IMPACT OF PLANT METABOLITES IN GLUCOSE METABOLISM FOR REGULATION OF BLOOD GLUCOSE LEVEL IN DIABETES: AN EXCLUSIVE UPDATE

Yıl 2025, Cilt: 49 Sayı: 2, 498 - 518, 19.05.2025

Pulak Majumder , Amrutanand Tripathy , Swathi K B

https://doi.org/10.33483/jfpau.1472409

Öz

Objective: To explore the molecular targets of plant chemicals and their role in regulating hyperglycemia, providing insights into potential strategies for developing new treatment for this condition.
Result and Discussion: Understanding the biochemical pathways involved in sugar regulation is crucial for developing treatments for conditions such as hyperglycemia. Phytochemicals derived from plants have shown promise in regulating blood sugar levels through various molecular targets. By targeting specific enzymes and pathways involved in glucose metabolism, these phytochemicals offer potential therapeutic benefits for managing hyperglycemia. Plant chemicals have demonstrated the ability to influence key enzymes and pathways in glucose metabolism. Phytochemicals have been found to modulate glycolysis, the Krebs cycle, and gluconeogenesis, offering the potential for regulating blood sugar levels. Additionally, these plant extracts have shown effects on processes such as cholesterol synthesis, glycogen synthesis and degradation, carbohydrate metabolism and absorption, as well as insulin production and release. The diverse impact of these medicinal plants on multiple physiological processes highlights their potential to address hyperglycemia through a multi-faceted approach. In this review, we will further explore the molecular targets and mechanisms of action of these plant chemicals, which can provide valuable insights for developing novel treatments for hyperglycemia.

Anahtar Kelimeler

Biochemical pathways, diabetes, medicinal plants, phytochemicals

Etik Beyan

The paper reflects the authors' own research and analysis in a truthful and complete manner.

Destekleyen Kurum

Faculty of Pharmacy, Sri Adichunchanagiri college of Pharmacy, Adichunchanagiri University

Proje Numarası

NA

DİYABETTE KAN GLUKOZ SEVİYESİNİN DÜZENLENMESİ İÇİN GLUKOZ METABOLİZMASINDA BİTKİ METABOLİTLERİNİN ETKİSİ: ÖZEL GÜNCELLEME

Öz

Amaç: Bu makalenin amacı, bitki kimyasallarının moleküler hedeflerini ve hiperglisemiyi düzenlemedeki rollerini araştırmak, bu durum için yeni tedaviler geliştirmeye yönelik potansiyel stratejiler hakkında fikir vermektir.
Sonuç ve Tartışma: Şeker regülasyonunda yer alan biyokimyasal yolların anlaşılması, hiperglisemi gibi durumlara yönelik tedavilerin geliştirilmesi açısından çok önemlidir. Bitkilerden elde edilen fitokimyasallar, çeşitli moleküler hedefler aracılığıyla kan şekeri seviyelerinin düzenlenmesinde umut vaat etmektedir. Glikoz metabolizmasında yer alan spesifik enzimleri ve yolakları hedef alan bu fitokimyasallar, hipergliseminin yönetilmesinde potansiyel terapötik faydalar sunar. Bitki kimyasalları, glikoz metabolizmasında yer alan anahtar enzimleri ve yolakları etkileme yeteneğini göstermiştir. Fitokimyasalların glikolizi, Krebs döngüsünü ve glukoneogenezi modüle ettiği ve kan şekeri seviyelerini düzenleme potansiyeli sunduğu bulunmuştur. Ek olarak, bu bitki özlerinin kolesterol sentezi, glikojen sentezi ve bozulması, karbonhidrat metabolizması ve emiliminin yanı sıra insülin üretimi ve salınımı gibi süreçler üzerinde de etkileri olduğu gösterilmiştir. Bu şifalı bitkilerin çoklu fizyolojik süreçler üzerindeki farklı etkisi, bunların hiperglisemiyi çok yönlü bir yaklaşımla ele alma potansiyelini vurgulamaktadır. Bu derlemede, bu bitki kimyasallarının moleküler hedeflerinin ve etki mekanizmalarının daha fazla araştırılması, hiperglisemiye yönelik yeni tedavilerin geliştirilmesi için değerli bilgiler sağlayabilir.

Anahtar Kelimeler

Biyokimyasal yolaklar, diyabet, fitokimyasallar, tıbbi bitkiler

Proje Numarası

NA

Kaynakça

• 1. Grover, J.K., Vats, V., Yadav, S. (2002). Medicinal plants of India with antidiabetic properties. Journal of Ethnopharmacology, 81, 81-100. [CrossRef]
• 2. Berg, J.M., Tymoczko, J.L., Stryer, L. (2002). Biochemistry, 5th ed. WH Freeman and Co., pp. 644-89.
• 3. Bhatti, R., Sharma, S., Singh, J., Ishar, M.P.S. (2011). Ameliorative effect of Aegle marmelos leaf extract on early stage alloxan-induced diabetic cardiomyopathy in rats. Pharmaceutical Biology, 49(11), 1137-1143. [CrossRef]
• 4. Prabhakar, P.K., Doble, M. (2008). A target based therapeutic approach towards diabetes mellitus using medicinal plants. Current Diabetes Reviews, 4(4), 291-308. [CrossRef]
• 5. Ramu, R., Shirahatti, P.S., Nayakavadi, S., Vadivelan, R., Zameer, F., Dhananjaya, B.L., Prasad, N. (2016). The effect of a plant extract enriched in stigmasterol and β-sitosterol on glycaemic status and glucose metabolism in alloxan-induced diabetic rats. Food & Function, 7(9), 3999-4011. [CrossRef]
• 6. Kianian, F., Marefati, N., Boskabady, M., Ghasemi, S.Z., Boskabady, M.H. (2021). Pharmacological properties of Allium cepa, preclinical and clinical evidences; A review. Iranian Journal of Pharmaceutical Research: IJPR, 20(2), 107.
• 7. Dorrigiv, M., Zareiyan, A., Hosseinzadeh, H. (2020). Garlic (Allium sativum) as an antidote or a protective agent against natural or chemical toxicities: A comprehensive update review. Phytotherapy Research, 34(8), 1770-1797. [CrossRef]
• 8. Saad, B., Zaid, H., Shanak, S., Kadan, S., Saad, B., Zaid, H., Kadan, S. (2017). Antidiabetic medicinal plants and their mechanisms of action. Anti-diabetes and Anti-obesity Medicinal Plants and Phytochemicals: Safety, Efficacy, and Action Mechanisms, 175-213.
• 9. Narayannasamy, A., Namasivayam, N., Radha, K. (2003). Effect of turmeric on the enzymes of glucose metabolism in diabetic rats. Journal of Herbs, Spices & Medicinal Plants, 10(1), 75-84. [CrossRef]
• 10. Zhang, D.W., Fu, M., Gao, S.H., Liu, J.L. (2013). Curcumin and diabetes: A systematic review. Evidence-Based Complementary and Alternative Medicine, 16-18 [CrossRef]
• 11. Sharma, S., Jayant, S.K., Mishra, V., Srivastava, N. (2018). Antihyperglycemic effects of Trigonella foenum-graecum seeds and Cinnamomum zeylanicum bark on key enzymes of carbohydrate metabolism in tissues of rats with experimental diabetes. Integr Obesity Diabetes, 4, 123-136.
• 12. Srinivasa, U.M., Naidu, M.M. (2021). Fenugreek (Trigonella foenum-graecum L.) seed: Promising source of nutraceutical. Studies in Natural Products Chemistry, 71, 141-184. [CrossRef]
• 13. Panda, A.K. (2014). Comprehensive ayurvedic care in Type-2 diabetes. Journal of Homeopathy Ayurveada Medecine, 3, e111. [CrossRef]
• 14. Akpoveso, O.O. P. (2016). PhD thesis. An Investigation of Antioxidant and Antidiabetic Effect of Aqueous Leaf Extracts of Mucuna Pruriens. Department of Pharmacognosy, University of Brighton.
• 15. Martin, A., Komada, M.R., Sane, D.C. (2003). Abnormal angiogenesis in diabetes mellitus. Medicinal Research Reviews, 23(2), 117-145. [CrossRef]
• 16. Jacob, B., Narendhirakannan, R.T. (2019). Role of medicinal plants in the management of diabetes mellitus: A review. 3 Biotech, 9, 1-17. [CrossRef]
• 17. Singh, R., Kazmi, I., Afzal, M., Imam, F., Alharbi, K.S. (2019). Dietary phytochemicals and their potential effects on diabetes mellitus 2. Plant and Human Health, Volume 3: Pharmacology and Therapeutic Uses, 65-86.
• 18. Yan, L. (2021). PhD thesis. Anti-Inflammatory and Anti-Glycolytic Effect of Momordica charantia Aqueous Extract and Charantin in Lipopolysaccharide Induced Raw 264. 7 Cells. University of Faculty of Engineering, Universitiy Teknologi, Malaysia.
• 19. Perumal, V., Khoo, W.C., Abdul-Hamid, A., Ismail, A., Saari, K., Murugesu, S., Khatib, A. (2015). Evaluation of antidiabetic properties of Momordica charantia in streptozotocin induced diabetic rats using metabolomics approach. International Food Research Journal, 22(3), 87-83.
• 20. Liu, J., Lei, Y., Guo, M., Wang, L. (2023). Research Progress on the hypoglycemic effects and mechanisms of action of Momordica charantia polysaccharide. Journal of Food Biochemistry. [CrossRef]
• 21. Wang, B.X., Zhou, Q.L., Yang, M., Wang, Y., Cui, Z.Y., Liu, Y.Q., Ikejima, T. (2003). Hypoglycemic mechanism of ginseng glycopeptide. Acta Pharmacologica Sinica, 24(1), 61-66.
• 22. Singh, S.N., Vats, P., Suri, S., Shyam, R., Kumria, M.M.L., Ranganathan, S., Sridharan, K. (2001). Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in streptozotocin induced diabetic rats. Journal of Ethnopharmacology, 76(3), 269-277. [CrossRef]
• 23. Goboza, M. (2019). PhD Thesis. Modulatory and Antidiabetic Effects of Vindoline and Catharanthus roseus in Type 2 Diabetes Mellitus Induced Male Wistar Rats and in RIN-5F Cell Line. Cape Peninsula University of Technology.
• 24. Anoja, S.A, Yun, P.Z, Jing, T.X., Ji, A.W., Liu, Z., Lucy, D., William, P. (2002). Antidiabetic Effects of Panax ginseng berry extract and the identification of an effective component. Diabetes, 51(6), 1851-1858. [CrossRef]
• 25. Su, X., Hao, S., Li, W., Li, X., Mo, Z., Li, Y., Wang, F. (2023). Gardenia fruit and Eucommia leaves combination improves hyperlipidemia and hyperglycemia via pancreatic lipase and AMPK-PPARα and Keap-1-Nrf2-HO-1 regulation. Journal of Functional Foods, 100, 105394. [CrossRef]
• 26. Robert, A.E., Luke, U.O., Udosen, E.O., Ufot, S.U., Effiong, A.E., Ekam, V.S. (2013). Anti-diabetic and anti-hyperlipedemic properties of ethanolic root extract of Gongronema Latifolium (Utazi) on streptozotocin (STZ) induced diabetic rats. ARPN Journal of Science and Technology, vol. 3 (10), 995-998.
• 27. Jayant, S.K., Srivastava, N. (2016). Effect of Ocimum sanctum against alloxan induced diabetes and biochemical alterations in rats. Integr Obesity Diabetes, 2(5), 1-4.
• 28. Mousavi, L., Salleh, R.M., Murugaiyah, V., Asmawi, M.Z. (2016). Hypoglycemic and anti-hyperglycemic study of Ocimum tenuiflorum L. leaves extract in normal and streptozotocin-induced diabetic rats. Asian Pacific Journal of Tropical Biomedicine, 6(12), 1029-1036. [CrossRef]
• 29. Liu, Z., Qu, C.Y., Li, J.X., Wang, Y.F., Li, W., Wang, C.Z., Yuan, C.S. (2021). Hypoglycemic and hypolipidemic effects of malonyl ginsenosides from American ginseng (Panax quinquefolius L.) on type 2 diabetic mice. ACS Omega, 6(49), 33652-33664. [CrossRef]
• 30. Sammy, J., Tamuno-Emine, D., Nwachuku, E. (2020). Evaluation of anti-diabetic, hepatoprotective and antilipidemic potentials of Syzygium aromaticum (Clove) on albino rat. Journal of Complementary and Alternative Medical Research, 11(1), 38-50.
• 31. Otunola, G.A. (2022). Culinary spices in food and medicine: An overview of Syzygium aromaticum (L.) Merr. and LM Perry [Myrtaceae]. Frontiers in Pharmacology, 12, 793200. [CrossRef]
• 32. Prabhakar, P.K. (2020). Hypoglycemic potential of mushroom and their metabolites. In New and Future Developments in Microbial Biotechnology and Bioengineering; Elsevier. pp. 197-208. [CrossRef]
• 33. Tchamgoue, A.D., Dzeufiet, P.D., Kuiata, J.R., Agbor, G.A. (2020). Costus afer modulates the activities of glycolytic and gluconeogenic enzymes in streptozotocin induced diabetic rats. Journal of Drug Delivery and Therapeutics, 10(4-s), 63-70. [CrossRef]
• 34. Alam, F., Shafique, Z., Amjad, S.T., Bin Asad, M.H.H. (2019). Enzymes inhibitors from natural sources with antidiabetic activity: A review. Phytotherapy Research, 33(1), 41-54. [CrossRef]
• 35. Gangwar, R., Rao, C.H.V. (2017). Antidiabetic efficacy of Murraya koeingii in streptozotocin induced diabetes mellitus in albino wistar rats. Journal of Scientific Research in Allied Sciences, 3(6), 442-451.
• 36. Sudha, M.J., Viveka, S., R Mohandas (2013). Study of hypoglycemic effect of Murraya koenigii leaf extract in streptozotocin induced diabetic rats. International journal of medical and applied sciences, Vol. 2(3), 191-199.
• 37. Andrade-Cetto, A. (2012). Effects of medicinal plant extracts on gluconeogenesis. Botanics: Targets and Therapy, 2, 1-6. [CrossRef]
• 38. Pundarikakshudu, K., Shah, P.A., Patel, M.G. (2024). A comprehensive review of Indian medicinal plants effective in diabetes management: Current status and future prospects. Antidiabetic Medicinal Plants, 3-73. [CrossRef]
• 39. Sarker, M., Sharmin, T., Akter, R., Chowdhury, D.U.S., Tumpa, N.J.S., Hosna, A., Islam, N.N. (2024). A comparative analysis of phytoconstituents, cytotoxicity and antidiabetic activity of three regional piper betle varieties: First report from Bangladesh. South Asian Research Journal of Natural Products, 7(1), 32-41.
• 40. Tabassum, H., Ahmad, I.Z. (2021). Trigonella foenum-graecum and Its Bioactive Compounds Having Potential Antidiabetic Activity. In: Naeem, M., Aftab, T., Khan, M.M.A. (eds) Fenugreek. Springer, Singapore; pp. 447-80. [CrossRef]
• 41. Jeyam, M., Priyadharsini, K., Ravikumar, P., Shalini, G. (2014). Evaluating multi-target efficiency of phytocompounds against diabetes mellitus-an in-silico approach. Bioinfo Drug targets, 2(1), 24-28.
• 42. Packirisamy, M., Ayyakkannu, P., Sivaprakasam, M. (2018). Antidiabetic effect of Coccinia grandis (L.) Voigt (Cucurbitales: Cucurbitaceae) on streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolizing enzymes. Brazilian Journal of Biological Sciences, 5(11), 683-698. [CrossRef]
• 43. Putra, I.M.W.A., Fakhrudin, N., Nurrochmad, A., Wahyuono, S. (2021). Antidiabetic activity of Coccinia grandis (L.) Voigt: Bioactive constituents, mechanisms of action, and synergistic effects. Journal of Applied Pharmaceutical Science, 12(1), 41-54.
• 44. Mahalanobish, S., Ghosh, N., Sil, P.C. (2022). 10 Panax quinquefolium. Herbs, Shrubs, and Trees of Potential Medicinal Benefits, CRC Press, 179.
• 45. Hossain, M.Z., Shibib, B.A., Rahman, R. (1992). Hypoglycemic effects of Coccinia indica: Inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. Indian Journal of Experimental Biology, 30(5), 418-420.
• 46. Wasana, K.G.P., Attanayake, A.P. (2023). Scarlet Gourd (Coccinia grandis L. Voigt): Use in diabetes, molecular, cellular metabolic effects. In Ancient and Traditional Foods, Plants, Herbs and Spices used in Diabetes, CRC Press, 347-364.
• 47. Supreetha, B.S., Veena, V., Selvakumar, J. (2022). Molecular insights of active plant-based antidiabetic drug molecules. In Antidiabetic Potential of Plants in the Era of Omics, Apple Academic Press, 235-259.
• 48. Rasineni, K., Gujjala, S., Sagree, S., Putakala, M., Bongu, S.B.R., Bellamkonda, R., Desireddy, S. (2017). Therapeutic efficacy of Catharanthus roseus in type 1 and type 2 diabetes mellitus in Wistar rats. Catharanthus roseus: Current Research and Future Prospects, 201-246.
• 49. Kantuchitani, S. (2023). PhD Thesis. The potential protective effect of Catharanthus roseus leaf extract against type1diabetes induced neuropathology in the adult Sprague Dawley rat forebrain. University of Johannesburg.
• 50. Rivadeneira, A.D. (2014). Identificación de especies vegetales utilizadas en el tratamiento de la diabetes mellitus tipo 2, mecanismos de acción y modelos experimentales. La Técnica, (13), 64-73.
• 51. Maroo, J., Vasu, V.T., Gupta, S. (2003). Dose dependent hypoglycemic effect of aqueous extract of Enicostemma littorale Blume in alloxan induced diabetic rats. Phytomedicine, 10(2-3), 196-199. [CrossRef]
• 52. Onyenibe, N.S., Nathaniel, N.A., Udogadi, N.S., Iyanu, O.O. (2019). Hypoglycemic and antioxidant capacity of Curcuma longa and Viscum album in alloxan induced diabetic male Wistar rats. International Journal of Diabetes Endocrinology, 4(1), 26.
• 53. Paul, T., Pathak, K., Saikia, R., Gogoi, U., Jyoti Sahariah, J., Das, A. (2024). The role of medicinal plants in the treatment and management of type 2 diabetes. Current Traditional Medicine, 10(2), 83-96. [CrossRef]
• 54. Sruthi, G., Pillai, H.H., Ullas, N., Jiju, V., Abraham, E. (2017). Role of antioxidants in the management diabetes mellitus. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN), 10(4), 3763-3767. [CrossRef]
• 55. Dixit, A.K., Alam, Q., Dixit, D., Nair, P.G., Prasad, P.V.V. (2022). Plant based bioactive molecules in diabetes with their therapeutic mechanism. Therapeutic Implications of Natural Bioactive Compounds, 3, 94-117.
• 56. Packirisamy, M., Ayyakkannu, P., Sivaprakasam, M. (2018). Antidiabetic effect of Coccinia grandis (L.) Voigt (Cucurbitales: Cucurbitaceae) on streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolizing enzymes. Brazilian Journal of Biological Sciences, 5(11), 683-698. [CrossRef]
• 57. Jose, E. (2009). PhD Thesis. Hypoglycaemic Effect of Coccinia indica (Ivy Gourd) Leaves and Its Interaction With Glibenclamide In Diabetic Rats. Department of Veterinary Pharmacology & Toxicology, COVAS, Mannuthy.
• 58. Rasineni, K., Gujjala, S., Sagree, S., Putakala, M., Bongu, S.B.R., Bellamkonda, R., Desireddy, S. (2017). Therapeutic efficacy of Catharanthus roseus in type 1 and type 2 diabetes mellitus in wistar rats. Catharanthus roseus: Current Research and Future Prospects, 201-246. [CrossRef]
• 61. Gajalakshmi, S., Vijayalakshmi, S., Devi, R.V. (2013). Pharmacological activities of Catharanthus roseus: a perspective review. International Journal of Pharma and Bio Sciences, 4(2), 431-439.
• 59. Pérez-Ramírez, I.F., González-Dávalos, M.L., Mora, O., Gallegos-Corona, M.A., Reynoso-Camacho, R. (2017). Effect of Ocimum sanctum and Crataegus pubescens aqueous extracts on obesity, inflammation, and glucose metabolism. Journal of Functional Foods, 35, 24-31. [CrossRef]
• 60. Santhakumari, P., Prakasam, A., Pugalendi, K.V. (2006). Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic rats. Journal of Medicinal Food, 9(1), 108-112. [CrossRef]
• 61. Bustanji, Y., Taha, M.O., Almasri, I.M., Al-Ghussein, M.A., Mohammad, M.K., Alkhatib, H.S. (2009). Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation. Journal of Enzyme Inhibition and Medicinal Chemistry, 24(3), 771-778. [CrossRef]
• 62. Aizman, R.I., Koroshchenko, G.A., Gaidarova, A.P., Sakharov, A.V., Subotyalov, M.A. (2014). The mechanisms of Curcuma longa rhizome action on glucose metabolism in alloxan-induced diabetic rats. International Ayurvedic Medical Journal, 2(5), 752-760.
• 63. Pahlavani, N., Roudi, F., Zakerian, M., Ferns, G.A., Navashenaq, J.G., Mashkouri, A., Rahimi, H. (2019). Possible molecular mechanisms of glucose‐lowering activities of Momordica charantia (karela) in diabetes. Journal of Cellular Biochemistry, 120(7), 10921-10929. [CrossRef]
• 64. Akinola, O., Dosumu, O., Akinola, O.S., Zatta, L., Dini, L., Caxton-Martins, E.A. (2010). Azadirachta indica leaf extract ameliorates hyperglycemia and hepatic glycogenosis in streptozotocin-induced diabetic wistar rats. International Journal of Phytomedicine, 2(3), 320-331.
• 65. Phatak, R.S., khanwelkar, C.C., Datkhile, K.D., Durgawale, P.P. (2018). Effect of Murraya koenigii leaves extract on gluconeogenesis and glycogenolysis in isolated rat hepatocytes culture. Asian Journal of Pharmaceutical Clinical Research, 11(11), 264-266.
• 66. Desai, R.R., Khanwelkar, C.C., Sunil Gidamudi, S.G., Phatak, R.S., Sujata Jadhav, S.J., Vandana Thorat, V.T., Pratibha Salve, P.S. (2019). Antidiabetic effect of Murraya koenigii leaves aqueous extract on blood sugar levels in alloxanized diabetic rats. Pravara Medical Review;11(2), 19-24.
• 67. Sathyan, A. (2004). PhD Thesis. Comparative Study of The Hypoglycemic Effect of Azadirachta indica (Neem), Ocimum sanctum Tulsi) and Tinospora cordifolia (Chittamruthu) and their combination in diabetic rats. Department of Pharmacology and Toxicology, College of Veterinary and Animal Sciences, Mannuthy.
• 68. Sharma, A.K., Bharti, S., Goyal, S., Arora, S., Nepal, S., Kishore, K., Arya, D.S. (2011). Upregulation of PPARγ by Aegle marmelos ameliorates insulin resistance and β‐cell dysfunction in high fat diet fed‐streptozotocin induced type 2 diabetic rats. Phytotherapy Research, 25(10), 1457-1465. [CrossRef]
• 69. Nair, S.A., Sabulal, B., Radhika, J., Arunkumar, R., Subramoniam, A. (2014). Promising anti-diabetes mellitus activity in rats of β-amyrin palmitate isolated from Hemidesmus indicus roots. European Journal of Pharmacology, 734, 77-82. [CrossRef]
• 70. Chen, Z., Du, X., Yang, Y., Cui, X., Zhang, Z., Li, Y. (2018). Comparative study of chemical composition and active components against α‐glucosidase of various medicinal parts of Morus alba L. Biomedical Chromatography, 32(11), e4328. [CrossRef]
• 71. Wei-Jia, X.I.E., Tanabe, G., Tsutsui, N., Xiao-Ming, W.U., Muraoka, O. (2013). Total synthesis of neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata. Chinese Journal of Natural Medicines, 11(6), 676-683. [CrossRef]
• 72. Tanabe, G., Xie, W., Balakishan, G., Amer, M.F., Tsutsui, N., Takemura, H., Muraoka, O. (2016). Hydrophobic substituents increase the potency of salacinol, a potent α-glucosidase inhibitor from Ayurvedic traditional medicine ‘Salacia’. Bioorganic & Medicinal Chemistry, 24(16), 3705-3715. [CrossRef]
• 73. Vasiliki, G., Charalampia, D., Haralabos, K.C. (2019). In vitro antioxidant, antithrombotic, antiatherogenic and antidiabetic activities of Urtica dioica, Sideritis euboea and Cistus creticus water extracts and investigation of pasta fortification with the most bioactive one. Current Pharmaceutical Biotechnology, 20(10), 874-880. [CrossRef]
• 74. Kim, M.J., Kim, H.S., Kim, A.J. (2018). Optimization of mixing ratio of mulberry leaf, mulberry fruit, and silkworm for amelioration of metabolic syndrome. Journal of Korean Medicine for Obesity Research, 18(2), 83-95. [CrossRef]
• 75. Pavithra, K.S., Annadurai, J., Ragunathan, R. (2018). Phytochemical, antioxidant and a study of bioactive compounds from Artemisia pallens. Journal of Pharmacognosy and Phytochemistry, 7(4), 664-675.
• 76. Kulkarni, Y.A., Garud, M.S. (2016). Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes. Biomedicine & Pharmacotherapy, 83, 122-129. [CrossRef]
• 77. Aljobouri, A.M., Rashid, K.I., Ibrahim, S.A., Zyer, A.J., Abbas, Z.N. (2015). Study the effect of Bauhinia variegate Linn. ethanolic extract on reducing glucose and lipid levels of white albino miceInternational Journal of Current Microbiology and Applied Sciences, 4(3), 652-658.
• 78. Jones, P.M., Persaud, S.J. (1998). Protein kinases, protein phosphorylation, and the regulation of insulin secretion from pancreatic cells. Endocrine Reviews, 19(4), 429-461. [CrossRef]
• 79. Temkitthawon, P., Viyoch, J., Limpeanchob, N., Pongamornkul, W., Sirikul, C., Kumpila, A., Ingkaninan, K. (2008). Screening for phosphodiesterase inhibitory activity of Thai medicinal plants. Journal of Ethnopharmacology, 119(2), 214-217. [CrossRef]
• 80. Noor, A., Gunasekaran, S., Vijayalakshmi, M.A. (2017). Improvement of insulin secretion and pancreatic β-cell function in streptozotocin-induced diabetic rats treated with Aloe vera extract. Pharmacognosy research, 9(Suppl 1), 99.
• 81. Iftikhar, A., Aslam, B., Iftikhar, M., Majeed, W., Batool, M., Zahoor, B., Latif, I. (2020). Effect of Caesalpinia bonduc polyphenol extract on alloxan-induced diabetic rats in attenuating hyperglycemia by upregulating insulin secretion and inhibiting JNK signalling pathway. Oxidative Medicine and Cellular Longevity.1-14. [CrossRef]
• 82. Abou Zaid, O.A., Sonbaty, S.E., Neama, M.A. (2017). Anti-diabetic activity of Agaricus bisporus: A biochemical and pathological study. International Journal of Pharmaceutical Sciences and Research, 7(2), 1740-1745.
• 83. Ansari, P., Islam, S.S., Akther, S., Khan, J.T., Shihab, J.A., Abdel-Wahab, Y.H. (2023). Insulin secretory actions of ethanolic extract of Acacia arabica bark in high fat-fed diet-induced obese Type 2 diabetic rats. Bioscience Reports, 43(5). [CrossRef]
• 84. Hegazy, G. A., Alnoury, A. M., Gad, H. G. (2013). The role of Acacia Arabica extract as an antidiabetic, antihyperlipidemic, and antioxidant in streptozotocin-induced diabetic rats. Saudi Medical Journal, 34(7), 727-733.
• 85. Haque, M.A., Hossain, M.S., Sayed, N.M.A., Islam, M.T., Khan, M.R., Ahmmed, F., Capasso, R. (2022). Abelmoschus esculentus (L.) moench pod extract revealed antagonistic effect against the synergistic antidiabetic activity of metformin and acarbose upon concomitant administration in glucose-induced hyperglycemic mice. Biologics, 2(2), 128-138. [CrossRef]
• 86. Venkatesh, S., Madhava Reddy, B., Dayanand Reddy, G., Mullangi, R., Lakshman, M. (2010). Antihyperglycemic and hypolipidemic effects of Helicteres isora roots in alloxan-induced diabetic rats: A possible mechanism of action. Journal of Natural Medicines, 64, 295-304. [CrossRef]
• 87. Akinlolu, A.A., Salau, B.A., Ekor, M., Otulana, J. (2015). Musa sapientum with exercises attenuates hyperglycemia and pancreatic islet cells degeneration in alloxan-diabetic rats. Journal of intercultural ethnopharmacology, 4(3), 202-207. [CrossRef]
• 88. Dey, P., Singh, J., Suluvoy, J.K., Dilip, K.J., Nayak, J. (2020). Utilization of Swertia chirayita plant extracts for management of diabetes and associated disorders: Present status, future prospects and limitations. Natural Products and Bioprospecting, 10, 431-443. [CrossRef]
• 89. Yao, X.G., Chen, F., Li, P., Quan, L., Chen, J., Yu, L., Shen, X. (2013). Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models. Journal of Ethnopharmacology, 150(1), 285-297. [CrossRef]
• 90. Elhassaneen, Y., Ragab, S., Abd El-Rahman, A., Arafa, S. (2021). Vinca (Catharanthus roseus) extracts attenuate alloxan-induced hyperglycemia and oxidative stress in rats. American Journal of Food Science and Technology, 9(4), 161-172.
• 91. Suryavanshi, A., Kumar, S., Kain, D. (2019). Medicinal plants: A source of antidiabetic drugs. Journal of Drug Research in Ayurvedic Science, 4(1), 39-45.
• 92. Kravchenko, G., Krasilnikova, O., Raal, A., Mazen, M., Chaika, N., Kireyev, I., Koshovyi, O. (2022). Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation for the management of insulin resistance: Chemical analysis and bioactivity. Natural Products and Bioprospecting, 12(1), 30. [CrossRef]
• 93. Ononamadu, C.J., Alhassan, A.J., Imam, A.A., Ibrahim, A., Ihegboro, G.O., Owolarafe, A.T., Sule, M.S. (2019). In vitro and in vivo anti-diabetic and anti-oxidant activities of methanolic leaf extracts of Ocimum canum. Caspian Journal of Internal Medicine, 10(2), 162.
• 94. Jacob, B., Narendhirakannan, R.T. (2019). Role of medicinal plants in the management of diabetes mellitus: A review. 3 Biotech, 9, 1-17. [CrossRef]
• 95. Prabhakar, P.K., Doble, M. (2008). A target based therapeutic approach towards diabetes mellitus using medicinal plants. Current Diabetes Reviews, 4(4), 291-308.
• 96. Khanum, F. (2021). Therapeutic Foods: An Overview. Advances in Processing Technology, CRC Press, 31-70.93.
• 97. Purintrapiban J, Suttajit M, Forsberg N.E. (2006). Differential activation of glucose transport in cultured muscle cells by polyphenolic compounds from Canna indica L. root. Biological and Pharmceutical Bulletin, 29(10), 1995-1998. [CrossRef]
• 98. Klein, G., Kim, J., Himmeldirk, K., Cao, Y., Chen, X. (2007). Antidiabetes and anti-obesity activity of Lagerstroemia speciosa. Evidence-Based Complementary and Alternative Medicine, 4, 401-407. [CrossRef]
• 99. Xu, H.Q., Hao, H.P. (2004). Effects of iridoid total glycoside from Cornus officinalis on prevention of glomerular overexpression of transforming growth factor beta 1 and matrixes in an experimental diabetes model. Biol Pharm Bull, 27(7), 1014-1018.
• 100. Lyu, S.Y., Shin, A.H., Hahn, D.R., Park, W.B. (2012). Antioxidant activity of cyanidins isolated from Ogapy (Acanthopanax divaricatus var. albeofructus) fruits in U937 macrophages. Food Science and Biotechnology, 21, 1445-1450. [CrossRef]
• 101. Afzal, I., Cunningham, P., Naftalin, R.J. (2002). Interactions of ATP, oestradiol, genistein and the anti-oestrogens, faslodex (ICI 182780) and tamoxifen, with the human erythrocyte glucose transporter, GLUT1. Biochemical Journal, 365(3), 707-719. [CrossRef]
• 102. Visvanathan, R., Williamson, G. (2023). Citrus polyphenols and risk of type 2 diabetes: Evidence from mechanistic studies. Critical Reviews in Food Science and Nutrition, 63(14), 2178-2202. [CrossRef]
• 103. Gao, J.L., Chen, Y.G. (2015). Natural compounds regulate glycolysis in hypoxic tumor microenvironment. BioMed Research International, 354143, 8. [CrossRef]
• 104. Zygmunt, K. (2009). Master Thesis. Effects of Naringenin on Glucose Uptake in L6 Skeletal Muscle Cells, Health Sciences, Brock University St. Catharines, ON.
• 105. Strobel, P., Allard, C., Perez-Acle, T., Calderon, R., Aldunate, R., Leighton, F. (2005). Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochemical Journal, 386(3), 471-478. [CrossRef]
• 106. Lee, A., Gu, H., Gwon, M.H., Yun, J.M. (2021). Hesperetin suppresses LPS/high glucose-induced inflammatory responses via TLR/MyD88/NF-κB signaling pathways in THP-1 cells. Nutrition Research and Practice, 15(5), 591. [CrossRef]
• 107. Hsieh, C.F., Tsuei, Y.W., Liu, C.W., Kao, C.C., Shih, L.J., Ho, L.T., Kao, Y.H. (2010). Green tea epigallocatechin gallate inhibits insulin stimulation of adipocyte glucose uptake via the 67-kilodalton laminin receptor and AMP-activated protein kinase pathways. Planta medica, 76(15), 1694-1698.
• 108. Nomura, M., Takahashi, T., Nagata, N., Tsutsumi, K., Kobayashi, S., Akiba, T., Miyamoto, K.I. (2008). Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells. Biological and Pharmaceutical Bulletin, 31(7), 1403-1409. [CrossRef]
• 109. Harmon, A.W., Patel, Y.M. (2004). Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: A mechanism for impaired cellular proliferation. Breast Cancer Research and Treatment, 85, 103-110. [CrossRef] 110. Zygmunt, K., Faubert, B., MacNeil, J., Tsiani, E. (2010). Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK. Biochemical and Biophysical Research Communications, 398(2), 178-183. [CrossRef]
• 111. Nomura, M., Takahashi, T., Nagata, N., Tsutsumi, K., Kobayashi, S., Akiba, T., Miyamoto, K.I. (2008). Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells. Biological and Pharmaceutical Bulletin, 31(7), 1403-1409. [CrossRef]
• 112. Rosenzweig, T., Sampson, S.R. (2021). Activation of insulin signaling by botanical products. International Journal of Molecular Sciences; 22(8), 4193. [CrossRef]
• 113. Strobel, P., Allard, C., Perez-Acle, T., Calderon, R., Aldunate, R., Leighton, F. (2005). Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochemical Journal, 386(3), 471-478. [CrossRef]
• 114. Shriwas, P. (2020). PhD Thesis. Characterization of a novel glucose transporter protein inhibitor as an anticancer agent. Department of Molecular and Cellular Biology, College of Arts and Sciences, Ohio University.
• 115. Shao, L., Liu, K., Huang, F., Guo, X., Wang, M., Liu, B. (2013). Opposite effects of quercetin, luteolin, and epigallocatechin gallate on insulin sensitivity under normal and inflammatory conditions in mice. Inflammation, 36, 1-14. [CrossRef]
• 116. Majumder, P., Paridhavi, M. (2019). A novel poly‐herbal formulation hastens diabetic wound healing with potent antioxidant potential: A comprehensive pharmacological investigation. Pharmacognosy Journal; 11(2), 324-331.
• 117. Majumder, P., Paridhavi, M. (2019). Hypoglycaemic activity of a novel polyherbal formulation in streptozotocin-induced diabetic rats: A therapeutic study. Asian Journal of Pharmaceutical and Clinical Research, 12(3), 218-223.
• 118. Ye, S., Shao, Q., Zhang, A. (2017). Anoectochilus roxburghii: A review of its phytochemistry, pharmacology, and clinical applications. Journal of Ethnopharmacology, 209, 184-202. [CrossRef]
• 119. Ghosh, T., Maity, T.K., Singh, J. (2011). Antihyperglycemic activity of bacosine, a triterpene from Bacopa monnieri, in alloxan-induced diabetic rats. Planta Medica, 77, 804-808. [CrossRef]
• 120. Potdar, D., Hirwani, R.R., Dhulap, S. (2012). Phyto-Chemical and pharmacological applications of Berberis aristata. Fitoterapia, 83, 817-830. [CrossRef]
• 121. Kobayashi, K., Ishihara, T., Khono, E., Miyase, T., Yoshizaki, F. (2006). Constituents of stem bark of callistemon rigidus showing inhibitory effects on mouse alpha-amylase activity. Biology and Pharma Bulletin, 29, 1275-1277. [CrossRef]
• 122. Eddouks, M, Lemhadri, A, Zeggwagh, N.A., Michel, J.B. (2005). Potent hypoglycaemic activity of the aqueous extract of Chamaemelum nobile in normal and streptozotocin-induced diabetic rats. Diabetes Research and Clinical Practices, 67, 189-195. [CrossRef]
• 123. Rani, M.P., Krishna, M.S., Padmakumari, K.P., Raghu, K.G., Sundaresan, A. (2012). Zingiber officinale extract exhibits antidiabetic potential via modulating glucose uptake, protein glycation and inhibiting adipocyte differentiation: An in vitro study. Journal of Science of Food and Agriculture, 92, 1948-1955. [CrossRef]
• 124. Ezzat, S.M., Ezzat, M.I., Okba, M.M., Menze, E.T., Abdel-Naim, A.B. (2018). The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity. Journal of Ethnopharmacology, 214, 113-123. [CrossRef]
• 125. Kim K.S., Yang H.J., Lee I.S., Kim K.H., Park J., Jeong H.S., Kim Y., Ahn K.S., Na Y.C., Jang H.J. (2015). The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. Scientific Reports, 5, 18325. [CrossRef]
• 126. Sanlier, N., Gencer, F. (2020). Role of spices in the treatment of diabetes mellitus: A minireview. Trends Food Science and Technology, 99, 441-449. [CrossRef]
• 127. Shane-McWhorter, L. (2001). Biological complementary therapies: A focus on botanical products in diabetes. Diabetes Spectrum, 14, 199-208. [CrossRef]
• 128. Shehadeh, Mayadah Bashir, Ghadeer A.R.Y. Suaifan, Ala’ Mustafa Abu-Odeh. (2021). Plants secondary metabolites as blood glucose-lowering molecules. Molecules, 26(14), 4333. [CrossRef]
• 129. Przeor, M. (2022). Some common medicinal plants with antidiabetic activity, known and available in europe (a mini review). Pharmaceuticals (Basel), 4, 15(1), 65. [CrossRef]