Molecular Docking Analysis of Ginger Active Compound on Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1)

https://doi.org/10.22146/ijc.28172

Fifteen Aprila Fajrin(1*), Agung Endro Nugroho(2), Rina Susilowati(3), Arief Nurrochmad(4)

(1) Faculty of Pharmacy, University of Jember
(2) Faculty of Pharmacy, Universitas Gadjah Mada
(3) Faculty of Medicine, Universitas Gadjah Mada
(4) Faculty of Pharmacy, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Ginger had been reported to ameliorate painful diabetic neuropathy (PDN) in an animal model. Gingerol and shogaol were active compounds of ginger that potentially act on transient receptor potential cation channel subfamily V member 1 (TRPV1), a key receptor in PDN. This study aims to predict the binding of gingerol and shogaol to TRPV1 using an in silico model. The ligands of the docking study were 3 chemical compounds of each gingerol and shogaol, i.e. 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8 gingerol and 10-gingerol. Capsaicin, a TRPV1 agonist, was used as a native ligand. The TRPV1 structure was taken from Protein Data Bank (ID 3J9J). The docking analysis was performed using Autodock Vina. The result showed that among the ginger active compounds, 6-shogaol had the strongest binding energy (-7.10 kcal/mol) to TRPV1. The 6-shogaol lacked the potential hydrogen bond to Ile265 of TRPV1 protein, which capsacin had. However, it's binding energy towards TRPV1 was not significantly different compared to capsaicin. Therefore, 6-shogaol had potential to be developed as a treatment for PDN.

Keywords


gingerol; shogaol; diabetes mellitus; painful diabetic neuropathy; TRPV1

Full Text:

Full Text PDF


References

[1] Alleman, C.J.M., Westerhout, K.Y., Hensen, M., Chambers, C., Stoker, M., Long, S., and van Nooten, F.E., 2015, Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature, Diabetes Res. Clin. Pract., 109 (2), 215–225.

[2] Whiting, D.R., Guariguata, L., Weil, C., and Shaw, J., 2011, IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030, Diabetes Res. Clin. Pract., 94 (3), 311–321.

[3] Shaw, J.E., Sicree, R.A., and Zimmet, P.Z., 2010, Global estimates of the prevalence of diabetes for 2010 and 2030, Diabetes Res. Clin. Pract., 87 (7), 4–14.

[4] Hartemann, A., Attal, N., Bouhassira, D., Dumont, I., Gin, H., Jeanne, S., Said, G., and Richard, J.L., 2011, Painful diabetic neuropathy: Diagnosis and management, Diabetes Metab., 37 (5), 377–388.

[5] Pabbidi, R.M., Yu, S.Q., Peng, S., Khardori, R., Pauza, M.E., and Premkumar, L.S., 2008, Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity, Mol. Pain, 4 (9).

[6] Luongo, L., Costa, B., D’Agostino, B., Guida, F., Comelli, F., Gatta, L., Matteis, M., Sullo, N., De Petrocellis, L., de Novellis, V., Maione, S., and Di Marzo, V., 2012, Palvanil, a non-pungent capsaicin analogue, inhibits inflammatory and neuropathic pain with little effects on bronchopulmonary function and body temperature, Pharmacol. Res., 66 (3), 243–250.

[7] Zhuo, M., 2013, Long-term potentiation in the anterior cingulate cortex and chronic pain, Philos. Trans. R. Soc. London, Ser. B, 369, 20130146.

[8] Haanpää, M., and Hietaharju, A., 2015, Halting the march of painful diabetic neuropathy, Pain Clin. Updates, 23 (2), 1–8.

[9] Brito, R., Sheth, S., Mukherjea, D., Rybak, L.P., and Ramkumar, V., 2014, TRPV1: A potential drug target for treating various diseases, Cells, 3 (3), 517–545.

[10] Shaqura, M., Khalefa, B.I., Shakibaei, M., Zöllner, C., Al-Khrasani, M., Fürst, S., Schäfer, M., and Mousa, S.A., 2014, New insights into mechanisms of opioid inhibitory effects on capsaicin-induced TRPV1 activity during painful diabetic neuropathy, Neuropharmacology, 85, 142–150.

[11] Chrubasik, S., Pittler, M.H., and Roufogalis, B.D., 2005, Zingiberis rhizoma: A comprehensive review on the ginger effect and efficacy profiles, Phytomedicine, 12 (9), 684–701.

[12] Semwal, R.B., Semwal, D.K., Combrinck, S., and Viljoen, A.M., 2015, Gingerols and shogaols: Important nutraceutical principles from ginger, Phytochemistry, 117, 554–568.

[13] Dedov, V.N., Tran, V.H., Duke, C.C., Connor, M., Christie, M.J., Mandadi, S., and Roufogalis, B.D., 2002, Gingerols: A novel class of vanilloid receptor (VR1) agonists, Br. J. Pharmacol., 137 (137), 793–798.

[14] Lu, D.L., Li, X.Z., Dai, F., Kang, Y.F., Li, Y., Ma, M.M., Ren, X.R., Du, G.W., Jin, X.L., and Zhou, B., 2014, Influence of side chain structure changes on antioxidant potency of the [6]-gingerol related compounds, Food Chem., 165, 191–197.

[15] Morera, E., De Petrocellis, L., Morera, L., Moriello, A.S., Nalli, M., Di Marzo, V., and Ortar, G., 2012, Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators, Bioorg. Med. Chem. Lett., 22 (4), 1674–1677.

[16] Dugasani, S., Pichika, M.R., Nadarajah, V.D., Balijepalli, M.K., Tandra, S., and Korlakunta, J.N., 2010, Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol, J. Ethnopharmacol., 127 (2), 515–520.

[17] Herowati, R., and Widodo, G.P., 2014, Molecular docking studies of chemical constituents of Tinospora cordofolia on glycogen phosphorylase, Procedia Chem., 13, 63–68.

[18] Trott, O.A., and Olson, J., 2011, Autodock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, J. Comput. Chem., 31 (2), 455–461.



DOI: https://doi.org/10.22146/ijc.28172

Article Metrics

Abstract views : 5008 | views : 3863


Copyright (c) 2017 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.