Soumya D, Srilatha B. Late stage complications of diabetes and insulin resistance. J Diabetes Metab. 2011;2:1000167. https://doi.org/10.4172/2155-6156.1000167.

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. https://doi.org/10.1016/j.diabres.2019.107843.

Article  PubMed  Google Scholar 

Rehman A, Saeed A, Kanwal R, Ahmad S, Changazi SH. Therapeutic effect of sunflower seeds and flax seeds on diabetes. Cureus. 2021;13:e17256. https://doi.org/10.7759/cureus.17256.

Article  PubMed  PubMed Central  Google Scholar 

Rask-Madsen C, King GL. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab. 2013;17:20–33. https://doi.org/10.1016/j.cmet.2012.11.012.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Stolf AM, Cardoso CC, Acco A. Effects of silymarin on diabetes mellitus complications: a review. Phytother Res. 2017;31:366–74. https://doi.org/10.1002/ptr.5768.

Article  PubMed  Google Scholar 

Ren B, Qin W, Wu F, Wang S, Pan C, Wang L, et al. Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. Eur J Pharm. 2016;773:13–23. https://doi.org/10.1016/j.ejphar.2016.01.002.

CAS  Article  Google Scholar 

Bai L, Li X, He L, Zheng Y, Lu H, Li J, et al. Antidiabetic potential of flavonoids from traditional Chinese medicine: a review. Am J Chin Med. 2019;47:933–57. https://doi.org/10.1142/S0192415X19500496.

CAS  Article  PubMed  Google Scholar 

Mirhoseini MBA, Rafieian-Kopaei M. Medicinal plants, diabetes mellitus and urgent needs. Herb Med Pharm. 2013;2:53–4.

Google Scholar 

Sharma A, Ghani A, Sak K, Tuli HS, Sharma AK, Setzer WN, et al. Probing into therapeutic anti-cancer potential of apigenin: recent trends and future directions. Recent Pat Inflamm Allergy Drug Disco. 2019;13:124–33. https://doi.org/10.2174/1872213X13666190816160240.

CAS  Article  Google Scholar 

Salehi B, Venditti A, Sharifi-Rad M, Kregiel D, Sharifi-Rad J, Durazzo A, et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019;20. https://doi.org/10.3390/ijms20061305.

Hostetler GL, Ralston RA, Schwartz SJ. Flavones: food sources, bioavailability, metabolism, and bioactivity. Adv Nutr. 2017;8:423–35. https://doi.org/10.3945/an.116.012948.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Nozhat Z, Heydarzadeh S, Memariani Z, Ahmadi A. Chemoprotective and chemosensitizing effects of apigenin on cancer therapy. Cancer Cell Int. 2021;21:574. https://doi.org/10.1186/s12935-021-02282-3.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Panda S, Kar A. Apigenin (4’,5,7-trihydroxyflavone) regulates hyperglycaemia, thyroid dysfunction and lipid peroxidation in alloxan-induced diabetic mice. J Pharm Pharmacol. 2007;59:1543–8. https://doi.org/10.1211/jpp.59.11.0012.

CAS  Article  PubMed  Google Scholar 

Lin CH, Chang CY, Lee KR, Lin HJ, Chen TH, Wan L. Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway. BMC Cancer. 2015;15:958. https://doi.org/10.1186/s12885-015-1965-7.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Fidelis QC, Faraone I, Russo D, Aragão Catunda-Jr FE, Vignola L, de Carvalho MG, et al. Chemical and biological insights of Ouratea hexasperma (A. St.-Hil.) Baill.: a source of bioactive compounds with multifunctional properties. Nat Prod Res. 2019;33:1500–3. https://doi.org/10.1080/14786419.2017.1419227.

CAS  Article  PubMed  Google Scholar 

DeRango-Adem EF, Blay J. Does oral apigenin have real potential for a therapeutic effect in the context of human gastrointestinal and other cancers. Front Pharmacol. 2021;12:681477. https://doi.org/10.3389/fphar.2021.681477.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Lim R, Barker G, Wall CA, Lappas M. Dietary phytophenols curcumin, naringenin and apigenin reduce infection-induced inflammatory and contractile pathways in human placenta, foetal membranes and myometrium. Mol Hum Reprod. 2013;19:451–62. https://doi.org/10.1093/molehr/gat015.

CAS  Article  PubMed  Google Scholar 

Zhou Z, Zhang Y, Lin L, Zhou J. Apigenin suppresses the apoptosis of H9C2 rat cardiomyocytes subjected to myocardial ischemia‑reperfusion injury via upregulation of the PI3K/Akt pathway. Mol Med Rep. 2018;18:1560–70. https://doi.org/10.3892/mmr.2018.9115.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, et al. Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: evidence from in vitro models and a human bioavailability study. J Funct foods. 2018;48:410–9. https://doi.org/10.1016/j.jff.2018.07.035.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Zafar A, Alruwaili NK, Imam SS, Hadal Alotaibi N, Alharbi KS, Afzal M, et al. Bioactive Apigenin loaded oral nano bilosomes: formulation optimization to preclinical assessment. Saudi Pharm J. 2021;29:269–79. https://doi.org/10.1016/j.jsps.2021.02.003.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Zhang J, Liu D, Huang Y, Gao Y, Qian S. Biopharmaceutics classification and intestinal absorption study of apigenin. Int J Pharm. 2012;436:311–7. https://doi.org/10.1016/j.ijpharm.2012.07.002.

CAS  Article  PubMed  Google Scholar 

Wong TY, Tsai MS, Hsu LC, Lin SW, Liang PH. Traversal of the blood-brain barrier by cleavable l-lysine conjugates of apigenin. J Agric Food Chem. 2018;66:8124–31. https://doi.org/10.1021/acs.jafc.8b01187.

CAS  Article  PubMed  Google Scholar 

Tang D, Chen K, Huang L, Li J. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert Opin Drug Metab Toxicol. 2017;13:323–30. https://doi.org/10.1080/17425255.2017.1251903.

CAS  Article  PubMed  Google Scholar 

Jung UJ, Cho YY, Choi MS. Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice. Nutrients. 2016;8. https://doi.org/10.3390/nu8050305.

Pan G, Zhao L, Xiao N, Yang K, Ma Y, Zhao X, et al. Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents. Eur J Med Chem. 2016;122:674–83. https://doi.org/10.1016/j.ejmech.2016.07.015.

CAS  Article  PubMed  Google Scholar 

Franke K, Porzel A, Schmidt J. Flavone-coumarin hybrids from Gnidia socotrana. Phytochemistry. 2002;61:873–8. https://doi.org/10.1016/s0031-9422(02)00358-8.

CAS  Article  PubMed  Google Scholar 

Sun H, Song X, Tao Y, Li M, Yang K, Zheng H, et al. Synthesis & α-glucosidase inhibitory & glucose consumption-promoting activities of flavonoid-coumarin hybrids. Future Med Chem. 2018;10:1055–66. https://doi.org/10.4155/fmc-2017-0293.

CAS  Article  PubMed  Google Scholar 

Su ZR, Fan SY, Shi WG, Zhong BH. Discovery of xanthine oxidase inhibitors and/or alpha-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin. Bioorg Med Chem Lett. 2015;25:2778–81. https://doi.org/10.1016/j.bmcl.2015.05.016.

CAS  Article  PubMed  Google Scholar 

Hakamata W, Nakanishi I, Masuda Y, Shimizu T, Higuchi H, Nakamura Y, et al. Planar catechin analogues with alkyl side chains: a potent antioxidant and an alpha-glucosidase inhibitor. J Am Chem Soc. 2006;128:6524–5. https://doi.org/10.1021/ja057763c.

CAS  Article  PubMed  Google Scholar 

Cheng N, Yi W-B, Wang Q-Q, Peng S-M, Zou X-Q. Synthesis and α-glucosidase inhibitory activity of chrysin, diosmetin, apigenin, and luteolin derivatives. Chin Chem Lett. 2014;25:1094–8. https://doi.org/10.1016/j.cclet.2014.05.021.

Wang QQ, Cheng N, Yi WB, Peng SM, Zou XQ. Synthesis, nitric oxide release, and α-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives. Bioorg Med Chem. 2014;22:1515–21. https://doi.org/10.1016/j.bmc.2014.01.038.

CAS  Article  PubMed  Google Scholar 

Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010;27:962–78. https://doi.org/10.1007/s11095-010-0089-7.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Wang M, Firrman J, Liu L, Yam K. A review on flavonoid apigenin: dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. BioMed Res Int. 2019;2019:7010467. https://doi.org/10.1155/2019/7010467.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Gurung RB, Kim EH, Oh TJ, Sohng JK. Enzymatic synthesis of apigenin glucosides by glucosyltransferase (YjiC) from Bacillus licheniformis DSM 13. Mol Cells. 2013;36:355–61. https://doi.org/10.1007/s10059-013-0164-0.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Vanegas KG, Larsen AB, Eichenberger M, Fischer D, Mortensen UH, Naesby M. Indirect and direct routes to C-glycosylated flavones in Saccharomyces cerevisiae. Microb Cell Factories. 2018;17:107. https://doi.org/10.1186/s12934-018-0967-y.

Article  Google Scholar 

Liu HJ, Fan YL, Liao HH, Liu Y, Chen S, Ma ZG, et al. Apigenin alleviates STZ-induced diabetic cardiomyopathy. Mol Cell Biochem. 2017;428:9–21. https://doi.org/10.1007/s11010-016-2913-9.

CAS  Article  PubMed  Google Scholar 

Rauter AP, Martins A, Borges C, Mota-Filipe H, Pinto R, Sepodes B, et al. Antihyperglycaemic and protective effects of flavonoids on streptozotocin-induced diabetic rats. Phytother Res. 2010;24:S133–8. https://doi.org/10.1002/ptr.3017.

Article  PubMed  Google Scholar 

Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 2019;9. https://doi.org/10.3390/biom9090430.

Babu PV, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem. 2013;24:1777–89. https://doi.org/10.1016/j.jnutbio.2013.06.003.

CAS