Volume: 43 Issue: 3
Dactyloidin from Myristica fatua Houtt. seed enhances glucose uptake through translocation of GLUT4 via upregulation of AMPK in L6 myotubes
Year: 2021, Page: 108-116, Doi: https://doi.org/10.62029/jmaps.v43i3.Prabha
Received: June 12, 2021 Accepted: Oct. 12, 2021 Published: Dec. 31, 2021
Dactyloidin (DTN), a diarylnonanoid, was isolated for the first time from the seeds of Myristica fatua Houtt. DTN displayed significant inhibitory activity on α-glucosidase enzyme with IC50 value of 55.08 ± 0.857 µM. Molecular docking studies showed that DTN effectively binds to the active sites of N- terminal human maltase glucoamylase (3TOP), which supported the observed α-glucosidase inhibition. DTN also exhibited an enhanced glucose uptake in L6 myotubes with 31.5%. Exhilarated with these observations, we investigated the molecular mechanism of DTN by investigating the modulation of AMPK. The results revealed that DTN increased the glucose uptake in L6 myotubes by stimulating the translocation and expression of GLUT4.
Keywords: AMPK pathway, Dactyloidin, Glucose uptake, GLUT4 translocation, Human maltase glucoamylase, -glucosidase inhibition
Adrover, M., Marín, L., Sanchis, P., Pauwels, K., Kraan, Y., Lebrun, P., Vilanova, B., Muñoz, F., Broersen, K., & Donoso, J. (2014). Mechanistic insights in glycation-induced protein aggregation. Biomacromolecules, 15(9), 3449–3462.
Ajish, K. R., Antu, K. A., Riya, M. P., Preetharani, M. R., Raghu, K. G., Dhanya, B. P., & Radhakrishnan, K. V. (2015). Studies on α-glucosidase, aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith. Natural Product Research, 29, 947–952.
Apostolidis, E., Kwon, Y. I., & Shetty, K. (2007). Inhibitory potential of herb-, fruit-, and fungal-enriched cheese against key enzymes linked to type 2 diabetes and hypertension. Innovative Food Science & Emerging Technologies, 8, 46–54.
Burnette, W. N. (1981). Western blotting: Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Analytical Biochemistry, 112, 195–203.
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., Simonson, D. C., Testa, M. A., & Weiss, R. (2015). Type 2 diabetes mellitus. Nature Reviews Disease Primers, 1, 1–22.
Dhanya, B. P., Gopalan, G., Reshmitha, T. R., Saranya, J., Sharathna, P., Shibi, I. G., Nisha, P., & Radhakrishnan, K. V. (2017). Synthesis and in vitro evaluation of zerumbone pendant derivatives: Potent candidates for antidiabetic and anti-proliferative activities. New Journal of Chemistry, 41, 6960–6964.
Fajriah, S., Darmawan, A., Megawati, Hudiyono, S., Kosela, S., Hanafi, M. (2017). New cytotoxic compounds from Myristica fatua Houtt. leaves against MCF-7 cell lines. Phytochemistry Letters, 20, 36–39.
Gopalan, G., Prabha, B., Joe, A., Reshmitha, T. R., Sherin, D. R., Sabu, M., Manojkumar, T. K., Radhakrishnan, K. V., & Nisha, P. (2019). Antidiabetic properties of apiforol, a potential lead isolated from the seeds of Musa balbisiana. Journal of the Science of Food and Agriculture, 99, 2521–2529.
Gopalan, G., Dhanya, B. P., Saranya, J., Reshmitha, T. R., Baiju, T. V., Meenu, M. T., Mangalam, S. N., Nisha, P., & Radhakrishnan, K. V. (2017). Metal-free trans-aziridination of zerumbone: Synthesis and biological evaluation of aziridine derivatives of zerumbone. European Journal of Organic Chemistry, 3072–3077.
Herath, H. M. T. B., Priyadarshani, A. M. A., & Jamie, J. (1998). Dactyloidin, a new diarylnonanoid from Myristica dactyloides. Natural Product Letters, 12, 91–95.
Huang, S., & Czech, M. P. (2007). The GLUT4 glucose transporter. Cell Metabolism, 5, 237–252.
Jedsadayanmata, A. (2005). In vitro antiglycation activity of arbutin. Journal of Naresuan University, 13, 35–41.
Kim, Y., & Park, C. W. (2016). Adenosine monophosphate–activated protein kinase in diabetic nephropathy. Kidney Research and Clinical Practice, 35, 69–77.
Megawati, Darmawan, A. (2017). Resorcinol compounds isolated from the bark of Myristica fatua Houtt. Indonesian Journal of Pharmacy, 28, 82–90.
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65, 55–63.
Pandey, R., Mahar, R., Hasanain, M., Shukla, S. K., Sarkar, J., Rameshkumar, K. B., & Kumar, B. (2016). Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity. Food Chemistry, 211, 483–493.
Prabha, B., Neethu, S., Krishnan, S. L., Sherin, D. R., Madhukrishnan, M., Ananthakrishnan, R., Rameshkumar, K. B., Manojkumar, T. K., Jayamurthy, P., & Radhakrishnan, K. V. (2018). Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair. Bioorganic & Medicinal Chemistry, 26, 3461–3467.
Prabha, B., Sini, S., Sherin, D. R., Neethu, S., Rameshkumar, K. B., Manojkumar, T. K., Jayamurthy, P., & Radhakrishnan, K. V. (2019). Promalabaricone B from Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair seeds demonstrate antidiabetic potential by inhibiting carbohydrate hydrolyzing enzymes, protein glycation and modulating glucose uptake via activation of AMPK in L6 myotubes. Natural Product Research.
Prabhakar, P. K., & Doble, M. (2011). Interaction of cinnamic acid derivatives with commercial hypoglycemic drugs on 2-deoxyglucose uptake in 3T3-L1 adipocytes. Journal of Agricultural and Food Chemistry, 59, 9835–9844.
Ren, L. M., Qin, X. H., Cao, X. F., Wang, L. L., Bai, F., Bai, G., & Shen, Y. (2011). Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Protein & Cell, 2, 827–836.
Sasikumar, P., Lekshmy, K., Sini, S., Prabha, B., Kumar, N. A., Sivan, V. V., Jithin, M. M., Jayamurthy, P., Shibi, I. G., & Radhakrishnan, K. V. (2019). Isolation and characterization of resveratrol oligomers from the stem bark of Hopea ponga (Dennst.) Mabb. and their antidiabetic effect by modulation of digestive enzymes, protein glycation and glucose uptake in L6 myocytes. Journal of Ethnopharmacology, 236, 196–204.
Sasikumar, P., Prabha, B., Reshmitha, T. R., Sheeba, V., Pradeep, A. K., Rohit, K. R., Dhanya, B. P., Sivan, V. V., Jithin, M. M., Anil Kumar, N., Shibi, I. G., Nisha, P., & Radhakrishnan, K. V. (2016). Comparison of antidiabetic potential of (+)- and (−)-hopeaphenol, a pair of enantiomers isolated from Ampelocissus indica (L.) and Vateria indica Linn., with respect to inhibition of digestive enzymes and induction of glucose uptake in L6 myotubes. RSC Advances, 6, 77075–77082.
Sasikumar, P., Sharathna, P., Prabha, B., Varughese, S., Kumar, N. A., Sivan, V. V., Sherin, D. R., Suresh, E., Manojkumar, T. K., & Radhakrishnan, K. V. (2018). Dihydro-β-agarofuran sesquiterpenoids from the seeds of Celastrus paniculatus Willd. and their α-glucosidase inhibitory activity. Phytochemistry Letters, 26, 1–8.
Sim, L., Quezada-Calvillo, R., Sterchi, E. E., Nichols, B. L., & Rose, D. R. (2008). Human intestinal maltase-glucoamylase: Crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. Journal of Molecular Biology, 375, 782–792.
Somwar, R., Sweeney, G., Ramlal, T., & Klip, A. (1998). Stimulation of glucose and amino acid transport and activation of the insulin signalling pathways by insulin lispro in L6 skeletal muscle cells. Clinical Therapeutics, 20, 125–140.
Tamrakar, A. K., Jaiswal, N., Yadav, P. P., Maurya, R., & Srivastava, A. K. (2011). Pongamol from Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4 levels in skeletal muscle cells. Molecular and Cellular Endocrinology, 339, 98–104.
Trapero, A., & Llebaria, A. (2012). A prospect for pyrrolidine iminosugars as antidiabetic β-glucosidase inhibitors. Journal of Medicinal Chemistry, 55, 10345–10346.
Victor, J. N., & John, R. S. (2006). Drug-related hepatotoxicity. New England Journal of Medicine, 354, 731–739.
Williams, L. K., Li, C., Withers, S. G., & Brayer, G. D. (2012). Order and disorder: Differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. Journal of Medicinal Chemistry, 55, 10177–10186.
Xio, Z., Storms, R., & Tsang, A. (2006). A quantitative starch–iodine method for measuring α-amylase and glucoamylase activities. Analytical Biochemistry, 351, 146–148.
© CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015
Prabha, B., Sini, S., Sherin, D. R., Neethu, S., Govind, M. G., Dan, M., Manojkumar, T. K., Jayamurthy, P., & Radhakrishnan, K. V. (2021). Dactyloidin from Myristica fatua Houtt. seed enhances glucose uptake through translocation of GLUT4 via upregulation of AMPK in L6 myotubes. Journal of Medicinal and Aromatic Plant Sciences, 43(3), 108–116.
