Chondrocytes, the unique cell type in jont cartilage, synthesize the extracellular matrix Sustainable weight loss joit maintain the homeostasis of cartilage, which is an avascular tissue and has a limited repair capacity. Fish Shellfish Immunol. Zhongguo Zhongyao Zazhi, 40 1 Curcumin turmeric and cancer.

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3 Healthy Foods High in Collagen, and Foods That Help Your Body Produce Collagen! Osteoarthritis OA is a Herbal supplements for athletes joint disease healtth with qnd inflammation. The nuclear factor-kappaB NF-κB pathway plays Yealth important role in nad Sustainable weight loss and healty NF-κB-mediated inflammation can be Sustainable weight loss potential strategy for treating OA. Flavonoids are a class of naturally occurring polyphenols with anti-inflammatory properties. Increasing evidence demonstrates that natural flavonoids exhibit protective activity against the pathological changes of OA by inhibiting the NF-κB signaling pathway. Potentially, natural flavonoids may suppress NF-κB signaling-mediated inflammatory responses, ECM degradation, and chondrocyte apoptosis. The different biological actions of natural flavonoids against the NF-κB signaling pathway in OA chondrocytes might be associated with the differentially substituted groups on the structures.

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Calycosin alleviates allergic contact dermatitis by repairing epithelial tight junctions via down-regulating HIF-1α. Nong, Y. Pharmacological targets and mechanisms of calycosin against meningitis. Aging Albany NY , , 12 19 , Ma, W.

Combined effects of fangchinoline from Stephania tetrandra Radix and formononetin and calycosin from Astragalus membranaceus Radix on hyperglycemia and hypoinsulinemia in streptozotocin-diabetic mice. Su, X. Ma, R. Calycosin alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress via the p38 MAPK and NF-κB signal pathways in mice.

Dong, L. Anti-inflammatory effect of Calycosin glycoside on lipopolysaccharide-induced inflammatory responses in RAW Gene , , , Ping, C. Antinociceptive effects of cardamonin in mice: possible involvement of TRPv1 glutamate, and opioid receptors. Molecules , , 23 9 , E Jin, J.

Cardamonin inhibits breast cancer growth by repressing HIF-1α;-dependent metabolic reprogramming. Cancer Res. Nawaz, J. Cardamonin: a new player to fight cancer via multiple cancer signaling pathways. Niu, P. Cardamonin ameliorates insulin resistance induced by high insulin and high glucose through the mTOR and signal pathway.

Planta Med. Daimary, U. Emerging roles of cardamonin, a multitargeted nutraceutical in the prevention and treatment of chronic diseases. Drug Discov. Benchabane, S. Voon, F. inhibits CFA-induced rheumatoid arthritis in rats. Jia, D. Cardamonin reduces chemotherapy-enriched breast cancer stem-like cells in vitro and in vivo.

Oncotarget , , 7 1 , Ren, G. The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis. Liver Physiol. Chen, H. Anti-inflammatory effects of cardamonin in ovarian cancer cells are mediated via mTOR suppression.

Li, Y. Anti-inflammatory activities of cardamonin from Alpinia katsumadai through heme oxygenase-1 induction and inhibition of NF-κB and MAPK signaling pathway in the carrageenan-induced paw edema.

Chow, Y. Wei, Z. Cardamonin protects septic mice from acute lung injury by preventing endothelial barrier dysfunction. Lee, M. Alpinia katsumadai H. AYATA seed extract inhibit LPS-induced inflammation by induction of heme oxygenase-1 in RAW Inflammation , , 35 2 , Mirzaei, H.

Phytosomal curcumin: a review of pharmacokinetic, experimental and clinical studies. Lestari, M. Profiles Drug Subst. Akbik, D. Curcumin as a wound healing agent. Unlu, A. Curcumin turmeric and cancer. BUON , , 21 5 , Nabavi, S.

Curcumin: a natural product for diabetes and its complications. Moghadamtousi, S. A review on antibacterial, antiviral, and antifungal activity of curcumin. Wang, Q. Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic effects.

Zheng, Z. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. Kloesch, B. Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes.

Ghandadi, M. Curcumin: an effective inhibitor of interleukin Gong, Z. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production.

Kumar, P. TNF-α; IL-6 and IL expressions, responsible for disparity in action of curcumin against cisplatin-induced nephrotoxicity in rats. Curcumin ameliorates glyoxylate-induced calcium oxalate deposition and renal injuries in mice. Phytomedicine , , 61 , Huang, G. Curcumin protects against collagen-induced arthritis via suppression of BAFF production.

Dai, Q. Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by targeting mTOR pathway in rats. Moon, D. Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model.

Jackson, J. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Yang, M. Curcumin in autoimmune and rheumatic diseases. Nutrients , , 11 5 , E Asteriou, E. Curcumin for the management of periodontitis and early acpa-positive rheumatoid arthritis: killing two birds with one stone.

Nutrients , , 10 7 , E Piovezana Bossolani, G. Rheumatoid arthritis induces enteric neurodegeneration and jejunal inflammation, and quercetin promotes neuroprotective and anti-inflammatory actions.

Cho, E. Anti-cancer effect of cyanidinglucoside from mulberry via caspase-3 cleavage and DNA fragmentation in vitro and in vivo. Agents Med. Zhang, P. Enzymatic acylation of cyanidinglucoside with fatty acid methyl esters improves stability and antioxidant activity. Matsukawa, T. Cyanidinglucoside derived from black soybeans ameliorate type 2 diabetes through the induction of differentiation of preadipocytes into smaller and insulin-sensitive adipocytes.

Molonia, M. CyanidinO-glucoside restores insulin signaling and reduces inflammation in hypertrophic adipocytes. Sun, Y. Cyanidinglucoside inhibits inflammatory activities in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis. Park, K.

Dual role of cyanidinglucoside on the differentiation of bone cells. Xiao, X. Antibacterial activity and mode of action of dihydromyricetin from Ampelopsis grossedentata leaves against food-borne bacteria.

Molecules , , 24 15 , E Gandhi, G. Citrus flavonoids as promising phytochemicals targeting diabetes and related complications: a systematic review of in vitro and in vivo studies. Nutrients , , 12 10 , E Kaewmool, C. CyanidinO-glucoside protects PC12 cells against neuronal apoptosis mediated by LPS-stimulated BV2 microglial activation.

Xia, Y. Bowel Dis. Yan, X. CyanidinO-glucoside attenuates acute lung injury in sepsis rats. Shen, X. Cyanidin 3-O-glucoside chloride attenuates Streptococcus suis-induced inflammation by inhibiting MAPK and NF-κB signaling pathways in murine macrophage J cells.

Zhang, Y. CyanidinO-beta-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IkappaBalpha phosphorylation in THP-1 cells. Fu, Y. CyanidinO-β-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model. Lipid Res.

M ] [PMID: ]. Tsuda, T. Cyanidin 3-O-beta-D-glucoside suppresses nitric oxide production during a zymosan treatment in rats. Tokyo , , 48 4 , Jiang, M. Anti-tumor effects and associated molecular mechanisms of myricetin.

Li, T. Microarray based functional analysis of myricetin and proteomic study on its anti-inflammatory property. Zhang, K. Neuropharmacology , , 61 , Yuan, X. Myricetin ameliorates the symptoms of collagen-induced arthritis in mice by inhibiting cathepsin K activity. Vargas-Ruiz, R.

Effect of phenolic compounds from Oenothera rosea on the kaolin-carrageenan induced arthritis model in mice. Lee, Y. Myricetin inhibits IL-1beta-induced inflammatory mediators in SW human synovial sarcoma cells.

Kan, X. Myricetin relieves LPS-induced mastitis by inhibiting inflammatory response and repairing the blood-milk barrier. Hassan, S. Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. Wang, F. M10, a novel derivative of myricetin, prevents ulcerative colitis and colorectal tumor through attenuating robust endoplasmic reticulum stress.

Carcinogenesis , , 39 7 , Sun, J. Protective functions of myricetin in LPS-induced cardiomyocytes H9c2 cells injury by regulation of MALAT1. Chen, S. Myricetin protects cardiomyocytes from LPS-induced injury. Herz , , 43 3 , Martínez-Coria, H.

Preclinical research of dihydromyricetin for brain aging and neurodegenerative diseases. Zhang, J. Recent update on the pharmacological effects and mechanisms of dihydromyricetin. Luo, Y. Apoptosis , , 22 8 , Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.

Atherosclerosis , , , Fan, T. Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma. Oncotarget , , 7 37 , Liang, H. Mechanism and antibacterial activity of vine tea extract and dihydromyricetin against Staphylococcus aureus.

Wu, T. Chu, J. Dihydromyricetin relieves rheumatoid arthritis symptoms and suppresses expression of pro-inflammatory cytokines via the activation of Nrf2 pathway in rheumatoid arthritis model.

Wang, Y. Dihydromyricetin alleviates sepsis-induced acute lung injury through inhibiting NLRP3 inflammasome-dependent pyroptosis in mice model. Inflammation , , 42 4 , Qiu, P. Sureda, A. Hypotensive effects of genistein: from chemistry to medicine.

Xie, J. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice.

World J. Wu, B. Dihydromyricetin protects against diabetic cardiomyopathy in streptozotocin-induced diabetic mice. Zhou, M. Choi, J. Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer.

Kasiri, N. Therapeutic potential of quercetin on human breast cancer in different dimensions. Inflammopharmacology , , 28 1 , Qi, W. Cheriet, T. Isolation and biological properties of the natural flavonoids pectolinarin and pectolinarigenin-a review.

Antibiotics Basel , , 9 7 , E Yang, Y. Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice.

Oncotarget , , 8 19 , Patel, K. A review on pharmacological and analytical aspects of diosmetin: a concise report. Hawas, U. Thalassiolin D: a new flavone O-glucoside Sulphate from the seagrass Thalassia hemprichii. Gomez-Chang, E.

Anti-helicobacter pylori potential of three edible plants known as quelites in Mexico. Food , , 21 11 , Park, Y. Complete assignments of NMR data of 13 hydroxymethoxyflavones. Shao, S. Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice.

Chen, Y. Diosmetin exhibits anti-proliferative and anti-inflammatory effects on TNF-α;-stimulated human rheumatoid arthritis fibroblast-like synoviocytes through regulating the Akt and NF-κB signaling pathways.

Liu, Q. Diosmetin alleviates lipopolysaccharide-induced acute lung injury through activating the Nrf2 pathway and inhibiting the NLRP3 inflammasome. Seoul , , 26 2 , Yu, G. Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-κ.

Lephart, E. Ageing Res. Tanaka, Y. Equol inhibits growth and spore formation of Clostridioides difficile. Yang, Z. Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway.

Martin, D. Understanding the cardiovascular actions of soy isoflavones: potential novel targets for antihypertensive drug development.

Drug Targets , , 8 4 , Lin, I. Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice. Deng, Z. Pharmacological activity of eriodictyol: the major natural polyphenolic flavanone.

eCAM , , , Bai, J. Eriodictyol inhibits high glucose-induced extracellular matrix accumulation, oxidative stress, and inflammation in human glomerular mesangial cells. Dunstan, M. Engineering Escherichia coli towards de novo production of gatekeeper 2S -flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol.

Habtemariam, S. Hameed, A. Dietary eriodictyol alleviates adiposity, hepatic steatosis, insulin resistance, and inflammation in diet-induced obese mice. Lei, Z. Liu, Y. Li, D. Eriodictyol attenuates myocardial ischemia-reperfusion injury through the activation of JAK2.

Daily, J. Equol decreases hot flashes in postmenopausal women: a systematic review and meta-analysis of randomized clinical trials. Food , , 22 2 , Kim, J. Eupatilin inhibits adipogenesis through suppression of PPARγ activity in 3T3-L1 cells.

Wu, Z. Eupatilin regulates proliferation and cell cycle of cervical cancer by regulating hedgehog signalling pathway. Cell Biochem. Serttas, R.

Eupatilin inhibits the proliferation and migration of prostate cancer cells through modulation of PTEN and NF-κB signaling.

Kim, T. Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal anti-inflammatory drug users. Sapkota, A. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation.

PLoS One , , 12 2 , e Eupatilin ameliorates collagen induced arthritis. Korean Med. Song, E. Eupatilin suppresses the allergic inflammatory response in vitro and in vivo. Phytomedicine , , 42 , Park, W. Eupatilin ameliorates cerulein-induced pancreatitis via inhibition of the protein kinase D1 signaling pathway in vitro.

Pancreas , , 49 2 , Pal, H. Fisetin and its role in chronic diseases. Maher, P. Modulation of the neuroprotective and anti-inflammatory activities of the flavonol fisetin by the transition metals iron and copper. Antioxidants Basel, Switzerland , , 9 11 , Sinha, R. In-vitro anti-proliferative and anti-oxidant activity of galangin, fisetin and quercetin: role of localization and intermolecular interaction in model membrane.

Garg, S. RumaRay; Bhatia, J. The molecular mechanism involved in cardioprotection by the dietary flavonoid fisetin as an agonist of PPAR-γ in a murine model of myocardial infarction. Lee, J. Flavonol-rich RVHxR from Rhus verniciflua Stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models.

Kumar, R. Seo, S. Li, P. Fisetin administration improves LPS-induced acute otitis media in mouse in vivo. Protective effect of genistein on nonalcoholic fatty liver disease NAFLD.

Nagaraju, G. Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases. Chae, H. Molecular targets of genistein and its related flavonoids to exert anticancer effects. Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala.

Psychiatry Res. Verdrengh, M. Phytoestrogen genistein as an anti-staphylococcal agent. Microbes Infect. Mohammad-Shahi, M. Comparison of the effects of genistein and daidzein with dexamethasone and soy protein on rheumatoid arthritis in rats.

Bioimpacts , , 1 3 , Genistein modulate immune responses in collagen-induced rheumatoid arthritis model. Maturitas , , 59 4 , Hu, Y. Li, J. Yang, R. Effect of genistein on myocardial fibrosis in diabetic rats and its mechanism. Zhu, Q. Effects of genistein on lipopolysaccharide-induced injury of mouse alveolar epithelial cells and its mechanism.

Ortega-Santos, C. Nutrients , , 12 11 , E Phytomedicine , , 63 , Hakobyan, A. Inhibition of African swine fever virus infection by genkwanin. Antiviral Res. Wang, X. Shu, Y. Studies on a simple and efficient method for large-scale preparation of genkwanin from Daphne genkwa SIEB.

ET ZUCC. Using normal-phase flash chromatography. Lucarini, R. Antibacterial and anti-inflammatory activities of an extract, fractions, and compounds isolated from Gochnatia pulchra aerial parts.

Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa. Gao, Y. PLoS One , , 9 5 , e Li, C. Health-promoting effects of the citrus flavanone hesperidin. Ahmad, S. Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in collagen-induced rheumatoid arthritis.

Ahmed, Y. Pharmacology , , 96 , Li, R. Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms. Elhelaly, A. Bungău, S. Protective effects of hesperidin and diosmin against acrylamide-induced liver, kidney, and brain oxidative damage in rats.

Zhou, Z. EXCLI J. Guazelli, C. Qian, X. Hesperetin protects crayfish Procambarus clarkii against white spot syndrome virus infection. Fish Shellfish Immunol. Kaul, T. Antiviral effect of flavonoids on human viruses. Lin, Z. The protective effect of hesperetin in osteoarthritis: an in vitro and in vivo study.

Alshatwi, A. The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways.

x ] [PMID: ]. Combination of hesperetin and platinum enhances anticancer effect on lung adenocarcinoma. Liu, H. Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss.

Choi, E. Effects of hesperetin on the production of inflammatory mediators in IL-1beta treated human synovial cells. Shirzad, M. Polat, F. Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid-induced experimental colitis model.

Ku, S. Anti-inflammatory effects of hyperoside in human endothelial cells and in mice. Inflammation , , 38 2 , Zhou, Y. Hyperoside suppresses lipopolysaccharide-induced inflammation and apoptosis in human umbilical vein endothelial cells.

Huang, J. Hyperoside attenuates bleomycin-induced pulmonary fibrosis development in mice. Han, J. Zhongguo Zhongyao Zazhi , , 40 1 , Yang, L.

Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway. Jin, X. Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis.

Acta Pharmacol. Del Carmen Juárez-Vázquez, M. Kaempferitrin induces immunostimulatory effects in vitro. Mello, C. Oswaldo Cruz , , 6 , Polyphenol extract of Moringa oleifera leaves alleviates colonic inflammation in dextran sulfate sodium-treated mice. Based Complement.

Kaempferitrin inhibits proliferation, induces apoptosis, and ameliorates inflammation in human rheumatoid arthritis fibroblast-like synoviocytes. Imran, M. Luteolin, a flavonoid, as an anticancer agent: a review. Aziz, N. Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies.

Ahmadi, S. Structure-antioxidant activity relationships of luteolin and catechin. Impellizzeri, D. Erratum to: Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice.

Arthritis Res. Luteolin suppresses IL-1beta-induced cytokines and MMPs production via p38 MAPK, JNK, NF-kappaB and AP-1 activation in human synovial sarcoma cell line, SW Hou, Y.

Luteolin inhibits proliferation and affects the function of stimulated rat synovial fibroblasts. Cell Biol. Zhang, B. Luteolin alleviates NLRP3 inflammasome activation and directs macrophage polarization in lipopolysaccharide-stimulated RAW Boeing, T.

Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties. Yan, Y. Biofactors , , 45 4 , Lee, G. Anticatabolic effects of morin through the counteraction of interleukin-1β-induced inflammation in rat primary chondrocytes.

Cells Tissues Organs , , 1 , Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2 mediated HO-1 expression in V Chinese hamster lung fibroblasts.

Jiang, B. Morin attenuates STZ-induced diabetic retinopathy in experimental animals. Saudi J. Qu, Y. Morin Exhibits anti-inflammatory effects on IL-1β-stimulated human osteoarthritis chondrocytes by activating the Nrf2 signaling pathway. Sultana, F. Targeted delivery of morin, a dietary bioflavanol encapsulated mannosylated liposomes to the macrophages of adjuvant-induced arthritis rats inhibits inflammatory immune response and osteoclastogenesis.

Zeng, N. Antiarthritis effect of morin is associated with inhibition of synovial angiogensis. Drug Dev. Jiang, A. Kandemir, F. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: a multi-biomarker approach. Jiang, K. Morin alleviates vincristine-induced neuropathic pain via nerve protective effect and inhibition of NF-κB pathway in rats.

Ola, M. Flavonoid, morin inhibits oxidative stress, inflammation and enhances neurotrophic support in the brain of streptozotocin-induced diabetic rats.

Goh, J. Nobiletin and derivatives: functional compounds from citrus fruit peel for colon cancer chemoprevention. Cancers Basel , , 11 6 , Wu, X. Anti-inflammatory effects of 4'-demethylnobiletin, a major metabolite of nobiletin.

Foods , , 19 Pt A , Yang, G. Bunbupha, S. Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats. Liu, Z. Li, W. Protective effects of nobiletin against endotoxic shock in mice through inhibiting TNF-α; IL-6, and HMGB1 and regulating NF-κB pathway.

Inflammation , , 39 2 , Güvenç, M. Nobiletin protects from renal ischemia-reperfusion injury in rats by suppressing inflammatory cytokines and regulating iNOS-eNOS expressions.

Inflammation , , 43 1 , Bi, J. Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats.

Elumalai, P. Actually, various MMPs and ADAMTS inhibitors have been developed and some of them are under clinical trial. Delphinidin anthocyanin , flavonol derivatives including quercetin, kaempferol, and hyperoside , and catechins with a galloyl moiety inhibit activities of gelatinases MMP-2 and -9 and neutrophil elastase MMP Melzig et al.

Green tea polyphenols including EGCG, theaflavin, and proanthocyanidins also inhibit membrane-type 1 matrix metalloproteinase MT1-MMP Oku et al. On the other hand, when ultraviolet UV -irradiated human skin, UV-irradiated human dermal fibroblasts HDFs , human vascular endothelial cells, and human synovial fibroblasts are treated with flavonoids, some flavonoids such as genistein, baicalein, quercetin, and nobiletin down-regulated MMP-1 expression Kang et al.

It was also revealed that certain flavonoid derivatives inhibited MMP induction in chondrocytes Lim et al. These reports have demonstrated that quercetin and kaempferol suppress MMP-1 expression via inhibition of mitogen-activated protein kinase MAPK and activator protein-1 AP-1 activation in human skin fibroblasts without inhibiting MMP expression in SW cells, a chondrocyte cell line.

Flavones such as apigenin and wogonin could decrease MMP-1 expression without affecting MAPK pathway in skin fibroblasts. As shown in these results, signaling pathways related to the expression of MMP-1 and MMP are differentially regulated depending on types of flavonoid and cells or tissues.

In addition, some flavonoids can inhibit ADAMTS-4 and -5 known to be key enzymes for aggrecan degradation during osteoarthritis Majumdar et al. Although clinical data are currently unavailable, it is certain that some flavonoids can act on animal models of joint inflammation.

They might be especially protective against cartilage destruction probably through down-regulation of MMP expression Fig. This point should be verified further in the future.

Cellular aging process comprises various aspects of cellular metabolism. Cells become larger and eventually stop their division known as cellular senescence that prevents cancer formation in general.

Thus, aging process is considered to provide some beneficial effects. However, recent studies have found that aged cells synthesize and secrete some inflammation-related molecules called senescence-associated secretory phenotype SASP , including inflammatory cytokines such as IL-6, IL-8, IL-1, and MMPs Tchkonia et al.

Serum IL-6 level in elderly humans has been found to be significantly elevated regardless of diseases Bruunsgaard et al. These secreted molecules affect nearby cells to provoke inflammatory responses, eventually producing aging-related chronic inflammation called inflammaging, one type of sterile persistent inflammation.

Thus, long-term stimulation by SASP molecules induces various metabolic changes including cardiovascular changes Franceschi and Campisi, Sometimes they lead to late-stage cancer Campisi, Thus, blocking SASP production may be effective for achieving healthy aging.

Many laboratories have been searching for agents to prevent the aging process itself. However, in our opinion, stopping cellular senescence may have other harmful effects on the body. Blocking cells to go into senescence cells means that they still have proliferating capacity, although they are old.

This may deleteriously lead to cancer formation. In this respect, inhibition of SASP formation without affecting aging capacity inhibition of inflammaging seems to be a safe new target for healthy aging. To prove the beneficial effect of flavonoids on senescence and SASP production, we have evaluated several types of flavonoid derivatives, and found that apigenin and specific synthetic flavone can strongly inhibit SASP production without changing aging markers in both in vitro and in vivo models Lim et al.

Moreover, apigenin strongly reduced gene and protein expression of IκBζ transcription factor both in vitro and in vivo. It has been previously shown that IκBζ is closely associated with SASP induction such as IL-6 and IL-8 Alexander et al. Flavonoids such as baicalin and kaempferol inhibited the production of some cytokines through NF-κB signaling in aged rat Kim et al.

Signaling molecules such as protein kinase D1, p38 MAPK, MAPK-activated protein kinase-2 MK2 , and mixed-lineage leukemia 1 MLL1 have been suggested to play essential roles in producing SASP molecules Alimbetov et al. Besides, several reports have demonstrated the regulation of SASP factors by some microRNAs Panda et al.

In case of dietary flavonoids, cohort studies have suggested that flavonoid intake is inversely associated with age-related diseases such as cardiovascular disease CVD , neurodegeneration, and type 2 diabetes Root et al.

In studies investigating the underlying mechanism for this phenomena, administration of fisetin and rutin in animal models has shown protective activity by preventing increased production of IL-1β and tumor necrosis factor-α TNF-α in age-related disorders such as neurodegeneration and metabolic dysfunction Li et al.

Uptake of luteolin, baicalin, genistein, and kaempferol also lowered the elevated level of inflammatory cytokines such as IL-1β and IL-6 or NF-κB activation in aged animal model Kim et al. Inflammasome activation is also associated with the aging process. Many damage-associated molecular patterns DAMPs such as uric acid and cholesterol crystal are increased with age, leading to chronic low-grade inflammation following inflammasome activation Huang et al.

Aging tissue has high degree of NF-κB activation. Aging can stimulate inflammasome activation to produce inflammatory cytokines such as IL-1β and IL Song et al.

With SASP, these cytokines may have more impacts on cells to accelerate the aging process. Expression of inflammasome gene modules including IL-1β is positively associated with human aging, especially in those aged over 85 years Furman et al. For neutralization of IL-1β, treatment with IL-1β antibody for patients with myocardial infarction and low-grade inflammation reduces cardiovascular mortality Ridker et al.

Recent studies have demonstrated the role of inflammasome in metabolic disease such as human diabetes that is more likely to develop with age Bauernfeind et al.

With respect to bacterial infection during aging, lipopolysaccharide LPS treatment in aged rat can lead to long-lasting neuroinflammation through NF-κB activation and excessive IL-1β release in the hippocampus Fu et al.

In the liver of aged rats, the expression of Nod-like receptor protein 3 NLRP3 -related components such as NLRP3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain ASC , caspase-1, and IL-1β are apparently increased than those in young rats during LPS-induced endotoxemia Chung et al.

In addition, due to elevation of NLRP3 inflammasome at basal level with age, it has been demonstrated that specific bacterial clearance does not properly work Krone et al. To develop a therapeutic tool to target inflammaging, it is necessary to find an inflammasome inhibitor that has the potential to suppress the expression of inflammasome components or directly block inflammasome activation itself.

Since flavonoids have effects on SASP production and inflammasome activation associated with aging Fig. Obesity causes chronic and persistent inflammation in adipose tissue which is closely linked to the development of metabolic disease such as insulin resistance, type 2 diabetes, and cancer Divella et al.

Adipocytes are known to secrete chemokines such as monocyte chemoattractant protein-1 MCP-1 that can induce macrophage infiltration into adipose tissue. Adipose tissue macrophages play a crucial role in obesity-associated inflammation and insulin resistance Amano et al.

Infiltrated macrophage is activated to M1 phenotype that secretes pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 to induce chronic inflammation.

These cytokines can lead to the development of insulin resistance and apoptosis of pancreatic beta-cells Appari et al. It is now clear that obesity produces inflammatory environment to the body that can lead to chronic inflammation and meta-inflammation, thus having deleterious effects on the body.

So far, many reports have demonstrated the anti-obesity activity of flavonoids by modulating the production of inflammatory molecules via affecting several cellular signaling pathways.

In particular, there have been several reports concerning quercetin in obesity-associated inflammation. Quercetin inhibited the inflammatory response of macrophages via activation of adenosine monophosphate-activated protein kinase AMPK a1 phosphorylation and sirtuin 1 SIRT1 expression Dong et al.

Quercetin also reduced obesity-induced hypothalamic inflammation accompanied by heme oxygenase HO -1 induction in microglia Yang et al. The effect of quercetin on HO-1 induction is correlated with macrophage phenotype switching effect in hepatic inflammation caused by obesity Kim et al.

These effects of quercetin have been proven in vivo by the finding that supplementation with quercetin into mice for 18 weeks reduced the number of macrophages in adipose tissue Kobori et al.

Besides, EGCG reduced macrophage infiltration and insulin resistance in high-fat diet HFD animal model and suppressed toll-like receptor 4 TLR4 expression which is strongly associated with obesity-induced inflammation due to the first trigger-action Bao et al.

Naringenin also inhibits macrophage infiltration involved in JNK pathway Yoshida et al. A recent study has shown that apigenin attenuated metabolic inflammation via peroxisome proliferator-activated receptor PPARγ activation and lowered malondialdehyde, IL-1β, and IL-6 colonic levels in HFD mouse model Feng et al.

Specific chalcone derivatives prevented HFD-induced heart and kidney injury via MAPK and NF-κB signaling pathway Fang et al. In addition, there have been several reports on anti-obesity effects of flavonoids such as isoflavone daidzein Sakamoto et al.

Cohort studies on flavonoid intake and obesity have been continuously carried out Bertoia et al. Considering with the anti-inflammatory effect of flavonoids, a recent cohort study has also shown that flavonoid intake is inversely associated with body mass index and level of C-reactive protein which is produced in response to inflammation Vernarelli and Lambert, All these studies suggest that flavonoids can reduce obesity and obesity-related chronic inflammation.

To finish an inflammatory process in the body, inflammatory resolution should properly work. Inflammatory resolution is tightly regulated by cellular pathways involving many signaling molecules and factors in the pathological progress of inflammatory diseases.

During resolution, not only pro-inflammatory mediators are negatively regulated, but also immune cell influx are stopped by the action of lipid mediators such as lipoxin A4 and resolvin E1 followed by clearance of recruited neutrophils from inflamed sites in the way of apoptosis or necrosis Schett and Neurath, However, dysregulation of acute inflammatory resolution can lead to chronic inflammation in which the balance between innate and adaptive immunity is inadequately controlled Fullerton and Gilroy, In particular, during inflammatory resolution, it has been demonstrated that the population of macrophage phenotype can specifically determine either deleterious or protective role depending on the type and state of inflammatory diseases Anders and Ryu, ; Liu et al.

Flavonoids are known to regulate macrophage polarization at post-resolution and down-regulate pro-inflammatory signals at initiation of resolution. Importantly, it has been found that chrysin induced anti-inflammatory M2 phenotype and decreased M1 phenotype in macrophages Feng et al.

It has also been demonstrated that pentamethoxyflavanone inhibited M1 phenotype but increased M2 phenotype macrophages Feng et al. In line with these observations, quercetin can inhibit hepatic M1 macrophage and gene expression of M1-related inflammatory cytokines in carbon tetrachloride-induced liver fibrosis and obesity-induced hepatic inflammation Dong et al.

Rutin also induced microglial polarization to M2 phenotype, suggesting its potential to possibly treat neurodegenerative disease Bispo da Silva et al. Baicalin and naringenin reduced inflammatory symptom caused by M1 to M2 macrophage polarization in inflammatory bowel disease and atopic dermatitis, respectively Karuppagounder et al.

Therefore, flavonoids can affect all phases of inflammatory responses. Since regulation of inflammatory resolution is important in chronic inflammatory disorders, it is suggested that flavonoids are promising agents that can alleviate symptoms of chronic inflammation.

For inflammasome activation as first-line defense of innate immunity, a priming step via TLR is a prerequisite for subsequent activation step, leading to the production of pro-forms of IL-1β and IL and NLRP3 protein through NF-κB activation He et al.

Until now, many flavonoids have been found to be able to inhibit the NLRP3 inflammasome pathway. Studies on flavonoids having inhibitory effects on the inflammasome have been mainly focused on inhibition of the expression of NLRP3 inflammasome-related components such as IL-1β, IL, NLRP3, and caspase Quercetin inhibited kidney injury in rats via regulation of NLRP3 inflammasome Wang et al.

In case of protective effect of flavonoids on gout arthritis, effects of quercetin, hesperidin methylchalcone, EGCG, and morin in relation to NLRP3 inflammasome have been demonstrated in several animal models Dhanasekar and Rasool, ; Jhang et al.

Luteoloside down-regulated protein expression levels of NLRP3, matured IL-1β, and caspase-1 in hepatocellular carcinoma cell line Fan et al. Rutin and morin also possess inhibitory effects on NLRP3 inflammasome in several animal models Aruna et al.

For instance, EGCG abundant in tea can inhibit NLRP3 inflammasome conjugation with thioredoxin-interacting protein TXNIP in THP-1 cells and ameliorate peritoneal inflammation by inhibiting NLRP3 expression and IL-1β release in monosodium urate MSU crystal-treated mice Jhang et al.

Quercetin can inhibit the expression of NLRP3 and IL-1β and caspase-1 activity in human colonic epithelial cells. It also has inhibitory effects on NLRP3 and absent in melanoma 2 AIM2 inflammasome by preventing ASC oligomerization in both in vitro and in vivo mouse vasculitis model Domiciano et al.

Apigenin can reduce IL-1β and IL release and NLRP3 expression in chronic unpredictable mild stress CUMS -induced rat brain Li et al. Isoliquiritigenin, a chalcone derivative, has shown similar dual activity in adipose tissue inflammation Honda et al.

As noted above, some flavonoid derivatives can inhibit IL-1β production. However, most of them only reduce IL-1β production via inhibition of pro-IL-1β expression. Only a few flavonoids such as quercetin could reduce NLRP3 activation and ASC oligomerization.

To clearly establish their pharmacological action on NLRP3 activation, many flavonoids have been further examined. In our previous study, several flavonoid derivatives have been found to be able to inhibit IL-1β production in MSU-treated THP-1 cells Lim et al.

Furthermore, apigenin administration can inhibit the number of infiltrated inflammatory cells in MSU-induced peritonitis in mice Lim et al. All these findings clearly indicate that some flavonoids can interrupt inflammasome production that could contribute to the anti-inflammatory activity of certain flavonoids both in vitro and in vivo.

Recently, besides canonical inflammasome pathways, the importance of noncanonical pathways has been emerged in inflammasome activation accompanied by components such as caspase-8, , and P2X7 receptor P2X7R Kayagaki et al.

It has been shown that apigenin supplementation can inhibit both caspase-1 and caspase in chronic ulcerative colitis model Márquez-Flores et al. However, in another report, the protective effect of apigenin against acute colitis has been suggested to be mediated by NLRP6 signaling pathway independent of caspase 1, 11, or ASC Radulovic et al.

Thus, whether flavonoids targeting inflammasome components in canonical pathway can also affect these components involved in noncanonical inflammasome pathways should be further studied.

Autophagy maintains internal homeostasis by clearing damaged organelles, proteins, and intracellular pathogens through lysosomal degradative pathway Glick et al. Impairment of autophagy can lead to many diseases such as cancer, cardiovascular disease, infectious disease, and neurodegenerative disease Jiang and Mizushima, Due to the protective role of autophagy in the pathophysiology, autophagy modulation has been focused as an important target to regulate these diseases Rubinsztein et al.

Many reports have proven that flavonoids with antioxidant activity as one of their detoxification ability can stimulate autophagy through mitochondria-endoplasmic reticulum and proteasome both in vitro and in vivo Hasima and Ozpolat, In various cancer cell lines, flavonoids such as quercetin, apigenin, silibinin, and EGCG can increase the expression of Beclin-1, LC3-II, and several types of autophagy-related ATG Jiang et al.

However, depending on the type or stage of cancer cell, autophagy can either promote or suppress cancer cells Gewirtz, Thus, cancer therapy targeting autophagy pathway using flavonoids requires accurate regulation under a precise understanding of autophagy.

Quercetin prevented β-amyloid aggregation by activating macroautophagy in Caenorhabditis elegans Regitz et al. It has been shown that fisetin degraded phosphorylated tau through autophagy activation mediated by transcription factors such as transcription factor EB TFEB and Nrf2 Kim et al.

EGCG also decreased phosphotau protein by increasing mRNA expression of autophagy adapter proteins in rat primary neuron culture Chesser et al. Flavonoids also have potential for cardioprotective therapy by activating cardiac autophagy.

For instance, nobiletin has shown myocardial protective effect by restoring autophagy flux after acute myocardial infarction model in rats Wu et al. Apigenin can relieve LPS-induced myocardial injury through modulation of autophagic components such as lysosomal-associated membrane protein 1 LAMP1 , ATG5, p62, and TFEB Li et al.

Due to positive effects of vitexin, rutin, EGCG, and luteolin on autophagy regulation, therapeutic potential of flavonoids against cardiovascular disease have also been suggested Hu et al. In addition, flavonoids such as naringenin, baicalin, EGCG, and quercetin have protective effects against bacteria or virus infection by promoting autophagy activation Tsai et al.

All these newly found effects suggest that flavonoids could be promising candidates based on their ability to modulate autophagy for the treatment of degenerative diseases associated with defective autophagy.

As mentioned above, various flavonoid derivatives possess anti-inflammatory activity in a variety of animal models of inflammation. Nonetheless, it is apparent that flavonoids in general do not show strong effects by oral administration enough for a clinical trial.

As reported by many researchers, most flavonoids possess low bioavailability by oral administration. In addition, they experience rapid metabolism in the body. After flavonoid ingestion as a form of daily food products or herbal remedy, maximum concentrations of flavonoids in the blood are expected to be generally very low in micromolar ranges.

In one study, actual plasma concentrations of orally administered flavonoids were found to be less than 1 μM except for several cases Chen et al.

Besides, low oral bioavailability of flavonoid ingestion has been demonstrated again and again. The maximum plasma concentration of quercetin therapeutically treated by oral administration to rats was less than 10 μM even if concentrations of various metabolites including methylated, sulfated, and glycosylated metabolites were combined Tran et al.

In one human study, plasma isoflavonoid genistein concentration in Japanese men having a high intake of genistein and genistin as soy products was approximately 0.

Several reviews have summarized findings of absorption and bioavailability of flavonoids Ross and Kasum, ; Lotito and Frei, Generally, all these previous observations suggest that the low bioavailability and rapid metabolism of oral flavonoids limit their therapeutic use for acute inflammatory conditions since biologically meaningful effects of flavonoids on inflammatory response possibly will appear at concentration higher than 10 μM.

Nonetheless, flavonoids may be promising therapeutics for chronic inflammatory conditions with less adverse effects as noted above since long-term administration is needed and few appropriate therapeutic agents are available in clinics to date.

An interesting notion is that some flavonoid glucuronides among glycosylated metabolites may show significant activity in the body by conjugation and deconjugation pathway Perez-Vizcaino et al.

In general, glucuronide conjugates of flavonoids are known to be less active in vivo than those of aglycone. However, it has been proposed that glucuronidated quercetin can act as precursor of aglycone in vivo which could be converted to active quercetin in situ by β-glucuronidase Terao et al.

Genistein 7- O -glucuronide can be converted to genistein by β-glucuronidase in inflamed mouse skin of pseudoinfection model. Such glucuronide derivative can increase phagocytic activities of macrophage Kaneko et al.

Glucuronidated kaempferol derivatives can inhibit several protein kinases and retain target selectivity in HepG2 cell line, although their potency is lower than aglycone Beekmann et al. These reports indicate that in therapeutic trial against inflammatory conditions, certain glucuronidated metabolites may play biologically meaningful roles by metabolic conversion in vivo.

Flavonoids affect all phases of inflammatory processes. Although there are some limitations of flavonoids by using the oral route of administration, treatment against chronic inflammation for long-term use is possible. Moreover, high concentrations of flavonoids may be obtained more easily by local treatment.

Especially, topical application through skin is one of plausible routes of flavonoid administration in human. Flavonoids may be efficiently used for skin inflammatory disorders topically if proper formulation such as nanoparticle or lipid nanocapsule is used Chuang et al.

As noted above, applicable disorders by using flavonoid therapy are expanding. In particular, flavonoids may be used for healthy aging. Various aspects of molecular mechanisms are to be explored further.

Clinical trial of certain flavonoids Fig. This study was financially supported by the Basic Research Program through the National Research Foundation NRFR1A2B and BKplus from the Ministry of Education.

The bioassay facility of New Drug Development Institute KNU was used. Title Author Keyword Volume Vol. Current Issue Online First Archives Most Cited Most Read.

College of Pharmacy, Kangwon National University, Chuncheon , Republic of Korea. Received : February 21, ; Revised : April 2, ; Accepted : April 4, ; Published online : April 19, Keywords : Flavonoid, Chronic inflammation, Therapeutics, Inflammaging, Meta-inflammation.

Effects on autophagy Autophagy maintains internal homeostasis by clearing damaged organelles, proteins, and intracellular pathogens through lysosomal degradative pathway Glick et al. Some basic chemical structures of flavonoids.

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.

IL-1R, IL-1 receptor; IL-6R, IL-6 receptor. 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.

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.

The suggested flavonoids with core structures showing reasonable inhibitory action on chronic inflammatory responses and clinical trials of some flavonoids.

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. Plasma concentrations of phyto-oestrogens in Japanese men..

Alexander, E, Hildebrand, DG, Kriebs, A, Obermayer, K, Manz, M, Rothfuss, O, Schulze-Osthoff, K, and Essmann, F IκBζ is a regulator of the senescence-associated secretory phenotype in DNA damage- and oncogene-induced senescence..

Cell Sci.. Alimbetov, D, Davis, T, Brook, AJ, Cox, LS, Faragher, RG, Nurgozhin, T, Zhumadilov, Z, and Kipling, D Suppression of the senescence-associated secretory phenotype SASP in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK Amano, SU, Cohen, JL, Vangala, P, Tencerova, M, Nicoloro, SM, Yawe, JC, Shen, Y, Czech, MP, and Aouadi, M Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation..

Cell Metab.. Anders, HJ, and Ryu, M Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis..

Kidney Int.. Appari, M, Channon, KM, and McNeill, E Metabolic regulation of adipose tissue macrophage function in obesity and diabetes.. Redox Signal.. Aruna, R, Geetha, A, and Suguna, P Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis..

Bao, S, Cao, Y, Fan, C, Fan, Y, Bai, S, Teng, W, and Shan, Z Epigallocatechin gallate improves insulin signaling by decreasing toll-like receptor 4 TLR4 activity in adipose tissues of high-fat diet rats.. Food Res.. Bauernfeind, F, Niepmann, S, Knolle, PA, and Hornung, V Aging-associated TNF production primes inflammasome activation and NLRP3-related metabolic disturbances..

Beekmann, K, de Haan, LH, Actis-Goretta, L, van Bladeren, PJ, and Rietjens, IM Food Chem.. Bertoia, ML, Rimm, EB, Mukamal, KJ, Hu, FB, Willett, WC, and Cassidy, A Dietary flavonoid intake and weight maintenance: three prospective cohorts of , US men and women followed for up to 24 years..

Bispo da Silva, A, Cerqueira Coelho, PL, Alves Oliveira Amparo, J, Alves de Almeida Carneiro, MM, Pereira Borges, JM, Dos Santos Souza, C, Dias Costa, MF, Mecha, M, Guaza Rodriguez, C, Amaral da Silva, VD, and Lima Costa, S Bruunsgaard, H, Pedersen, M, and Pedersen, BK Aging and proinflammatory cytokines..

Burton, MD, Rytych, JL, Amin, R, and Johnson, RW dietary luteolin reduces proinflammatory microglia in the brain of senescent mice.. Rejuvenation Res..

Campisi, J Aging, cellular senescence, and cancer.. Cao, Y, Bao, S, Yang, W, Zhang, J, Li, L, Shan, Z, and Teng, W Epigallocatechin gallate prevents inflammation by reducing macrophage infiltration and inhibiting tumor necrosis factor-α signaling in the pancreas of rats on a high-fat diet..

Capell, BC, Drake, AM, Zhu, J, Shah, PP, Dou, Z, Dorsey, J, Simola, DF, Donahue, G, Sammons, M, Rai, TS, Natale, C, Ridky, TW, Adams, PD, and Berger, SL MLL1 is essential for the senescence-associated secretory phenotype..

Genes Dev.. Chamcheu, JC, Siddiqui, IA, Adhami, VM, Esnault, S, Bharali, DJ, Babatunde, AS, Adame, S, Massey, RJ, Wood, GS, Longley, BJ, Mousa, SA, and Mukhtar, H Chen, C, Zhang, C, Cai, L, Xie, H, Hu, W, Wang, T, Lu, D, and Chen, H Baicalin suppresses IL-1β-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models..

Chen, X, Yin, OQ, Zuo, Z, and Chow, MS Pharmacokinetics and modeling of quercetin and metabolites.. Chen, X, Yu, W, Li, W, Zhang, H, Huang, W, Wang, J, Zhu, W, Fang, Q, Chen, C, Li, X, and Liang, G An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation..

Chesser, AS, Ganeshan, V, Yang, J, and Johnson, GV Epigallocatechingallate enhances clearance of phosphorylated tau in primary neurons.. Chi, YS, Cheon, BS, and Kim, HP Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW Chi, YS, Lim, H, Park, H, and Kim, HP Effect of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression..

Choy, E Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology Oxford. Chuang, SY, Lin, YK, Lin, CF, Wang, PW, Chen, EL, and Fang, JY Elucidating the skin delivery of aglycone and glycoside flavonoids: how the structures affect cutaneous absorption..

Chung, KW, Lee, EK, Kim, DH, An, HJ, Kim, ND, Im, DS, Lee, J, Yu, BP, and Chung, HY Aging Cell. Chunzhi, G, Zunfeng, L, Chengwei, Q, Xiangmei, B, and Jingui, Y Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways..

Cohen, SB, Proudman, S, Kivitz, AJ, Burch, FX, Donohue, JP, Burstein, D, Sun, YN, Banfield, C, Vincent, MS, Ni, L, and Zack, DJ A randomized, double-blind study of AMG a fully human monoclonal antibody to IL-1R1 in patients with osteoarthritis of the knee..

Arthritis Res. Cordero, MD, Williams, MR, and Ryffel, B AMP-Activated Protein Kinase Regulation of the NLRP3 Inflammasome during Aging.. Trends Endocrinol. Cui, HX, Chen, JH, Li, JW, Cheng, FR, and Yuan, K Dancevic, CM, and McCulloch, DR Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis..

Dhanasekar, C, and Rasool, M Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators.. Divella, R, De Luca, R, Abbate, I, Naglieri, E, and Daniele, A Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation..

Djerir, D, Iddir, M, Bourgault, S, Lamy, S, and Annabi, B Biophysical evidence for differential gallated green tea catechins binding to membrane type-1 matrix metalloproteinase and its interactors.. Domiciano, TP, Wakita, D, Jones, HD, Crother, TR, Verri, WA, Arditi, M, and Shimada, K Quercetin inhibits inflammasome activation by interfering with asc oligomerization and prevents interleukin-1 mediated mouse vasculitis..

Dong, J, Zhang, X, Zhang, L, Bian, HX, Xu, N, Bao, B, and Liu, J Lipid Res.. El-Horany, HE, El-Latif, RN, ElBatsh, MM, and Emam, MN Engin, A The pathogenesis of obesity-associated adipose tissue inflammation..

Fan, SH, Wang, YY, Lu, J, Zheng, YL, Wu, DM, Li, MQ, Hu, B, Zhang, ZF, Cheng, W, and Shan, Q Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome..

PLoS ONE. Fang, Q, Wang, J, Wang, L, Zhang, Y, Yin, H, Li, Y, Tong, C, Liang, G, and Zheng, C Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice..

Feng, L, Song, P, Zhou, H, Li, A, Ma, Y, Zhang, X, Liu, H, Xu, G, Zhou, Y, Wu, X, Shen, Y, Sun, Y, Wu, X, and Xu, Q a. Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice.. Feng, X, Qin, H, Shi, Q, Zhang, Y, Zhou, F, Wu, H, Ding, S, Niu, Z, Lu, Y, and Shen, P b.

Feng, X, Weng, D, Zhou, F, Owen, YD, Qin, H, Zhao, J, Wen, Y, Huang, Y, Chen, J, Fu, H, Yang, N, Chen, D, Li, J, Tan, R, and Shen, P Activation of PPARγ by a natural flavonoid modulator, apigenin ameliorates obesity-related inflammation via regulation of macrophage polarization.. Ferrucci, L, Corsi, A, Lauretani, F, Bandinelli, S, Bartali, B, Taub, DD, Guralnik, JM, and Longo, DL The origins of age-related proinflammatory state..

Fox, DA, Gizinski, A, Morgan, R, and Lundy, SK Cell-cell interactions in rheumatoid arthritis synovium.. North Am.. Franceschi, C, and Campisi, J Chronic inflammation inflammaging and its potential contribution to age-associated diseases.. A Biol. Fu, HQ, Yang, T, Xiao, W, Fan, L, Wu, Y, Terrando, N, and Wang, TL Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats..

Fullerton, JN, and Gilroy, DW Resolution of inflammation: a new therapeutic frontier.. Drug Discov.. Furman, D, Chang, J, Lartigue, L, Bolen, CR, Haddad, F, Gaudilliere, B, Ganio, EA, Fragiadakis, GK, Spitzer, MH, Douchet, I, Daburon, S, Moreau, JF, Nolan, GP, Blanco, P, Déchanet-Merville, J, Dekker, CL, Jojic, V, Kuo, CJ, Davis, MM, and Faustin, B Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states..

Galindo, P, Rodriguez-Gómez, I, González-Manzano, S, Dueñas, M, Jiménez, R, Menéndez, C, Vargas, F, Tamargo, J, Santos-Buelga, C, Pérez-Vizcaíno, F, and Duarte, J Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation..

Gao, M, Ma, Y, and Liu, D Rutin suppresses palmitic acids-triggered inflammation in macrophages and blocks high fat diet-induced obesity and fatty liver in mice.. Gentile, D, Fornai, M, Colucci, R, Pellegrini, C, Tirotta, E, Benvenuti, L, Segnani, C, Ippolito, C, Duranti, E, Virdis, A, Carpi, S, Nieri, P, Németh, ZH, Pistelli, L, Bernardini, N, Blandizzi, C, and Antonioli, L The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity..

Gewirtz, DA The four faces of autophagy: implications for cancer therapy.. Cancer Res.. Glick, D, Barth, S, and Macleod, KF Autophagy: cellular and molecular mechanisms.. Goldring, MB The role of the chondrocyte in osteoarthritis..

Arthritis Rheum.. Goldring, MB, and Otero, M Inflammation in osteoarthritis.. Grosso, G, Micek, A, Godos, J, Pajak, A, Sciacca, S, Galvano, F, and Giovannucci, EL dietary flavonoid and lignan intake and mortality in prospective cohort studies: systematic review and dose-response meta-analysis..

Guazelli, CFS, Staurengo-Ferrari, L, Zarpelon, AC, Pinho-Ribeiro, FA, Ruiz-Miyazawa, KW, Vicentini, FTMC, Vignoli, JA, Camilios-Neto, D, Georgetti, SR, Baracat, MM, Casagrande, R, and Verri, WA Quercetin attenuates zymosan-induced arthritis in mice..

Gurung, P, Anand, PK, Malireddi, RK, VandeWalle, L, Van Opdenbosch, N, Dillon, CP, Weinlich, R, Green, DR, Lamkanfi, M, and Kanneganti, TD

Immune system vitality, Samuel Hoint. Critical Reviews in Food Science and Sustainable weight loss, 57 Rheumatoid arthritis RA is an hdalth condition Flavonoids and joint health mainly Flavpnoids peripheral joints. Although immunosuppressive drugs and non-steroidal anti-inflammatory drugs NSAIDs are used to treat this condition, these drugs have severe side effects. Flavonoids are the most abundant phenolic compounds which exhibit antioxidant, anti-inflammatory and immunomodulatory properties. Many bioactive flavonoids have powerful anti-inflammatory effects.