# Flavonoids in Medicine and Food Homology Substances: Structure–Activity Relationship, Application Challenges, and Cutting-Edge Technological Breakthroughs **Authors:** Xuejiao Wang, Ying Li, Xiaodan Zhao, Daqi Fu PMC · DOI: 10.3390/foods15040658 · 2026-02-11 ## TL;DR Flavonoids from medicine and food homology substances have health benefits but face challenges in application, which are being addressed with new technologies and future innovations. ## Contribution The paper introduces cutting-edge strategies and future directions for overcoming flavonoid application challenges using advanced technologies like AI and nanodelivery systems. ## Key findings - Flavonoids show antioxidant, anti-inflammatory, and antitumor activities linked to their chemical structure. - Advanced extraction and nanodelivery systems improve flavonoid solubility and bioavailability. - Future integration of AI and synthetic biology will enhance flavonoid research and application. ## Abstract Flavonoids, as natural and safe bioactive compounds, demonstrate significant potential in antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Medicine and food homology substances constitute a vast treasure trove of flavonoids, characterized by high activity and high content. Their biological effects are closely linked to chemical features like hydroxyl group position, substituent type, and glycosylation degree. However, in practical applications, flavonoids in medicine and food homology substances still face bottlenecks, such as difficult separation and purification, challenging quality control, poor solubility, and low bioavailability. Current strategies include advanced extraction techniques (e.g., ultrasound/microwave-assisted, supercritical CO2). Quality control is achieved through establishing GAP bases, integrating data on the origins of Medicine and food homology substances, employing UHPLC-MS, and constructing fingerprint spectra. Enhancing solubility through structural modifications such as glycosylation. Utilizing nanodelivery systems such as lipid nanoparticles, polymeric nanoparticles, and microencapsulation technology to enhance bioavailability. Future research on flavonoids in medicine and food homology substances will integrate artificial intelligence (for activity prediction and formulation optimization), synthetic biology (for targeted flavonoid synthesis), and materials science (for designing novel delivery materials), advancing their applications in precision nutrition and personalized medicine. Provide a reference for fundamental research and applied development of flavonoids in medicine and food homology substances. ## Full-text entities - **Genes:** Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, Vdr (vitamin D (1,25-dihydroxyvitamin D3) receptor) [NCBI Gene 22337] {aka Nr1i1}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Mfn2 (mitofusin 2) [NCBI Gene 170731] {aka D630023P19Rik, Fzo}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, Gstp1 (glutathione S-transferase, pi 1) [NCBI Gene 14870] {aka GstpiB}, Nlrc4 (NLR family, CARD domain containing 4) [NCBI Gene 268973] {aka 9530011P19Rik, CLAN, CLAN1, CLANA, CLANB, CLANC}, Jak2 (Janus kinase 2) [NCBI Gene 16452] {aka Fd17}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Nlrp1a (NLR family, pyrin domain containing 1A) [NCBI Gene 195046] {aka CARD7, DEFCAP, Gm14, Gm15, NAC, Nalp1}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, Knl1 (kinetochore scaffold 1) [NCBI Gene 76464] {aka 2310043D08Rik, 5730505K17Rik, Casc5}, Comt (catechol-O-methyltransferase) [NCBI Gene 12846] {aka Comt1, D16Wsu103e, D330014B15Rik}, Lepr (leptin receptor) [NCBI Gene 16847] {aka B219, LEP-R, LEPROT, Leprb, Modb1, OB-RGRP}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Clec4e (C-type lectin domain family 4, member e) [NCBI Gene 56619] {aka Clecsf9, Mincle}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Tnfsf11 (TNF superfamily member 11) [NCBI Gene 117516] {aka ODF, OPGL, RANKL, TRANCE}, Ikbkb (inhibitor of kappaB kinase beta) [NCBI Gene 16150] {aka IKK-2, IKK-B, IKK-beta, IKK2, IKK[b], IKKbeta}, Gpx4 (glutathione peroxidase 4) [NCBI Gene 625249] {aka GPx-4, GSHPx-4, PHGPx, mtPHGPx, snGPx}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Renbp (renin binding protein) [NCBI Gene 19703] {aka Age, Rnbp}, Tnfrsf11b (TNF receptor superfamily member 11B) [NCBI Gene 25341] {aka Opg}, Tnfsf11 (tumor necrosis factor (ligand) superfamily, member 11) [NCBI Gene 21943] {aka Ly109l, ODF, OPGL, RANKL, Trance}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Cnr1 (cannabinoid receptor 1) [NCBI Gene 12801] {aka CB-R, CB1, CB1A, CB1B, CB1R}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Ager (advanced glycosylation end product-specific receptor) [NCBI Gene 11596] {aka RAGE}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mir451a (microRNA 451a) [NCBI Gene 723870] {aka Mir451, Mirn451, mir-451a, mmu-mir-451, mmu-mir-451a}, Glo1 (glyoxalase 1) [NCBI Gene 109801] {aka 0610009E22Rik, 1110008E19Rik, 2510049H23Rik, GLY1, Glo-1, Glo-1r}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Gsdmd (gasdermin D) [NCBI Gene 69146] {aka 1810036L03Rik, DF5L, Dfna5l, GsdmD-1, Gsdmdc1, M2-4}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 17395] {aka B/MMP9, Clg4b, Gel B, MMP-9, pro-MMP-9}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Src (src proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 20779] {aka pp60c-src}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Slpi (secretory leukocyte peptidase inhibitor) [NCBI Gene 20568] {aka ALP}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Tnfrsf11b (tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)) [NCBI Gene 18383] {aka OCIF, Opg, TR1}, Myb (Myb proto-oncogene, transcription factor) [NCBI Gene 17863] {aka c-myb}, Cdk4 (cyclin dependent kinase 4) [NCBI Gene 12567] {aka Crk3}, Ar (androgen receptor) [NCBI Gene 11835] {aka Tfm}, Chek2 (checkpoint kinase 2) [NCBI Gene 50883] {aka CHK2, Cds1, HUCDS1, Rad53}, Rock2 (Rho-associated coiled-coil containing protein kinase 2) [NCBI Gene 19878] {aka B230113H15Rik, ROKalpha, Rho-kinase, Rock-II, Rock2m, mKIAA0619}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, Dapk2 (death-associated protein kinase 2) [NCBI Gene 13143], Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Nos2 (nitric oxide synthase 2) [NCBI Gene 24599] {aka Nos2a, iNos}, Plau (plasminogen activator, urokinase) [NCBI Gene 18792] {aka u-PA, uPA}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132} - **Diseases:** sepsis (MESH:D018805), cognitive impairment (MESH:D003072), acne (MESH:D000152), HCC (MESH:D006528), dysregulation of glucose and (MESH:D018149), pulmonary fibrosis (MESH:D011658), cardiac dysfunction (MESH:D006331), liver (MESH:D017093), hepatic damage (MESH:D056486), neuralgia (MESH:D009437), breast cancer (MESH:D001943), inflammatory bowel disease (MESH:D015212), neuronal damage (MESH:D009410), diabetic type 2 (MESH:D003924), alcoholic liver injury (MESH:D008108), liver and gastric damage (MESH:D013272), osteoporosis (MESH:D010024), insulin resistance (MESH:D007333), dry eye (MESH:D015352), colitis (MESH:D003092), colorectal cancer (MESH:D015179), atherosclerosis (MESH:D050197), programmed cell death (MESH:D003643), glucose and lipid metabolism disorders (MESH:D052439), rheumatoid arthritis (MESH:D001172), metastasis (MESH:D009362), arthritis (MESH:D001168), mastitis (MESH:D008413), damage (MESH:D020263), cardiotoxicity (MESH:D066126), motor deficits (MESH:D009461), airway obstruction (MESH:D000402), metabolic disorders (MESH:D008659), AKI (MESH:D058186), stroke (MESH:D020521), acute pulmonary inflammation (MESH:D011014), cardiomyopathy (MESH:D009202), obese (MESH:D009765), hepatic steatosis (MESH:D005234), cerebral oedema (MESH:D001929), weight gain (MESH:D015430), oesophageal carcinoma (MESH:D000077277), swelling (MESH:D004487), osteoporotic (MESH:D058866), neuroinflammation (MESH:D000090862), anxiety (MESH:D001007), TBI (MESH:D000070642), liver fibrosis (MESH:D008103), diabetic (MESH:D003920), SAE (MESH:D065166), cancer (MESH:D009369), Alzheimer's disease (MESH:D000544), Parkinson's disease (MESH:D010300), mitochondrial dysfunction (MESH:D028361), coronary heart disease (MESH:D003327), pain (MESH:D010146), prostate cancer (MESH:D011471), fibrosis (MESH:D005355), PDAC (MESH:D021441), neurodegenerative disease (MESH:D019636) - **Chemicals:** baicalin (MESH:C038044), calcium (MESH:D002118), ROS (MESH:D017382), glycosides (MESH:D006027), glucose (MESH:D005947), 5-HT (MESH:D012701), baicalein (MESH:C006680), Flavonoids (MESH:D005419), eriodictyol (MESH:C007619), alcohol (MESH:D000438), (-)-epigallocatechin (MESH:C057580), isorhamnetin (MESH:C047368), anthocyanin (MESH:D000872), hydrogen (MESH:D006859), Flavones (MESH:D047309), Luteolin (MESH:D047311), swertisin (MESH:C556941), Naringenin (MESH:C005273), Eriocitrin (MESH:C114706), MPTP (MESH:D015632), lipopolysaccharide (MESH:D008070), lipid (MESH:D008055), CO2 (MESH:D002245), Vitexin (MESH:C032731), daidzin (MESH:C013908), daidzein (MESH:C004742), piperine (MESH:C008922), Flavanones (MESH:D044950), phenoxy radicals (MESH:C042329), MTT (MESH:C070243), Isoflavones (MESH:D007529), DOX (MESH:D004317), soybean oil (MESH:D013024), TAA (MESH:D013853), puerarin (MESH:C033607), Zingiber officinale Roscoe flavonoids (-), hydrogen peroxide (MESH:D006861), 3-methoxyflavone (MESH:C000590233), D-galactose (MESH:D005690), 3-hydroxyflavone (MESH:C041477), EDU (MESH:C022811), genistein (MESH:D019833), Apigenin (MESH:D047310), myricetin (MESH:C040015), Kaempferol (MESH:C006552), Neohesperidin (MESH:C546526), hesperetin (MESH:C013015), CCK-8 (MESH:D012844), water (MESH:D014867), carbon (MESH:D002244), Eudragit E PO (MESH:C518398), Flavonols (MESH:D044948), Quercetin (MESH:D011794), polysaccharide (MESH:D011134), AOM (MESH:D001397), nitrosomethane (MESH:C097158), sugar (MESH:D000073893), flavone (MESH:C043562), diosmin (MESH:D004145), Galangin (MESH:C037032) - **Species:** gut metagenome (species) [taxon 749906], Gallus gallus (bantam, species) [taxon 9031], Pseudocydonia sinensis (Chinese quince, species) [taxon 36622], Alpinia oxyphylla (sharp-leaf galangal, species) [taxon 125261], Portulaca oleracea (species) [taxon 46147], Perilla frutescens (beefsteak-mint, species) [taxon 48386], Passiflora caerulea (species) [taxon 159428], Homo sapiens (human, species) [taxon 9606], Citrus medica (citron, species) [taxon 171251], Lonicera japonica (Japanese honeysuckle, species) [taxon 105884], Rattus norvegicus (brown rat, species) [taxon 10116], Chrysanthemum (genus) [taxon 13422], Glycyrrhiza uralensis (Chinese licorice, species) [taxon 74613], Euryale ferox (species) [taxon 4414], Emblica officinalis (amla, species) [taxon 296036], Rubus idaeus (European red raspberry, species) [taxon 32247], Zingiber officinale (ginger, species) [taxon 94328], Lophatherum gracile (species) [taxon 29683], C. elegans [taxon 328850], Cistanche deserticola (species) [taxon 161395], Ganoderma lucidum (species) [taxon 5315], Polygonatum odoratum (yu zhu, species) [taxon 82207], Illicium verum (Chinese star-anise, species) [taxon 124778], Prunus mume (Japanese apricot, species) [taxon 102107], Mentha canadensis (American wild mint, species) [taxon 294733], Ecklonia kurome [taxon 399530], Taraxacum mongolicum (species) [taxon 90037], Crataegus pinnatifida (Chinese hawthorn, species) [taxon 510735], Scutellaria baicalensis (Baikal skullcap, species) [taxon 65409], Houttuynia cordata (chameleon-plant, species) [taxon 16752], Hippophae rhamnoides (sallowthorn, species) [taxon 193516], Mus musculus (house mouse, species) [taxon 10090], Dendrobium officinale (species) [taxon 142615], Alpinia officinarum (Chinese-ginger, species) [taxon 199623], Glycine max (soybean, species) [taxon 3847], Cinnamomum aromaticum (species) [taxon 119260], Myristica fragrans (mace, species) [taxon 51089] - **Mutations:** C3 of the C, C797S, T790M, L858R - **Cell lines:** A7r5 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0137), HSC-T6 — Rattus norvegicus (Rat), Transformed cell line (CVCL_0315), KYSE30 — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_1351), HepG2 liver cancer — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027) ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939643/full.md --- Source: https://tomesphere.com/paper/PMC12939643