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Review
. 2019 May 1;27(3):241-253.
doi: 10.4062/biomolther.2019.034.

Flavonoids: Broad Spectrum Agents on Chronic Inflammation

Hyun Lim  1 , Moon Young Heo  1 , Hyun Pyo Kim  1
Affiliations
Review

Flavonoids: Broad Spectrum Agents on Chronic Inflammation

Hyun Lim et al. Biomol Ther (Seoul). .

Abstract

Flavonoids are major plant constituents with numerous biological/pharmacological actions both in vitro and in vivo. Of these actions, their anti-inflammatory action is prominent. They can regulate transcription of many proinflammatory genes such as cyclooxygenase- 2/inducible nitric oxide synthase and many cytokines/chemokines. Recent studies have demonstrated that certain flavonoid derivatives can affect pathways of inflammasome activation and autophagy. Certain flavonoids can also accelerate the resolution phase of inflammation, leading to avoiding chronic inflammatory stimuli. All these pharmacological actions with newly emerging activities render flavonoids to be potential therapeutics for chronic inflammatory disorders including arthritic inflammation, meta-inflammation, and inflammaging. Recent findings of flavonoids are summarized and future perspectives are presented in this review.

Keywords: Chronic inflammation; Flavonoid; Inflammaging; Meta-inflammation; Therapeutics.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Some basic chemical structures of flavonoids.
Fig. 2.
Fig. 2.
Effects of flavonoids on the expression of MMP and ADAMTS in osteoarthritis. MMP and ADAMTS are enzymes that play crucial roles in ECM degradation in osteoarthritis progression. Flavonoids such as apigenin and 2′,3′,5,7-tetrahydroxyflavone inhibit MMP-13 expression via c-Fos/AP-1 and JAK2/STAT1/2 pathway in IL-1β-treated chondrocyte cell line. In animal OA model, flavonoids such as silibinin, chrysin, baicalin, and wogonin show protective effects by downregulation of ADAMTS-4 and/or -5 expression through PI3K/Akt, NF-κB and/or Nrf2 signaling pathways. IL-1R, IL-1 receptor; IL-6R, IL-6 receptor.
Fig. 3.
Fig. 3.
Effects of flavonoids on inflammaging. Cellular aging causes low-grade chronic inflammation, called inflammaging. Some flavonoids have potential as therapeutic candidates for healthy aging by modulating the markers of aging-associated inflammation such as NF-κB activation, inflammasome activation and SASP production.
Fig. 4.
Fig. 4.
Effects of flavonoids on signaling pathway of NLRP3 inflammasome activation. Many flavonoids possess anti-inflammatory activities by interrupting various signaling stages of NLRP3 inflammasome pathway both in vitro and in vivo. They inhibit the expression of NLRP3 inflammasome-related components such as IL-1β, IL-18, NLRP3, and caspase-1 and/or block inflammasome assembly which are mediated through signaling molecules such as TLR4/NF-κB/NLRP3, PPARγ, TXNIP and Syk/Pyk2, etc.
Fig. 5.
Fig. 5.
The suggested flavonoids with core structures showing reasonable inhibitory action on chronic inflammatory responses and clinical trials of some flavonoids. Among a variety of flavonoids, flavonoids such as EGCG, apigenin, kaempferol, quercetin, and 2′,3′,5,7-tetrahydroxyflavone have shown anti-inflammatory activities in many previous reports. In particular, their inhibitory actions are effective for blocking chronic inflammatory mechanisms such as arthritis, inflammaging, meta-inflammation, inflammatory resolution, autophagy and inflammasome-related diseases (A). So far, clinical trials of some flavonoids such as EGCG and quercetin have been processed for several diseases but there is a necessity of more clinical trials for chronic disorders accompanying with these inflammatory responses. Some recent completed clinical trials of flavonoids, EGCG and quercetin, are demonstrated (B). N/A, Not applicable.
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References

    1. Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993;342:1209–1210. doi: 10.1016/0140-6736(93)92188-Y. - DOI - PubMed
    1. Alexander E, Hildebrand DG, Kriebs A, Obermayer K, Manz M, Rothfuss O, Schulze-Osthoff K, Essmann F. IκBζ is a regulator of the senescence-associated secretory phenotype in DNA damage- and oncogene-induced senescence. J. Cell Sci. 2013;126:3738–3745. doi: 10.1242/jcs.128835. - DOI - PubMed
    1. Alimbetov D, Davis T, Brook AJ, Cox LS, Faragher RG, Nurgozhin T, Zhumadilov Z, Kipling D. Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2. Biogerontology. 2016;17:305–315. doi: 10.1007/s10522-015-9610-z. - DOI - PMC - PubMed
    1. Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC, Shen Y, Czech MP, Aouadi M. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab. 2014;19:162–171. doi: 10.1016/j.cmet.2013.11.017. - DOI - PMC - PubMed
    1. Anders HJ, Ryu M. Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis. Kidney Int. 2011;80:915–925. doi: 10.1038/ki.2011.217. - DOI - PubMed