Kaempferol from Medicinal Plants: A Comprehensive Review of its Anti-Diabetic Effects

Document Type : Full Issue File

Authors

1 College of Nursing, Al-Bayan University, Baghdad, Iraq

2 Department of Psychiatric and mental health Nursing, College of Nursing, University of Baghdad, Baghdad, Iraq

3 Department of Nursing, Al-kut university college, Iraq

4 Department of Adult Nursing, College of Nursing, University of Baghdad, Iraq

5 Ibn Khaldun Private University College, Baghdad, Iraq

6 Department of Nursing, Ferdows Faculty of Medical Sciences, Birjand University of Medical Sciences, Birjand, Iran

7 Ferdows Rasoul Hospital ,Birjand University of Medical Sciences ,Ferdows ,Iran

Abstract

Due to the high prevalence of diabetes and the promising effects of Kaempferol, this review assesses its molecular, cellular, and metabolic effects relevant to diabetes. A comprehensive search of PubMed, Scopus, Web of Science, Science Direct, and Google Scholar was conducted for articles published between 2010 and 2023 using relevant keywords. Kaempferol modulates glucose metabolism, enhances hepatic enzyme activity, and improves lipid profiles through multiple mechanisms. Specifically, it protects pancreatic β-cells by inhibiting apoptosis, promoting proliferation, and increasing their number, which is valuable in preventing and treating type 2 Diabetes Mellitus. Studies show that kaempferol reduces serum HbA1c levels (by an average of 20% if used for more than six months (and fasting blood glucose while increasing insulin sensitivity. Oral administration of kaempferol (5 mg/kg) reduced blood glucose levels as compared to metformin (50 mg/kg), while it does not have the harmful effects of metformin and other medications. Meanwhile, another therapeutic difference between Kaempferol is that, compared to other supplements and medications, it has positive effects on other systems of the body rather than destructive and negative effects, including on the liver and kidney systems. However, effects on weight vary across studies, possibly due to differences in dosage and study duration. Kaempferol also plays a multi-target role in diabetic nephropathy therapy, primarily via anti-oxidative stress and anti-inflammatory effects. Further clinical trials are needed to clarify conflicting results and fully establish its therapeutic potential in diabetes management.

Keywords

Main Subjects

References

  1. Talebi Mehrdar M., Ebadi G. Increased levels of serum Adenosine deaminase (ADA) enzyme and increased risk of T cell activation markers in type 2 diabetes. Cellular, Molecular and Biomedical Reports. 2024;4(3): 159-167. doi: 10.55705/cmbr.2023.423332.1186
  2. Teo Z.L., Tham Y-C., Yu M., Chee M.L., Rim TH., Cheung N., et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580-91.
  3. Corcóstegui B., Durán S., González-Albarrán M.O., Hernández C., Ruiz-Moreno J.M., Salvador J., et al. Update on diagnosis and treatment of diabetic retinopathy: a consensus guideline of the working group of ocular health (Spanish Society of Diabetes and Spanish Vitreous and Retina Society). Journal of Ophthalmology; 2017; (1):1-10.
  4. Lima V.C., Cavalieri G.C., Lima M.C., Nazario N.O., Lima G.C. Risk factors for diabetic retinopathy: a case–control study. International Journal of Retina And Vitreous. 2016;2(1):1-7.
  5. Moghimi H., Borzouei S., Zamani A., Behzad M. Evaluation of the Effect of Empagliflozin Therapy on T Helper 22 Cell-Related Factors in Patients with Type 2 Diabetes Mellitus. Avicenna Journal of Clinical Medicine. 2021;27(4):193-200.
  6. Williams E.D., Bird  D.,  Forbes  A.W.,  Russell  A.,  Ash  S.,  Friedman  R.,  et  al.  Randomised  controlled trial  of  an  automated,  interactive  telephone  intervention  (TLC  Diabetes)  to  improve  type  2 diabetes  management:  baseline  findings  and  six-month  outcomes.  BMC  Public  Health. 2012;12(1):602.
  7. Kleinridders A., Ferris H.A., Cai W., Kahn C.R. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014;63(7):2232-43.
  8. Wong F.K.Y., Mok M.PH., Chan T., Tsang M.W. Nurse follow-up of patients with diabetes: randomized controlled trial. Journal of Advanced Nursing. 2005;50(4):391-402.
  9. Khan R.A., Hossain R., Siyadatpanah A., Al-Khafaji K., Khalipha A.B.R., Dey D., Asha U.H., Biswas P., Saikat A.S.M., Chenari H.A., Wilairatana P., Islam M.T. Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study. Molecules. 2021;26(22):6821

10.Bain S.C., Klufas M.A., Ho A., Matthews D.R. Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review. Diabetes, Obesity and Metabolism. 2019;21(3):454-66.

  1. Dale J., Caramlau I., Sturt J., Friede T., Walker R. Telephone peer-delivered intervention for diabetes motivation and support: the telecare exploratory RCT. Patient Education and Counseling. 2009;75(1):91-8.
  2. Naserrudin N.A., Jeffree M.S., Kaur N., Syed Abdul Rahim S.S., Ibrahim M.Y. Diabetic retinopathy among type 2 diabetes mellitus patients in Sabah primary health clinics–Addressing the underlying factors. PLOS ONE. 2022;17(1):1-11.
  3. Ghavami H., Ahmadi F., Mehin S., Meamarian R., Entezami H. Assessment of the relation between diabetic neuropathy & HbA1C concentration. Razi Journal of Medical Sciences. 2007;13(53):141-7.
  4. Riazi H., Larijani B., Langarizadeh M., Shahmoradi L. Managing diabetes mellitus using information technology: a systematic review. Journal of Diabetes & Metabolic Disorders. 2015;14(1):49.
  5. Fan Y.P., Wu C.T., Lin J.L., Hsiung C.A., Liu H.Y., Lai J.N., et al. Metformin Treatment Is Associated with a Decreased Risk of Nonproliferative Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study. J Diabetes Res. 2020;4(3):12-1.
  6. Shureshi, P., Ahmadi Chenari, H., Ahmadi, M., Jesmi, A. A. Effect of Education by Lecture and Pamphlet Methods on Soldiers Knowledge about Meningitis Disease. Journal of Military Medicine. 2022; 17(3): 181-186.
  7. Rastgoo Haghi A., Seifrabiei M.A. Correlation between the Mean Platelet Volume and Blood Glucose Levels in Patients with Type 2 Diabetes Mellitus. Avicenna Journal of Clinical Medicine. 2017; 24 (2).
  8. Schernthaner G., Gross J.L., Rosenstock J., Guarisco M., Fu M., Yee J., Kawaguchi M., Canovatchel W., Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013;36(9):2508-15.
  9. Da Rocha R.B., Silva C.S., Cardoso V.S. Self-Care in Adults with Type 2 Diabetes Mellitus: A Systematic Review. Curr Diabetes Rev. 2020;16(6):598-607.
  10. Al-Numair K.S., Chandramohan G., Veeramani C., Alsaif M.A. Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats. Redox Report. 2015;20(5):198-209
  11. Alkhalidy H., Moore W., Wang A., Luo J., McMillan R.P., Wang Y., Zhen W., Hulver M.W., Liu D. Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice. Journal of Nutritional Biochemistry. 2018;58:90-101.
  12. Alkandahri M.Y., Pamungkas B.T., Oktoba Z., Shafirany M.Z., Sulastri L., Arfania M., Anggraeny E.N., Pratiwi A., Astuti F.D., Indriyani Dewi S.Y., Hamidah S.Z. Hepatoprotective Effect of Kaempferol: A Review of the Dietary Sources, Bioavailability, Mechanisms of Action, and Safety. Advances in Pharmacological and Pharmaceutical Sciences. 2023 27;2023:1387665
  13. Ali M.M., Agha F.G. Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. Scandinavian Journal of Clinical and Laboratory Investigation. 2009;69:371–9
  14. Ojochenemi Ejeh Y., Chinedu I., Christopher SH., John A. Ameh Daniel Simon: Effects of Ethanolic Leaf and Stem-bark Extracts of Adansonia digitata in Alloxan-induced Diabetic Wistar Rats. Journal of Pharmacology and Toxicology. 2020; 15: 1.
  15. Yang Y., Chen Z., Zhao X., Xie H., Du L., Gao H., et al. Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review. Frontiers in Endocrinology. 2022;13.
  16. Hu Q., Qu C., Xiao X., Zhang W., Jiang Y., Wu Z., Song D., Peng X., Ma X., Zhao Y. Flavonoids on diabetic nephropathy: advances and therapeutic opportunities. Chinese Medicine. 2021;16(1):74.
  17. Bermont F., Hermant A., Benninga R., Chabert C., Jacot G., Santo-Domingo J., Kraus M.R., Feige J.N., De Marchi U. Targeting Mitochondrial Calcium Uptake with the Natural Flavonol Kaempferol, to Promote Metabolism/Secretion Coupling in Pancreatic β-cells. Nutrients. 2020;12(2):538
  18. Mohan S., Nandhakumar L. Role of various flavonoids: Hypotheses on novel approach to treat diabetes. Journal of Medical Hypotheses and Ideas. 2014;8(1):1-6.
  19. Bai L., Li X., He L., Zheng Y., Lu H., Li J., Zhong L., Tong R., Jiang Z., Shi J., Li J. Antidiabetic Potential of Flavonoids from Traditional Chinese Medicine: A Review. The American Journal of Chinese Medicine. 2019;47(5):933-957.
  20. Ren J., Lu Y., Qian Y., Chen B., Wu T., Ji G. Recent progress regarding kaempferol for the treatment of various diseases. Experimental and Therapeutic Medicine. 2019;18(4):2759-2776.
  21. Wronka M., Krzemińska J., Młynarska E., Rysz J., Franczyk B. The Influence of Lifestyle and Treatment on Oxidative Stress and Inflammation in Diabetes. International Journal of Molecular Sciences. 2022; 23(24):15743
  22. Al-Ishaq R.K., 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 1;9(9):430.
  23. Jesus A.R., Vila-Viçosa D., Machuqueiro M., Marques A.P., Dore T.M., Rauter A.P. Targeting Type 2 Diabetes with C-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation. Journal of Medicinal Chemistry. 2017;60(2):568-579.
  24. Luo C., Yang H., Tang C., Yao G., Kong L., He H., Zhou Y. Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats. International Immunopharmacology. 2015;28(1):744-50
  25. Fang X.K., Gao J., D.N. Zhu. Kaempferol and quercetin isolated from Euonymus Alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity. Life Sciences. 82: 615–622, 2008.
  26. Khoubnasabjafari M., Ansarin K., Jouyban A. Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders. Bioimpacts. 2015;5(3):123-127.
  27. Suh K.S., Choi E.M., Kwon M., et al. Kaempferol attenuates 2-deoxy-d-ribose-induced oxidative cell damage in MC3T3-E1 osteoblastic cells. Biological and Pharmaceutical Bulletin. 2009;32(4):746-749.
  28. Ghorbani A., Rashidi R., Shafiee-Nick R. Flavonoids for preserving pancreatic beta cell survival and function: A mechanistic review. Biomedicine & Pharmacotherapy. 2019;111:947–957
  29. Mylonis I, Lakka A, Tsakalof A, Simos G. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions. Biochemical and Biophysical Research Communications. 2010;398(1):74-78.
  30. Sharma D., Gondaliya P., Tiwari V., Kalia K. Kaempferol attenuates diabetic nephropathy by inhibiting RhoA/Rho-kinase mediated inflammatory signalling. Biomedicine & Pharmacotherapy. 2019;109:1610-9.
  31. Halliwell B. Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Archives of Biochemistry and Biophysics. 2008;476:107–112
  32. Calderon-Montano J.M., Burgos-Moron E., Perez-Guerrero C., Lopez-Lazaro M. A review on the dietary flavonoid kaempferol. Mini-Reviews in Medicinal Chemistry. 2011;11:298–344.
  33. Noroozi M., Angerson W.J., Lean M.E. Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. The American Journal of Clinical Nutrition. 1998;67(6):1210-8.
  34. Rangel-Ordonez L., Noldner M., Schubert-Zsilavecz M., Wurglics M. Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761(R). Planta Medica. 2010;76:1683–1690
  35. Radtke J., Linseisen J., Wolfram G. Fasting plasma concentrations of selected flavonoids as markers of their ordinary dietary intake. European Journal of Nutrition. 2002;41:203–209.
  36. DuPont M.S., Day A.J., Bennett R.N., Mellon F.A., Kroon P.A. Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans. European Journal of Clinical Nutrition. 2004;58:947–954.
  37. Rorsman P., Braun M., Zhang Q. Regulation of calcium in pancreatic alpha- and beta-cells in health and disease. Cell Calcium. 2012;51:300–308.
  38. Montero M., Lobaton C.D., Hernandez-Sanmiguel E., Santodomingo J., Vay L., Moreno A., Alvarez J. Direct activation of the mitochondrial calcium uniporter by natural plant flavonoids. Biochemical Journal. 2004;(38):19–24.
  39. Wu P., Meng X., Zheng H., Zeng Q., Chen T., Wang W., Zhang X., Su J. Kaempferol Attenuates ROS-Induced Hemolysis and the Molecular Mechanism of Its Induction of Apoptosis on Bladder Cancer. Molecules. 2018; 23(10):2592
  40. Shirani K., Riahi-Zanjani B., Omidkhoda S.N., Barangi S., Karimi G. The hematopoietic potential of methanolic and aqueous extracts of Portulaca oleracea in a phenylhydrazine model of anemia. Avicenna Journal of Phytomedicine. 2023; 13(1):85-96.
  41. Asgary S., Naderi G., Askari N. Protective effect of flavonoids against red blood cell hemolysis by free radicals. Experimental & Clinical Cardiology. 2005;10(2):88-90.
  42. hikawa T., Suzukawa M., Ito T., et al. Effect of tea flavonoid supplementation on the susceptibility of low-density lipoprotein to oxidative modification. The American Journal of Clinical Nutrition. 1997;66:261–6
  43. Lale A., Herbert J.M., Augereau J.M., Billon M., Leconte M., Gleye J. Ability of different flavonoids to inhibit the procoagulant activity of adherent human monocytes. Journal of Natural Products. 1996;59:273–6
Journal of Medicinal plants and By-products
Volume 15, Issue 1
January and February 2026
Pages 139-145

Files

Share

How to cite

Statistics