of regulation. Curr Opin Immunol 22(1):20–27

    Article  CAS  PubMed  Google Scholar 

  • Mertens C, Darnell JE Jr (2007) SnapShot: JAK-STAT signaling. Cell 131(3):612

    Article  CAS  PubMed  Google Scholar 

  • Michaud-Levesque J, Bousquet-Gagnon N, Beliveau R (2012) Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration. Exp Cell Res 318(8):925–935

    Article  CAS  PubMed  Google Scholar 

  • Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M (2012) IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond) 122(4):143–159

    Article  CAS  Google Scholar 

  • Miao LC, Tao HX, Peng Y et al (2019) The anti-inflammatory effects of purslane extract by partial suppression on NF-κB and MAPK activation. Food Chem 290:239–245

    Article  CAS  PubMed  Google Scholar 

  • Morris R, Kershaw NJ, Babon JJ (2018) The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci 27(12):1984–2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nafees S, Rashid S, Ali N, Hasan SK, Sultana S (2015) Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway. Chem Biol Interact 231:98–107

    Article  CAS  PubMed  Google Scholar 

  • Nguyen NH, Nguyen CT (2019) Pharmacological effects of ginseng on infectious diseases. Inflammopharmacology 27(5):871–883

    Article  CAS  PubMed  Google Scholar 

  • Nika K, Soldani C, Salek M et al (2010) Constitutively active lck kinase in T cells drives antigen receptor signal transduction. Immunity 32(6):766–777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noha N et al (2014) Anti-inflammatory activity of fruit fractions in vitro, mediated through toll-like receptor 4 and 2 in the context of inflammatory bowel disease. Nutrients 6(11)

    Google Scholar 

  • Nunes C, Almeida L, Barbosa RM, Laranjinha J (2017) Luteolin suppresses the JAK/STAT pathway in a cellular model of intestinal inflammation. Food Funct 8(1):387–396

    Article  CAS  PubMed  Google Scholar 

  • Orban C, Vasarhelyi Z, Bajnok A et al (2018) Effects of caffeine and phosphodiesterase inhibitors on activation of neonatal T lymphocytes. Immunobiology 223(11):627–633

    Article  CAS  PubMed  Google Scholar 

  • Palanisamy N, Kannappan S, Anuradha CV (2011) Genistein modulates NF-κB-associated renal inflammation, fibrosis and podocyte abnormalities in fructose-fed rats. Eur J Pharmacol 667(1–3):355–364

    Article  CAS  PubMed  Google Scholar 

  • Pan M-H, Lai C-S, Dushenkov S, Ho C-T (2009) Modulation of inflammatory genes by natural dietary bioactive compounds. J Agric Food Chem 57(11):4467–4477

    Article  CAS  PubMed  Google Scholar 

  • Pan W, Yu H, Huang S, Zhu P (2016) Resveratrol protects against TNF-α-induced injury in human umbilical endothelial cells through promoting sirtuin-1-induced repression of NF-KB and p38 MAPK. PLoS One 11(1):e0147034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pan Z, Zhou Y, Luo X, Ruan Y, Zhou L, Wang Q, Chen J (2018) Against NF-κB/thymic stromal lymphopoietin signaling pathway, catechin alleviates the inflammation in allergic rhinitis. Int Immunopharmacol 61:241–248

    Article  CAS  PubMed  Google Scholar 

  • Pan P, Huang YW, Oshima K, Yearsley M, Zhang J, Arnold M et al (2019) The immunomodulatory potential of natural compounds in tumor-bearing mice and humans. Crit Rev Food Sci Nutr 59(6):992–1007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M (2015) Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res 29(3):323–331

    Article  CAS  PubMed  Google Scholar 

  • Park SJ, Youn HS (2010) Suppression of homodimerization of toll-like receptor 4 by isoliquiritigenin. Phytochemistry 71(14–15):1736–1740

    Article  CAS  PubMed  Google Scholar 

  • Park KH, Gu DR, So HS et al (2015) Dual role of cyanidin-3-glucoside on the differentiation of bone cells. J Dent Res 994(12):1676–1683

    Article  CAS  Google Scholar 

  • Park SH, Kim JY, Cheon YH et al (2016) Protocatechuic acid attenuates osteoclastogenesis by downregulating JNK/c-Fos/NFATc1 signaling and prevents inflammatory bone loss in mice. Phytother Res 30(4):604–612

    Article  CAS  PubMed  Google Scholar 

  • Patra MC, Shah M, Choi S (2020) Toll-like receptor-induced cytokines as immunotherapeutic targets in cancers and autoimmune diseases. Semin Cancer Biol 64:61–82

    Article  CAS  PubMed  Google Scholar 

  • Pedro A, Ruiz Dirk H (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NF-κB IRF and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136(3):664–671. https://doi.org/10.1093/jn/136.3.664

    Article  Google Scholar 

  • Peluso I, Yarla NS, Ambra R, Pastore G, Perry G (2017) MAPK signalling pathway in cancers: olive products as cancer preventive and therapeutic agents. Semin Cancer Biol 56:185–195

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Berezo T et al (2011) Cocoa-enriched diets modulate intestinal and systemic humoral immune response in young adult rats. Mol Nutr Food Res 55(Supplement 1):S56–S66

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Berezo T et al (2012) Mechanisms involved in down-regulation of intestinal IgA in rats by high cocoa intake. J Nutrit Biochem 23(7):838–844

    Article  CAS  Google Scholar 

  • Pérez-Jiménez J, Díaz-Rubio ME, Saura-Calixto F (2013) Non-extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects. Nutr Res Rev 26(02):118–129

    Article  PubMed  CAS  Google Scholar 

  • Pergola C, Rossi A, Dugo P, Cuzzocrea S, Sautebin L (2006) Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. Nitric Oxide 15(1):30–39

    Article  CAS  PubMed  Google Scholar 

  • Pianetti S, Guo S, Kavanagh KT, Sonenshein GEJCR (2002) Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells. Cancer Res 62(3):652–655

    CAS  PubMed  Google Scholar 

  • Pinho-Ribeiro FA, Zarpelon AC, Mizokami SS, Borghi SM, Bordignon J, Silva RL, Verri WA Jr (2016) The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-κB activation. J Nutr Biochem 33:8–14

    Article  CAS  PubMed  Google Scholar 

  • Qi Y, Gao F, Hou L et al (2017) Anti-inflammatory and immunostimulatory activities of astragalosides. Am J Chin Med 45(6):1157–1167

    Article  CAS  PubMed  Google Scholar 

  • Qiao H et al (2012) Luteolin downregulates TLR4, TLR5, NF-κB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia. Brain Res 1448:71–81

    Article  CAS  PubMed  Google Scholar 

  • Qiao J, Liu J, Jia K, Li N, Liu B, Zhang Q, Zhu R (2016) Diosmetin triggers cell apoptosis by activation of the p53/Bcl-2 pathway and inactivation of the Notch3/NF-κB pathway in HepG2 cells. Oncol Lett 12(6):5122–5128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahimifard M et al (2017) Targeting the TLR4 signaling pathway by polyphenols: a novel therapeutic strategy for neuroinflammation. Ageing Res Rev 36:11–19

    Article  CAS  PubMed  Google Scholar 

  • Rehman MU, Rather IA (2020) Myricetin abrogates cisplatin-induced oxidative stress, inflammatory response, and goblet cell disintegration in colon of wistar rats. Plan Theory 9(1):28

    CAS  Google Scholar 

  • Rengasamy KRR, Khan H, Gowrishankar S et al (2019) The role of flavonoids in autoimmune diseases: therapeutic updates. Pharmacol Ther 194:107–131

    Article  CAS  PubMed  Google Scholar 

  • Rock FL et al (1998) A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A 95(2):588–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rudolph MG, Stanfield RL, Wilson IA (2006) How TCRs bind MHCs, peptides, and coreceptors. Annu Rev Immunol 24:419–466

    Article  CAS  PubMed  Google Scholar 

  • Ruiz PA, Haller D (2006) Functional diversity of flavonoids in the inhibition of the proinflammatory NFkappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 136(3):664–71

    Article  CAS  PubMed  Google Scholar 

  • Sah JF, Balasubramanian S, Eckert RL, Rorke EA (2004) Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway evidence for direct inhibition of ERK1/2 and AKT kinases. J Biol Chem 279(13):12755–12762

    Article  CAS  PubMed  Google Scholar 

  • Sahu BD, Tatireddy S, Koneru M, Borkar RM, Kumar JM, Kuncha M, Sistla R (2014) Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicol Appl Pharmacol 277(1):8–20

    Article  CAS  PubMed  Google Scholar 

  • Samarpita S, Ganesan R, Rasool M (2020) Cyanidin prevents the hyperproliferative potential of fibroblast-like synoviocytes and disease progression via targeting IL-17A cytokine signalling in rheumatoid arthritis. Toxicol Appl Pharmacol 391:114917

    Article  CAS  PubMed  Google Scholar 

  • Samelson LE (2002) Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol 20:371–394

    Article  CAS  PubMed  Google Scholar 

  • Scanga CA et al (2002) Cutting edge: MyD88 is required for resistance to toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells. J Immunol 168(12):5997–6001

    Article  CAS  PubMed  Google Scholar 

  • Sen R, Baltimore D (1986) Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47(6):921–928

    Article  CAS  PubMed  Google Scholar 

  • Seo EJ, Fischer N, Efferth T (2018) Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease. Pharmacol Res 129:262–273

    Article  CAS  PubMed  Google Scholar 

  • Shariati M, Shaygannejad V, Abbasirad F et al (2019) Silymarin restores regulatory T cells (tregs) function in multiple sclerosis (MS) patients in vitro. Inflammation 42(4):1203–1214

    Article  CAS  PubMed  Google Scholar 

  • Shih P-H, Yeh C-T, Yen G-CJJ, o. a., & chemistry, f. (2007) Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis. J Agric Food Chem 55(23):9427–9435

    Article  CAS  PubMed  Google Scholar 

  • Shim JH, Choi HS, Pugliese A et al (2008) (−)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in leukemia through the inhibition of ZAP-70 kinase. J Biol Chem 283(42):28370–28379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shuto T et al (2010) Curcumin decreases toll-like receptor-2 gene expression and function in human monocytes and neutrophils. Biochem Biophys Res Commun 398(4):647–652

    Article  CAS  PubMed  Google Scholar 

  • Smith-Garvin JE, Koretzky GA, Jordan MS (2009) T cell activation. Annu Rev Immunol 27:591–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soundharrajan I, Kim DH, Kuppusamy P, Choi KC (2019) Modulation of osteogenic and myogenic differentiation by a phytoestrogen formononetin via p38MAPK-dependent JAK-STAT and Smad-1/5/8 signaling pathways in mouse myogenic progenitor cells. Sci Rep 9(1):9307

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Spagnuolo C, Moccia S, Russo GL (2018) Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 153:105–115

    Article  CAS  PubMed  Google Scholar 

  • Srivastava RM, Singh S, Dubey SK, Misra K, Khar A (2011) Immunomodulatory and therapeutic activity of curcumin. Int Immunopharmacol 11(3):331–341

    Article  CAS  PubMed  Google Scholar 

  • Starr TK, Jameson SC, Hogquist KA (2003) Positive and negative selection of T cells. Annu Rev Immunol 21:139–176

    Article  CAS  PubMed  Google Scholar 

  • Suh N, Paul S, Hao X, Simi B, Xiao H, Rimando AM, Reddy BS (2007) Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clin Cancer Res 13(1):350–355

    Article  CAS  PubMed  Google Scholar 

  • Takeda K, Akira S (2004) Microbial recognition by Toll-like receptors. J Dermatol Sci 34(2):73–82

    Article  CAS  PubMed  Google Scholar 

  • Takeda K, Akira S (2015) Toll-like receptors. Curr Protoc Immunol 109:14.12.1–14.12.10

    Article  Google Scholar 

  • Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Curr Protoc Immunol 21:335–376

    CAS  Google Scholar 

  • Takeuchi O, Hoshino K, Akira S (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol 165(10):5392–5396

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T, Narazaki M, Kishimoto T (2018) Interleukin (IL-6) immunotherapy. Cold Spring Harb Perspect Biol 10(8):a028456

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tang Y, Abe N, Qi H et al (2014) Tea catechins inhibit cell proliferation through hydrogen peroxide-dependent and -independent pathways in human T lymphocytic leukemia jurkat cells. Food Sci Technol Res 20(6):1245–1249

    Article  CAS  Google Scholar 

  • Teng WJ, Chen P, Zhu FY, Di K, Zhou C, Zhuang J, Cao XJ, Yang J, Deng LJ, Sun CG (2015) Effect of Rhizoma paridis total saponins on apoptosis of colorectal cancer cells and imbalance of the JAK/STAT3 molecular pathway induced by IL-6 suppression. Genet Mol Res 14(2):5793–5803

    Article  CAS  PubMed  Google Scholar 

  • Triebel S, Trieu H-L, Richling E (2012) Modulation of inflammatory gene expression by a bilberry (Vaccinium myrtillus L.) extract and single anthocyanins considering their limited stability under cell culture conditions. J Agric Food Chem 60(36):8902–8910

    Article  CAS  PubMed  Google Scholar 

  • Truong VL, Jun M, Jeong WS (2018) Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors 44(1):36–49

    Article  CAS  PubMed  Google Scholar 

  • Tsai HY, Ho CT, Chen YK (2017) Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene. J Food Drug Anal 25(1):134–147

    Article  CAS  PubMed  Google Scholar 

  • Tu CT, Li J, Wang FP et al (2012) Glycyrrhizin regulates CD4+ T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway. Int Immunopharmacol 14(4):410–421

    Article  CAS  PubMed  Google Scholar 

  • van der Merwe PA, Dushek O (2011) Mechanisms for T cell receptor triggering. Nat Rev Immunol 1 1(1):47–55

    Article  CAS  Google Scholar 

  • Villarino AV, Gadina M, O’Shea JJ, Kanno Y (2020) SnapShot: Jak-STAT signaling II. Cell 181(7):1696–1696.e1691

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Li XK (2011) Immunosuppressive and anti-inflammatory activities of sinomenine. Int Immunopharmacol 11(3):373–376

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Smith C, Yin H (2013) Targeting Toll-like receptors with small molecule agents. Chem Soc Rev 42:4859–4866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Yan SJ, Zhang HT et al (2017a) Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model. Oncol Lett 13(2):681–685

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Sun B, Zhu F (2017b) Epigallocatechin-3-gallate inhibit replication of white spot syndrome virus in Scylla paramamosain. Fish Shellfish Immunol 67:612–619

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Zhang Y, Jin W, Xing Y, Yang A (2018) Catechin weakens diabetic retinopathy by inhibiting the expression of NF-κB signaling pathway-mediated inflammatory factors. Ann Clin Lab Sci 48(5):594–600

    CAS  PubMed  Google Scholar 

  • Wang B et al (2020a) Resveratrol attenuates TLR-4 mediated inflammation and elicits therapeutic potential in models of sepsis. Sci Rep 10(1):18837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang YJ, Chen YY, Hsiao CM, Pan MH, Wang BJ, Chen YC, Chen RJ (2020b) Induction of autophagy by pterostilbene contributes to the prevention of renal fibrosis via attenuating NLRP3 inflammasome activation and epithelial-mesenchymal transition. Front Cell Dev Biol 8:436

    Article  PubMed  PubMed Central  Google Scholar 

  • Wen Y, Jing Y, Yang L, Kang D, Jiang P, Li N, Cheng J, Li J, Li X, Peng Z, Sun X, Miller H, Sui Z, Gong Q, Ren B, Yin W, Liu C (2019) The regulators of BCR signaling during B cell activation. Blood Sci 1(2):119–129

    Article  PubMed  PubMed Central  Google Scholar 

  • Wenjun O, O’Garra A (2019) IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity 50(4):871–891

    Article  CAS  Google Scholar 

  • Wong CP, Nguyen LP, Noh SK et al (2011) Induction of regulatory T cells by green tea polyphenol EGCG. Immunol Lett 139(1–2):7–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu D et al (2009a) Green tea EGCG suppresses T cell proliferation through impairment of IL-2/IL-2 receptor signaling. Free Radic Biol Med 47(5):636–643

    Article  CAS  PubMed  Google Scholar 

  • Wu Y et al (2009b) Renoprotective effect of total glucosides of paeony (TGP) and its mechanism in experimental diabetes. J Pharmacol Ences 109(1):78–87

    CAS  Google Scholar 

  • Wu X, Shao F, Yang Y, Gu L, Zheng W, Wu X, Gu Y, Shu Y, Sun Y, Xu Q (2014) Epigallocatechin-3-gallate sensitizes IFN-gamma-stimulated CD4+ T cells to apoptosis via alternative activation of STAT1. Int Immunopharmacol 23(2):434–441

    Article  CAS  PubMed  Google Scholar 

  • Xagorari A, Roussos C, Papapetropoulos A (2002) Inhibition of LPS-stimulated pathways in macrophages by the flavonoid luteolin. Br J Pharmacol 136(7):1058–1064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie C, Li X, Zhu J, Wu J, Geng S, Zhong C (2019) Magnesium isoglycyrrhizinate suppresses LPS-induced inflammation and oxidative stress through inhibiting NF-κB and MAPK pathways in RAW264. 7 cells. Bioorg Med Chem 27(3):516–524

    Article  CAS  PubMed  Google Scholar 

  • Xiong X et al (2020) Pterostilbene reduces endothelial cell apoptosis by regulation of the Nrf2mediated TLR4/MyD88/NFκB pathway in a rat model of atherosclerosis. Exp Ther Med 20(3):2090–2098

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav VS, Mishra KP, Singh DP, Mehrotra S, Singh VK (2005) Immunomodulatory effects of curcumin. Immunopharmacol Immunotoxicol 27(3):485–497

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Matsunami E, Komori K et al (2019) The isoflavone puerarin induces Foxp3(+) regulatory T cells by augmenting retinoic acid production, thereby inducing mucosal immune tolerance in a murine food allergy model. Biochem Biophys Res Commun 516(3):626–631

    Article  CAS  PubMed  Google Scholar 

  • Yang Z et al (2015) Bovine TLR2 and TLR4 mediate Cryptosporidium parvum recognition in bovine intestinal epithelial cells. Microb Pathog 85:29–34

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Liu G, Zhu X, Luo Y, Shang Y, Gu XL (2019) The anti-inflammatory and antioxidant effects of leonurine hydrochloride after lipopolysaccharide challenge in broiler chicks. Poult Sci 98(4):1648–1657

    Article  CAS  PubMed  Google Scholar 

  • Yin W, Lei Y (2018) Leonurine inhibits IL-1beta induced inflammation in murine chondrocytes and ameliorates murine osteoarthritis. Int Immunopharmacol 65:50–59

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Wang L, Chen S (2010) Endogenous toll-like receptor ligands and their biological significance. J Cell Mol Med 14(11):2592–2603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng W, Jin L, Zhang F, Zhang C, Liang W (2018) Naringenin as a potential immunomodulator in therapeutics. Pharmacol Res 135:122–126

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Yuan L, Zhang Q, Gao Y, Liu G, Xiu M, Liu D (2015) Resveratrol attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation. Int Immunopharmacol 28(1):578–587

    Article  CAS  PubMed  Google Scholar 

  • Zhang R, Xu J, Zhao J, Chen Y (2017a) Genistein improves inflammatory response and colonic function through NF-κB signal in DSS-induced colonic injury. Oncotarget 8(37):61385

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Wang Y, Xiao C, Wei Z, Wang J, Yang Z, Fu Y (2017b) Resveratrol inhibits LPS-induced mice mastitis through attenuating the MAPK and NF-κB signaling pathway. Microb Pathog 107:462–467

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Kong W, Jiang J (2017c) Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms. Sci China Life Sci 60(6):601–616

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Chen Y, Chen Y, Ji S, Wang T (2020) Comparison of the protective effects of resveratrol and pterostilbene against intestinal damage and redox imbalance in weanling piglets. J Anim Sci Biotechnol 11(1):1–16

    Article  CAS  Google Scholar 

  • Zhao W, Ma L, Cai C, Gong X (2019) Caffeine inhibits nlrp3 inflammasome activation by suppressing mapk/nf-κb and a2ar signaling in lps-induced thp-1 macrophages. Int J Biol Sci 15(8):1571–1581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhe M et al (2013) Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways. Acta Pharmacol Sin 99(7):E13–E13

    Google Scholar 

  • Zheng Y, Yang Y, Li Y, Xu L, Wang Y, Guo Z, Song H, Yang M, Luo B, Zheng A, Li P, Zhang Y, Ji G, Yu Y (2013) Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3beta pathway. Cell Mol Immunol 10(4):330–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng J, Wu J, Chen J, Liu J, Lu Y, Huang C, Zeng Y (2016) Therapeutic effects of quercetin on early inflammation in hypertriglyceridemia-related acute pancreatitis and its mechanism. Pancreatology 16(2):200–210

    Article  CAS  PubMed  Google Scholar 

  • Zhou X, Yuan L, Zhao X, Hou C, Ma W, Yu H, Xiao R (2014) Genistein antagonizes inflammatory damage induced by β-amyloid peptide in microglia through TLR4 and NF-κB. Nutrition 30(1):90–95

    Article  PubMed  CAS  Google Scholar 

  • Zhou Z, Zhou X, Dong Y, Li M, Xu Y (2019) Formononetin ameliorates high glucose induced endothelial dysfunction by inhibiting the JAK/STAT signaling pathway. Mol Med Rep 20(3):2893–2901

    CAS  PubMed  Google Scholar 

  • Zhu HT et al (2014) Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury. J Neuroinflammation 11(1):59

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zielińska-Przyjemska M, Ignatowicz E (2008) Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative metabolism. Phytother Res 22(12):1557–1562

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. College of Biosystems Engineering and Food Science/Ningbo Research Institute, Zhejiang University, Hangzhou, China

    Jing Wang

  2. College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China

    Lingjun Ma

  3. College of Standardization, China Jiliang University, Hangzhou, China

    Fei Zhou

  4. College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, China

    Fang Wang

  5. College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China

    Lei Chen

  6. Department of Analytical Chemistry and Food Science, University of Vigo, Vigo, Spain

    Jianbo Xiao

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  1. Jing Wang
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  2. Lingjun Ma
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  3. Fei Zhou
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  4. Fang Wang
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  5. Lei Chen
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  6. Jianbo Xiao
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Correspondence to Jianbo Xiao .

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  1. Department of Biochemistry, Central University of Haryana, Mahendergarh, Haryana, India

    Neelam S. Sangwan

  2. Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Mohamed A. Farag

  3. Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Brazil

    Luzia Valentina Modolo

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Wang, J., Ma, L., Zhou, F., Wang, F., Chen, L., Xiao, J. (2022). Pathway and Genomics of Immunomodulator Natural Products. In: Sangwan, N.S., Farag, M.A., Modolo, L.V. (eds) Plants and Phytomolecules for Immunomodulation. Springer, Singapore. https://doi.org/10.1007/978-981-16-8117-2_4

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