Evaluation of Anti-inflammatory Activity and Identification of a Monoterpenoidhydroxylactone (-)-loliolide from Tribulus terrestris L.: In-vivo and In-silico Approaches

Year 2024, , 131 - 142, 01.06.2024

Wadah Osman Shaza Shantier , Mona Mohamed

https://doi.org/10.52794/hujpharm.1179460

Abstract

The management and reduction of inflammatory incidents often require medications that can cause adverse effects. Therefore, it is crucial to discover natural anti-inflammatory substances that can offer improved therapeutic outcomes while decreasing the likelihood of adverse reactions. The main objective of this study was to evaluate the anti-inflammatory properties of Tribulus terrestris L (aerial parts) and identify the anti-inflammatory compounds present in the active extracts and fractions. The mechanism of action and ADMET properties of these compounds were predicted through in silico analysis. The efficacy of various extracts in reducing inflammation was assessed in rats with carrageenan-induced
edema. The phytoconstituents of the active fraction were identified using Thermo Scientific DFS high-resolution GC-MS. GC-MS analysis revealed 13 compounds, with (−)-loliolide being the most abundant by peak area. Autodock 4.0 was employed to assess the binding affinity of the compound to three crucial enzymes implicated in the inflammatory response, namely cyclooxygenase (COX 1 and 2) and 5-lipooxygenase (5-LOX). It showed good binding energies which are lower than standard compounds. The favorable binding energy, drug-like qualities, and favorable pharmacokinetic parameters of (−)-loliolide indicate that it could be an effective inhibitor, but additional research is necessary to confirm its potential.

Keywords

(-)-Loliolide, Tribulus Terrestris L, anti-enflamatuar, GC-MS analizi, COX ve 5-LOX

References

• 1. Mohammed MS, Khalid HS, Muddathir AE, El Tahir K, Khan AA, Algadir HA, Osman WJ, Siddiqui NA. Effect of some plants’ extracts used in Sudanese folkloric medicines on carrageenan-induced inflammation. Pak J of Pharm Sci. 2015;28:159-65.
• 2. Charles NS, Catherine G. Endogenous anti-inflammatory and proresolving lipid mediators in renal disease. Regenerative Nephrology. 2011;69-92. https://doi.org/10.1016/B978-0-12- 380928-5.10004-1
• 3. Nakamura E, Kitagawa Y, Ozawa S, Suda K, Ando N, Ueda M, Kitajima M. Role of steroid administration to reduce inflammation after thoracotomy in a rat surgical stress model. J Surg Res. 2006;135(2):364-9. https://doi.org/10.1016/j. jss.2006.04.015
• 4. Chapman KE, Odermatt A. Steroids: Modulators of inflammation and immunity. J Steroid Biochem Mol Biol. 2010;120(2-3):67-8. https://doi.org/10.1016/j.jsbmb.2010.04.022
• 5. Gwaltney-Brant SM. Non Steroidal Anti-inflammatory Drug- induced Toxicity. Comprehensive Toxicology (Second Edi- tion), 2010;10:59-161. https://doi.org/10.1016/B978-0-08- 046884-6.00849-6
• 6. Mohammed MS, Alajmi MF, Alam P, Khalid HS, Mahmoud AM, Ahmed WJ. Chromatographic finger print analysis of anti-inflammatory active extract fractions of aerial parts of Tribulus terrestris by HPTLC technique. Asian Pac J Trop Biomed. 2014;4(3):203-8. https://doi.org/10.1016/S2221- 1691(14)60232-X
• 7. Mona SM, Wadah JA, Elrashied AEG, Zuheir O, Bashier O, Hassan SK, Magdi AM. Secondary metabolites as anti-inflammatory agents. J Phytopharmacol. 2014;3(4):275-85. https://doi.org/10.31254/phyto.2014.3409
• 8. Sudhir S, Budhiraja RD, Miglani GP, Arora B, Gupta LC, Garg KN. Pharmacological studies on leaves of Withania somnifera. Planta Med. 1986;1:61-3. https://doi. org/10.1055/s-2007-969072
• 9. Daina A, Michielin O, Zoete V. Swiss ADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7: 42717. https://doi.org/10.1038/srep42717.
• 10. Shang XF, Morris-Natschke SL, Yang GZ, Liu YQ, Guo X, Xu XS, Goto M, Li JC, Zhang JY, Lee KH. Biologically active quinoline and quinazoline alkaloids Part II. Med Res Rev. 2018;38(5):1614-60. https://doi.org/10.1002/med.21492
• 11. Schmidtke P, Le Guilloux V, Maupetit J, Tufféry P. fpocket: online tools for protein ensemble pocket detection and tracking. Nucleic Acids Res. 2010;38:W582-9. https://doi.org/10.1093/nar/gkq383
• 12. Mona G, Sina O, Mohammad BO. Review of anti-inflammatory herbal medicines. Adv Pharmacolog Pharmaceut Sci. 2016;9130979. https://doi.org/10.1155/2016/9130979
• 13. Baburao B, Rajyalakshmi G, Venkatesham A, Kiran G, Shyamsunder A, Gangarao B. Anti-inflammatory and antimicrobial activities of methanolic extract of Tribulus terrestris Linn plant. Int J Chem Sci. 2009;7(3):1867–72.
• 14. De Combarieu E, Fuzzati N, Lovati M, Mercalli E. Furostanol saponins from Tribulus terrestris. Fitoterapia. 2003;74(6):583-91. https://doi.org/10.1016/s0367-326x(03)00152-7
• 15. Oh JS, Baik SH, Ahn EK, Jeong W, Hong SS. Anti-inflammatory activity of Tribulus terrestris in RAW264.7 cells. J Immuno. 2012;188(1_Supplement):54.2. https://doi.org/10.4049/ jimmunol.188.Supp.54.2
• 16. Chhatre S, Nesari T, Somani G, Kanchan D, Sathaye S. Phytopharmacological overview of Tribulus terrestris. Pharmacogn Rev. 2014;8(15):45-51. https://doi.org/10.4103/09737847.125530.
• 17. Tuncer MA, Yaymaci B, Sati L, Cayli S, Acar G, Altug T, De- mir R. Influence of Tribulus terrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet. Acta Histochem. 2009;111(6):488-500. https://doi.org/10.1016/j.acthis.2008.06.004
• 18. Cyril J, Estelle P. Exploring metabolome with GC/MS-Chapter Six. Adv Bot Res. 2013;67: 303-29.
• 19. Lee DK, Yoon MH, Kang YP, Yu J, Park JH, Lee J, Kwon SW. Comparison of primary and secondary metabolites for suitability to discriminate the origins of Schisandra chinensis by GC/ MS and LC/MS. Food Chem. 2013;141(4):3931-7. https://doi. org/10.1016/j.foodchem.2013.06.064
• 20. Małgorzata G, Katarzyna W, Wanda M, Bartłomiej P, Mirosław A. Loliolide - the most ubiquitous lactone. Acta Universitatis Lodziensis, Folia Biologica et Oecologica. 2015;11:1-8.
• 21. Palm K, Stenberg P, Luthman K, Artursson P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm Res. 1997;14(5):568-71. https://doi.org/10.1023/a:1012188625088
• 22. Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2005;2(4):541-53. https://doi.org/10.1602/neurorx.2.4.541
• 23. Montanari F, Ecker GF. Prediction of drug-ABC-transporter interaction-Recent advances and future challenges. Adv Drug Deliv Rev. 2015;86:17-26. https://doi.org/10.1016/j.addr.2015.03.001
• 24. Abdallah HM, Al-Abd AM, El-Dine RS, El-Halawany AM. P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review. J Adv Res. 2015;6(1):45-62. https://doi.org/10.1016/j.jare.2014.11.008
• 25. Hollenberg PF. Characteristics and common properties of inhibitors, inducers, and activators of CYP enzymes. Drug Metab Rev. 2002;34(1-2):17-35. https://doi.org/10.1081/dmr120001387
• 26. Adnan M, Nazim Uddin Chy M, Mostafa Kamal ATM, Azad MOK, Paul A, Uddin SB, et al. Investigation of the biological activities and characterization of bioactive constituents of Ophiorrhiza rugosa var. prostrata (D.Don) & Mondal leaves through in vivo, in vitro, and in silico approaches. Molecules. 2019;24(7):1367. https://doi.org/10.3390/molecules24071367
• 27. Roschek B Jr, Fink RC, Li D, McMichael M, Tower CM, Smith RD, et al. Pro-inflammatory enzymes, cyclooxygenase 1, cyclooxygenase 2, and 5-lipooxygenase, inhibited by stabilized rice bran extracts. J Med Food. 2009;12(3):615-23. https://doi.org/10.1089/jmf.2008.0133
• 28. Kurumbail RG, Kiefer JR, Marnett LJ. Cyclooxygenase enzymes: catalysis and inhibition. Curr Opin Struct Biol. 2001;11(6):752-60. https://doi.org/10.1016/s0959440x(01)00277-9
• 29. Zarghi A, Arfaei S. Selective COX-2 inhibitors: A review of their structure-activity relationships. Iran J Pharm Res. 2011;10(4):655-83.
• 30. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, et al. A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003;278(46):45763-9. https://doi.org/10.1074/jbc.M305481200
• 31. Gilbert NC, Bartlett SG, Waight MT, Neau DB, Boeglin WE, Brash AR, et al. The structure of human 5-lipoxygenase. Science. 2011;331(6014):217-9. https://doi.org/10.1126/science.1197203