Plants Today Drugs Tomorrow: Cordia grandicalyx A Possible Future Anti-Hypoglycaemic?

Document Type : Research Paper

Authors

1 Department of Biomedical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, South Africa

2 Department of Biochemistry, Sefako Makgatho Health Science University, Medunsa, South Africa

Abstract

Lowering blood glucose levels by enhancing glucose uptake and GLUT4 translocation is an important strategy in glucose homeostasis in insulin-sensitive tissues. Similarly, traditional medicinal plants are used by several traditional healers, and plants are a possible avenue for the discovery and development of antidiabetic drugs. The study aimed to investigate the effects of Cordia grandicalyx Oberm.  bark, fruit, and leaf extracts through glucose uptake activity by preadipocytes, liver and skeletal muscle cells, relative to their capability on increasing GLUT4 translocation. In addition, the protein expression and phosphorylation of diabetes-related proteins were performed. The C. grandicalyx extracts increased glucose uptake activity by enhancing GLUT4 translocation. Moreover, it was established that the co-usage of insulin with plant extracts increased the glucose uptake activity in comparison to insulin. The extracts upregulated total insulin receptor substrate expression and increased the phosphorylation of Akt levels. This data, therefore, suggests that C. grandicalyx enhances glucose uptake by modulating insulin signalling, potentially through GLUT4 translocation and upregulation of diabetes-related proteins, possibly mimicking the PI3-K/Akt pathway. This, therefore, suggests that C. grandicalyx is a possible candidate for the management of diabetes.

Keywords

References

  1. Arnold S.E., Arvanitakis Z., Macauley R,, Shannon L., Koenig A.M., Wang H., Yan A., Rexford S., Craft S., Gandy S.B., Christoph S., Luke E. Holtzman D.M., Nathan D.M. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nature Reviews Neurology. 2018;14 (3):168-181.
  2. Olson A.L., Humphries K.. Recent advances in understanding glucose transport and glucose disposal. 2020;9:F1000.
  3. Kim S.H., Park Mi.Jung. Effects of growth hormone on glucose metabolism and insulin resistance in human. Annals of Pediatric Endocrinology & Metabolism. 2017;22 (3):145-152.
  4. Schreiber I., Dörpholz G., Ott C.Eric., Kragesteen B., Schanze N., Lee C.Th., Köhrle J., Mundlos S., Ruschke K., Knaus P. BMPs as new insulin sensitizers: enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation. Scientific Reports. 2017;7 (1):1-3.
  5. Ceddia R.B. Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis. Inter J Obesity. 2005;29 (10):1175-1183.
  6. Kalinkovich A., Gregory L. Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Reviews. 2017;35:200-21.
  7. Kumar Guru I.P., Chandrakumar A., Lite S.S., Saraswathi CH., Arasu N.T., Al-Dhabi M.V, Arshad N.A., Jesu A.A. Molecular process of glucose uptake and glycogen storage due to hamamelitannin via insulin signalling cascade in glucose metabolism. Molecular Biology Reports. 2020;47:6727–6740.
  8. Świderska Ewa., Adam Wróblewski J.S., Szemraj J., Drzewoski J., ŚliwińskaA. Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake. Blood Glucose Levels. 2018;1:1-18.
  9. Sayem A.S.M., Arya A., Karimian H., Krishnasamy N., Hasamnis A.A., Hossain Ch.F. Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation. Molecules. 2018;23 (2):258.
  10. Zlobin A., Bloodworth J.C., Osipo C. Mitogen-activated protein kinase (MAPK) signaling. Predictive Biomarkers in Oncology. Springer, Cham. 2019;213-221.
  11. Leite N.C., Salles, G.F., Araujo A.L.E., Villela-Nogueira C.A., Cardoso C.R.L. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Inter. 2009;29(1):113-119.
  12. Pillon N.J., Frendo-Cumbo S., Jacobson M.R., Liu Zh., Milligan P.L., Bui H.H., Zierath J.R., Bilan Ph.J., Brozinick J.T., Klip A. Cell-autonomous sphingolipid changes do not underlie fatty acid-induced insulin resistance of GLUT4 translocation or pro-inflammatory signaling in muscle cells. J Lipid Res. 2018;59(7):1148-1163
  13. Ueda M., Nishiumi S., Nagayasu H., Fukuda I., Yoshida K, Ashida H. Epigallocatechin gallate promotes GLUT4 translocation in skeletal muscle. Biochemical and Biophysical Res Communications. 2008;377(1):286-290.
  14. Vijayakumar A., Aryal P., Wen J., Syed I., Vazirani R.P., Moraes-Vieira P.M., Camporez JP, Gallop M.R., Perry R.J., Peroni O.D., Shulman G.I., Saghatelian A., McGraw T.E., Kahn B.B. Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes Systemic Insulin Resistance and Impairs Glucose Transport. Cell Rep. 2017;21(4):1021-1035.
  15. Araujo Nunes E., Rafacho A. Implications of Palmitoleic Acid (Palmitoleate) On Glucose Homeostasis, Insulin Resistance and Diabetes. Current Drug Targets. 2017;18(6):619-628.
  16. Huang X., Liu G., Guo J., Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. International J Biological Sci. 2018;14(11):1483-1496.
  17. Fatemeh J.K., Zahra L., Hossein A.KH. Medicinal plants: Past history and future perspective. J Herbmed Pharmaco. 2018;7 (1):1-7.
  18. Süntar I. Importance of ethnopharmacological studies in drug discovery: role of medicinal plants. Phytochemistry Reviews. 2020;19 (5):1199-1209.
  19. Shanak S., Saad B., Zaid H. Metabolic and Epigenetic Action Mechanisms of Antidiabetic Medicinal Plants. Evidence-Based Complementary and Alternative Med. 2019;3583067.
  20. Unuofin J.O., Lebelo S.L. Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review. Oxidative Med & Cell Longevity. 2020;1356893.
  21. Wickramasinghe A.S.D., Kalansuriya P., Attanayake A.P. Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus. Evidence-Based Complementary & Alternative Medicine. 2021;2920530.
  22. Fatima S., Akhtar M.F., Ashraf K.M., Sharif A., Saleem A., Akhtar B., Peerzada S., Shabbir M., Ali S., Ashraf W. Antioxidant and alpha amylase inhibitory activities of Fumaria officinalis and its antidiabetic potential against alloxan induced diabetes. Cell & Mol Biol. 2019;65(2):50–57.
  23. Salmi D., Riou C., Issawi M., Titouche Y., Ambrosini V., Smail-Saadoun N., Abbaci H., Houali K. Antibacterial and antioxidant activities of endophytic fungi and nettle (Urtica dioica L.) leaves as their host. Cell & Mol Biol. 2021;67 (3),204–211.
  24. Oza M.J., Kulkarni Y.A. Traditional uses, phytochemistry and pharmacology of the medicinal species of the genus Cordia (Boraginaceae). J Pharmacy & Pharmaco. 2017;6(7):755-789.
  25. Prajapati S., Kar M., Maurya S., Pandey R., Dhakar R.C. Exploring phytochemicals and pharmacological uses of Cordia dichotoma (Indian Cherry): a review. J Drug Delivery and Therapeutics. 2017;7(6):125-131.
  26. Heinrich M., Ankli A., Frei B., Weimann C., Sticher O. Medicinal plants in Mexico: healers' consensus and cultural importance. Social Sci Med. 1998;47(11):1859-1871.
  27. Pu J., Li Linghai P.G., Liu N.H., Liu Pingsheng Y. Palmitic acid acutely stimulates glucose uptake via activation of Akt and ERK1/2 in skeletal muscle cells. J Lipid Res. 2011;527):1319-1327.
  28. Kadan S., Bashar S., Yoel S., Hilal Z. In Vitro Evaluations of Cytotoxicity of Eight Antidiabetic Medicinal Plants and Their Effect on GLUT4 Translocation. Evidence-Based Complementary and Alternative Medicine. 2013;549345.
  29. Anandharajan R., Jaiganesh S., Shankernarayanan N.P., Viswakarma R.A., Balakrishnan A. In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARγ in L6 myotubes. Phytomedicine. 2006;13 (6):434-441.
  30. Ben Khedher M.R.M., Arch M., Jonathan R.S. Hislop David C., Wargent E.D., Edward T. Kępczyńska, Małgorzata A. Zaibi, Mohamed S. Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone. 2018;6:e4166.
  31. Yang Q., W. Y., Shen J, Chen M.M., Wen J.H., Li Z.M., Liang Y.Z., Xia N. Guava Leaf Extract Attenuates Insulin Resistance via the PI3K/Akt Signaling Pathway in a Type 2. Diabetes Metab Syndr Obes. 2020;13:713-718.
  32. Fahmida A., Islam A., Khalil I., Hua Gan S. Metabolic Control of Type 2 Diabetes by Targeting the GLUT4 Glucose Transporter: Intervention Approaches. Current Pharmaceutical Design. 2016;22:3034-3049.
  33. Babu S., Madhan K., Ponnulakshmi R., Vijayalakshmi P., Vishnupriya V., Ramajayam G., Selvaraj J. Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats. European J Pharmaco. 2020;873:173004.
  34. Dai B., Qinxuan Wu., Chengxi Z., Jiani Z., Luting C., Zizeng X., Menglin Y. The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance. J Ethnopharmaco. 2016;192:382-389.
  35. Boucher J., André K., Kahn C. Ronald. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harbor Perspectives in Biology. 2014;6 (1):a009191.
  36. Fischer A.W., Kirstin A., Christian S., Frederike S., Krott Lucia M., Hartwig S., Philip G., Ludger S., Joerg H. PID1 regulates insulin-dependent glucose uptake by controlling intracellular sorting of GLUT4-storage vesicles. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2019;1865 (6):1592-1603.
  37. Yang J., Hamid S., Cai J., Liu Q., Xu S., Zhang Z. Selenium deficiency-induced thioredoxin suppression and thioredoxin knock down disbalanced insulin responsiveness in chicken cardiomyocytes through PI3K/Akt pathway inhibition. Cellular Signalling. 2017;38:192-200.
  38. Li R., Chen Q., Liu O., Tan B., Dong X., Chi S., Yang Q., Zhang S. Molecular characterization and expression analysis of glucose transporter 4 from Trachinotus ovatus, Rachycentron canadums and Oreochromis niloticus in response to different dietary carbohydrate-to-lipid ratios. Aquaculture. 2019;501:430-440.
  39. Huang X., Liu G., Guo J.S.Z. The PI3K/AKT pathway in obesity and type 2 diabetes." Inter J Biological sci. 2018;14 (11):1483-1496.
  40. Anurag M., Prasad G.G. Antidiabetic activity of Alangium Salvifolium in alloxan induced diabetic rats. Inter Res J Pharmacy. 2011;6:101-105.
  41. Ezequiel V.V., Azucena O.C., Javier M.M., Pilar C.R. Antioxidant, cytotoxic and alpha-glucosidase inhibition activities from the Mexican berry “Anacahuita” (Cordia boissieri). Órgano Oficial de la Sociedad Latinoamericana de Nutrición. 2016;66 (3):211-218.
  42. Jamkhande P.G., Barde S.R., Patwekar S.L., Tidke P.S. Plant profile, phytochemistry and pharmacology of Cordia dichotoma (Indian cherry): A review. Asian Pacific J Tropical Biomedicine. 2013;3(12):1009-1012.
  43. Nazim H., Dr. Kakoti B.B. Review on ethnobotany and phytopharmacology of Cordia dichotoma. J Drug Delivery & Therapeutics. 2013;3(1):110-113.
  44. Wang Z.F., Pan Z.Y, Xu C.S, Li Z.Q. Activation of G-protein coupled estrogen receptor 1 improves early-onset cognitive impairment via PI3K/Akt pathway in rats with traumatic brain injury. Bioch & Biophysical Res Communications. 2017;482(4):948-953.
  45. Klip A., McGraw T.E., James D.E. Thirty sweet years of GLUT4. J Biological Chem. 2019;294 (30):11369-11381.
Journal of Medicinal plants and By-product
Volume 12, Issue 1
March 2023
Pages 93-105

Files

Share

How to cite

Statistics