# Flavonoids improve type 2 diabetes mellitus and its complications: a review **Authors:** Xinrui Yi, Mosi Dong, Naifei Guo, Jinlong Tian, Ping Lei, Song Wang, Yufeng Yang, Yan Shi PMC · DOI: 10.3389/fnut.2023.1192131 · 2023-05-31 ## TL;DR This review explores how flavonoids, natural plant compounds, may help manage type 2 diabetes and its complications by reducing blood sugar and inflammation. ## Contribution The paper highlights flavonoids as a promising natural alternative for managing type 2 diabetes and its complications. ## Key findings - Flavonoids have hypoglycemic, anti-oxidative, and anti-inflammatory effects that benefit T2DM. - They improve glucose and lipid metabolism and reduce insulin resistance. - Flavonoids may serve as a foundation for developing new diabetes medications. ## Abstract The prevalence of type 2 diabetes mellitus (T2DM) is increasing every year. Medications are currently the most common therapy for T2DM. However, these medications have certain adverse effects. In order to find safe and effective ways to improve this disease, researchers have discovered that some natural products can decrease blood sugar. Flavonoids are one of the most essential low molecular weight phenolic chemicals in the plant world, which widely exist in plant roots, stems, leaves, flowers, and fruits. They possess a variety of biological activities, including organ protection, hypoglycemic, lipid-lowering, anti-oxidative and anti-inflammatory effects. Some natural flavonoids ameliorate T2DM and its complications through anti-oxidation, anti-inflammatory action, glucose and lipid metabolism regulation, insulin resistance management, etc. Hence, this review aims at demonstrating the potential benefits of flavonoids in T2DM and its complications. This laid the foundation for the development of novel hypoglycemic medications from flavonoids. ## Linked entities - **Diseases:** type 2 diabetes mellitus (MONDO:0005148) ## Full-text entities - **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, CAT (catalase) [NCBI Gene 847], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Mir1 (microRNA 1) [NCBI Gene 100314077] {aka rno-mir-1}, Src (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 83805], Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Tnfsf11 (TNF superfamily member 11) [NCBI Gene 117516] {aka ODF, OPGL, RANKL, TRANCE}, Sirt1 (sirtuin 1) [NCBI Gene 309757] {aka Sir2}, Ilk (integrin-linked kinase) [NCBI Gene 170922] {aka ILK-1, ILK-2, p59ILK}, Ucp3 (uncoupling protein 3) [NCBI Gene 25708], Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Shc1 (SHC adaptor protein 1) [NCBI Gene 85385] {aka P66shc}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, TRIB3 (tribbles pseudokinase 3) [NCBI Gene 57761] {aka C20orf97, NIPK, SINK, SKIP3, TRB3}, Ephb1 (Eph receptor B1) [NCBI Gene 24338] {aka Ephb2, Erk, elk}, Runx2 (RUNX family transcription factor 2) [NCBI Gene 367218] {aka CBF-alpha-1, Cbfa1, OSF-2}, Trib3 (tribbles pseudokinase 3) [NCBI Gene 246273] {aka NIPK}, Ager (advanced glycosylation end product-specific receptor) [NCBI Gene 81722] {aka RAGE}, Hmgb1 (high mobility group box 1) [NCBI Gene 25459] {aka Ac2-008, Hmg1}, Nphs1 (NPHS1 adhesion molecule, nephrin) [NCBI Gene 64563], MIR145 (microRNA 145) [NCBI Gene 406937] {aka MIRN145, miR-145, miRNA145}, Akt2 (AKT serine/threonine kinase 2) [NCBI Gene 25233], NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}, Ddit3 (DNA-damage inducible transcript 3) [NCBI Gene 29467] {aka CHOP, CHOP-10, Chop10, Gadd153, RM4}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}, Kl (Klotho) [NCBI Gene 83504], Sirt3 (sirtuin 3) [NCBI Gene 293615], Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404] {aka GSHPx, GSHPx-1}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, G6pc1 (glucose-6-phosphatase catalytic subunit 1) [NCBI Gene 14377] {aka G6Pase, G6pc, G6pt, Glc-6-Pase}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, Hsd17b7 (hydroxysteroid (17-beta) dehydrogenase 7) [NCBI Gene 29540], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Igf1r (insulin-like growth factor 1 receptor) [NCBI Gene 25718] {aka IGF-1 receptor, IGFIRC, Igfr1, JTK13}, Becn1 (beclin 1) [NCBI Gene 114558] {aka Beclin1}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 81687], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Ptk2 (protein tyrosine kinase 2) [NCBI Gene 25614] {aka FAK, FRNK, p125FAK}, Pik3cg (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma) [NCBI Gene 298947] {aka Pi3k}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 25747] {aka PPAR}, Rhoa (ras homolog family member A) [NCBI Gene 117273] {aka Arha, Arha2}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Mir145 (microRNA 145) [NCBI Gene 100314036] {aka rno-mir-145}, RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, Cyp2j3 (cytochrome P450, family 2, subfamily j, polypeptide 3) [NCBI Gene 313375] {aka Cyp2j9}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, Rps6kb1 (ribosomal protein S6 kinase B1) [NCBI Gene 83840] {aka p70 S6K-alpha}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, Tlr4 (toll-like receptor 4) [NCBI Gene 29260], INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10} - **Diseases:** microaneurysm (MESH:D000071071), myocardial ischemia (MESH:D017202), diabetic lipid/metabolic disorders (MESH:D052439), hypoglycemic (MESH:C000721848), glomerulosclerosis (MESH:D005921), retinal complication (MESH:D012164), fatigue (MESH:D005221), diabetic osteoporosis (MESH:D010024), Vascular complications (MESH:D003925), muscular dysfunction (MESH:D009135), diabetic testicular damage (MESH:D013733), disease (MESH:D004194), metabolic syndrome (MESH:D024821), blindness (MESH:D001766), Endothelial dysfunction (MESH:D014652), fibrotic damage (MESH:D020263), DME (MESH:D008269), obese (MESH:D009765), coronary artery disease (MESH:D003324), anti- (MESH:D006679), renal (MESH:D006030), KIM-1 (MESH:D058186), hypertension (MESH:D006973), DN (MESH:D003928), endothelial (MESH:D005642), cardiovascular disease (MESH:D002318), cardiac hypertrophy (MESH:D006332), inflammatory cytokines (MESH:D000080424), glucose intolerance (MESH:D018149), myocardial infarction (MESH:D009203), heart dysfunction (MESH:D006331), retinopathy (MESH:D058437), NPDR (OMIM:603933), glomerular sclerosis (MESH:D007674), infarcts (MESH:D007238), stroke (MESH:D020521), hyperlipidemia (MESH:D006949), hyperglycemic (MESH:D006944), Hyperglycemia (MESH:D006943), abdominal obesity (MESH:D056128), DR (MESH:D003930), retinal inflammatory (MESH:D012173), cardiotoxicity (MESH:D066126), hypertrophy (MESH:D006984), muscle atrophy (MESH:D009133), heart failure (MESH:D006333), thrombosis (MESH:D013927), apoptosis (MESH:D065703), atherogenic (MESH:D050197), Insulin resistance (MESH:D007333), T2DM (MESH:D003924), proteinuria (MESH:D011507), valvular heart disease (MESH:D006349), inflammation (MESH:D007249), end-stage renal disease (MESH:D007676), memory difficulty (MESH:D008569), DM (MESH:D003920), weight reduction (MESH:D015431), DCM (MESH:D058065), gastrointestinal symptoms (MESH:D012817) - **Species:** Brassica oleracea (wild cabbage, species) [taxon 3712], Syzygium cumini (jaman, species) [taxon 260142], Mus musculus (house mouse, species) [taxon 10090], Trifolium pratense (peavine clover, species) [taxon 57577], Citrus x aurantium (bitter orange, species) [taxon 43166], Lycium ruthenicum (species) [taxon 112879], Citrus (genus) [taxon 2706], Bacillus sp. AE (species) [taxon 1196772], Rattus norvegicus (brown rat, species) [taxon 10116], Medicago sativa (alfalfa, species) [taxon 3879], Erigeron breviscapus (species) [taxon 244311], Homo sapiens (human, species) [taxon 9606] - **Cell lines:** Huh-7.5.1 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_E049), ARPE-19 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145), C57BL/ — Homo sapiens (Human), Burkitt lymphoma, Cancer cell line (CVCL_C152), NRK-52E — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0468), RPTEC — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_K278), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), H9C2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286) ## Figures 25 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10265523/full.md --- Source: https://tomesphere.com/paper/PMC10265523