Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 05 2023
27 05 2023
Historique:
received:
03
01
2023
accepted:
13
05
2023
medline:
29
5
2023
pubmed:
28
5
2023
entrez:
27
5
2023
Statut:
epublish
Résumé
Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery.
Identifiants
pubmed: 37244921
doi: 10.1038/s41598-023-35161-0
pii: 10.1038/s41598-023-35161-0
pmc: PMC10224994
doi:
Substances chimiques
gingerol
925QK2Z900
Curcumin
IT942ZTH98
Lipoxygenase
EC 1.13.11.12
Capsaicin
S07O44R1ZM
Lipoxygenase Inhibitors
0
Cyclooxygenase 2
EC 1.14.99.1
Cyclooxygenase 2 Inhibitors
0
Anti-Inflammatory Agents
0
Arachidonate 5-Lipoxygenase
EC 1.13.11.34
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8656Informations de copyright
© 2023. The Author(s).
Références
Curr Cardiol Rev. 2010 Nov;6(4):274-9
pubmed: 22043203
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W29-33
pubmed: 23609542
Ann Rheum Dis. 2003 Jun;62(6):501-9
pubmed: 12759283
J Biochem Mol Toxicol. 2022 Jul;36(7):e23073
pubmed: 35437840
Fundam Clin Pharmacol. 1996;10(1):1-17
pubmed: 8900495
Toxicol Sci. 2011 Oct;123(2):333-48
pubmed: 21821733
J Evid Based Complementary Altern Med. 2017 Jul;22(3):494-501
pubmed: 27707902
Phytother Res. 2019 Sep;33(9):2274-2287
pubmed: 31309655
Cytokine. 2020 Nov;135:155224
pubmed: 32763761
Arch Biochem Biophys. 1978 Jan 30;185(2):584-91
pubmed: 626512
J Med Food. 2016 Aug;19(8):717-29
pubmed: 27533649
Sci Rep. 2022 Oct 22;12(1):17796
pubmed: 36273239
J Chem Inf Model. 2014 Dec 22;54(12):3284-301
pubmed: 25382374
Sci Rep. 2020 Sep 29;10(1):15965
pubmed: 32994508
Oncotarget. 2017 Dec 14;9(6):7204-7218
pubmed: 29467962
J Comput Aided Mol Des. 2013 Mar;27(3):221-34
pubmed: 23579614
J Biol Chem. 2012 Jul 13;287(29):24619-30
pubmed: 22637474
J Med Chem. 2015 May 14;58(9):4066-72
pubmed: 25860834
J Enzyme Inhib Med Chem. 2023 Dec;38(1):246-266
pubmed: 36458373
J Nutr. 2005 Dec;135(12 Suppl):2993S-3001S
pubmed: 16317160
Pain Med. 2011 Dec;12(12):1808-18
pubmed: 22054010
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
J Med Chem. 2007 Apr 5;50(7):1425-41
pubmed: 17341061
Front Med (Lausanne). 2018 Nov 27;5:316
pubmed: 30538987
J Biomol Struct Dyn. 2022;40(20):10437-10453
pubmed: 34182889
Drug Discov Today. 2019 May;24(5):1157-1165
pubmed: 30890362
Nature. 2000 May 4;405(6782):97-101
pubmed: 10811226
Maturitas. 2012 Mar;71(3):227-39
pubmed: 22226987
Biochemistry. 2015 Oct 20;54(41):6333-42
pubmed: 26427761
Sci Rep. 2017 Mar 03;7:42717
pubmed: 28256516
Eur J Med Chem. 2020 Oct 15;204:112620
pubmed: 32738413
Mediators Inflamm. 2011;2011:385780
pubmed: 21765617
J Pharm Pharm Sci. 2013;16(5):821-47
pubmed: 24393558
Trends Mol Med. 2008 Oct;14(10):461-9
pubmed: 18774339
Biochem Pharmacol. 2001 Dec 1;62(11):1433-8
pubmed: 11728379
Mini Rev Med Chem. 2004 Aug;4(6):633-8
pubmed: 15279597
J Med Chem. 2000 Oct 5;43(20):3714-7
pubmed: 11020286
Lancet. 1999 Jan 23;353(9149):307-14
pubmed: 9929039
Front Pharmacol. 2021 Mar 03;12:613104
pubmed: 33746752
Expert Opin Drug Discov. 2012 Oct;7(10):863-75
pubmed: 22992175
ACS Synth Biol. 2019 Mar 15;8(3):482-490
pubmed: 30762338
Surg Neurol Int. 2010 Dec 13;1:80
pubmed: 21206541
ACS Chem Biol. 2018 Jan 19;13(1):36-44
pubmed: 29202222
ChemMedChem. 2006 Sep;1(9):920-37
pubmed: 16952133
Pharm Res. 1992 May;9(5):663-9
pubmed: 1608900
J Chem Inf Comput Sci. 2004 May-Jun;44(3):1000-5
pubmed: 15154768
Curr Med Chem. 2001 Jun;8(7):797-807
pubmed: 11375750
ChemMedChem. 2016 Jun 6;11(11):1117-21
pubmed: 27218427
J Exp Psychol Appl. 2009 Jun;15(2):125-39
pubmed: 19586251
Biochemistry. 2010 Aug 24;49(33):7069-79
pubmed: 20669977
Front Plant Sci. 2015 Aug 25;6:655
pubmed: 26379683
Biomolecules. 2020 Aug 09;10(8):
pubmed: 32784891
Inflamm Res. 2017 May;66(5):389-398
pubmed: 28238167
J Cheminform. 2009 Jun 10;1(1):8
pubmed: 20298526
Biochim Biophys Acta. 2015 Apr;1851(4):331-9
pubmed: 25152163
FASEB J. 2012 Aug;26(8):3222-9
pubmed: 22516296
Chem Pharm Bull (Tokyo). 1992 Feb;40(2):387-91
pubmed: 1606634
Eur J Med Chem. 2003 Jul-Aug;38(7-8):645-59
pubmed: 12932896
J Med Chem. 2005 May 5;48(9):3164-70
pubmed: 15857122
Medchemcomm. 2018 Nov 30;10(1):148-157
pubmed: 30774861
ChemMedChem. 2008 Mar;3(3):435-44
pubmed: 18064617
Am J Physiol Lung Cell Mol Physiol. 2020 Feb 1;318(2):L296-L303
pubmed: 31800263