In-silico Assessment of Polyherbal Oils as Anti-diabetic Therapeutics


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Abstract

Background:Diabetes mellitus (DM) is characterized by elevated blood glucose levels either due to insufficient insulin production, defective insulin action, or both. It affects nearly 537 million individuals worldwide. Pharmacological treatment involves the use of oral antidiabetic agents as mono or combination therapy that effectively aids in controlling hyperglycemia. Despite providing therapeutic benefits, these medications limit their use owing to adverse side effects. Certain natural products, including essential oils, have promising anti-diabetic properties.

Objective:The present study explores the effectiveness of two polyherbal oils and their compound towards the treatment of DM based on an In-silico approach to drug investigations.

Methods:Compounds present in the polyherbal oil formulation were identified using GCMS/ MS analysis. Selected compounds undergo molecular docking with the receptor, and proteins play an important role in DM. The potential compounds showing higher interactions than the known inhibitors or inducers were evaluated using molecular dynamic simulations RMSD values.

Results:The compounds identified through GC-MS analysis possess anti-diabetic and antiinflammatory properties. With the aid of in silico prediction methods, compounds such as geraniol, cinnamaldehyde, anethole, caryophyllene, terpinyl acetate, cymene, linalool, menthol, Phenol,2-methoxy-3-(2-propenyl), and 2,6- octadienal,3,7-dimethyl were identified as strong binders of GLUT4 and insulin receptor proteins. Geraniol and Phenol,2-methoxy-3-(2-propenyl) interaction with GLUT4 were of particular importance owing to their conformational stability.

Conclusion:Our data suggest an agonistic effect of compounds on target proteins aiding in enhanced insulin activity and could serve as a potential anti-diabetic agent.

About the authors

Amul Bahl

Department of Research, Development and Innovation,, God’s Own Store LLP

Email: info@benthamscience.net

Vipin Verma

Deptartment of Pharmacology, All India Institute of Medical Sciences

Email: info@benthamscience.net

Vaishali Prajapati

Deptartment of Pharmacology, All India Institute of Medical Sciences

Email: info@benthamscience.net

Jagriti Bhatia

Deptartment of Pharmacology, All India Institute of Medical Sciences

Email: info@benthamscience.net

Dharamvir Arya

Deptartment of Pharmacology, All India Institute of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Magliano, D.J.; Boyko, E.J.; Atlas, I.D. Global picture.IDF Diabetes Atlas, 10th ed; International Diabetes Federation, 2021.
  2. Olokoba, A.B.; Obateru, O.A.; Olokoba, L.B. Type 2 diabetes mellitus: A review of current trends. Oman Med. J., 2012, 27(4), 269-273. doi: 10.5001/omj.2012.68 PMID: 23071876
  3. Wong, C.Y.; Al-Salami, H.; Dass, C.R. Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment. J. Control. Release, 2017, 264, 247-275. doi: 10.1016/j.jconrel.2017.09.003 PMID: 28887133
  4. Brownlee, M. Biochemistry and molecular cell biology of diabetic complications. Nature, 2001, 414(6865), 813-820. doi: 10.1038/414813a PMID: 11742414
  5. Hoogwerf, B.J.; Sferra, J.; Donley, B.G. Diabetes mellitus-overview. Foot Ankle Clin., 2006, 11(4), 703-715. doi: 10.1016/j.fcl.2006.06.014 PMID: 17097511
  6. Padhi, S.; Nayak, A.K.; Behera, A. Type II diabetes mellitus: A review on recent drug based therapeutics. Biomed. Pharmacother., 2020, 131, 110708. doi: 10.1016/j.biopha.2020.110708 PMID: 32927252
  7. Patil, P.D.; Mahajan, U.; Patil, K.R.; Chaudhari, S.; Patil, C.R.; Agrawal, Y.O.; Ojha, S.; Goyal, S.N. Past and current perspective on new therapeutic targets for Type-II diabetes. Drug Des. Devel. Ther., 2017, 11, 1567-1583. doi: 10.2147/DDDT.S133453 PMID: 28579755
  8. Seino, S.; Sugawara, K.; Yokoi, N.; Takahashi, H. β-Cell signalling and insulin secretagogues: A path for improved diabetes therapy. Diabetes Obes. Metab., 2017, 19(Suppl. 1), 22-29. doi: 10.1111/dom.12995 PMID: 28880474
  9. Kalra, S.; Bahendeka, S.; Sahay, R.; Ghosh, S.; Md, F.; Orabi, A.; Ramaiya, K.; Al Shammari, S.; Shrestha, D.; Shaikh, K.; Abhayaratna, S.; Shrestha, P.K.; Mahalingam, A.; Askheta, M.; A Rahim, A.A.; Eliana, F.; Shrestha, H.K.; Chaudhary, S.; Ngugi, N.; Mbanya, J.C.; Aye, T.T.; Latt, T.S.; Akanov, Z.A.; Syed, A.R.; Tandon, N.; Unnikrishnan, A.G.; Madhu, S.V.; Jawa, A.; Chowdhury, S.; Bajaj, S.; Das, A.K. Consensus recommendations on sulfonylurea and sulfonylurea combinations in the management of Type 2 diabetes mellitus–International Task Force. Indian J. Endocrinol. Metab., 2018, 22(1), 132-157. doi: 10.4103/ijem.IJEM_556_17 PMID: 29535952
  10. Rubiño; Carrillo, E.; Alcalá; Domínguez-Martín, A.; Marchal; Boulaiz, H. Phenformin as an anticancer agent: Challenges and prospects. Int. J. Mol. Sci., 2019, 20(13), 3316. doi: 10.3390/ijms20133316 PMID: 31284513
  11. Alam, F.; Islam, M.A.; Mohamed, M.; Ahmad, I.; Kamal, M.A.; Donnelly, R.; Idris, I.; Gan, S.H. Efficacy and safety of pioglitazone monotherapy in type 2 diabetes mellitus: A systematic review and meta-analysis of randomised controlled trials. Sci. Rep., 2019, 9(1), 5389. doi: 10.1038/s41598-019-41854-2 PMID: 30926892
  12. Jain, N.; Bhansali, S.; Kurpad, A.V.; Hawkins, M.; Sharma, A.; Kaur, S.; Rastogi, A.; Bhansali, A. Effect of a dual PPAR α/γ agonist on insulin sensitivity in patients of type 2 diabetes with hypertriglyceridemia- randomized double-blind placebo-controlled trial. Sci. Rep., 2019, 9(1), 19017. doi: 10.1038/s41598-019-55466-3 PMID: 30626917
  13. Fonseca, V.A.; Kulkarni, K.D. Management of type 2 diabetes: oral agents, insulin, and injectables. J. Am. Diet. Assoc., 2008, 108(4)(Suppl. 1), S29-S33. doi: 10.1016/j.jada.2008.01.047 PMID: 18358251
  14. Talaviya, P.A.; Saboo, B.D.; Dodiya, H.G.; Rao, S.K.; Joshi, S.R.; Modh, V.B.; Ghadiya, S.V. Retrospective comparison of voglibose or acarbose as an add-on therapy to sulfonylureas in Western Indian patients with uncontrolled overweight/obese type 2 diabetes. Diabetes Metab. Syndr., 2016, 10(2), 88-91. doi: 10.1016/j.dsx.2015.09.021 PMID: 26777258
  15. Aulinger, B.A.; Bedorf, A.; Kutscherauer, G.; de Heer, J.; Holst, J.J.; Göke, B.; Schirra, J. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes, 2014, 63(3), 1079-1092. doi: 10.2337/db13-1455 PMID: 24296715
  16. Gallwitz, B. Clinical use of DPP-4 inhibitors. Front. Endocrinol., 2019, 10, 389. doi: 10.3389/fendo.2019.00389 PMID: 31275246
  17. Alam, F.; Asiful Islam, M.; Ibrahim Khalil, M.; Hua Gan, S. Metabolic control of type 2 diabetes by targeting the GLUT4 glucose transporter: Intervention approaches. Curr. Pharm. Des., 2016, 22(20), 3034-3049. doi: 10.2174/1381612822666160307145801 PMID: 26951104
  18. Phung, O.J.; Scholle, J.M.; Talwar, M.; Coleman, C.I. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA, 2010, 303(14), 1410-1418. doi: 10.1001/jama.2010.405 PMID: 20388897
  19. Tzoulaki, I.; Molokhia, M.; Curcin, V.; Little, M.P.; Millett, C.J.; Ng, A.; Hughes, R.I.; Khunti, K.; Wilkins, M.R.; Majeed, A.; Elliott, P. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: Retrospective cohort study using UK general practice research database. BMJ, 2009, 339, b4731. doi: 10.1136/bmj.b4731 PMID: 19959591
  20. Van Staa, T.; Abenhaim, L.; Monette, J. Rates of hypoglycemia in users of sulfonylureas. J. Clin. Epidemiol., 1997, 50(6), 735-741. doi: 10.1016/S0895-4356(97)00024-3 PMID: 9250272
  21. Chinetti, G.; Lestavel, S.; Bocher, V.; Remaley, A.T.; Neve, B.; Torra, I.P.; Teissier, E.; Minnich, A.; Jaye, M.; Duverger, N.; Brewer, H.B.; Fruchart, J.C.; Clavey, V.; Staels, B. PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat. Med., 2001, 7(1), 53-58. doi: 10.1038/83348 PMID: 11135616
  22. Feingold, KR Oral and injectable (Non-Insulin) pharmacological agents for the treatment of type 2 diabetes. In: Endotext Internet; MDText.com, Inc.: South Dartmouth (MA), 2022.
  23. Rahman, M.; Islam, M.; Islam, M.; Harun-Or-Rashid, M.; Islam, M.; Abdullah, S.; Uddin, M.; Das, S.; Rahaman, M.; Ahmed, M.; Alhumaydhi, F.; Emran, T.; Mohamed, A.; Faruque, M.; Khandaker, M.; Mostafa-Hedeab, G. Stem cell transplantation therapy and neurological disorders: Current status and future perspectives. Biology, 2022, 11(1), 147. doi: 10.3390/biology11010147 PMID: 35053145
  24. Patel, D.K.; Prasad, S.K.; Kumar, R.; Hemalatha, S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac. J. Trop. Biomed., 2012, 2(4), 320-330. doi: 10.1016/S2221-1691(12)60032-X PMID: 23569923
  25. Talpur, N.; Echard, B.; Ingram, C.; Bagchi, D.; Preuss, H. Effects of a novel formulation of essential oils on glucose- insulin metabolism in diabetic and hypertensive rats: A pilot study. Diabetes Obes. Metab., 2005, 7(2), 193-199. doi: 10.1111/j.1463-1326.2004.00386.x PMID: 15715893
  26. 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. Type 2 diabetes mellitus. Nat. Rev. Dis. Primers, 2015, 1(1), 15019. doi: 10.1038/nrdp.2015.19 PMID: 27189025
  27. El Azab, E.F.; Mostafa, H.S. Geraniol ameliorates the progression of high fat‐diet/streptozotocin‐induced type 2 diabetes mellitus in rats via regulation of caspase‐3, Bcl‐2, and Bax expression. J. Food Biochem., 2022, 46(7), e14142. doi: 10.1111/jfbc.14142 PMID: 35312192
  28. Bahl, A.S.; Verma, V.K.; Bhatia, J.; Arya, D.S. Integrating in silico and in vivo approach for investigating the role of polyherbal oil in prevention and treatment of COVID-19 infection. Chem. Biol. Interact., 2022, 367, 110179. doi: 10.1016/j.cbi.2022.110179 PMID: 36113631
  29. Verma, V.K.; Sehgal, N.; Prakash, O. Characterization and screening of bioactive compounds in the extract prepared from aerial roots of Ficus benghalensis. Int. J. Pharm. Sci. Res., 2015, 6(5056), 5056-5069.
  30. Kim, S.; Chen, J.; Cheng, T.; Gindulyte, A.; He, J.; He, S.; Li, Q.; Shoemaker, B.A.; Thiessen, P.A.; Yu, B.; Zaslavsky, L.; Zhang, J.; Bolton, E.E. PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res., 2021, 49(D1), D1388-D1395. doi: 10.1093/nar/gkaa971 PMID: 33151290
  31. Madhavi Sastry, G.; Adzhigirey, M.; Day, T.; Annabhimoju, R.; Sherman, W. Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des., 2013, 27(3), 221-234. doi: 10.1007/s10822-013-9644-8 PMID: 23579614
  32. Kapoor, K.; Finer-Moore, J.S.; Pedersen, B.P.; Caboni, L.; Waight, A.; Hillig, R.C.; Bringmann, P.; Heisler, I.; Müller, T.; Siebeneicher, H.; Stroud, R.M. Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides. Proc. Natl. Acad. Sci. USA, 2016, 113(17), 4711-4716. doi: 10.1073/pnas.1603735113 PMID: 27078104
  33. Berger, J.P.; SinhaRoy, R.; Pocai, A.; Kelly, T.M.; Scapin, G.; Gao, Y.D.; Pryor, K.A.D.; Wu, J.K.; Eiermann, G.J.; Xu, S.S.; Zhang, X.; Tatosian, D.A.; Weber, A.E.; Thornberry, N.A.; Carr, R.D. A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice. Endocrinol. Diabetes Metab., 2018, 1(1), e00002. doi: 10.1002/edm2.2 PMID: 30815539
  34. Howard, E.I.; Sanishvili, R.; Cachau, R.E.; Mitschler, A.; Chevrier, B.; Barth, P.; Lamour, V.; Van Zandt, M.; Sibley, E.; Bon, C.; Moras, D.; Schneider, T.R.; Joachimiak, A.; Podjarny, A. Ultrahigh resolution drug design I: Details of interactions in human aldose reductase-inhibitor complex at 0.66 Å. Proteins, 2004, 55(4), 792-804. doi: 10.1002/prot.20015 PMID: 15146478
  35. Lee, M.A.; Tan, L.; Yang, H.; Im, Y.G.; Im, Y.J. Structures of PPARγ complexed with lobeglitazone and pioglitazone reveal key determinants for the recognition of antidiabetic drugs. Sci. Rep., 2017, 7(1), 16837. doi: 10.1038/s41598-017-17082-x PMID: 29203903
  36. Yang, J.; Yan, R.; Roy, A.; Xu, D.; Poisson, J.; Zhang, Y. The I-TASSER Suite: Protein structure and function prediction. Nat. Methods, 2015, 12(1), 7-8. doi: 10.1038/nmeth.3213 PMID: 25549265
  37. Laskowski, R.A.; MacArthur, M.W.; Moss, D.S.; Thornton, J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Cryst., 1993, 26(2), 283-291. doi: 10.1107/S0021889892009944
  38. Colovos, C.; Yeates, T.O. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Sci., 1993, 2(9), 1511-1519. doi: 10.1002/pro.5560020916 PMID: 8401235
  39. Tian, W.; Chen, C.; Lei, X.; Zhao, J.; Liang, J. CASTp 3.0: Computed atlas of surface topography of proteins. Nucleic Acids Res., 2018, 46(W1), W363-W367. doi: 10.1093/nar/gky473 PMID: 29860391
  40. Halgren, T.A. Identifying and characterizing binding sites and assessing druggability. J. Chem. Inf. Model., 2009, 49(2), 377-389. doi: 10.1021/ci800324m PMID: 19434839
  41. Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem., 2006, 49(21), 6177-6196. doi: 10.1021/jm051256o PMID: 17034125
  42. Rastelli, G.; Del Rio, A.; Degliesposti, G.; Sgobba, M. Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA. J. Comput. Chem., 2010, 31(4), 797-810. PMID: 19569205
  43. Wallace, A.C.; Laskowski, R.A.; Thornton, J.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Eng. Des. Sel., 1995, 8(2), 127-134. doi: 10.1093/protein/8.2.127 PMID: 7630882
  44. Mandel, N.; Agarwal, N. Role of SUMOylation in Neurodegenerative Diseases. Cells, 2022, 11(21), 3395. doi: 10.3390/cells11213395 PMID: 36359791
  45. Habtemariam, S. Antidiabetic potential of monoterpenes: A case of small molecules punching above their weight. Int. J. Mol. Sci., 2017, 19(1), 4. doi: 10.3390/ijms19010004 PMID: 29267214
  46. Al-Trad, B.; Alkhateeb, H.; Alsmadi, W.; Al-Zoubi, M. Eugenol ameliorates insulin resistance, oxidative stress and inflammation in high fat-diet/streptozotocin-induced diabetic rat. Life Sci., 2019, 216, 183-188. doi: 10.1016/j.lfs.2018.11.034 PMID: 30448265
  47. Oroojan, A.A. Eugenol improves insulin secretion and content of pancreatic islets from male mouse. Int. J. Endocrinol., 2020, 2020, 1-5. doi: 10.1155/2020/7416529 PMID: 32831835
  48. Sen, A.; Yokokura, T.; Kankel, M.W.; Dimlich, D.N.; Manent, J.; Sanyal, S.; Artavanis-Tsakonas, S. Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling. J. Cell Biol., 2011, 192(3), 481-495. doi: 10.1083/jcb.201004016 PMID: 21300852
  49. Katare, Y.S.; Bhujbal, S.S.; Bafna, A.R.; Shyale, S.S.; Shelar, M.K.; Kadam, S.D. Evaluation of anxiolytic effect of a polyherbal for mulation in mice. Eur. J. Exp. Biol., 2012, 2, 2093-2098.
  50. Ben Ammar, R. Potential effects of geraniol on cancer and inflammation-related diseases: A review of the recent research findings. Molecules, 2023, 28(9), 3669. doi: 10.3390/molecules28093669 PMID: 37175079
  51. Wang, Q. Biomaterials Translational-The new vehicle for translational medicine. Biomater Transl., 2020, 1(1), 1-2. doi: 10.3877/cma.j.issn.2096-112X.2020.01.001 PMID: 35837655
  52. Triffitt, JT; Wang, Q Application of stem cells in translational medicine. Biomater Transl., 2021, 2(4), 285-286. doi: 10.12336/biomatertransl.2021.04.002

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