Journal of Medicinal and Aromatic Plant Sciences

Volume: 43 Issue: 3

  • subscription
  • Original Research Article

Dactyloidin from Myristica fatua Houtt. seed enhances glucose uptake through translocation of GLUT4 via upregulation of AMPK in L6 myotubes

PRABHA B1, SINI S2, SHERIN DR3, NEETHU S1,4, GOVIND MG5, DAN M6,*, MANOJKUMAR TK3,*, JAYAMURTHY P2,4,*, RADHAKRISHNAN KV4,*

*Corresponding author; Email: [email protected]
1Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram- 695019, India, 2Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram-695019, India, 3School of Digital Sciences, Kerala University of Digital Sciences Innovation and Technology, Thiruvananthapuram-695 317, India, 4Academy of Scientific and Innovative Research (AcSIR), Thiruvananthapuram-695019, India, 5Plant Genetics Resource Division, Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Palode, Thiruvananthapuram-695562, India.
 

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

Abstract

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

References

Adrover M, Laura MarinÞ, Sanchis P, Pauwels K, Kraan Y, Lebrun P, Vilanova B, MunÞoz F, Broersen K, Donoso J. 2014. Mechanistic insights in glycationinduced protein aggregation. Biomacromolecules 15: 3449-3462.

Ajish KR, Antu KA, Riya MP, Preetharani MR, Raghu KG, Dhanya BP, Radhakrishnan KV. 2015. Studies on á-glucosidase, aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith. Nat Prod Res 29: 947-952.

Apostolidis E, Kwon YI, Shetty K. 2007. Inhibitory potential of herb, fruit, and fungal- enriched cheese against key enzymes linked to type 2 diabetes and hypertension. Innov Food Sci Emerg 8: 46-54.

Burnette WN. 1981. Western blotting: electrophoretic transfer of proteins from sodium dodecyl sulfatepolyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 112: 195-203.

DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, Hu FB, Kahn CR, Raz I, Shulman GI, Simonson DC, Testa MA, Weiss R. 2015. Type 2 diabetes mellitus. Nat Rev Dis Primers 1:1-22.

Dhanya BP, Gopalan G, Reshmitha TR, Saranya J, Sharathna P, Shibi IG, Nisha P, Radhakrishnan KV. 2017. Synthesis and in vitro evaluation of zerumbone pendant derivatives: potent candidates for antidiabetic and anti-proliferative activities. New J Chem 41: 6960-6964.

Fajriah S, Darmawan A, Megawati, Hudiyono S, Kosela S, Hanafi M. 2017. New cytotoxic compounds from Myristica fatuaHoutt. Leaves against MCF-7 cell lines. Phytochem Lett 20: 36-39.

Gopalan G, Prabha B, Joe A, Reshmitha TR, Sherin DR, Sabu M, Manojkumar TK, Radhakrishnan KV, Nisha P. 2019. Antidiabetic properties of apiforol, a potential lead isolated from the seeds of Musa balbisiana. J Sci Food Agric 99: 2521-2529.

Gopalan G, Dhanya BP, Saranya J, Reshmitha TR, Baiju TV, Meenu MT, Mangalam SN, Nisha P, Radhakrishnan KV. 2017. Metal free trans aziridination of zerumbone: Synthesis and biological evaluation of aziridine derivatives of zerumbone. Eur J Org Chem 3072-3077.

Herath HMTB, Priyadarshani AMA, Jamie J. 1998. Dactyloidin, a new diarylnonanoid from Myristica dactyloides. Nat Prod Lett 12: 91-95.

Huang S, Czech MP, 2007. The Glut4 glucose transporter. Cell Metab 5: 237 -252.

Jedsadayanmata A. 2005. In vitro antiglycation activity of arbutin. J Naresun Univ 13: 35-41.

Kim Y, Park CW. 2016. Adenosine monophosphate– activated protein kinase in diabetic nephropathy. Kidney Res Clin Pract 35: 69-77.

Megawati, Darmawan A. 2017. Resorcinol compounds isolated from the bark of Myristica fatuaHoutt. Indonesian J Pharm 28: 82-90.

Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 65: 55-63.

Pandey R, Mahar R, Hasanain M, Shukla SK, Sarkar J, Rameshkumar KB, Kumar B, 2016. Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and they’re in vitro antiproliferative activity. Food Chem 211: 483-493.

Prabha B, Neethu S, Lekshmy Krishnan S, Sherin DR, Madhukrishnan M, Ananthakrishnan R, Rameshkumar KB, Manojkumar TK, Jayamurthy P, Radhakrishnan KV. 2018. Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatuaHoutt. var. Magnifica (Bedd.) Sinclair. Bioorg Med Chem 26: 3461-3467.

Prabha B, Sini S, Sherin DR, Neethu S, Rameshkumar KB, Manojkumar TK, Jayamurthy P, Radhakrishnan KV. 2019. Promalabaricone B from Myristica fatuaHoutt. var. Magnifica(Bedd.) Sinclair seeds demonstrate antidiabetic potential by inhibiting carbohydrate hydrolyzing enzymes protein glycation and modulating glucose uptake via the activation of AMPK in L6 myotubes. Nat Prod Reshttps://doi.org/10.1080/14786419. 1607852.

Prabhakar PK, Doble M. 2011. Interaction of cinnamic acid derivatives with commercial hypoglycemic drugs on 2-deoxyglucose uptake in 3T3-L1 adipocytes. J Agric Food Chem 59: 9835-9844.

Ren LM, Qin XH, Cao XF, Wang LL, Bai F, Bai G, Shen Y. 2011. Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Prot Cell 2: 827-836.

Sasikumar P, Lekshmy K, Sini S, Prabha B, Kumar NA, Sivan VV, Jithin MM, Jayamurthy P, Shibi IG, Radhakrishnan KV. 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. J Ethnopharmacol 236: 196-204.

Sasikumar P, Prabha B, Reshmitha TR, Sheeba V, Pradeep AK, Rohit KR, Dhanya BP, Sivan VV, Jithin MM, Anil Kumar N, Shibi IG, Nisha P, Radhakrishnan KV. 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 Adv 6: 77075- 77082.

Sasikumar P, Sharathna P, Prabha B, Varughese S, Kumar NA, Sivan VV, Sherin DR, Suresh E, Manojkumar TK, Radhakrishnan KV. 2018. Dihydro-ß-agarofuran sesquiterpenoids from the seeds of Celastrus paniculatus Willd. and their α- glucosidase inhibitory activity. Phytochem Lett 26: 1-8.

Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR. 2008. Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol 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 lisproin L6 skeletal muscle cells. Clin Ther 20: 125-140.

Tamrakar AK, Jaiswal N, Yadav PP, Maurya R, Srivastava AK. 2011. Pongamol from Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4 levels in skeletal muscle cells. Mol Cell Endocrinol 339: 98-104.

Trapero A, Llebaria A. 2012. A prospect for pyrrolidine iminosugars as antidiabetic ß-glucosidase inhibitors. J Med Chem 55: 10345-10346.

Victor JN, John RS. 2006. Drug-related hepatotoxicity. N Engl J Med 354: 731-739.

Williams LK, Li C, Withers SG, Brayer GD. 2012. Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. J Med Chem 55: 10177-10186.

Xio Z, Storms R, Tsang A. 2006. A quantitative starch– iodine method for measuring alpha-amylase and glucoamylase activities. Anal Biochem 351: 146-148.
 

Cite this article

Prabha B, Sini S, Sherin DR, Neethu S, Govind MG, Dan M, Manojkumar TK, Jayamurthy P, Radhakrishnan KV. 2021. Dactyloidin from Myristica fatua Houtt. seed enhances glucose uptake through translocation of GLUT4 via upregulation of AMPK in L6 myotubes. J Med aromat Plant Sci 43: 108-116.

Views
312
Downloads
1
Citations