Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

doi:10.1007/s13659-023-00424-w

Natural Products and Bioprospecting ›› 2024, Vol. 14 ›› Issue (1): 4-4.DOI: 10.1007/s13659-023-00424-w

• REVIEWS • Previous Articles Next Articles

Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

Thua-Phong Lam^1,2, Ngoc-Vi Nguyen Tran^1,2, Long-Hung Dinh Pham^1,3, Nghia Vo-Trong Lai¹, Bao-Tran Ngoc Dang¹, Ngoc-Lam Nguyen Truong¹, Song-Ky Nguyen-Vo¹, Thuy-Linh Hoang⁴, Tan Thanh Mai¹, Thanh-Dao Tran¹

1. Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 700000, Ho Chi Minh City, Vietnam;
2. Faculty of Pharmacy, Uppsala University, 75105, Uppsala, Sweden;
3. Department of Chemistry, Imperial College London, London, W12 0BZ, UK;
4. California Northstate University College of Pharmacy, California, 95757, USA

Received:2023-11-09 Online:2024-02-19 Published:2024-02-24
Contact: Tan Thanh Mai,E-mail:mthtan@ump.edu.vn;Thanh-Dao Tran,E-mail:daott@ump.edu.vn
Supported by:
This research is funded by the University of Medicine and Pharmacy at Ho Chi Minh City under grant number 162/2019/HĐ-ĐHYD for Thanh-Dao Tran. The funding organization does not affect the transparency and the findings of the review. We would like to thank Phuc Quang Vu (School of Global Public Health, New York University) for the aid with numerical data processing and presentation and Lam-Duy Pham (Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City) for the aid with manuscript formatting.

Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

1. Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 700000, Ho Chi Minh City, Vietnam;
2. Faculty of Pharmacy, Uppsala University, 75105, Uppsala, Sweden;
3. Department of Chemistry, Imperial College London, London, W12 0BZ, UK;
4. California Northstate University College of Pharmacy, California, 95757, USA

通讯作者: Tan Thanh Mai,E-mail:mthtan@ump.edu.vn;Thanh-Dao Tran,E-mail:daott@ump.edu.vn
基金资助:
This research is funded by the University of Medicine and Pharmacy at Ho Chi Minh City under grant number 162/2019/HĐ-ĐHYD for Thanh-Dao Tran. The funding organization does not affect the transparency and the findings of the review. We would like to thank Phuc Quang Vu (School of Global Public Health, New York University) for the aid with numerical data processing and presentation and Lam-Duy Pham (Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City) for the aid with manuscript formatting.

Abstract

Abstract: Diabetes mellitus remains a major global health issue, and great attention is directed at natural therapeutics. This systematic review aimed to assess the potential of flavonoids as antidiabetic agents by investigating their inhibitory effects on α-glucosidase and α-amylase, two key enzymes involved in starch digestion. Six scientific databases (PubMed, Virtual Health Library, EMBASE, SCOPUS, Web of Science, and WHO Global Index Medicus) were searched until August 21, 2022, for in vitro studies reporting IC₅₀ values of purified flavonoids on α-amylase and α-glucosidase, along with corresponding data for acarbose as a positive control. A total of 339 eligible articles were analyzed, resulting in the retrieval of 1643 flavonoid structures. These structures were rigorously standardized and curated, yielding 974 unique compounds, among which 177 flavonoids exhibited inhibition of both α-glucosidase and α-amylase are presented. Quality assessment utilizing a modified CONSORT checklist and structure–activity relationship (SAR) analysis were performed, revealing crucial features for the simultaneous inhibition of flavonoids against both enzymes. Moreover, the review also addressed several limitations in the current research landscape and proposed potential solutions. The curated datasets are available online at https://github.com/MedChemUMP/FDIGA.

Key words: Systematic review, Flavonoids, Dual-target, Glucosidase, Amylase, PRISMA, SAR

摘要： Diabetes mellitus remains a major global health issue, and great attention is directed at natural therapeutics. This systematic review aimed to assess the potential of flavonoids as antidiabetic agents by investigating their inhibitory effects on α-glucosidase and α-amylase, two key enzymes involved in starch digestion. Six scientific databases (PubMed, Virtual Health Library, EMBASE, SCOPUS, Web of Science, and WHO Global Index Medicus) were searched until August 21, 2022, for in vitro studies reporting IC₅₀ values of purified flavonoids on α-amylase and α-glucosidase, along with corresponding data for acarbose as a positive control. A total of 339 eligible articles were analyzed, resulting in the retrieval of 1643 flavonoid structures. These structures were rigorously standardized and curated, yielding 974 unique compounds, among which 177 flavonoids exhibited inhibition of both α-glucosidase and α-amylase are presented. Quality assessment utilizing a modified CONSORT checklist and structure–activity relationship (SAR) analysis were performed, revealing crucial features for the simultaneous inhibition of flavonoids against both enzymes. Moreover, the review also addressed several limitations in the current research landscape and proposed potential solutions. The curated datasets are available online at https://github.com/MedChemUMP/FDIGA.

关键词: Systematic review, Flavonoids, Dual-target, Glucosidase, Amylase, PRISMA, SAR

Thua-Phong Lam, Ngoc-Vi Nguyen Tran, Long-Hung Dinh Pham, Nghia Vo-Trong Lai, Bao-Tran Ngoc Dang, Ngoc-Lam Nguyen Truong, Song-Ky Nguyen-Vo, Thuy-Linh Hoang, Tan Thanh Mai, Thanh-Dao Tran. Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies[J]. Natural Products and Bioprospecting, 2024, 14(1): 4-4.

References

[1] International Diabetes Federation. IDF Diabetes Atlas, 10th edition. Brussels, Belgium: 2021. [2] ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. Classification and diagnosis of diabetes: standards of care in diabetes—2023. Diabetes Care. 2023;46(1):S19–40. https://doi.org/10.2337/dc23-S002. [3] Dahlén AD, Dashi G, Maslov I, Attwood MM, Jonsson J, Trukhan V, et al. Trends in antidiabetic drug discovery: FDA approved drugs, new drugs in clinical trials and global sales. Front Pharmacol. 2022;12:4119. https://doi.org/10.3389/fphar.2021.807548. [4] Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753–86. https://doi.org/10.2337/dci22-0034. [5] ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. Pharmacologic approaches to glycemic treatment: standards of care in diabetes—2023. Diabetes Care. 2023;46(1):S140–57. https://doi.org/10.2337/dc23-S009. [6] Dhital S, Lin AH-M, Hamaker BR, Gidley MJ, Muniandy A. Mammalian mucosal α-glucosidases coordinate with α-amylase in the initial starch hydrolysis stage to have a role in starch digestion beyond glucogenesis. PLoS ONE. 2013;8(4):e62546. https://doi.org/10.1371/journal.pone.0062546. [7] Ren L, Qin X, Cao X, Wang L, Bai F, Bai G, et al. Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Protein Cell. 2011;2(10):827–36. https://doi.org/10.1007/s13238-011-1105-3. [8] Koepsell H. Glucose transporters in the small intestine in health and disease. Pflug Arch Eur J Physiol. 2020;472(9):1207–48. https://doi.org/10.1007/s00424-020-02439-5. [9] Ghani U. Chapter one—introduction, rationale and the current clinical status of oral α-glucosidase inhibitors. In: Ghani U, editor. Alpha-glucosidase inhibitors. Saudi Arabia: Elsevier; 2020. p. 1–15. [10] Yee HS, Fong NT. A review of the safety and efficacy of acarbose in diabetes mellitus. Pharmacotherapy. 1996;16(5):792–805. https://doi.org/10.1002/j.1875-9114.1996.tb02997.x. [11] Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019;299: 125124. https://doi.org/10.1016/j.foodchem.2019.125124. [12] Agati G, Brunetti C, Fini A, Gori A, Guidi L, Landi M, et al. Are flavonoids effective antioxidants in plants? Twenty years of our investigation. Antioxidants. 2020;9(11):1098. https://doi.org/10.3390/antiox9111098. [13] Lam T-P, Tran V-H, Mai TT, Lai NV, Dang B-TN, Le M-T, et al. Identification of diosmin and flavin adenine dinucleotide as repurposing treatments for monkeypox virus: A computational study. Int J Mol Sci. 2022;23(19):11570. https://doi.org/10.3390/ijms231911570. [14] Vo C-VT, Nguyen LC, Le TTA, Dang TN, Dao MQ, Nguyen TH, et al. Natural mimetic 4-benzyloxychalcones as potent pancreatic lipase inhibitors: virtual screening, synthesis and biological evaluation. Phytochem Lett. 2022;51:28–33. https://doi.org/10.1016/j.phytol.2022.06.011. [15] Collado-González J, Grosso C, Valentão P, Andrade PB, Ferreres F, Durand T, et al. Inhibition of α-glucosidase and α-amylase by Spanish extra virgin olive oils: the involvement of bioactive compounds other than oleuropein and hydroxytyrosol. Food Chem. 2017;235:298–307. https://doi.org/10.1016/j.foodchem.2017.04.171. [16] Sun L, Warren FJ, Netzel G, Gidley MJ. 3 or 3'-galloyl substitution plays an important role in association of catechins and theaflavins with porcine pancreatic α-amylase: the kinetics of inhibition of α-amylase by tea polyphenols. J Funct Foods. 2016;26:144–56. https://doi.org/10.1016/j.jff.2016.07.012. [17] Tundis R, Bonesi M, Sicari V, Pellicanò T, Tenuta MC, Leporini M, et al. Poncirus trifoliata (L.) Raf.: chemical composition, antioxidant properties and hypoglycaemic activity via the inhibition of α-amylase and α-glucosidase enzymes. J Funct Foods. 2016;25:477–85. https://doi.org/10.1016/j.jff.2016.06.034. [18] Proença C, Ribeiro D, Freitas M, Fernandes E. Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: a review. Crit Rev Food Sci Nutr. 2022;62(12):3137–207. https://doi.org/10.1080/10408398.2020.1862755. [19] Zhu J, Chen C, Zhang B, Huang Q. The inhibitory effects of flavonoids on α-amylase and α-glucosidase. Crit Rev Food Sci Nutr. 2020;60(4):695–708. https://doi.org/10.1080/10408398.2018.1548428. [20] Şöhretoğlu D, Sari S. Flavonoids as alpha-glucosidase inhibitors: mechanistic approaches merged with enzyme kinetics and molecular modelling. Phytochem Rev. 2020;19(5):1081–92. https://doi.org/10.1007/s11101-019-09610-6. [21] Mahapatra DK, Asati V, Bharti SK. Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. Eur J Med Chem. 2015;92:839–65. https://doi.org/10.1016/j.ejmech.2015.01.051. [22] Rocha S, Ribeiro D, Fernandes E, Freitas M. A systematic review on anti-diabetic properties of chalcones. Curr Med Chem. 2020;27(14):2257–321. https://doi.org/10.2174/0929867325666181001112226. [23] Xiao J, Ni X, Kai G, Chen X. A review on structure-activity relationship of dietary polyphenols inhibiting α-amylase. Crit Rev Food Sci Nutr. 2013;53(5):497–506. https://doi.org/10.1080/10408398.2010.548108. [24] Visvanathan R, Qader M, Jayathilake C, Jayawardana BC, Liyanage R, Sivakanesan R. Critical review on conventional spectroscopic α-amylase activity detection methods: merits, demerits, and future prospects. J Sci Food Agric. 2020;100(7):2836–47. https://doi.org/10.1002/jsfa.10315. [25] Yi J, Zhao T, Zhang Y, Tan Y, Han X, Tang Y, et al. Isolated compounds from Dracaena angustifolia Roxb and acarbose synergistically/additively inhibit alpha-glucosidase and alpha-amylase: an in vitro study. BMC Complement Altern Med. 2022;22(1):177. https://doi.org/10.1186/s12906-022-03649-3. [26] Zhang LL, Han L, Yang SY, Meng XM, Ma WF, Wang M. The mechanism of interactions between flavan-3-ols against a-glucosidase and their in vivo antihyperglycemic effects. Bioorg Chem. 2019;85:364–72. https://doi.org/10.1016/j.bioorg.2018.12.037. [27] Lima Júnior JPD, Franco RR, Saraiva AL, Moraes IB, Espindola FS. Anacardium humile St. Hil as a novel source of antioxidant, antiglycation and α-amylase inhibitors molecules with potential for management of oxidative stress and diabetes. J Ethnopharmacol. 2021;268:113667. https://doi.org/10.1016/j.jep.2020.113667. [28] Nazir N, Zahoor M, Ullah R, Ezzeldin E, Mostafa GAE. Curative effect of catechin isolated from Elaeagnus umbellata Thunb. berries for diabetes and related complications in streptozotocin-induced diabetic rats model. Molecules. 2020;26(1):137. https://doi.org/10.3390/molecules26010137. [29] Jiang P, Zhao Y, Xiong J, Wang F, Xiao L, Bao S, et al. Extraction, purification, and biological activities of flavonoids from branches and leaves of Taxus cuspidata S. et Z. BioResources. 2021;16(2):2655–82. https://doi.org/10.15376/biores.16.2.2655-2682. [30] Wu Q, Min Y, Xiao J, Feng N, Chen Y, Luo Q, et al. Liquid state fermentation vinegar enriched with catechin as an antiglycative food product. Food Funct. 2019;10(8):4877–87. https://doi.org/10.1039/c8fo01892h. [31] Liu J, Lu JF, Kan J, Wen XY, Jin CH. Synthesis, characterization and in vitro anti-diabetic activity of catechin grafted inulin. Int J Biol Macromol. 2014;64:76–83. https://doi.org/10.1016/j.ijbiomac.2013.11.028. [32] Ray S, Samanta T, Mitra A, De B. Effect of extracts and components of black tea on the activity of beta-glucuronidase, lipase, alpha-amylase, alpha-glucosidase: an in vitro study. Curr Nutr Food Sci. 2014;10(3):181–6. https://doi.org/10.2174/1573401310666140529205646. [33] Tian JL, Si X, Wang YH, Gong ES, Xie X, Zhang Y, et al. Bioactive flavonoids from Rubus corchorifolius inhibit α-glucosidase and α-amylase to improve postprandial hyperglycemia. Food Chem. 2021;341: 128149. https://doi.org/10.1016/j.foodchem.2020.128149. [34] Zhou H, Li HM, Du YM, Yan RA, Ou SY, Chen TF, et al. C-geranylated flavanones from YingDe black tea and their antioxidant and α-glucosidase inhibition activities. Food Chem. 2017;235:227–33. https://doi.org/10.1016/j.foodchem.2017.05.034. [35] Numonov S, Edirs S, Bobakulov K, Qureshi MN, Bozorov K, Sharopov F, et al. Evaluation of the antidiabetic activity and chemical composition of Geranium collinum root extracts—computational and experimental investigations. Molecules. 2017;22(6):983. https://doi.org/10.3390/molecules22060983. [36] Deutschlander MS, Lall N, Van De Venter M, Hussein AA. Hypoglycemic evaluation of a new triterpene and other compounds isolated from Euclea undulata Thunb. Var. Myrtina (Ebenaceae) root bark. J Ethnopharmacol. 2011;133(3):1091–5. https://doi.org/10.1016/j.jep.2010.11.038. [37] Zhao L, Wen L, Lu Q, Liu R. Interaction mechanism between alpha-glucosidase and A-type trimer procyanidin revealed by integrated spectroscopic analysis techniques. Int J Biol Macromol. 2020;143:173–80. https://doi.org/10.1016/j.ijbiomac.2019.12.021. [38] Zhang H, Yerigui, Yang Y, Ma C. Structures and antioxidant and intestinal disaccharidase inhibitory activities of A-type proanthocyanidins from peanut skin. J Agric Food Chem. 2013;61(37):8814–20. https://doi.org/10.1021/jf402518k. [39] He XF, Chen JJ, Huang XY, Hu J, Zhang XK, Guo YQ, et al. The antidiabetic potency of Amomum tsao-ko and its active flavanols, as PTP1B selective and α-glucosidase dual inhibitors. Ind Crops Prod. 2021;160: 112908. https://doi.org/10.1016/j.indcrop.2020.112908. [40] Gong T, Yang X, Bai F, Li D, Zhao T, Zhang J, et al. Young apple polyphenols as natural α-glucosidase inhibitors: in vitro and in silico studies. Bioorg Chem. 2020;96: 103625. https://doi.org/10.1016/j.bioorg.2020.103625. [41] Giang Thanh Thi H, Kase ET, Wangensteen H, Barsett H. Effect of phenolic compounds from Elderflowers on glucose- and fatty acid uptake in human myotubes and HepG2-cells. Molecules. 2017;22(1):90. https://doi.org/10.3390/molecules22010090. [42] Wang X, Liu Q, Zhu H, Wang H, Kang J, Shen Z, et al. Flavanols from the Camellia sinensis var. assamica and their hypoglycemic and hypolipidemic activities. Acta Pharm Sin B. 2017;7(3):342–6. https://doi.org/10.1016/j.apsb.2016.12.007. [43] Dat NT, Dang NH, le Thanh N. New flavonoid and pentacyclic triterpene from Sesamum indicum leaves. Nat Prod Res. 2016;30(3):311–5. https://doi.org/10.1080/14786419.2015.1057730. [44] Li S, Lo C-Y, Pan M-H, Lai C-S, Ho C-T. Black tea: chemical analysis and stability. Food Funct. 2013;4(1):10–8. https://doi.org/10.1039/C2FO30093A. [45] Wu X, Hu M, Hu X, Ding H, Gong D, Zhang G. Inhibitory mechanism of epicatechin gallate on α-amylase and α-glucosidase and its combinational effect with acarbose or epigallocatechin gallate. J Mol Liq. 2019;290: 111202. https://doi.org/10.1016/j.molliq.2019.111202. [46] Chen Y, Ye X, Wang L, Shao J, Jing H, Jiang C, et al. Three flavanols delay starch digestion by inhibiting alpha-amylase and binding with starch. Int J Biol Macromol. 2021;172:503–14. https://doi.org/10.1016/j.ijbiomac.2021.01.070. [47] Xu L, Li W, Chen Z, Guo Q, Wang C, Santhanam RK, et al. Inhibitory effect of epigallocatechin-3-O-gallate on alpha-glucosidase and its hypoglycemic effect via targeting PI3K/AKT signaling pathway in L6 skeletal muscle cells. Int J Biol Macromol. 2019;125:605–11. https://doi.org/10.1016/j.ijbiomac.2018.12.064. [48] Su J, Tang Z. Effects of (-)-epigallocatechin gallate and quercetin on the activity and structure of alpha-amylase. Trop J Pharm Res. 2019;18(3):585–90. https://doi.org/10.4314/tjpr.v18i3.20. [49] Thuy NTL, Thuy PT, Tung BT, Loc HT, Dang TTT, Ngoc LL, et al. A new flavone glycoside from Lumnitzera littorea with in vitro α-glucosidase inhibitory activity. Nat Prod Commun. 2019. https://doi.org/10.1177/1934578X19851361. [50] Choi CI, Lee SR, Kim KH. Antioxidant and α-glucosidase inhibitory activities of constituents from Euonymus alatus twigs. Ind Crops Prod. 2015;76:1055–60. https://doi.org/10.1016/j.indcrop.2015.08.031. [51] Uddin S, Brooks PR, Tran TD. Chemical characterization, α-glucosidase, α-amylase and lipase inhibitory properties of the Australian honey bee propolis. Foods. 2022;11(13):1964. https://doi.org/10.3390/foods11131964. [52] Tang H, Huang L, Sun C, Zhao D. Exploring the structure-activity relationship and interaction mechanism of flavonoids and alpha-glucosidase based on experimental analysis and molecular docking studies. Food Funct. 2020;11(4):3332–50. https://doi.org/10.1039/c9fo02806d. [53] Zhang X, Liu Z, Bi X, Liu J, Li W, Zhao Y. Flavonoids and its derivatives from Callistephus chinensis flowers and their inhibitory activities against α-glucosidase. EXCLI J. 2013;12:956–66. [54] Zhang Y, Xiao Z, Zhang X, Sun H. Hypoglycemic and hypolipidemic dual activities of extracts and flavonoids from Desmodium caudatum and an efficient synthesis of the most potent 8-prenylquercetin. Fitoterapia. 2022;156: 105083. https://doi.org/10.1016/j.fitote.2021.105083. [55] Fang HL, Liu ML, Li SY, Song WQ, Ouyang H, Xiao ZP, et al. Identification, potency evaluation, and mechanism clarification of alpha-glucosidase inhibitors from tender leaves of Lithocarpus polystachyus Rehd. Food Chem. 2022;371: 131128. https://doi.org/10.1016/j.foodchem.2021.131128. [56] Priscilla DH, Roy D, Suresh A, Kumar V, Thirumurugan K. Naringenin inhibits alpha-glucosidase activity: a promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats. Chem Biol Interact. 2014;210(1):77–85. https://doi.org/10.1016/j.cbi.2013.12.014. [57] Sun H, Wang D, Song X, Zhang Y, Ding W, Peng X, et al. Natural prenylchalconaringenins and prenylnaringenins as antidiabetic agents: alpha-glucosidase and alpha-amylase inhibition and in vivo antihyperglycemic and antihyperlipidemic effects. J Agric Food Chem. 2017;65(8):1574–81. https://doi.org/10.1021/acs.jafc.6b05445. [58] Qin NB, Jia CC, Xu J, Li DH, Xu FX, Bai J, et al. New amides from seeds of Silybum marianum with potential antioxidant and antidiabetic activities. Fitoterapia. 2017;119:83–9. https://doi.org/10.1016/j.fitote.2017.04.008. [59] Ren D, Meng FC, Liu H, Xiao T, Lu JJ, Lin LG, et al. Novel biflavonoids from Cephalotaxus oliveri Mast. Phytochem Lett. 2018;24:150–3. https://doi.org/10.1016/j.phytol.2018.02.005. [60] Zhang K, Ding Z, Duan W, Mo M, Su Z, Bi Y, et al. Optimized preparation process for naringenin and evaluation of its antioxidant and α-glucosidase inhibitory activities. J Food Process Preserv. 2020;44(12): e14931. https://doi.org/10.1111/jfpp.14931. [61] Xu J, Wang X, Yue J, Sun Y, Zhang X, Zhao Y. Polyphenols from Acorn leaves (Quercus liaotungensis) protect pancreatic beta cells and their inhibitory activity against α-glucosidase and protein tyrosine phosphatase 1B. Molecules. 2018;23(9):2167. https://doi.org/10.3390/molecules23092167. [62] Zhao BT, Duc Dat L, Phi Hung N, Ali MY, Choi J-S, Min BS, et al. PTP1B, alpha-glucosidase, and DPP-IV inhibitory effects for chromene derivatives from the leaves of Smilax china L. Chem Biol Interact. 2016;253:27–37. https://doi.org/10.1016/j.cbi.2016.04.012. [63] Nguyen TP, Le TD, Minh PN, Dat BT, Pham NKT, Do TML, et al. A new dihydrofurocoumarin from the fruits of Pandanus tectorius Parkinson ex Du Roi. Nat Prod Res. 2016;30(21):2389–95. https://doi.org/10.1080/14786419.2016.1188095. [64] Zhou Q, Lei X, Niu J, Chen Y, Shen X, Zhang N. A new hemiacetal chromone racemate and α-glucosidase inhibitors from Ficus tikoua Bur. Nat Prod Res. 2022. https://doi.org/10.1080/14786419.2022.2068544. [65] Jia Y, Ma Y, Cheng G, Zhang Y, Cai S. Comparative study of dietary flavonoids with different structures as alpha-glucosidase inhibitors and insulin sensitizers. J Agric Food Chem. 2019;67(37):10521–33. https://doi.org/10.1021/acs.jafc.9b04943. [66] Habtemariam S. The anti-obesity potential of sigmoidin A. Pharm Biol. 2012;50(12):1519–22. https://doi.org/10.3109/13880209.2012.688838. [67] Luyen NT, Tram LH, Hanh TTH, Binh PT, Dang NH, Van Minh C, et al. Inhibitors of a-glucosidase, a-amylase and lipase from Chrysanthemum morifolium. Phytochem Lett. 2013;6(3):322–5. https://doi.org/10.1016/j.phytol.2013.03.015. [68] Li K, Yao F, Xue Q, Fan H, Yang L, Li X, et al. Inhibitory effects against α-glucosidase and α-amylase of the flavonoids-rich extract from Scutellaria baicalensis shoots and interpretation of structure-activity relationship of its eight flavonoids by a refined assign-score method. Chem Cent J. 2018;12(1):82. https://doi.org/10.1186/s13065-018-0445-y. [69] Sahnoun M, Trabelsi S, Bejar S. Citrus flavonoids collectively dominate the α-amylase and α-glucosidase inhibitions. Biologia. 2017;72(7):764–73. https://doi.org/10.1515/biolog-2017-0091. [70] Kong F, Ding Z, Zhang K, Duan W, Qin Y, Su Z, et al. Optimization of extraction flavonoids from Exocarpium Citri Grandis and evaluation its hypoglycemic and hypolipidemic activities. J Ethnopharmacol. 2020;262: 113178. https://doi.org/10.1016/j.jep.2020.113178. [71] Taslimi P, Caglayan C, Gulcin I. The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and alpha-glycosidase enzymes: an antidiabetic, anticholinergic, and antiepileptic study. J Biochem Mol Toxicol. 2017;31(12): e21995. https://doi.org/10.1002/jbt.21995. [72] Qurtam AA, Mechchate H, Es-Safi I, Al-Zharani M, Nasr FA, Noman OM, et al. Citrus flavanone narirutin, in vitro and in silico mechanistic antidiabetic potential. Pharmaceutics. 2021;13(11):1818. https://doi.org/10.3390/pharmaceutics13111818. [73] Pyrzynska K. Hesperidin: a review on extraction methods, stability and biological activities. Nutrients. 2022;14(12):2387. https://doi.org/10.3390/nu14122387. [74] Zhao Y, Kongstad KT, Jager AK, Nielsen J, Staerk D. Quadruple high-resolution alpha-glucosidase/alpha-amylase/PTP1B/radical scavenging profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude root bark of Morus alba L. J Chromatogr A. 2018;1556:55–63. https://doi.org/10.1016/j.chroma.2018.04.041. [75] Bui TT, Nguyen KPT, Nguyen PPK, Le DT, Nguyen TLT. Anti-inflammatory and α-glucosidase inhibitory activities of chemical constituents from Bruguiera parviflora leaves. J Chem. 2022. https://doi.org/10.1155/2022/3049994. [76] Jing P, Xiaomin Y, Shujuan Z, Jun C, Yihai W, Chunyu L, et al. Bioactive phenolics from mango leaves (Mangifera indica L.). Ind Crops Prod. 2018;111:400–6. https://doi.org/10.1016/j.indcrop.2017.10.057. [77] Khalid MF, Rehman K, Irshad K, Chohan TA, Akash MSH. Biochemical investigation of inibitory activities of plant-derived bioactive compounds against carbohydrate and glucagon-like peptide-1 metabolizing enzymes. Dose-Response. 2022. https://doi.org/10.1177/15593258221093275. [78] Su H, Ruan YT, Li Y, Chen JG, Yin ZP, Zhang QF. In vitro and in vivo inhibitory activity of taxifolin on three digestive enzymes. Int J Biol Macromol. 2020;150:31–7. https://doi.org/10.1016/j.ijbiomac.2020.02.027. [79] Yoon KD, Lee JY, Kim TY, Kang H, Ha KS, Ham TH, et al. In vitro and in vivo anti-hyperglycemic activities of taxifolin and its derivatives isolated from pigmented rice (Oryzae sativa L. cv. Superhongmi). J Agric Food Chem. 2020;68(3):742–50. https://doi.org/10.1021/acs.jafc.9b04962. [80] Yang J, Li H, Wang X, Zhang C, Feng G, Peng X. Inhibition mechanism of alpha-amylase/alpha-glucosidase by silibinin, its synergism with acarbose, and the effect of milk proteins. J Agric Food Chem. 2021;69(36):10515–26. https://doi.org/10.1021/acs.jafc.1c01765. [81] Van Thanh B, Van Anh NT, Ha CTT, Giang DH, Lien TT, Tung NKT, et al. A new 2,3-dioxygenated flavanone and other constituents from Dysosma difformis. Rec Nat Prod. 2022;16(1):92–7. https://doi.org/10.25135/rnp.256.21.03.2017. [82] Wu S, Tian L. A new flavone glucoside together with known ellagitannins and flavones with anti-diabetic and anti-obesity activities from the flowers of pomegranate (Punica granatum). Nat Prod Res. 2019;33(2):252–7. https://doi.org/10.1080/14786419.2018.1446009. [83] Nguyen TTH, Nguyen VT, Van Cuong P, Nguyen Thanh T, Le Thi TA, Mai Huong DT, et al. A new flavonoid from the leaves of Garcinia mckeaniana Craib and α-glucosidase and acetylcholinesterase inhibitory activities. Nat Prod Res. 2021;36(19):5074–80. https://doi.org/10.1080/14786419.2021.1916019. [84] Chang CC, Ho SL, Lee SS. Acylated glucosylflavones as α-glucosidase inhibitors from Tinospora crispa leaf. Bioorg Med Chem. 2015;23(13):3388–96. https://doi.org/10.1016/j.bmc.2015.04.053. [85] Vi LNT, Tuan NN, Hung QT, Trinh PTN, Danh TT, Ly NT, et al. Alpha-glucosidase inhibitory activity of extracts and compounds from the leaves of Ruellia tuberosa L. Nat Prod J. 2022;12(5):63–8. https://doi.org/10.2174/2210315511666210218214955. [86] Choi CI, Eom HJ, Kim KH. Antioxidant and α-glucosidase inhibitory phenolic constituents of Lactuca indica L. Russ J Bioorganic Chem. 2016;42(3):310–5. https://doi.org/10.1134/S1068162016030079. [87] Fidelis QC, Faraone I, Russo D, Aragao 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(10):1500–3. https://doi.org/10.1080/14786419.2017.1419227. [88] Tian X, Guo S, Zhang S, Li P, Wang T, Ho CT, et al. Chemical characterization of main bioactive constituents in Paeonia ostii seed meal and GC-MS analysis of seed oil. J Food Biochem. 2020;44(1): e13088. https://doi.org/10.1111/jfbc.13088. [89] Nguyen DH, Le DD, Ma ES, Min BS, Woo MH. Development and validation of an HPLC-PDA method for quantitation of ten marker compounds from Eclipta prostrata (L.) and evaluation of their protein tyrosine phosphatase 1B, alpha-glucosidase, and acetylcholinesterase inhibitory activities. Nat Prod Sci. 2020;26(4):326–33. https://doi.org/10.20307/nps.2020.26.4.326. [90] Su ZR, Fan SY, Shi WG, Zhong BH. Discovery of xanthine oxidase inhibitors and/or α-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin. Bioorg Med Chem Lett. 2015;25(14):2778–81. https://doi.org/10.1016/j.bmcl.2015.05.016. [91] Li M, Bao X, Zhang X, Ren H, Cai S, Hu X, et al. Exploring the phytochemicals and inhibitory effects against α-glucosidase and dipeptidyl peptidase-IV in Chinese pickled chili pepper: insights into mechanisms by molecular docking analysis. LWT. 2022;162: 113467. https://doi.org/10.1016/j.lwt.2022.113467. [92] Dao TBN, Nguyen TMT, Nguyen VQ, Tran TMD, Tran NMA, Nguyen CH, et al. Flavones from Combretum quadrangulare growing in Vietnam and their alpha-glucosidase inhibitory activity. Molecules. 2021;26(9):2531. https://doi.org/10.3390/molecules26092531. [93] Abbasi MA, Hussain G, Aziz ur R, Ahmad VU. Flavonoids from Rhynchosia pseudo-cajan as suitable alpha-glucosidase inhibitors and free radical scavengers. Int Res J Pharm. 2014;5(8):636–41. https://doi.org/10.7897/2230-8407.0508130. [94] Proença C, Freitas M, Ribeiro D, Oliveira EFT, Sousa JLC, Tomé SM, et al. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study. J Enzyme Inhib Med Chem. 2017;32(1):1216–28. https://doi.org/10.1080/14756366.2017.1368503. [95] Duong TH, Nguyen HT, Nguyen CH, Tran NMA, Danova A, Tran TMD, et al. Identification of highly potent alpha-glucosidase inhibitors from Artocarpus integer and molecular docking studies. Chem Biodivers. 2021;18(12): e2100499. https://doi.org/10.1002/cbdv.202100499. [96] Assefa ST, Yang EY, Asamenew G, Kim HW, Cho MC, Lee J. Identification of α-glucosidase inhibitors from leaf extract of pepper (Capsicum spp.) through metabolomic analysis. Metabolites. 2021;11(10):649. https://doi.org/10.3390/metabo11100649. [97] Wang X, Yang J, Li H, Shi S, Peng X. Mechanistic study and synergistic effect on inhibition of α-amylase by structurally similar flavonoids. J Mol Liq. 2022;360: 119485. https://doi.org/10.1016/j.molliq.2022.119485. [98] Quan YS, Zhang XY, Yin XM, Wang SH, Jin LL. Potential alpha-glucosidase inhibitor from Hylotelephium erythrostictum. Bioorg Med Chem Lett. 2020;30(24): 127665. https://doi.org/10.1016/j.bmcl.2020.127665. [99] Lianwu X, Qiachi F, Shuyun S, Jiawei L, Xinji Z. Rapid and comprehensive profiling of alpha-glucosidase inhibitors in Buddleja Flos by ultrafiltration HPLC-QTOF-MS/MS with diagnostic ions filtering strategy. Food Chem. 2021;344:128651. https://doi.org/10.1016/j.foodchem.2020.128651. [100] Li H, Song F, Xing J, Tsao R, Liu Z, Liu S. Screening and structural characterization of α-glucosidase Inhibitors from Hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MSn and SORI-CID FTICR MS. J Am Soc Mass Spectrom. 2009;20(8):1496–503. https://doi.org/10.1016/j.jasms.2009.04.003. [101] Wu B, Song HP, Zhou X, Liu XG, Gao W, Dong X, et al. Screening of minor bioactive compounds from herbal medicines by in silico docking and the trace peak exposure methods. J Chromatogr A. 2016;1436:91–9. https://doi.org/10.1016/j.chroma.2016.01.062. [102] Wang YM, Zhao JQ, Yang JL, Tao YD, Mei LJ, Shi YP. Separation of antioxidant and alpha-glucosidase inhibitory flavonoids from the aerial parts of Asterothamnus centrali-asiaticus. Nat Prod Res. 2017;31(12):1365–9. https://doi.org/10.1080/14786419.2016.1247083. [103] Cheng N, Yi WB, Wang QQ, Peng SM, Zou XQ. Synthesis and α-glucosidase inhibitory activity of chrysin, diosmetin, apigenin, and luteolin derivatives. Chin Chem Lett. 2014;25(7):1094–8. https://doi.org/10.1016/j.cclet.2014.05.021. [104] Huang Q, Chen JJ, Pan Y, He XF, Wang Y, Zhang XM, et al. Chemical profiling and antidiabetic potency of Paeonia delavayi: comparison between different parts and constituents. J Pharm Biomed Anal. 2021;198: 113998. https://doi.org/10.1016/j.jpba.2021.113998. [105] Silva EL, Lobo JFR, Vinther JM, Borges RM, Staerk D. High-resolution alpha-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of anti-diabetic compounds in Eremanthus crotonoides (Asteraceae). Molecules. 2016;21(6):782. https://doi.org/10.3390/molecules21060782. [106] Vonia S, Hartati R, Insanu M. In vitro alpha-glucosidase inhibitory activity and the isolation of luteolin from the flower of Gymnanthemum amygdalinum (Delile) Sch. Bip ex Walp Molecules. 2022;27(7):2132. https://doi.org/10.3390/molecules27072132. [107] Djeujo FM, Ragazzi E, Urettini M, Sauro B, Cichero E, Tonelli M, et al. Magnolol and luteolin inhibition of alpha-glucosidase activity: kinetics and type of interaction detected by in vitro and in silico studies. Pharmaceuticals. 2022;15(2):205. https://doi.org/10.3390/ph15020205. [108] Yang Y, Gu L, Xiao Y, Liu Q, Hu H, Wang Z, et al. Rapid identification of α-glucosidase inhibitors from Phlomis tuberosa by sepbox chromatography and thin-layer chromatography bioautography. PLoS ONE. 2015;10(2): e0116922. https://doi.org/10.1371/journal.pone.0116922. [109] Ablat A, Halabi MF, Mohamad J, Hasnan MH, Hazni H, Teh SH, et al. Antidiabetic effects of Brucea javanica seeds in type 2 diabetic rats. BMC Complement Altern Med. 2017;17(1):94. https://doi.org/10.1186/s12906-017-1610-x. [110] Hlila MB, Majouli K, Ben Jannet H, Mastouri M, Aouni M, Selmi B. Antioxidant and anti alpha-glucosidase of luteolin and luteolin 7-O-glucoside isolated from Scabiosa arenaria Forssk. J Coast Life Med. 2017;5(7):317–20. https://doi.org/10.12980/jclm.5.2017J7-66. [111] Bo-wei Z, Xia L, Wen-long S, Yan X, Zhi-long X, Chun-lin Z, et al. Dietary flavonoids and acarbose synergistically inhibit alpha-glucosidase and lower postprandial blood glucose. J Agric Food Chem. 2017;65(38):8319–30. https://doi.org/10.1021/acs.jafc.7b02531. [112] Yan J, Zhang G, Pan J, Wang Y. α-Glucosidase inhibition by luteolin: kinetics, interaction and molecular docking. Int J Biol Macromol. 2014;64:213–23. https://doi.org/10.1016/j.ijbiomac.2013.12.007. [113] Kuroda M, Iwabuchi K, Mimaki Y. Chemical constituents of the aerial parts of Scutellaria lateriflora and their alpha-glucosidase inhibitory activities. Nat Prod Commun. 2012;7(4):471–4. https://doi.org/10.1177/1934578x1200700413. [114] Park MJ, Kang Y-H. Isolation of isocoumarins and flavonoids as α-glucosidase inhibitors from Agrimonia pilosa L. Molecules. 2020;25(11):2572. https://doi.org/10.3390/molecules25112572. [115] Matsui T, Kobayashi M, Hayashida S, Matsumoto K. Luteolin, a flavone, does not suppress postprandial glucose absorption through an inhibition of alpha-glucosidase action. Biosci Biotechnol Biochem. 2002;66(3):689–92. https://doi.org/10.1271/bbb.66.689. [116] Dej-Adisai S, Rais IR, Wattanapiromsakul C, Pitakbut T. Alpha-glucosidase inhibitory assay-screened isolation and molecular docking model from Bauhinia pulla active compounds. Molecules. 2021;26(19):5970. https://doi.org/10.3390/molecules26195970. [117] Lo Piparo E, Scheib H, Frei N, Williamson G, Grigorov M, Chou CJ. Flavonoids for controlling starch digestion: Structural requirements for inhibiting human alpha-amylase. J Med Chem. 2008;51(12):3555–61. https://doi.org/10.1021/jm800115x. [118] Xiao Z, Hou X, Zhang T, Yuan Y, Xiao J, Song W, et al. Starch-digesting product analysis based on the hydrophilic interaction liquid chromatography coupled mass spectrometry method to evaluate the inhibition of flavonoids on pancreatic α-amylase. Food Chem. 2022;372: 131175. https://doi.org/10.1016/j.foodchem.2021.131175. [119] Yang JR, Luo JG, Kong LY. Determination of α-glucosidase inhibitors from ScutScutellaria baicalensis using liquid chromatography with quadrupole time of flight tandem mass spectrometry coupled with centrifugal ultrafiltration. Chin J Nat Med. 2015;13(3):208–14. https://doi.org/10.1016/S1875-5364(15)30006-6. [120] Meesakul P, Richardson C, Pyne SG, Laphookhieo S. α-Glucosidase inhibitory flavonoids and oxepinones from the leaf and twig extracts of Desmos cochinchinensis. J Nat Prod. 2019;82(4):741–7. https://doi.org/10.1021/acs.jnatprod.8b00581. [121] Do LTM, Sichaem J. New flavonoid derivatives from Melodorum fruticosum and their α-glucosidase inhibitory and cytotoxic activities. Molecules. 2022;27(13):4023. https://doi.org/10.3390/molecules27134023. [122] Hari Babu T, Rama Subba Rao V, Tiwari AK, Suresh Babu K, Srinivas PV, Ali AZ, et al. Synthesis and biological evaluation of novel 8-aminomethylated oroxylin A analogues as alpha-glucosidase inhibitors. Bioorg Med Chem Lett. 2008;18(5):1659–62. https://doi.org/10.1016/j.bmcl.2008.01.055. [123] Kumar GS, Tiwari AK, Rao VRS, Prasad KR, Ali AZ, Babu KS. Synthesis and biological evaluation of novel benzyl-substituted flavones as free radical (DPPH) scavengers and-glucosidase inhibitors. J Asian Nat Prod Res. 2010;12(11):978–84. https://doi.org/10.1080/10286020.2010.511190. [124] Ha K-N, Nguyen T-V-A, Mai D-T, Tran N-M-A, Nguyen N-H, Vo GV, et al. Alpha-glucosidase inhibitors from Nervilia concolor, Tecoma stans, and Bouea macrophylla. Saudi J Biol Sci. 2022;29(2):1029–42. https://doi.org/10.1016/j.sjbs.2021.09.070. [125] Nickavar B, Abolhasani L. Bioactivity-guided separation of an α-amylase inhibitor flavonoid from Salvia virgata. Iran J Pharm Res. 2013;12(1):57–61. [126] Gao H, Kawabata J. Alpha-glucosidase inhibition of 6-hydroxyflavones. Part 3: synthesis and evaluation of 2,3,4-trihydroxybenzoyl-containing flavonoid analogs and 6-aminoflavones as alpha-glucosidase inhibitors. Bioorg Med Chem. 2005;13(5):1661–71. https://doi.org/10.1016/j.bmc.2004.12.010. [127] Nguyen MTT, Nguyen NT, Nguyen HX, Huynh TNN, Min BS. Screening of alpha-glucosidase inhibitory activity of Vietnamese medicinal plants: Isolation of active principles from Oroxylum indicum. Nat Prod Sci. 2012;18(1):47–51. [128] Gulcin I, Taslimi P, Aygun A, Sadeghian N, Bastem E, Kufrevioglu OI, et al. Antidiabetic and antiparasitic potentials: inhibition effects of some natural antioxidant compounds on alpha-glycosidase, alpha-amylase and human glutathione S-transferase enzymes. Int J Biol Macromol. 2018;119:741–6. https://doi.org/10.1016/j.ijbiomac.2018.08.001. [129] Uddin MJ, Faraone I, Haque MA, Rahman MM, Halim MA, Soennichsen FD, et al. Insights into the leaves of Ceriscoides campanulata: natural proanthocyanidins alleviate diabetes, inflammation, and esophageal squamous cell cancer via in vitro and in silico models. Fitoterapia. 2022;158: 105164. https://doi.org/10.1016/j.fitote.2022.105164. [130] Demir Y, Durmaz L, Taslimi P, Gulçin İ. Antidiabetic properties of dietary phenolic compounds: inhibition effects on α-amylase, aldose reductase, and α-glycosidase. Biotechnol Appl Biochem. 2019;66(5):781–6. https://doi.org/10.1002/bab.1781. [131] Sadasivam M, Kumarasamy C, Thangaraj A, Govindan M, Kasirajan G, Vijayan V, et al. Phytochemical constituents from dietary plant Citrus hystrix. Nat Prod Res. 2018;32(14):1721–6. https://doi.org/10.1080/14786419.2017.1399386. [132] Ha MT, Seong SH, Nguyen TD, Cho WK, Ah KJ, Ma JY, et al. Chalcone derivatives from the root bark of Morus alba L. act as inhibitors of PTP1B and α-glucosidase. Phytochemistry. 2018;155:114–25. https://doi.org/10.1016/j.phytochem.2018.08.001. [133] Kwon RH, Thaku N, Timalsina B, Park SE, Choi JS, Jung HA. Inhibition mechanism of components isolated from Morus alba branches on diabetes and diabetic complications via experimental and molecular docking analyses. Antioxidants. 2022;11(2):383. https://doi.org/10.3390/antiox11020383. [134] 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(9):1055–66. https://doi.org/10.4155/fmc-2017-0293. [135] Asghari B, Salehi P, Sonboli A, Ebrahimi SN. Flavonoids from Salvia chloroleuca with alpha-amylase and alpha-glucosidase inhibitory effect. Iran J Pharm Res. 2015;14(2):609–15. [136] Dubey K, Dubey R, Gupta R, Gupta A. Exploration of diosmin to control diabetes and its complications-an in vitro and in silico approach. Curr Comput Aided Drug Des. 2021;17(2):307–13. https://doi.org/10.2174/1573409916666200324135734. [137] Wu C, Shen J, He P, Chen Y, Li L, Zhang L, et al. The alpha-glucosidase inhibiting isoflavones isolated from Belamcanda chinensis leaf extract. Rec Nat Prod. 2012;6(2):110–20. [138] Sadeghi M, Miroliaei M, Ghanadian M. Inhibitory effect of flavonoid glycosides on digestive enzymes: In silico, in vitro, and in vivo studies. Int J Biol Macromol. 2022;217:714–30. https://doi.org/10.1016/j.ijbiomac.2022.07.086. [139] Proença C, Freitas M, Ribeiro D, Tomé SM, Oliveira EFT, Viegas MF, et al. Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure–activity relationship. J Enzyme Inhib Med Chem. 2019;34(1):577–88. https://doi.org/10.1080/14756366.2018.1558221. [140] Crozier A, Jaganath IB, Clifford MN. Phenols, polyphenols and tannins: an overview. In: Crozier A, Clifford MN, Ashihara H, editors. Plant secondary metabolites. United Kingdom: Blackwell Publishing; 2006. p. 1–24. [141] Liu Y, Zhan L, Xu C, Jiang H, Zhu C, Sun L, et al. α-Glucosidase inhibitors from Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit: molecular docking and interaction mechanism of flavonols with different B-ring hydroxylations. RSC Adv. 2020;10(49):29347–61. https://doi.org/10.1039/d0ra05015f. [142] Sun J, Dong S, Wu Y, Zhao H, Li X, Gao W. Inhibitor discovery from pomegranate rind for targeting human salivary alpha-amylase. Med Chem Res. 2018;27(6):1559–77. https://doi.org/10.1007/s00044-018-2164-2. [143] Phuong NH, Thuy NTL, Duc NT, Tuyet NTA, Mai NTT, Phung NKP. A new glycoside and in vitro evalution of alpha-glucosidase inhibitory activity of constituents of the mangrove Lumnitzera racemosa. Nat Prod Commun. 2017;12(11):1751–4. https://doi.org/10.1177/1934578x1701201125. [144] Habtemariam S. Alpha-glucosidase inhibitory activity of kaempferol-3-O-rutinoside. Nat Prod Commun. 2011;6(2):201–3. https://doi.org/10.1177/1934578x1100600211. [145] Wang Y, Xiang L, Wang C, Tang C, He X. Antidiabetic and antioxidant effects and phytochemicals of Mulberry fruit (Morus alba L.) polyphenol enhanced extract. PLoS ONE. 2013;8(7):e71144. https://doi.org/10.1371/journal.pone.0071144. [146] Vu NK, Kim CS, Ha MT, Ngo QT, Park SE, Kwon H, et al. Antioxidant and antidiabetic activities of flavonoid derivatives from the outer skins of Allium cepa L. J Agric Food Chem. 2020;68(33):8797–811. https://doi.org/10.1021/acs.jafc.0c02122. [147] Jibril S, Sirat HM, Basar N. Bioassay-guided isolation of antioxidants and alpha-glucosidase inhibitors from the root of Cassia sieberiana D.C. (Fabaceae). Rec Nat Prod. 2017;11(4):406–10. [148] Adhikari-Devkota A, Elbashir SMI, Watanabe T, Devkota HP. Chemical constituents from the flowers of Satsuma mandarin and their free radical scavenging and alpha-glucosidase inhibitory activities. Nat Prod Res. 2019;33(11):1670–3. https://doi.org/10.1080/14786419.2018.1425856. [149] Li YQ, Zhou FC, Gao F, Bian JS, Shan F. Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase. J Agric Food Chem. 2009;57(24):11463–8. https://doi.org/10.1021/jf903083h. [150] Lyu Q, Kuo T-H, Sun C, Chen K, Hsu C-C, Li X. Comprehensive structural characterization of phenolics in litchi pulp using tandem mass spectral molecular networking. Food Chem. 2019;282:9–17. https://doi.org/10.1016/j.foodchem.2019.01.001. [151] Praparatana R, Maliyam P, Barrows LR, Puttarak P. Flavonoids and phenols, the potential anti-diabetic compounds from Bauhinia strychnifolia Craib. stem. Molecules. 2022;27(8):2393. https://doi.org/10.3390/molecules27082393. [152] Devkota HP, Kurizaki A, Tsushiro K, Adhikari-Devkota A, Hori K, Wada M, et al. Flavonoids from the leaves and twigs of Lindera sericea (Seibold et Zucc.) Blume var. sericea (Lauraceae) from Japan and their bioactivities. Funct Foods Health Dis. 2021;11(1):34–43. https://doi.org/10.31989/ffhd.v11i1.769. [153] Manaharan T, Appleton D, Cheng HM, Palanisamy UD. Flavonoids isolated from Syzygium aqueum leaf extract as potential antihyperglycaemic agents. Food Chem. 2012;132(4):1802–7. https://doi.org/10.1016/j.foodchem.2011.11.147. [154] Shan-Shan Z, Niu-Niu Z, Sen G, Shao-Jing L, Yu-Fei H, Shiming L, et al. Glycosides and flavonoids from the extract of Pueraria thomsonii Benth leaf alleviate type 2 diabetes in high-fat diet plus streptozotocin-induced mice by modulating the gut microbiota. Food Funct. 2022;13(7):3931–45. https://doi.org/10.1039/d1fo04170c. [155] Jin DX, He JF, Zhang KQ, Luo XG, Zhang TC. α-Glucosidase inhibition action of major flavonoids identified from Hypericum attenuatum Choisy and their synergistic effects. Chem Biodivers. 2021;18(10): e2100244. https://doi.org/10.1002/cbdv.202100244. [156] Flores-Bocanegra L, Pérez-Vásquez A, Torres-Piedra M, Bye R, Linares E, Mata R. α-Glucosidase inhibitors from Vauquelinia corymbosa. Molecules. 2015;20(8):15330–42. https://doi.org/10.3390/molecules200815330. [157] Tasnuva ST, Qamar UA, Ghafoor K, Sahena F, Jahurul MHA, Rukshana AH, et al. α-glucosidase inhibitors isolated from Mimosa pudica L. Nat Prod Res. 2019;33(10):1495–9. https://doi.org/10.1080/14786419.2017.1419224. [158] Wang W, Xu H, Chen H, Tai K, Liu F, Gao Y. In vitro antioxidant, anti-diabetic and antilipemic potentials of quercetagetin extracted from marigold (Tagetes erecta L.) inflorescence residues. J Food Sci Technol. 2016;53(6):2614–24. https://doi.org/10.1007/s13197-016-2228-6. [159] Lian-Xin P, Li-Juan W, Qian Y, Gui-Hua C, Zhen-Dong Y, Zhu-Yun Y, et al. In vitro potential of flavonoids from tartary buckwheat on antioxidants activity and starch digestibility. Int J Food Sci Technol. 2019;54(6):2209–18. https://doi.org/10.1111/ijfs.14131. [160] Fang H, Peng Z, Hao-Yue W, Gang-Xiu C, Zhong-Wen X, Guan-Hu B. Inhibition of alpha-glucosidase and alpha-amylase by flavonoid glycosides from Lu’an GuaPian tea: molecular docking and interaction mechanism. Food Funct. 2018;9(8):4173–83. https://doi.org/10.1039/c8fo00562a. [161] Hyun TK, Eom SH, Kim JS. Molecular docking studies for discovery of plant-derived α-glucosidase inhibitors. Plant OMICS. 2014;7(3):166–70. [162] Li N, Zhu HT, Wang D, Zhang M, Yang CR, Zhang YJ. New flavoalkaloids with potent α-glucosidase and acetylcholinesterase inhibitory activities from Yunnan Black Tea ‘Jin-Ya’. J Agric Food Chem. 2020;68(30):7955–63. https://doi.org/10.1021/acs.jafc.0c02401. [163] Kim TH, Lee J, Kim HJ, Jo C. Plasma-induced degradation of quercetin associated with the enhancement of biological activities. J Agric Food Chem. 2017;65(32):6929–35. https://doi.org/10.1021/acs.jafc.7b00987. [164] Islam MN, Jung HA, Sohn HS, Kim HM, Choi JS. Potent alpha-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris. Arch Pharm Res. 2013;36(5):542–52. https://doi.org/10.1007/s12272-013-0069-7. [165] Arumugam B, Palanisamy UD, Chua KH, Kuppusamy UR. Potential antihyperglycaemic effect of myricetin derivatives from Syzygium malaccense. J Funct Foods. 2016;22:325–36. https://doi.org/10.1016/j.jff.2016.01.038. [166] Qu X, Li J, Yan P, Wang G, Liu W, Zeng Y, et al. Quercetin of Potentilla bifurca 3-glycosylation substitution impact the inhibitory activity on alpha-glucosidase. Pharmacogn Mag. 2022;18(78):458–62. https://doi.org/10.4103/pm.pm_522_21. [167] Wang L, Liu Y, Luo Y, Huang K, Wu Z. Quickly screening for potential α-glucosidase Inhibitors from Guava leaves tea by bioaffinity ultrafiltration coupled with HPLC-ESI-TOF/MS Method. J Agric Food Chem. 2018;66(6):1576–82. https://doi.org/10.1021/acs.jafc.7b05280. [168] Sun H, Li Y, Zhang X, Lei Y, Ding W, Zhao X, et al. Synthesis, α-glucosidase inhibitory and molecular docking studies of prenylated and geranylated flavones, isoflavones and chalcones. Bioorg Med Chem Lett. 2015;25(20):4567–71. https://doi.org/10.1016/j.bmcl.2015.08.059. [169] Liu Y, Wang R, Ren C, Pan Y, Li J, Zhao X, et al. Two myricetin-derived flavonols from Morella rubra leaves as potent alpha-glucosidase inhibitors and structure-activity relationship study by computational chemistry. Oxid Med Cell Longev. 2022;2022:9012943. https://doi.org/10.1155/2022/9012943. [170] Kashchenko NI, Chirikova NK, Olennikov DN. Acylated flavonoids from Spiraea genus as inhibitors of α-amylase. Russ J Bioorganic Chem. 2018;44(7):876–86. https://doi.org/10.1134/S1068162018070051. [171] Wang H, Du YJ, Song HC. Alpha-glucosidase and alpha-amylase inhibitory activities of Guava leaves. Food Chem. 2010;123(1):6–13. https://doi.org/10.1016/j.foodchem.2010.03.088. [172] Zhou Y, Jiang Q, Ma S, Zhou X. Effect of quercetin on the in vitro Tartary buckwheat starch digestibility. Int J Biol Macromol. 2021;183:818–30. https://doi.org/10.1016/j.ijbiomac.2021.05.013. [173] Nickavar B, Amin G. Enzyme assay guided isolation of an α-amylase inhibitor flavonoid from Vaccinium arctostaphylos leaves. Iran J Pharm Res. 2011;10(4):849–53. [174] Varghese GK, Bose LV, Habtemariam S. Antidiabetic components of Cassia alata leaves: identification through alpha-glucosidase inhibition studies. Pharm Biol. 2013;51(3):345–9. https://doi.org/10.3109/13880209.2012.729066. [175] Sohretoglu D, Sari S, Barut B, Ozel A. Discovery of potent alpha-glucosidase inhibitor flavonols: insights into mechanism of action through inhibition kinetics and docking simulations. Bioorg Chem. 2018;79:257–64. https://doi.org/10.1016/j.bioorg.2018.05.010. [176] Li R, Wang Q, Zhao M, Yang P, Hu X, Ouyang D. Flavonoid glycosides from seeds of Hippophae rhamnoides subsp. Sinensis with alpha-glucosidase inhibition activity. Fitoterapia. 2019;137: 104248. https://doi.org/10.1016/j.fitote.2019.104248. [177] Peng X, Zhang G, Liao Y, Gong D. Inhibitory kinetics and mechanism of kaempferol on alpha-glucosidase. Food Chem. 2016;190:207–15. https://doi.org/10.1016/j.foodchem.2015.05.088. [178] Ajish KR, Antu KA, Riya MP, Preetharani MR, Raghu KG, Dhanya BP, et al. Studies on alpha-glucosidase, aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith. Nat Prod Res. 2015;29(10):947–52. https://doi.org/10.1080/14786419.2014.956741. [179] Li S, Wang R, Hu X, Li C, Wang L. Bio-affinity ultra-filtration combined with HPLC-ESI-qTOF-MS/MS for screening potential α-glucosidase inhibitors from Cerasus humilis (Bge.) Sok. leaf-tea and in silico analysis. Food Chem. 2022;373:131528. https://doi.org/10.1016/j.foodchem.2021.131528. [180] Li Q, Zhang X, Cao J, Guo Z, Lou Y, Ding M, et al. Depside derivatives with anti-hepatic fibrosis and anti-diabetic activities from Impatiens balsamina L. flowers. Fitoterapia. 2015;105:234–9. https://doi.org/10.1016/j.fitote.2015.07.007. [181] Chen J, Wu Y, Zou J, Gao K. α-Glucosidase inhibition and antihyperglycemic activity of flavonoids from Ampelopsis grossedentata and the flavonoid derivatives. Bioorg Med Chem. 2016;24(7):1488–94. https://doi.org/10.1016/j.bmc.2016.02.018. [182] Li Z, Guowen Z, Suyun L, Deming G. Inhibitory mechanism of apigenin on alpha-glucosidase and synergy analysis of flavonoids. J Agric Food Chem. 2016;64(37):6939–49. https://doi.org/10.1021/acs.jafc.6b02314. [183] Yu Z, Jian-Nan MA, Chun-Li MA, Zhi QI, Chao-Mei MA. Simultaneous quantification of ten constituents of Xanthoceras sorbifolia Bunge using UHPLC-MS methods and evaluation of their radical scavenging, DNA scission protective, and α-glucosidase inhibitory activities. Chin J Nat Med. 2015;13(11):873–80. https://doi.org/10.3724/SP.J.1009.2015.00873. [184] Williams LK, Li C, Withers SG, Brayer GD. Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. J Med Chem. 2012;55(22):10177–86. https://doi.org/10.1021/jm301273u. [185] Yue Y, Chen Y, Geng S, Liang G, Liu B. Antioxidant and α-glucosidase inhibitory activities of fisetin. Nat Prod Commun. 2018;13(11):1489–92. https://doi.org/10.1177/1934578x1801301119. [186] Barber E, Houghton MJ, Williamson G. Flavonoids as human intestinal α-glucosidase inhibitors. Foods. 2021;10(8):1939. https://doi.org/10.3390/foods10081939. [187] Ahmed S, Al-Rehaily AJ, Alam P, Alqahtani AS, Hidayatullah S, Rehman MT, et al. Antidiabetic, antioxidant, molecular docking and HPTLC analysis of miquelianin isolated from Euphorbia schimperi C. Presl Saudi Pharm J. 2019;27(5):655–63. https://doi.org/10.1016/j.jsps.2019.03.008. [188] Renda G, Sari S, Barut B, Šoral M, Liptaj T, Korkmaz B, et al. α-Glucosidase inhibitory effects of polyphenols from Geranium asphodeloides: Inhibition kinetics and mechanistic insights through in vitro and in silico studies. Bioorg Chem. 2018;81:545–52. https://doi.org/10.1016/j.bioorg.2018.09.009. [189] Tao Y, Chen Z, Zhang Y, Wang Y, Cheng Y. Immobilized magnetic beads based multi-target affinity selection coupled with high performance liquid chromatography-mass spectrometry for screening anti-diabetic compounds from a Chinese medicine “Tang-Zhi-Qing.” J Pharm Biomed Anal. 2013;78:190–201. https://doi.org/10.1016/j.jpba.2013.02.024. [190] Escandon-Rivera S, Gonzalez-Andrade M, Bye R, Linares E, Navarrete A, Mata R. Alpha-glucosidase inhibitors from Brickellia cavanillesii. J Nat Prod. 2012;75(5):968–74. https://doi.org/10.1021/np300204p. [191] Olennikov DN, Kashchenko NI. Componential profile and amylase inhibiting activity of phenolic compounds from Calendula officinalis L. leaves. Sci World J. 2014;2014:654193. https://doi.org/10.1155/2014/654193. [192] Ye R, Fan YH, Ma CM. Identification and enrichment of alpha-glucosidase-inhibiting dihydrostilbene and flavonoids from Glycyrrhiza uralensis leaves. J Agric Food Chem. 2017;65(2):510–5. https://doi.org/10.1021/acs.jafc.6b04155. [193] Fan YH, Ye R, Xu HY, Feng XH, Ma CM. Structures and in vitro antihepatic fibrosis activities of prenylated dihydrostilbenes and flavonoids from Glycyrrhiza uralensis leaves. J Food Sci. 2019;84(5):1224–30. https://doi.org/10.1111/1750-3841.14592. [194] Ashraf J, Mughal EU, Sadiq A, Naeem N, Muhammad SA, Qousain T, et al. Design and synthesis of new flavonols as dual ɑ-amylase and ɑ-glucosidase inhibitors: structure-activity relationship, drug-likeness, in vitro and in silico studies. J Mol Struct. 2020;1218: 128458. https://doi.org/10.1016/j.molstruc.2020.128458. [195] Wan C, Yuan T, Cirello AL, Seeram NP. Antioxidant and α-glucosidase inhibitory phenolics isolated from highbush blueberry flowers. Food Chem. 2012;135(3):1929–37. https://doi.org/10.1016/j.foodchem.2012.06.056. [196] Zhang L, Tu ZC, Yuan T, Wang H, Xie X, Fu ZF. Antioxidants and α-glucosidase inhibitors from Ipomoea batatas leaves identified by bioassay-guided approach and structure-activity relationships. Food Chem. 2016;208:61–7. https://doi.org/10.1016/j.foodchem.2016.03.079. [197] Hong HC, Li SL, Zhang XQ, Ye WC, Zhang QW. Flavonoids with alpha-glucosidase inhibitory activities and their contents in the leaves of Morus atropurpurea. Chin Med. 2013;8(1):19. https://doi.org/10.1186/1749-8546-8-19. [198] López-Angulo G, Miranda-Soto V, López-Valenzuela JA, Montes-Avila J, Díaz-Camacho SP, Garzón-Tiznado JA, et al. α-Glucosidase inhibitory phenolics from Echeveria subrigida (B. L. Rob & Seaton) leaves. Nat Prod Res. 2022;36(4):1058–61. https://doi.org/10.1080/14786419.2020.1844695. [199] Monzón Daza G, Meneses Macías C, Forero AM, Rodríguez J, Aragón M, Jiménez C, et al. Identification of α-amylase and α-glucosidase inhibitors and ligularoside A, a new triterpenoid saponin from Passiflora ligularis Juss (Sweet Granadilla) Leaves, by a nuclear magnetic resonance-based metabolomic study. J Agric Food Chem. 2021;69(9):2919–31. https://doi.org/10.1021/acs.jafc.0c07850. [200] Zhang L, Tu ZC, Yuan T, Ma H, Niesen DB, Wang H, et al. New gallotannin and other phytochemicals from Sycamore Maple (Acer pseudoplatanus) leaves. Nat Prod Commun. 2015;10(11):1977–80. https://doi.org/10.1177/1934578x1501001143. [201] Nile A, Gansukh E, Park GS, Kim DH, Hariram NS. Novel insights on the multi-functional properties of flavonol glucosides from red onion (Allium cepa L) solid waste—in vitro and in silico approach. Food Chem. 2021;335: 127650. https://doi.org/10.1016/j.foodchem.2020.127650. [202] Tan C, Zuo J, Yi X, Wang P, Luo C, Hu Y, et al. Phenolic constituents from Sarcopyramis nepalensis and their α-glucosidase inhibitory activity. Afr J Tradit Complement Altern Med. 2015;12(3):156–60. https://doi.org/10.4314/ajtcam.v12i3.20. [203] Şöhretoğlu D, Sari S, Šoral M, Barut B, Özel A, Liptaj T. Potential of Potentilla inclinata and its polyphenolic compounds in α-glucosidase inhibition: kinetics and interaction mechanism merged with docking simulations. Int J Biol Macromol. 2018;108:81–7. https://doi.org/10.1016/j.ijbiomac.2017.11.151. [204] Braham N, Phi-Hung N, Bing-Tian Z, Quoc-Hung V, Byung Sun M, Mi HW. Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated from Agrimonia pilosa. Pharm Biol. 2016;54(3):474–80. https://doi.org/10.3109/13880209.2015.1048372. [205] Tao Y, Zhang Y, Cheng Y, Wang Y. Rapid screening and identification of α-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed Chromatogr. 2013;27(2):148–55. https://doi.org/10.1002/bmc.2761. [206] Marmouzi I, Ezzat SM, Mostafa ES, El Jemli M, Radwan RA, Faouzi MEA, et al. Isolation of secondary metabolites from the mediterranean sponge species; Hemimycale columella and its biological properties. SN Appl Sci. 2021;3(2):207. https://doi.org/10.1007/s42452-020-04052-8. [207] Zhang Y, Xiao G, Sun L, Wang Y, Wang Y, Wang Y. A new flavan-3-ol lactone and other constituents from Euonymus alatus with inhibitory activities on a-glucosidase and differentiation of 3T3-L1 cells. Nat Prod Res. 2013;27(17):1513–20. https://doi.org/10.1080/14786419.2012.725400. [208] Fan P, Terrier L, Hay AE, Marston A, Hostettmann K. Antioxidant and enzyme inhibition activities and chemical profiles of Polygonum sachalinensis F.Schmidt ex Maxim (Polygonaceae). Fitoterapia. 2010;81(2):124–31. https://doi.org/10.1016/j.fitote.2009.08.019. [209] Yan S, Zhang X, Wen X, Lv Q, Xu C, Sun C, et al. Purification of flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) fruit extracts and alpha-glucosidase inhibitory activities of different fractionations. Molecules. 2016;21(9):1148. https://doi.org/10.3390/molecules21091148. [210] Sheliya MA, Rayhana B, Ali A, Pillai KK, Aeri V, Sharma M, et al. Inhibition of alpha-glucosidase by new prenylated flavonoids from Euphorbia hirta L. herb. J Ethnopharmacol. 2015;176:1–8. https://doi.org/10.1016/j.jep.2015.10.018. [211] Anh LTT, Son NT, Van Tuyen N, Thuy PT, Quan PM, Ha NTT, et al. Antioxidative and α-glucosidase inhibitory constituents of Polyscias guilfoylei: experimental and computational assessments. Mol Divers. 2022;26(1):229–43. https://doi.org/10.1007/s11030-021-10206-6. [212] Lee HE, Kim JA, Whang WK. Chemical constituents of Smilax china L. stems and their inhibitory activities against glycation, aldose reductase, alpha-glucosidase, and lipase. Molecules. 2017;22(3):451. https://doi.org/10.3390/molecules22030451. [213] Parveen A, Farooq MA, Kyunn WW. A new oleanane type saponin from the aerial parts of Nigella sativa with anti-oxidant and anti-diabetic potential. Molecules. 2020;25(9):2171. https://doi.org/10.3390/molecules25092171. [214] Astiti MA, Jittmittraphap A, Leaungwutiwong P, Chutiwitoonchai N, Pripdeevech P, Mahidol C, et al. LC-QTOF-MS/MS based molecular networking approach for the isolation of α-glucosidase inhibitors and virucidal agents from Coccinia grandis (L.) voigt. Foods. 2021;10(12):3041. https://doi.org/10.3390/foods10123041. [215] Tan C, Wang Q, Luo C, Chen S, Li Q, Li P. Yeast alpha-glucosidase inhibitory phenolic compounds isolated from Gynura medica leaf. Int J Mol Sci. 2013;14(2):2551–8. https://doi.org/10.3390/ijms14022551. [216] Swilam N, Nawwar MAM, Radwan RA, Mostafa ES. Antidiabetic activity and in silico molecular docking of polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: structure elucidation of undescribed acylated flavonol diglucoside. Plants. 2022;11(3):452. https://doi.org/10.3390/plants11030452. [217] Yoshikawa M, Shimada H, Nishida N, Li Y, Toguchida I, Yamahara J, et al. Antidiabetic principles of natural medicines. Li. Aldose reductase and α-glucosidase inhibitors from brazilian natural medicine, the leaves of Myrcia multiflora DC. (Myrtaceae): structures of myrciacitrins I and II and myrciaphenones A and B. Chem Pharm Bull (Tokyo). 1998;46(1):113–9. https://doi.org/10.1248/cpb.46.113. [218] Oueslati MH, Bouajila J, Guetat A, Al-Gamdi F, Hichri F. Cytotoxic, alpha-glucosidase, and antioxidant activities of flavonoid glycosides isolated from flowers of Lotus lanuginosus Vent. (Fabaceae). Pharmacogn Mag. 2020;16(68):22–7. https://doi.org/10.4103/pm.pm_232_19. [219] Chen YG, Li P, Li P, Yan R, Zhang XQ, Wang Y, et al. α-glucosidase inhibitory effect and simultaneous quantification of three major flavonoid glycosides in Microctis folium. Molecules. 2013;18(4):4221–32. https://doi.org/10.3390/molecules18044221. [220] Chen JG, Wu SF, Zhang QF, Yin ZP, Zhang L. α-Glucosidase inhibitory effect of anthocyanins from Cinnamomum camphora fruit: inhibition kinetics and mechanistic insights through in vitro and in silico studies. Int J Biol Macromol. 2020;143:696–703. https://doi.org/10.1016/j.ijbiomac.2019.09.091. [221] Akkarachiyasit S, Charoenlertkul P, Yibchok-Anun S, Adisakwattana S. Inhibitory activities of cyanidin and its glycosides and synergistic effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase. Int J Mol Sci. 2010;11(9):3387–96. https://doi.org/10.3390/ijms11093387. [222] Ho GT, Kase ET, Wangensteen H, Barsett H. Phenolic Elderberry extracts, anthocyanins, procyanidins, and metabolites influence glucose and fatty acid uptake in human skeletal muscle cells. J Agric Food Chem. 2017;65(13):2677–85. https://doi.org/10.1021/acs.jafc.6b05582. [223] Kim JH, Kim HY, Jin CH. Mechanistic investigation of anthocyanidin derivatives as alpha-glucosidase inhibitors. Bioorg Chem. 2019;87:803–9. https://doi.org/10.1016/j.bioorg.2019.01.033. [224] Xu Y, Xie L, Xie J, Liu Y, Chen W. Pelargonidin-3-O-rutinoside as a novel α-glucosidase inhibitor for improving postprandial hyperglycemia. Chem Commun (Camb). 2018;55(1):39–42. https://doi.org/10.1039/c8cc07985d. [225] Homoki JR, Nemes A, Fazekas E, Gyémánt G, Balogh P, Gál F, et al. Anthocyanin composition, antioxidant efficiency, and α-amylase inhibitor activity of different Hungarian sour cherry varieties (Prunus cerasus L.). Food Chem. 2016;194:222–9. https://doi.org/10.1016/j.foodchem.2015.07.130. [226] Nickavar B, Amin G. Bioassay-guided separation of an alpha-amylase inhibitor anthocyanin from Vaccinium arctostaphylos berries. Z Naturforsch C J Biosci. 2010;65(9):567–70. https://doi.org/10.1515/znc-2010-9-1006. [227] Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z. Chalcone: a privileged structure in medicinal chemistry. Chem Rev. 2017;117(12):7762–810. https://doi.org/10.1021/acs.chemrev.7b00020. [228] Tran T-D, Nguyen T-T-N, Do T-H, Huynh T-N-P, Tran C-D, Thai K-M. Synthesis and antibacterial activity of some heterocyclic chalcone analogues alone and in combination with antibiotics. Molecules. 2012;17(6):6684–96. https://doi.org/10.3390/molecules17066684. [229] Rocha S, Sousa A, Ribeiro D, Correia CM, Silva VLM, Santos CMM, et al. A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives. Food Funct. 2019;10(9):5510–20. https://doi.org/10.1039/c9fo01298b. [230] Saleem F, Kanwal, Khan KM, Chigurupati S, Solangi M, Nemala AR, et al. Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies. Bioorg Chem. 2021;106:104489. https://doi.org/10.1016/j.bioorg.2020.104489. [231] Mphahlele MJ, Agbo EN, Choong YS. Synthesis, structure, carbohydrate enzyme inhibition, antioxidant activity, in silico drug-receptor interactions and drug-like profiling of the 5-styryl-2-aminochalcone Hybrids. Molecules. 2021;26(9):2692. https://doi.org/10.3390/molecules26092692. [232] Şöhretoğlu D, Sari S, Özel A, Barut B. α-Glucosidase inhibitory effect of Potentilla astracanica and some isoflavones: inhibition kinetics and mechanistic insights through in vitro and in silico studies. Int J Biol Macromol. 2017;105:1062–70. https://doi.org/10.1016/j.ijbiomac.2017.07.132. [233] Ha LM, Luyen NT, Phuong NT, Huyen DTT, Huong LM, Quan PM, et al. Isoflavonoids from Desmodium heterophyllum aerial parts. Nat Prod Commun. 2018;13(6):699–700. https://doi.org/10.1177/1934578x1801300612. [234] Seong SH, Roy A, Jung HA, Jung HJ, Choi JS. Protein tyrosine phosphatase 1B and alpha-glucosidase inhibitory activities of Pueraria lobata root and its constituents. J Ethnopharmacol. 2016;194:706–16. https://doi.org/10.1016/j.jep.2016.10.007. [235] Jiang W, Kan H, Li P, Liu S, Liu Z. Screening and structural characterization of potential α-glucosidase inhibitors from Radix Astragali flavonoids extract by ultrafiltration LC-DAD-ESI-MSn. Anal Methods. 2015;7(1):123–8. https://doi.org/10.1039/c4ay02081b. [236] Jeong SY, Nguyen PH, Zhao BT, Ali MY, Choi JS, Min BS, et al. Chemical constituents of Euonymus alatus (Thunb.) Sieb. and their PTP1B and alpha-glucosidase inhibitory activities. Phytother Res. 2015;29(10):1540–8. https://doi.org/10.1002/ptr.5411. [237] Yue T, Sheng Q, Luo Y, Xiao Z, Wang Y, Song W, et al. Biflavonoids and oligomeric flavonoids from food. In: Xiao J, Sarker SD, Asakawa Y, editors., et al., Handbook of dietary phytochemicals. Singapore: Springer Singapore; 2021. p. 155–203. [238] Laishram S, Sheikh Y, Moirangthem DS, Deb L, Pal BC, Talukdar NC, et al. Anti-diabetic molecules from Cycas pectinata Griff. traditionally used by the Maiba-Maibi. Phytomedicine. 2015;22(1):23–6. https://doi.org/10.1016/j.phymed.2014.10.007. [239] Keskes H, Belhadj S, Jlail L, El Feki A, Damak M, Sayadi S, et al. LC-MS-MS and GC-MS analyses of biologically active extracts and fractions from tunisian Juniperus phoenice leaves. Pharm Biol. 2017;55(1):88–95. https://doi.org/10.1080/13880209.2016.1230139. [240] Faggion CM Jr. Guidelines for reporting pre-clinical in vitro studies on dental materials. J Evid Based Dent Pract. 2012;12(4):182–9. https://doi.org/10.1016/j.jebdp.2012.10.001. [241] Silva JP, Coelho A, Paula A, Amaro I, Saraiva J, Ferreira MM, et al. The influence of irrigation during the finishing and polishing of composite resin restorations—a systematic review of in vitro studies. Materials. 2021;14(7):1675. https://doi.org/10.3390/ma14071675. [242] Li C, Begum A, Numao S, Park KH, Withers SG, Brayer GD. Acarbose rearrangement mechanism implied by the kinetic and structural analysis of human pancreatic α-amylase in complex with analogues and their elongated counterparts. Biochemistry. 2005;44(9):3347–57. https://doi.org/10.1021/bi048334e. [243] Williams LK, Zhang X, Caner S, Tysoe C, Nguyen NT, Wicki J, et al. The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif. Nat Chem Biol. 2015;11(9):691–6. https://doi.org/10.1038/nchembio.1865. [244] Tysoe CR, Caner S, Calvert MB, Win-Mason A, Brayer GD, Withers SG. Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase. Chem Sci. 2019;10(48):11073–7. https://doi.org/10.1039/C9SC02610J. [245] Pyner A, Nyambe-Silavwe H, Williamson G. Inhibition of human and rat sucrase and maltase activities to assess antiglycemic potential: optimization of the assay using acarbose and polyphenols. J Agric Food Chem. 2017;65(39):8643–51. https://doi.org/10.1021/acs.jafc.7b03678. [246] Lim J, Ferruzzi MG, Hamaker BR. Structural requirements of flavonoids for the selective inhibition of α-amylase versus α-glucosidase. Food Chem. 2022;370: 130981. https://doi.org/10.1016/j.foodchem.2021.130981. [247] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71. https://doi.org/10.1136/bmj.n71.

Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Xiaoxia Gu, Xiaotian Zhang, Xueke Zhang, Xinyu Wang, Weiguang Sun, Yonghui Zhang, Zhengxi Hu. Unveiling the mechanism of action of a novel natural dual inhibitor of SARS-CoV-2 Mpro and PLpro with molecular dynamics simulations [J]. Natural Products and Bioprospecting, 2025, 15(1): 3-3.
[2]	María I. Osella, Mario O. Salazar, Carlos M. Solís, Ricardo L. E. Furlan. New semisynthetic α-glucosidase inhibitor from a doubly-chemically engineered extract [J]. Natural Products and Bioprospecting, 2025, 15(1): 4-4.
[3]	Ya-Ya Yang, Shun-Li Jing, Jia-Li Shao, Ji-Xuan Chen, Wei-Feng Zhang, Si-Yuan Wan, Yu-Ping Shen, Huan Yang, Wei Yu. Purification and immobilization of β-glucosidase using surface modified mesoporous silica Santa Barbara Amorphous 15 for eco-friendly preparation of sagittatoside A [J]. Natural Products and Bioprospecting, 2024, 14(6): 50-50.
[4]	Qiantong Liu, Yanyun Liu, Tingting Liu, Jinbao Fan, Zanxian Xia, Yingjun Zhou, Xu Deng. Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments [J]. Natural Products and Bioprospecting, 2024, 14(6): 55-55.
[5]	Ismail Ware, Katrin Franke, Andrej Frolov, Kseniia Bureiko, Elana Kysil, Maizatulakmal Yahayu, Hesham Ali El Enshasy, Ludger A. Wessjohann. Comparative metabolite analysis of Piper sarmentosum organs approached by LC-MS-based metabolic profiling [J]. Natural Products and Bioprospecting, 2024, 14(4): 30-30.
[6]	Shi-Hui Qin, Zhi-Lan Li, Liu Yang, Jiang-Miao Hu. Gastrodinol derivatives and prenylated flavones from the flower branch of Gastrodia elata [J]. Natural Products and Bioprospecting, 2024, 14(3): 22-22.
[7]	Shi-Yan Feng, Na Jiang, Jia-Ying Yang, Lin-Yao Yang, Jiang-Chao Du, Xuan-Qin Chen, Dan Liu, Rong-Tao Li, Jin-Dong Zhong. Antiviral and anti-inflammatory activities of chemical constituents from twigs of Mosla chinensis Maxim [J]. Natural Products and Bioprospecting, 2024, 14(3): 26-26.
[8]	Chunsong Hu. Marine natural products and human immunity: novel biomedical resources for anti-infection of SARS-CoV-2 and related cardiovascular disease [J]. Natural Products and Bioprospecting, 2024, 14(2): 2-2.
[9]	Jin-Ning Chu, Premanand Krishnan, Kuan-Hon Lim. A comprehensive review on the chemical constituents, sesquiterpenoid biosynthesis and biological activities of Sarcandra glabra [J]. Natural Products and Bioprospecting, 2023, 13(6): 53-53.
[10]	Luan Wen, Zhou-Wei Wu, Li-Wu Lin, Abdulbaset Al-Romaima, Xing-Rong Peng, Ming-Hua Qiu. Structural characterizations and α-glucosidase inhibitory activities of four Lepidium meyenii polysaccharides with different molecular weights [J]. Natural Products and Bioprospecting, 2023, 13(3): 18-18.
[11]	Prabhakar Semwal, Abdur Rauf, Ahmed Olatunde, Pooja Singh, Mohamed Y. Zaky, Md. Mozahidul Islam, Anees Ahmed Khalil, Abdullah S. M. Aljohani, Waleed Al Abdulmonem, Giovanni Ribaudo. The medicinal chemistry of Urtica dioica L.: from preliminary evidence to clinical studies supporting its neuroprotective activity [J]. Natural Products and Bioprospecting, 2023, 13(3): 16-16.
[12]	Willy Cely-Veloza, Lydia Yamaguchi, Diego Quiroga, Massuo J. Kato, Ericsson Coy-Barrera. Antifungal activity against Fusarium oxysporum of quinolizidines isolated from three controlled-growth Genisteae plants: structure–activity relationship implications [J]. Natural Products and Bioprospecting, 2023, 13(2): 9-9.
[13]	Yang, Li Zhu, Li Deng, Yu Tang, Xian, Zhe Fan, Yang Han, Mei Pan, Li, Jun Zhang, and Hai, Bing Liao. New polychlorinated bibenzyls from Rhododendron minutiflorum [J]. Natural Products and Bioprospecting, 2023, 13(1): 2-2.
[14]	Hong-Xing Liu, Jun-Zeng Ma, Yan-Song Ye, Jian-Jun Zhao, Shi-Jie Wan, Xin-Yue Hu, Gang Xu. α-Glucosidase inhibitive diarylheptanoids from Ottelia acuminata var. acuminata, a traditional vegetable of Bai Nationality in Yunnan [J]. Natural Products and Bioprospecting, 2022, 12(4): 22-22.
[15]	Wenting Liu, Weikang Zheng, Liping Cheng, Ming Li, Jie Huang, Shuzheng Bao, Qiang Xu, Zhaocheng Ma. Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2 [J]. Natural Products and Bioprospecting, 2022, 12(1): 1-10.