Effectiveness of Hydroalcoholic Extract Powder Combination of Six Anti-Diabetic Plants Used in Persian Medicine on Blood Glucose Control in Type 2 Diabetic Patients: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Document Type : Research Paper

Authors

1 Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran

2 Department of Medical Sciences, Shahrood Branch, Islamic Azad University, Shahrood, Iran

3 Department of Internal Medicine, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

4 Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran

5 Department of Physiology and Pharmacology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

Abstract

In Persian Medicine, herbal therapists prescribe several herbs with different combinations for the treatment of diabetic patients. Among these plants, an herbal combination including Silybum marianum (L.) Gaertn. (silymarin), Melissa officinalis L. (lemon balm), Vaccinium arctostaphylos L. (Caucasian whortleberry), Trigonella foenum-graecum L. (fenugreek), Urtica dioica L. (nettle), and Citrullus colocynthis (L.) Schrad. (colocynth) is prescribed for treatment of diabetic patients by some herbalists. The efficacy and safety of this herbal combination were evaluated in animal and cell culture studies in the Institute of Medicinal Plants. However, no clinical studies have been conducted to confirm its clinical safety and effectiveness. The present study was performed to investigate the efficacy and safety of this herbal combination on the blood glucose control in type 2 diabetic patients. The herbal combination and placebo capsules (500 mg) were provided by the Institute of Medicinal Plants. Sixty eligible type 2 diabetic patients referred to the Diabetes Research Center affiliated to the Alborz University of Medical Sciences were selected. Patients were randomly divided into two groups of 30 people. Patients in both groups continued their standard anti-diabetic therapy. In addition, one group was administered one 500 mg herbal capsule and the other group placebo capsule every 12 hours for three months. The blood biochemical tests including, fasting glucose, glycosylated hemoglobin, lipid profile, creatinine, urea and liver enzymes including SGOT, SGPT, ALP were performed at the baseline, and then, at the end of the study after 3 months. The results showed that the fasting blood glucose level and glycosylated hemoglobin in the patients treated with herbal combination decreased significantly after 3 months compared with the baseline and also the placebo (p = 0.000). No significant (p > 0.05) changes were observed in the blood lipid profile, liver enzymes and kidney function tests. No side effects were observed during the study in both groups. In conclusion, the present study showed that, consumption of this herbal combination for 3 months has anti-diabetic effect without any side effects.

Keywords

Main Subjects

References

  1. Balaji R., Duraisamy R., Kumar M. Complications of diabetes mellitus: A review. Drug Invention Today. 2019;12(1).
  2. Huseini H.F., Larijani B., Heshmat R., Fakhrzadeh H., Radjabipour B., Toliat T., Raza M. The efficacy of Silybum marianum (L.) Gaertn.(silymarin) in the treatment of type II diabetes: a randomized, double‐blind, placebo‐controlled, clinical trial. Phytotherapy Research: An International J Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2006;20(12):1036-1039.
  3. Soto C.P., Perez B.L., Favari L.P., Reyes J.L. Prevention of alloxan-induced diabetes mellitus in the rat by silymarin. Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology. 1998;119(2):125-129.
  4. Soto C., Pérez J., García V., Uría E., Vadillo M., Raya L. Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus. Phytomedicine. 2010;17(14):1090-1094.
  5. Soto C., Recoba R., Barron H., Alvarez C., Favari L. Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2003;136(3):205-212.
  6. Weidner C., Wowro S.J., Freiwald A., Kodelja V., Abdel‐Aziz H., Kelber O., Sauer S. Lemon balm extract causes potent antihyperglycemic and antihyperlipidemic effects in insulin‐resistant obese mice. Molecular Nutrition & Food Research. 2014;58(4):903-907.
  7. Chung M.J., Cho S.-Y., Bhuiyan M.J.H., Kim K.H., Lee S.-J. Anti-diabetic effects of lemon balm (Melissa officinalis) essential oil on glucose-and lipid-regulating enzymes in type 2 diabetic mice. British Journal of Nutrition. 2010;104(2):180-188.
  8. EL-Kassaby M.I., Salama A.A., Mourad H.H., Abdel-Wahhab K.G. Effect of lemon balm (Melissa officinalis) aqueous extract on streptozotocin-induced diabetic rats. Egyptian Pharmaceutical Journal. 2019;18(4):296-303.
  9. Kianbakht S., Hajiaghaee R. Anti-hyperglycemic effects of vaccinium arctostaphylos L. fruit and leaf extracts in alloxan-induced diabetic rats. Journal of Medicinal Plants. 2013;12(45):43-50.
  10. Firouzeh M., Shahanipour K. The effects of Vaccinium arctostaphylos L. extract on the levels of glucose, oxidation indicators, HDL and cholesterol in diabetic rats (Wistar). Pars Journal of Medical Sciences. 2022;13(4):23-32.
  11. Xue W.-L., Li X.-S., Zhang J., Liu Y.-H., Wang Z.-L., Zhang R.-J. Effect of Trigonella foenum-graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocin-induced diabetic rats. Asia Pacific Journal of Clinical Nutrition. 2007;16(Suppl 1):422-426.
  12. Mohammadi A., Gholamhosseinian A., Fallah H. Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats. Advanced Biomedical Research. 2016;5(1):54.
  13. Beiranvand F., Alizadeh M. Plants for remedies of diabetes mellitus in Iran. Plant Biotechnology Persa. 2019;1(1):36-38.
  14. Fathi A.F., Garjani A., Maleki N., Ranj D.S. Study of the hypoglycemic activity of the hydroalcoholic extract of urtica dioica in normal and diabetic ratss. 2005.
  15. Sasan T.A., Goodarzi M.T., Jamshid K., Panah M.H. Antidiabetic effects of the aqueous extract of Urtica dioica on high-fructose fed rats. Clinical Biochemistry. 2011;13(44):S332.
  16. Hussain A.I., Rathore H.A., Sattar M.Z., Chatha S.A., Sarker S.D., Gilani A.H. Citrullus colocynthis (L.) Schrad (bitter apple fruit): A review of its phytochemistry, pharmacology, traditional uses and nutritional potential. Journal of Ethnopharmacology. 2014;155(1):54-66.
  17. Bernard S.A., Olayinka O.A. Search for a novel antioxidant, anti-inflammatory/analgesic or anti-proliferative drug: Cucurbitacins hold the ace. Journal of Medicinal Plants Research. 2010;4(25):2821-2826.
  18. Ghauri A.O., Ahmad S., Rehman T. In vitro and in vivo anti-diabetic activity of Citrullus colocynthis pulpy flesh with seeds hydro-ethanolic extract. Journal of Complementary and Integrative Medicine. 2020;17(2):20180228.
  19. Gutfinger T. Polyphenols in olive oils. Journal of the American Oil Chemists' Society 1981;58(11):966-968.
  20. Yoo K.M., Lee C.H., Lee H., Moon B., Lee C.Y. Relative antioxidant and cytoprotective activities of common herbs. Food Chemistry. 2008;106(3):929-936.
  21. Tavakoli S., Khalighi-Sigaroodi F., Hagiaghaee R., Yaghoobi M., Ghafarzadegan R. Purification, identification, and standardization of silybin A & B composition from Silybum marianum (L.) Gaertn. Journal of Medicinal Plants. 2022;21(81):1-11.
  22. Öztürk N., Tunçel M., Uysal U.D., Oncu-Kaya E.M., Koyuncu O. Determination of rosmarinic acid by high-performance liquid chromatography and its application to certain Salvia species and rosemary. Food Analytical Methods. 2011;4:300-306.
  23. Chan E.W., Lim Y.Y., Tan S.P. Standardised herbal extract of chlorogenic acid from leaves of Etlingera elatior (Zingiberaceae). Pharmacognosy Research. 2011;3(3):178.
  24. Shailajan S., Sayed N., Menon S., Singh A., Mhatre M. A validated RP-HPLC method for quantitation of trigonelline from herbal formulations containing Trigonella foenum-graecum (L.) seeds. Pharmaceutical Methods. 2011;2(3):157-160.
  25. Gargari B.P., Mobasseri M., Valizadeh H., Asghari-Jafarabadi M. Effects of Silybum marianum (L.) Gaertn.(silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial. Phytomedicine. 2015;22(2):290-296.
  26. Ramezani M., Azarabadi M., Abdi H., Baher G., Huseini M. The effects of Silybum marianum (L.) Gaertn. seed extract on glycemic control in type II diabetic patient’s candidate for insulin therapy visiting endocrinology clinic in baqiyatallah hospital in the years of 2006. Journal of Medicinal Plants. 2008;7(26):79-84.
  27. Mohammadi S., Afkhami Ardacani M., Salami M., Bolurani S. Effects of silymarin on insulin resistance and blood lipid profile in first-degree relatives of type 2 diabetic patients. Journal of Medicinal Plants. 2013;12(46):170-176.
  28. Asadi A., Shidfar F., Safari M., Hosseini A.F., Fallah Huseini H., Heidari I., Rajab A. Efficacy of Melissa officinalis L.(lemon balm) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: a randomized, double‐blind, clinical trial. Phytotherapy Research. 2019;33(3):651-659.
  29. Kianbakht S., Abasi B., Dabaghian F.H. Anti-hyperglycemic effect of Vaccinium arctostaphylos in type 2 diabetic patients: A randomized controlled trial. Forschende Komplementärmedizin/Research in Complementary Medicine 2013;20(1):17-22.
  30. Mohtashami R., Huseini H.F., Nabati F., Hajiaghaee R., Kianbakht S. Effects of standardized hydro-alcoholic extract of Vaccinium arctostaphylos leaf on hypertension and biochemical parameters in hypertensive hyperlipidemic type 2 diabetic patients: a randomized, double-blind and placebo-controlled clinical trial. Avicenna Journal of Phytomedicine. 2019;9(1):44.
  31. Sauvaire Y., Petit P., Broca C., Manteghetti M., Baissac Y., Fernandez-Alvarez J., Gross R., Roye M., Leconte A., Gomis R. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes. 1998;47(2):206-210.
  32. Uemura T., Hirai S., Mizoguchi N., Goto T., Lee J.Y., Taketani K., Nakano Y., Shono J., Hoshino S., Tsuge N. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. Molecular Nutrition Food Research. 2010;54(11):1596-1608.
  33. Najdi R.A., Hagras M.M., Kamel F.O., Magadmi R.M. A randomized controlled clinical trial evaluating the effect of Trigonella foenum-graecum (fenugreek) versus glibenclamide in patients with diabetes. African Health Science 2019;19(1):1594-1601.
  34. Kianbakht S., Khalighi-Sigaroodi F., Dabaghian F.H. Improved glycemic control in patients with advanced type 2 diabetes mellitus taking Urtica dioica leaf extract: a randomized double-blind placebo-controlled clinical trial. Clinical Laboratory. 2013;59(9-10):1071-1076.
  35. Khajeh-Mehrizi R., Mozaffari-Khosravi H., Ghadiri-Anari A., Dehghani A. The effect of Urtica dioica extract on glycemic control and insulin resistance indices in patients with type 2 diabetes: a randomized, double-blind clinical trial. Iranian Journal of Diabetes and Obesity. 2014;6(4):149-155.
  36. Tarighat E.A., Namazi N., Bahrami A., Ehteshami M. Effect of hydroalcoholic extract of nettle (Urtica dioica) on glycemic index and insulin resistance index in type 2 diabetic patients. 2012.
  37. Huseini H.F., Darvishzadeh F., Heshmat R., Jafariazar Z., Raza M., Larijani B. The clinical investigation of Citrullus colocynthis (L.) schrad fruit in treatment of Type II diabetic patients: a randomized, double blind, placebo‐controlled clinical trial. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2009;23(8):1186-1189.
  38. Gong L., Feng D., Wang T., Ren Y., Liu Y., Wang J. (1987). Inhibitors of α‐amylase and α‐glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia. Food Science and Nutrition. 2020; 8 (12): 6320-6337.
  39. Fallah Huseini H., Asghari B., Asgarpanah J., Eghbali Zarch T., Babai Zarch A. Investigation of α-Amylase and α-Glucosidases Inhibitory Effects of Silybum marianum (L. Gaertn) Seed Extracts In Vitro. Journal of Medicinal Plants. 2012;11(41):239-247.
  40. Zhu F., Wang J., Takano H., Xu Z., Nishiwaki H., Yonekura L., Yang R., Tamura H. Rosmarinic acid and its ester derivatives for enhancing antibacterial, α‐glucosidase inhibitory, and lipid accumulation suppression activities. Journal of Food Biochemistry. 2019;43(2):e12719.
  41. Nickavar B., Amin G. Enzyme assay guided isolation of an α-amylase inhibitor flavonoid from Vaccinium arctostaphylos leaves. Iranian Journal of Pharmaceutical Research: IJPR. 2011;10(4):849.
  42. Ganeshpurkar A., Diwedi V., Bhardwaj Y. In vitro α-amylase and α-glucosidase inhibitory potential of Trigonella foenum-graecum leaves extract. AYU (An International quarterly Journal Research in Ayurveda). 2013;34(1):109-112.
  43. Salim B., Said G., Kambouche N., Kress S. Identification of phenolic compounds from nettle as new candidate inhibitors of main enzymes responsible on type-II diabetes. Current Drug Discovery Technology. 2020;17(2):197-202.
  44. Alblooshi M., Devarajan A.R., Singh B.P., Ramakrishnan P., Mostafa H., Kamal H., Mudgil P., Maqsood S. Multifunctional bioactive properties of hydrolysates from colocynth (Citrullus colocynthis) seeds derived proteins: Characterization and biological properties. Plant Physiology and Biochemistry. 2023;194:326-334.
  45. Park S.Y., Gautier J.-F., Chon S. Assessment of insulin secretion and insulin resistance in human. Diabetes & Metabolism Journal. 2021;45(5):641.
  46. Honka M.-J., Latva-Rasku A., Bucci M., Virtanen K.A., Hannukainen J.C., Kalliokoski K.K., Nuutila P. Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: a positron emission tomography study. European Journal of Endocrinology. 2018;178(5):523-531.
  47. Rath P., Prakash D., Ranjan A., Chauhan A., Jindal T., Alamri S., Alamri T., Harakeh S., Haque S. Modulation of insulin resistance by Silybum marianum leaves, and its synergistic efficacy with Gymnema sylvestre, Momordica charantia, Trigonella-foenum graecum against protein tyrosine phosphatase 1B. Biotechnology and Genetic Engineering Reviews. 2023:1-23.
  48. Domola M.S., Vu V., Robson‐Doucette C.A., Sweeney G., Wheeler M.B. Insulin mimetics in Urtica dioica: structural and computational analyses of Urtica dioica extracts. Phytotherapy Research. 2010;24(S2):S175-S82.
  49. Vijayakumar M.V., Singh S., Chhipa R.R., Bhat M.K. The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway. British Journal of Pharmacology. 2005;146(1):41-48.
  50. Iatcu C.O., Steen A., Covasa M. Gut microbiota and complications of type-2 diabetes. Nutrients. 2021;14(1):166.
  51. Xu S., Jiang X., Jia X., Jiang X., Che L., Lin Y., Zhuo Y., Feng B., Fang Z., Li J. Silymarin modulates microbiota in the gut to improve the health of sow from late gestation to lactation. Animals. 2022;12(17):2202.
  52. Brochot A., Azalbert V., Landrier J.F., Tourniaire F., Serino M. A two‐week treatment with plant extracts changes gut microbiota, caecum metabolome, and markers of lipid metabolism in ob/ob mice. Molecular Nutrition and Food Research. 2019;63(17):1900403.
  53. Bruce-Keller A.J., Richard A.J., Fernandez-Kim S.-O., Ribnicky D.M., Salbaum J.M., Newman S., Carmouche R., Stephens J.M. Fenugreek counters the effects of high fat diet on gut microbiota in mice: Links to metabolic benefit. Scientific Reports. 2020;10(1):1245.
  54. Fan S., Raychaudhuri S., Page R., Shahinozzaman M., Obanda D.N. Metagenomic insights into the effects of Urtica dioica vegetable on the gut microbiota of C57BL/6J obese mice, particularly the composition of Clostridia. The Journal of Nutritional Biochemistry. 2021;91:108594.
  55. Oguntibeju O.O. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. International Journal of Physiology, Pathophysiology and Pharmacology. 2019;11(3):45.
  56. Dastmalchi K., Dorman H.D., Oinonen P.P., Darwis Y., Laakso I., Hiltunen R. Chemical composition and in vitro antioxidative activity of a lemon balm (Melissa officinalis L.) extract. LWT-Food Science and Technology. 2008;41(3):391-400.
  57. Soltani R., Hakimi M., Asgary S., Ghanadian S.M., Keshvari M., Sarrafzadegan N. Evaluation of the effects of Vaccinium arctostaphylos L. Fruit extract on serum lipids and hs-CRP levels and oxidative stress in adult patients with hyperlipidemia: a randomized, double-blind, placebo-controlled clinical trial. Evidence-Based Complementary and Alternative Medicine. 2014;2014.
  58. Tharaheswari M., Jayachandra Reddy N., Kumar R., Varshney K., Kannan M., Sudha Rani S. Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage in pancreas and enhance adipose tissue PPARγ activity in type 2 diabetic rats. Molecular and Cellular Biochemistry. 2014;396:161-174.
  59. Jaiswal V., Lee H.-J. Antioxidant activity of Urtica dioica: An important property contributing to multiple biological activities. Antioxidants. 2022;11(12):2494.
  60. Huseini H.F., Zaree A., Heshmat R., Larijani B., Fakhrzadeh H., Sharifabadi R.R., Naderi G., Samani A. The effect of Citrullus colocynthis (L.) Schrad. fruit on oxidative stress parameters in type II diabetic patients. Journal of Medicinal Plants. 2016;5(2):55-60.
Journal of Medicinal plants and By-Products
Volume 14, Issue 3
May and June 2025
Pages 245-251

Files

Share

How to cite

Statistics