Skip to content
2000
Volume 21, Issue 5
  • ISSN: 1570-1646
  • E-ISSN: 1875-6247

Abstract

Background

Insulin is a key hormone in our systems. Upon binding of insulin to its receptors in fat and muscle tissues, tens of proteins in the insulin signaling pathway are involved in the process of GLUT4 vesicle recruitment to the Plasma Membrane (PM) and the absorption of serum glucose. Deficits in the aforementioned pathway lead to insulin resistance and eventually to Type II Diabetes Mellitus.

Objective

We appreciate the contribution of phytochemicals in the treatment of diabetes. Yet, and studies are needed to validate the safety and efficacy of the phytochemicals, plus their action mechanisms.

Methods

Herein, we tested two phytochemicals, caffeic acid and ferulic acid and . We shed light on the insulin signaling proteins as plausible therapeutic targets using studies, AutoDock and SwissADME.

Results

Results obtained indicate that Caffeic Acid (CA) increased GLUT4 translocation at 125µM by 31% in the absence of insulin, and 24.5% in presence of insulin, when compared to the control. Ferulic Acid (FA) was less potent as an enhancer of GLUT4 translocation. Best docking results were found for the binding of the phytochemicals CA and FA to PDK1, AKT, IRS1 and PTEN proteins of the insulin signaling, with comparable results.

Conclusion

These findings indicate that CA and FA possess a limited anti-diabetic potency by increasing GLUT4 trafficking to the PM in skeletal muscles. These results suggest that these compounds are candidates for further investigation in pre-clinical and clinical stages of drug discovery.

Loading

Article metrics loading...

/content/journals/cp/10.2174/0115701646334678240913105521
2024-10-04
2025-06-21
Loading full text...

Full text loading...

References

  1. HarreiterJ. RodenM. Diabetes mellitus — Definition, classification, diagnosis, screening and prevention (update 2019).Wien. Klin. Wochenschr.2019131S161510.1007/s00508‑019‑1450‑430980151
    [Google Scholar]
  2. LarterC.Z. FarrellG.C. Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat?J. Hepatol.200644225326110.1016/j.jhep.2005.11.03016364488
    [Google Scholar]
  3. O’RahillyS. BarrosoI. WarehamN.J. Genetic factors in type 2 diabetes: The end of the beginning?Science2005307570837037310.1126/science.110434615662000
    [Google Scholar]
  4. DiMeglioL.A. Evans-MolinaC. OramR.A. Type 1 diabetes.Lancet2018391101382449246210.1016/S0140‑6736(18)31320‑529916386
    [Google Scholar]
  5. PopoviciuM.S. KakaN. SethiY. PatelN. ChopraH. CavaluS. Type 1 diabetes mellitus and autoimmune diseases: A critical review of the association and the application of personalized medicine.J. Pers. Med.202313342210.3390/jpm1303042236983604
    [Google Scholar]
  6. AkilA.A.S. YassinE. Al-MaraghiA. AliyevE. Al-MalkiK. FakhroK.A. Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.J. Transl. Med.202119113710.1186/s12967‑021‑02778‑633794915
    [Google Scholar]
  7. Galicia-GarciaU. Benito-VicenteA. JebariS. Larrea-SebalA. SiddiqiH. UribeK.B. OstolazaH. MartínC. Pathophysiology of type 2 diabetes mellitus.Int. J. Mol. Sci.20202117627510.3390/ijms2117627532872570
    [Google Scholar]
  8. TomicD. ShawJ.E. MaglianoD.J. The burden and risks of emerging complications of diabetes mellitus.Nat. Rev. Endocrinol.202218952553910.1038/s41574‑022‑00690‑735668219
    [Google Scholar]
  9. Omar-HmeadiM. Idevall-HagrenO. Insulin granule biogenesis and exocytosis.Cell. Mol. Life Sci.20217851957197010.1007/s00018‑020‑03688‑433146746
    [Google Scholar]
  10. RahmanM.S. HossainK.S. DasS. KunduS. AdegokeE.O. RahmanM.A. HannanM.A. UddinM.J. PangM.G. Role of insulin in health and disease: An update.Int. J. Mol. Sci.20212212640310.3390/ijms2212640334203830
    [Google Scholar]
  11. BaghaieL. BunsickD.A. SzewczukM.R. Insulin receptor signaling in health and disease.Biomolecules202313580710.3390/biom1305080737238677
    [Google Scholar]
  12. Le Marchand-BrustelY. Molecular mechanisms of insulin action in normal and insulin-resistant states.Exp. Clin. Endocrinol. Diabetes1999107212613210.1055/s‑0029‑121208710320053
    [Google Scholar]
  13. WatersS.B. PessinJ.E. Insulin receptor substrate 1 and 2 (IRS1 and IRS2): what a tangled web we weave.Trends Cell Biol.1996611410.1016/0962‑8924(96)81024‑515157524
    [Google Scholar]
  14. HuangR. DaiQ. YangR. DuanY. ZhaoQ. HaybaeckJ. YangZ. A Review: PI3K/AKT/mTOR signaling pathway and its regulated eukaryotic translation initiation factors may be a potential therapeutic target in esophageal squamous cell carcinoma.Front. Oncol.20221281791610.3389/fonc.2022.81791635574327
    [Google Scholar]
  15. TruebesteinL. HorneggerH. AnratherD. HartlM. FlemingK.D. StarihaJ.T.B. PardonE. SteyaertJ. BurkeJ.E. LeonardT.A. Structure of autoinhibited Akt1 reveals mechanism of PIP 3 -mediated activation.Proc. Natl. Acad. Sci. USA202111833e210149611810.1073/pnas.210149611834385319
    [Google Scholar]
  16. StorzP. TokerA. 3′-phosphoinositide-dependent kinase-1 (PDK-1) in PI 3-kinase signaling.Front. Biosci.200271-3d886d90210.2741/storz11897568
    [Google Scholar]
  17. VaraJ.Á.F. CasadoE. de CastroJ. CejasP. Belda-IniestaC. González-BarónM. PI3K/Akt signalling pathway and cancer.Cancer Treat. Rev.200430219320410.1016/j.ctrv.2003.07.00715023437
    [Google Scholar]
  18. ZhengX. CarteeG.D. Insulin-induced effects on the subcellular localization of AKT1, AKT2 and AS160 in rat skeletal muscle.Sci. Rep.2016613923010.1038/srep3923027966646
    [Google Scholar]
  19. SakamotoK. HolmanG.D. Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic.Am. J. Physiol. Endocrinol. Metab.20082951E29E3710.1152/ajpendo.90331.200818477703
    [Google Scholar]
  20. HommaY. HiragiS. FukudaM. Rab family of small GTPases: An updated view on their regulation and functions.FEBS J.20212881365510.1111/febs.1545332542850
    [Google Scholar]
  21. XuL. NagaiY. KajiharaY. ItoG. TomitaT. The regulation of Rab GTPases by phosphorylation.Biomolecules2021119134010.3390/biom1109134034572553
    [Google Scholar]
  22. HutagalungA.H. NovickP.J. Role of Rab GTPases in membrane traffic and cell physiology.Physiol. Rev.201191111914910.1152/physrev.00059.200921248164
    [Google Scholar]
  23. AltoN.M. SoderlingJ. ScottJ.D. Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.J. Cell Biol.2002158465966810.1083/jcb.20020408112186851
    [Google Scholar]
  24. Cohen-SolalK.A. SoodR. MarinY. Crespo-CarboneS.M. SinsimerD. MartinoJ.J. RobbinsC. MakalowskaI. TrentJ. ChenS. Identification and characterization of mouse Rab32 by mRNA and protein expression analysis.Biochim. Biophys. Acta. Proteins Proteomics200316511-2687510.1016/S1570‑9639(03)00236‑X14499590
    [Google Scholar]
  25. WasmeierC. RomaoM. PlowrightL. BennettD.C. RaposoG. SeabraM.C. Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.J. Cell Biol.2006175227128110.1083/jcb.20060605017043139
    [Google Scholar]
  26. CaiH. ReinischK. Ferro-NovickS. Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle.Dev. Cell200712567168210.1016/j.devcel.2007.04.00517488620
    [Google Scholar]
  27. ChavrierP. PartonR.G. HauriH.P. SimonsK. ZerialM. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.Cell199062231732910.1016/0092‑8674(90)90369‑P2115402
    [Google Scholar]
  28. CallaghanJ. SimonsenA. GaullierJ.M. TohB.H. StenmarkH. The endosome fusion regulator early-endosomal autoantigen 1 (EEA1) is a dimer.Biochem. J.1999338253954310.1042/bj338053910024533
    [Google Scholar]
  29. ChristoforidisS. McBrideH.M. BurgoyneR.D. ZerialM. The Rab5 effector EEA1 is a core component of endosome docking.Nature1999397672062162510.1038/1761810050856
    [Google Scholar]
  30. IshikuraS. BilanP.J. KlipA. Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating GLUT4 traffic in muscle cells.Biochem. Biophys. Res. Commun.200735341074107910.1016/j.bbrc.2006.12.14017208202
    [Google Scholar]
  31. SanoH. EguezL. TeruelM.N. FukudaM. ChuangT.D. ChavezJ.A. LienhardG.E. McGrawT.E. Rab10, a target of the AS160 Rab GAP, is required for insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane.Cell Metab.20075429330310.1016/j.cmet.2007.03.00117403373
    [Google Scholar]
  32. SunY. BilanP.J. LiuZ. KlipA. Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells.Proc. Natl. Acad. Sci. USA201010746199091991410.1073/pnas.100952310721041651
    [Google Scholar]
  33. ChenC.Y. ChenJ. HeL. StilesB.L. PTEN: Tumor suppressor and metabolic regulator.Front. Endocrinol. (Lausanne)2018933810.3389/fendo.2018.0033830038596
    [Google Scholar]
  34. DempseyD.R. ViennetT. IwaseR. ParkE. HenriquezS. ChenZ. JeliazkovJ.R. PalanskiB.A. PhanK.L. CooteP. The structural basis of PTEN regulation by multi-site phosphorylation.Nat. Struct. Mol. Biol.2021281085886810.1038/s41594‑021‑00668‑5
    [Google Scholar]
  35. PosnerB.I. insulin signalling: The inside story.Can. J. Diabetes201741110811310.1016/j.jcjd.2016.07.00227614806
    [Google Scholar]
  36. TokarzV.L. MacDonaldP.E. KlipA. The cell biology of systemic insulin function.J. Cell Biol.201821772273228910.1083/jcb.20180209529622564
    [Google Scholar]
  37. AhmedZ. PillayT.S. Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling.Biochem. J.2003371240541210.1042/bj2002158912521378
    [Google Scholar]
  38. LiangJ. OyangL. RaoS. HanY. LuoX. YiP. LinJ. XiaL. HuJ. TanS. TangL. PanQ. TangY. ZhouY. LiaoQ. Rac1, a potential target for tumor therapy.Front. Oncol.20211167442610.3389/fonc.2021.67442634079763
    [Google Scholar]
  39. HopkinsB.D. GoncalvesM.D. CantleyL.C. Insulin–PI3K signalling: An evolutionarily insulated metabolic driver of cancer.Nat. Rev. Endocrinol.202016527628310.1038/s41574‑020‑0329‑932127696
    [Google Scholar]
  40. ChengZ. WhiteM.F. The AKTion in non-canonical insulin signaling.Nat. Med.201218335135310.1038/nm.269422395698
    [Google Scholar]
  41. ShanakS. BassalatN. BarghashA. KadanS. ArdahM. ZaidH. Drug discovery of plausible lead natural compounds that target the insulin signaling pathway: Bioinformatics approaches.Evid. Based Complement. Alternat. Med.2022202214210.1155/2022/283288935356248
    [Google Scholar]
  42. ChiuT.T. JensenT.E. SylowL. RichterE.A. KlipA. Rac1 signalling towards GLUT4/glucose uptake in skeletal muscle.Cell. Signal.201123101546155410.1016/j.cellsig.2011.05.02221683139
    [Google Scholar]
  43. MottD.M. StoneK. GesselM.C. BuntJ.C. BogardusC. Palmitate action to inhibit glycogen synthase and stimulate protein phosphatase 2A increases with risk factors for type 2 diabetes.Am. J. Physiol. Endocrinol. Metab.20082944E807E80710.1152/ajpendo.zh1‑5299‑corr.2008
    [Google Scholar]
  44. UgiS. ImamuraT. MaegawaH. EgawaK. YoshizakiT. ShiK. ObataT. EbinaY. KashiwagiA. OlefskyJ.M. Protein phosphatase 2A negatively Akt (protein kinase B) activity in 3T3-L1 adipocytes.Mol. Cell. Biol.200424198778878910.1128/MCB.24.19.8778‑8789.200415367694
    [Google Scholar]
  45. TeimouriM. HosseiniH. ArabSadeghabadiZ. Babaei-KhorzoughiR. Gorgani-FiruzjaeeS. MeshkaniR. The role of protein tyrosine phosphatase 1B (PTP1B) in the pathogenesis of type 2 diabetes mellitus and its complications.J. Physiol. Biochem.202278230732210.1007/s13105‑021‑00860‑734988903
    [Google Scholar]
  46. BerenguerM. MartinezL. Giorgetti-PeraldiS. Le Marchand-BrustelY. GoversR. A serum factor induces insulin-independent translocation of GLUT4 to the cell surface which is maintained in insulin resistance.PLoS One2010512e1556010.1371/journal.pone.001556021187969
    [Google Scholar]
  47. ZaidH. ShanakS. TamrakarA. Computer-aided drug design of natural candidates for the treatment of non-communicable diseases.Evid. Based Complement Alternat. Med.20222022976917310.1155/2022/9769173
    [Google Scholar]
  48. Naceiri MrabtiH. BouyahyaA. Naceiri MrabtiN. JaradatN. DoudachL. FaouziM.E.A. Ethnobotanical survey of medicinal plants used by traditional healers to treat diabetes in the Taza region of Morocco.Evid. Based Complement. Alternat. Med.2021202111610.1155/2021/551563433986815
    [Google Scholar]
  49. ZaidH. TamrakarA.K. RazzaqueM.S. EfferthT. Diabetes and metabolism disorders medicinal plants: A Glance at the past and a look to the future 2018.Evid. Based Complement. Alternat. Med.201820181584329810.1155/2018/584329830364074
    [Google Scholar]
  50. ZaidH. MahdiA.A. TamrakarA.K. SaadB. RazzaqueM.S. DasguptaA. Natural active ingredients for diabetes and metabolism disorders treatment.Evid. Based Complement Alternat. Med.20162016296521410.1155/2016/2965214
    [Google Scholar]
  51. ShanakS. SaadB. ZaidH. Metabolic and epigenetic action mechanisms of antidiabetic medicinal plants.Evid. Based Complement. Alternat. Med.2019201911810.1155/2019/358306731191707
    [Google Scholar]
  52. KadanS. SassonY. SaadB. ZaidH. Gundelia tournefortii antidiabetic efficacy: chemical composition and GLUT4 translocation.Evid. Based Complement. Alternat. Med.201820181829432010.1155/2018/829432029853973
    [Google Scholar]
  53. KadanS. MelamedS. BenvalidS. TietelZ. SassonY. ZaidH. Gundelia tournefortii: Fractionation, chemical composition and GLUT4 translocation enhancement in muscle cell line.Molecules20212613378510.3390/molecules2613378534206320
    [Google Scholar]
  54. KadanS. SaadB. SassonY. ZaidH. In vitro evaluation of anti-diabetic activity and cytotoxicity of chemically analysed Ocimum basilicum extracts.Food Chem.20161961066107410.1016/j.foodchem.2015.10.04426593590
    [Google Scholar]
  55. O’BoyleN.M. BanckM. JamesC.A. MorleyC. VandermeerschT. HutchisonG.R. Open Babel: An open chemical toolbox.J. Cheminform.2011313310.1186/1758‑2946‑3‑3321982300
    [Google Scholar]
  56. BassalatN. KadanS. MelamedS. YaronT. TietelZ. KaramD. KmailA. MasalhaM. ZaidH. In vivo and in vitro antidiabetic efficacy of aqueous and methanolic extracts of Orthosiphon stamineus benth.Pharmaceutics202315394510.3390/pharmaceutics1503094536986806
    [Google Scholar]
  57. Abu-LafiS. RayanB. KadanS. Abu-LafiM. RayanA. Anticancer activity and phytochemical composition of wild Gundelia tournefortii. Oncol. Lett.201817171371710.3892/ol.2018.960230655821
    [Google Scholar]
  58. HaniN. AbulailaK. HowesM.J.R. MattanaE. BacciS. SleemK. SarkisL. EddineN.S. BaydounS. ApostolidesN.A. UlianT. Gundelia tournefortii L. (Akkoub): A review of a valuable wild vegetable from Eastern Mediterranean.Genet. Resour. Crop Evol.202410.1007/s10722‑024‑01927‑2
    [Google Scholar]
  59. KadanS. SaadB. SassonY. ZaidH. In vitro evaluations of cytotoxicity of eight antidiabetic medicinal plants and their effect on GLUT4 translocation.Evid. Based Complement. Alternat. Med.201320131910.1155/2013/54934523606883
    [Google Scholar]
  60. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep4271728256516
    [Google Scholar]
  61. Domínguez-VillaF.X. Durán-IturbideN.A. Ávila-ZárragaJ.G. Synthesis, molecular docking, and in silico ADME/Tox profiling studies of new 1-aryl-5-(3-azidopropyl)indol-4-ones: Potential inhibitors of SARS CoV-2 main protease.Bioorg. Chem.202110610449710.1016/j.bioorg.2020.10449733261847
    [Google Scholar]
  62. ZaidH. Talior-VolodarskyI. AntonescuC. LiuZ. KlipA. GAPDH binds GLUT4 reciprocally to hexokinase-II and regulates glucose transport activity.Biochem. J.2009419247548410.1042/BJ2008131919140804
    [Google Scholar]
  63. KimS. ThiessenP.A. BoltonE.E. ChenJ. FuG. GindulyteA. HanL. HeJ. HeS. ShoemakerB.A. WangJ. YuB. ZhangJ. BryantS.H. PubChem substance and compound databases.Nucleic Acids Res.201644D1D1202D121310.1093/nar/gkv95126400175
    [Google Scholar]
  64. LoweD.M. CorbettP.T. Murray-RustP. GlenR.C. Chemical name to structure: OPSIN, an open source solution.J. Chem. Inf. Model.201151373975310.1021/ci100384d21384929
    [Google Scholar]
  65. RizviS.M.D. ShakilS. HaneefM. A simple click by click protocol to perform docking: AutoDock 4.2 made easy for non-bioinformaticians.EXCLI J.20131283185726648810
    [Google Scholar]
  66. SriramuluD.K. LeeS.G. Effect of molecular properties of the protein-ligand complex on the prediction accuracy of AutoDock.J. Mol. Graph. Model.202110610792110.1016/j.jmgm.2021.10792133887523
    [Google Scholar]
  67. BermanH.M. KleywegtG.J. NakamuraH. MarkleyJ.L. The Protein Data Bank archive as an open data resource.J. Comput. Aided Mol. Des.201428101009101410.1007/s10822‑014‑9770‑y25062767
    [Google Scholar]
  68. BorsariC. KelesE. RageotD. TreyerA. BohnackerT. BisseggerL. De PascaleM. MeloneA. SriramaratnamR. BeaufilsF. HamburgerM. HebeisenP. LöscherW. FabbroD. HillmannP. WymannM.P. 4-(difluoromethyl)-5-(4-((3 R, 5 S )-3,5-dimethylmorpholino)-6-(( R )-3-methylmorpholino)-1,3,5-triazin-2-yl)pyridin-2-amine (PQR626), a potent, orally available, and brain-penetrant mTOR inhibitor for the treatment of neurological disorders.J. Med. Chem.20206322135951361710.1021/acs.jmedchem.0c0062033166139
    [Google Scholar]
  69. Garcia-VilocaM. BayascasJ.R. LluchJ.M. González-LafontÀ. Molecular insights into the regulation of 3-phosphoinositide-dependent protein kinase 1: Modeling the interaction between the kinase and the pleckstrin homology domains.ACS Omega2022729251862519910.1021/acsomega.2c0202035910176
    [Google Scholar]
  70. Du-CunyL. SongZ. MosesS. PowisG. MashE.A. MeuilletE.J. ZhangS. Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.Bioorg. Med. Chem.200917196983699210.1016/j.bmc.2009.08.02219734051
    [Google Scholar]
  71. ChirgadzeY.N. BattaileK.P. LikhachevI.V. BalabaevN.K. GordonR.D. RomanovV. LinA. KarischR. LamR. RuzanovM. BrazhnikovE.V. PaiE.F. NeelB.G. ChirgadzeN.Y. Signal transfer in human protein tyrosine phosphatase PTP1B from allosteric inhibitor P00058.J. Biomol. Struct. Dyn.20224024138231383210.1080/07391102.2021.199487934705594
    [Google Scholar]
  72. CaiW. SakaguchiM. KleinriddersA. Gonzalez-Del PinoG. DreyfussJ.M. O’NeillB.T. RamirezA.K. PanH. WinnayJ.N. BoucherJ. EckM.J. KahnC.R. Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression.Nat. Commun.2017811489210.1038/ncomms1489228345670
    [Google Scholar]
  73. XingY. XuY. ChenY. JeffreyP.D. ChaoY. LinZ. LiZ. StrackS. StockJ.B. ShiY. Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins.Cell2006127234135310.1016/j.cell.2006.09.02517055435
    [Google Scholar]
  74. HubbardS.R. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog.EMBO J.199716185572558110.1093/emboj/16.18.55729312016
    [Google Scholar]
  75. ParkS.Y. JinW. WooJ.R. ShoelsonS.E. Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation.J. Biol. Chem.201128620181301813810.1074/jbc.M110.21732321454505
    [Google Scholar]
  76. LeeJ.O. YangH. GeorgescuM.M. Di CristofanoA. MaehamaT. ShiY. DixonJ.E. PandolfiP. PavletichN.P. Crystal structure of the PTEN tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association.Cell199999332333410.1016/S0092‑8674(00)81663‑310555148
    [Google Scholar]
  77. ShanakS. BassalatN. AlbzoorR. KadanS. ZaidH. In vitro and in silico evaluation for the inhibitory action of O. basilicum methanol extract on α-glucosidase and α-amylase.Evid. Based Complement. Alternat. Med.202120211910.1155/2021/551577534306136
    [Google Scholar]
  78. ChenT. ShuX. ZhouH. BeckfordF.A. MisirM. Algorithm selection for protein–ligand docking: Strategies and analysis on ACE.Sci. Rep.2023131821910.1038/s41598‑023‑35132‑537217655
    [Google Scholar]
  79. ZhengY. WangX. ZhuangY. LiY. TianH. ShiP. LiG. Isolation of novel ACE-inhibitory and antioxidant peptides from quinoa bran albumin assisted with an in silico approach: Characterization, in vivo antihypertension, and molecular docking.Molecules20192424456210.3390/molecules2424456231842519
    [Google Scholar]
  80. ForliS. HueyR. PiqueM.E. SannerM.F. GoodsellD.S. OlsonA.J. Computational protein–ligand docking and virtual drug screening with the AutoDock suite.Nat. Protoc.201611590591910.1038/nprot.2016.05127077332
    [Google Scholar]
  81. SeeligerD. de GrootB.L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina.J. Comput. Aided Mol. Des.201024541742210.1007/s10822‑010‑9352‑620401516
    [Google Scholar]
  82. MonteiroA.F.M. VianaJ.D.O. NayarisseriA. ZondegoumbaE.N. Mendonça JuniorF.J.B. ScottiM.T. ScottiL. Computational studies applied to flavonoids against alzheimer’s and parkinson’s diseases.Oxid. Med. Cell. Longev.201820181791276510.1155/2018/791276530693065
    [Google Scholar]
  83. KaramiT.K. HailuS. FengS. GrahamR. GukasyanH.J. Eyes on Lipinski’s rule of five: A new “Rule of Thumb” for physicochemical design space of ophthalmic drugs.J. Ocul. Pharmacol. Ther.2022381435510.1089/jop.2021.006934905402
    [Google Scholar]
  84. ZaidH. AntonescuC.N. RandhawaV.K. KlipA. Insulin action on glucose transporters through molecular switches, tracks and tethers.Biochem. J.2008413220121510.1042/BJ2008072318570632
    [Google Scholar]
  85. AntonescuC.N. IshikuraS. BilanP.J. KlipA. Measurement of GLUT4 Traffic to and from the Cell Surface in Muscle Cells.Curr. Protoc.202336e80310.1002/cpz1.80337367531
    [Google Scholar]
  86. TokarzV.L. MylvaganamS. KlipA. Palmitate-induced insulin resistance causes actin filament stiffness and GLUT4 mis-sorting without altered Akt signalling.J. Cell Sci.202313621jcs26130010.1242/jcs.26130037815440
    [Google Scholar]
  87. ChenL. TengH. CaoH. Chlorogenic acid and caffeic acid from Sonchus oleraceus Linn synergistically attenuate insulin resistance and modulate glucose uptake in HepG2 cells.Food Chem. Toxicol.201912718218710.1016/j.fct.2019.03.03830914352
    [Google Scholar]
  88. BhattacharyaS. OksbjergN. YoungJ.F. JeppesenP.B. Caffeic acid, naringenin and quercetin enhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells.Diabetes Obes. Metab.201416760261210.1111/dom.1223624205999
    [Google Scholar]
  89. NarasimhanA. ChinnaiyanM. KarundeviB. Ferulic acid exerts its antidiabetic effect by modulating insulin-signalling molecules in the liver of high-fat diet and fructose-induced type-2 diabetic adult male rat.Appl. Physiol. Nutr. Metab.201540876978110.1139/apnm‑2015‑000226201855
    [Google Scholar]
  90. PrabhakarP.K. PrasadR. AliS. DobleM. Synergistic interaction of ferulic acid with commercial hypoglycemic drugs in streptozotocin induced diabetic rats.Phytomedicine201320648849410.1016/j.phymed.2012.12.00423490007
    [Google Scholar]
  91. EspíndolaK.M.M. FerreiraR.G. NarvaezL.E.M. Silva RosarioA.C.R. da SilvaA.H.M. SilvaA.G.B. VieiraA.P.O. MonteiroM.C. Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma.Front. Oncol.2019954110.3389/fonc.2019.0054131293975
    [Google Scholar]
  92. SalauV.F. ErukainureO.L. IbejiC.U. OlasehindeT.A. KoorbanallyN.A. IslamM.S. Ferulic acid modulates dysfunctional metabolic pathways and purinergic activities, while stalling redox imbalance and cholinergic activities in oxidative brain injury.Neurotox. Res.202037494495510.1007/s12640‑019‑00099‑731422569
    [Google Scholar]
  93. RuamyodK. WatanapaW.B. KakhaiC. NambunditP. TreewareeS. WongsanupaP. Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation.J. Integr. Med.20232119910510.1016/j.joim.2022.11.00336481247
    [Google Scholar]
  94. PavlíkováN. Caffeic Acid and Diseases—Mechanisms of Action.Int. J. Mol. Sci.202224158810.3390/ijms2401058836614030
    [Google Scholar]
  95. ZhaiY. WangT. FuY. YuT. DingY. NieH. Ferulic acid: A review of pharmacology, toxicology, and therapeutic effects on pulmonary diseases.Int. J. Mol. Sci.2023249801110.3390/ijms2409801137175715
    [Google Scholar]
  96. Rebollo-HernanzM. ZhangQ. AguileraY. Martín-CabrejasM.A. Gonzalez de MejiaE. Relationship of the phytochemicals from coffee and cocoa by-products with their potential to modulate biomarkers of metabolic syndrome in vitro.Antioxidants20198827910.3390/antiox808027931387271
    [Google Scholar]
/content/journals/cp/10.2174/0115701646334678240913105521
Loading
/content/journals/cp/10.2174/0115701646334678240913105521
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test