Anti-inflammatory and analgesic activity of carnosol and carnosic acid in vivo and in vitro and in silico analysis of their target interactions

British Journal of Pharmacology

Volumn 174, Issue 11, 2017, Pages 1497-1508

  Maione, Francesco ^a   Cantone, Vincenza ^b   Pace, Simona ^c   Chini, Maria Giovanna ^b   Bisio, Angela ^d   Romussi, Giovanni ^d   Pieretti, Stefano ^e   Werz, Oliver ^c   Koeberle, Andreas ^c   Mascolo, Nicola ^a   Bifulco, Giuseppe ^b  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY OF SALERNO   (Italy)

^c FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^d UNIVERSITY OF GENOA   (Italy)

^e ISTITUTO SUPERIORE DI SANITÀ   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ARACHIDONATE 5 LIPOXYGENASE; CARNOSIC ACID; CARNOSOL; PROSTAGLANDIN E2; ABIETANE DERIVATIVE; ANALGESIC AGENT; ANTIINFLAMMATORY AGENT; LIPOXYGENASE INHIBITOR; PROSTAGLANDIN E SYNTHASE;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BINDING KINETICS; CONTROLLED STUDY; DRUG EFFICACY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ANALYSIS; HUMAN; HUMAN CELL; HYPERALGESIA; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INFLAMMATORY PAIN; MALE; MOLECULAR DOCKING; MOLECULAR INTERACTION; MONOCYTE; MOUSE; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; COMPUTER SIMULATION; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECTS; ISOLATION AND PURIFICATION; METABOLISM; PAIN; PATHOLOGY; SALVIA;

ANALGESICS; ANIMALS; ANTI-INFLAMMATORY AGENTS; COMPUTER SIMULATION; DISEASE MODELS, ANIMAL; DITERPENES, ABIETANE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INFLAMMATION; LIPOXYGENASE INHIBITORS; MALE; MICE; MOLECULAR DOCKING SIMULATION; MONOCYTES; NEUTROPHILS; PAIN; PROSTAGLANDIN-E SYNTHASES; SALVIA;

EID: 84982987879     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13545     Document Type: Article

References (74)

1. Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015). The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol 172: 6024–6109.
2. Amici R, Bigogno C, Boggio R, Colombo A, Courtney SM, Dal Zuffo R et al. (2014). Chiral resolution and pharmacological characterization of the enantiomers of the Hsp90 inhibitor 2-amino-7-[4-fluoro-2-(3-pyridyl)phenyl]-4-methyl-7,8-dihydro-6H-quinazolin-5-one oxime. ChemMedChem 9: 1574–1585.
3. Bauer J, Kuehnl S, Rollinger JM, Scherer O, Northoff H, Stuppner H et al. (2012). Carnosol and carnosic acids from Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1. J Pharmacol Exp Ther 342: 169–176.
4. Bruna S, Giovannini A, De Benedetti L, Principato MC, Ruffoni B (2006). Molecular analysis of Salvia spp. through RAPID markers. Acta Hort 723 (Proceedings of the Ist International Symposium on the Labiatae: Advances in Production, Biotechnology and Utilisation, 2006): 157–160.
5. Chae IG, Yu MH, Im NK, Jung YT, Lee J, Chun KS et al. (2012). Effect of Rosemarinus officinalis L. on MMP-9, MCP-1 levels, and cell migration in RAW 264.7 and smooth muscle cells. J Med Food 15: 879–886.
6. Chini MG, Ferroni C, Cantone V, Dambruoso P, Varchi G, Pepe A et al. (2015). Elucidating new structural features of the triazole scaffold for the development of mPGES-1 inhibitors. Med Chem Commun 6: 75–79.
7. Colucci M, Maione F, Bonito MC, Piscopo A, Di Giannuario A, Pieretti S (2008). New insights of dimethyl sulphoxide effects (DMSO) on experimental in vivo models of nociception and inflammation. Pharmacol Res 57: 419–425.
8. Curtis MJ, Bond RA, Spina D, Ahluwalia A, Alexander SP, Giembycz MA et al. (2015). Experimental design and analysis and their reporting: new guidance for publication in BJP. Br J Pharmacol 172: 3461–3471.
9. Di Lorenzo C, Dell'Agli M, Badea M, Dima L, Colombo E, Sangiovanni E et al. (2013). Plant food supplements with anti-inflammatory properties: A systematic review (II). Crit Rev Food Sci Nutr 53: 507–516.
10. Emami F, Ali-Beig H, Farahbakhsh S, Mojabi N, Rastegar-Moghadam B, Arbabian S et al. (2013). Hydroalcoholic extract of Rosemary (Rosmarinus officinalis L.) and its constituent carnosol inhibit formalin-induced pain and inflammation in mice. Pak J Biol Sci 16: 309–316.
11. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT et al. (2004). Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47: 1739–1749.
12. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA et al. (2006). Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49: 6177–6196.
13. Giamperi L, Bucchini A, Bisio A, Giacomelli E, Romussi G, Ricci D (2012). Total phenolic content and antioxidant activity of Salvia spp. exudates. Nat Prod Commun 7: 201–202.
14. Gilbert NC, Bartlett SG, Waight MT, Neau DB, Boeglin WE, Brash AR et al. (2011). The structure of human 5-lipoxygenase. Science 331: 217–219.
15. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT et al. (2004). Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47: 1750–1759.
16. Induced Fit Docking, protocol 2013-3, Glide version 6.1, Prime version 3.4. (2013). Schrödinger, LLC: New York, NY.
17. Iranshahi M, Chini MG, Masullo M, Sahebkar A, Javidnia A, Yazdi MC et al. (2015). Can small chemical modifications of natural pan-inhibitors modulate the biological selectivity? The case of curcumin prenylated derivatives acting as HDAC or mPGES-1 inhibitors. J Nat Prod 78: 2867–2879.
18. Johnson JJ (2011). Carnosol: A promising anti-cancer and anti-inflammatory agent. Cancer Lett 305: 1–7.
19. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, Group NCRRGW (2010). Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577–1579.
20. Koeberle A, Siemoneit U, Buehring U, Northoff H, Laufer S, Albrecht W et al. (2008). Licofelone suppresses prostaglandin E(2) formation by interference with the inducible microsomal prostaglandin E(2) synthase-1. J Pharmacol Exp Ther 326: 975–982.
21. Koeberle A, Northoff H, Werz O (2009). Identification of 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 as functional targets of the anti-inflammatory and anti-carcinogenic garcinol. Biochem Pharmacol 77: 1513–1521.
22. Koeberle A, Munoz E, Appendino GB, Minassi A, Pace S, Rossi A et al. (2014). SAR studies on curcumin's pro-inflammatory targets: discovery of prenylated pyrazolocurcuminoids as potent and selective novel inhibitors of 5-lipoxygenase. J Med Chem 57: 5638–5648.
23. Koeberle A, Werz O (2014). Multi-target approach for natural products in inflammation. Drug Discov Today 19: 1871–1882.
24. Koeberle A, Werz O (2015). Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders. Biochem Pharmacol 98: 1–15.
25. Kundu JK, Shin YK, Kim SH, Surh YJ (2006). Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappa B in mouse skin by blocking I kappa B kinase activity. Carcinogenesis 27: 1465–1474.
26. Laughton MJ, Evans PJ, Moroney MA, Hoult JR, Halliwell B (1991). Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives. Relationship to antioxidant activity and to iron ion-reducing ability. Biochem Pharmacol 42: 1673–1681.
27. Li D, Howe N, Dukkipati A, Shah STA, Bax BD, Edge C et al. (2014). Crystallizing membrane proteins in the lipidic mesophase. Experience with human prostaglandin E2 synthase 1 and an evolving strategy. Cryst Growth Des 14: 2034–2047.
28. LigPrep, version 2.8. (2013). Schrödinger, LLC: New York, NY.
29. Lo AH, Liang YC, Lin-Shiau SY, Ho CT, Lin JK (2002). Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages. Carcinogenesis 23: 983–991.
30. Loeser JD, Treede RD (2008). The Kyoto protocol of IASP Basic Pain Terminology. Pain 137: 473–477.
31. Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D et al. (2015). Crystal structures of mpges-1 inhibitor complexes form a basis for the rational design of potent analgesic and anti-inflammatory therapeutics. J Med Chem 58: 4727–4737.
32. Maestro, version 9.6. (2013). Schrödinger, LLC: New York, NY.
33. Maione F, Bonito MC, Colucci M, Cozzolino V, Bisio A, Romussi G et al. (2009). First evidence for an anxiolytic effect of a diterpenoid from Salvia cinnabarina. Nat Prod Commun 4: 469–472.
34. Maione F, Cicala C, Musciacco G, De Feo V, Amat AG, Ialenti A et al. (2013). Phenols, alkaloids and terpenes from medicinal plants with antihypertensive and vasorelaxant activities. A review of natural products as leads to potential therapeutic agents. Nat Prod Commun 8: 539–544.
35. Maione F, De Feo V, Caiazzo E, De Martino L, Cicala C, Mascolo N (2014). Tanshinone IIA, a major component of Salvia milthorriza Bunge, inhibits platelet activation via Erk-2 signaling pathway. J Ethnopharmacol 155: 1236–1242.
36. Maione F, Cantone V, Chini MG, De Feo V, Mascolo N, Bifulco G (2015a). Molecular mechanism of tanshinone IIA and cryptotanshinone in platelet anti-aggregating effects: an integrated study of pharmacology and computational analysis. Fitoterapia 100: 174–178.
37. Maione F, Russo R, Khan H, Mascolo N (2015b). Medicinal plants with anti-inflammatory activities. Nat Prod Res : 1–10.
38. Martin D, Rojo AI, Salinas M, Diaz R, Gallardo G, Alam J et al. (2004). Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 279: 8919–8929.
39. McGrath JC, Lilley E (2015). Implementing guidelines on reporting research using animals (ARRIVE etc.): new requirements for publication in BJP. Br J Pharmacol 172: 3189–3193.
40. Mengoni ES, Vichera G, Rigano LA, Rodriguez-Puebla ML, Galliano SR, Cafferata EE et al. (2011). Suppression of COX-2, IL-1 beta and TNF-alpha expression and leukocyte infiltration in inflamed skin by bioactive compounds from Rosmarinus officinalis L. Fitoterapia 82: 414–421.
41. Mirjalili MH, Salehi P, Sonboli A, Vala MM (2006). Essential oil variation of Salvia officinalis aerial parts during its phenological cycle. Chem Nat Comp 42: 19–23.
42. Miyata T (2007). Pharmacological basis of traditional medicines and health supplements as curatives. J Pharmacol Sci 103: 127-131.
43. Moran AE, Carothers AM, Weyant MJ, Redston M, Bertagnolli MM (2005). Carnosol inhibits beta-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse. Cancer Res 65: 1097–1104.
44. Morris CJ (2003). Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol 225: 115–121.
45. Muhammad N, Shrestha RL, Adhikari A, Wadood A, Khan H, Khan AZ et al. (2015). First evidence of the analgesic activity of govaniadine, an alkaloid isolated from Corydalis govaniana Wall. Nat Prod Res 29: 430–437.
46. Noguchi K, Okubo M (2011). Leukotrienes in nociceptive pathway and neuropathic/inflammatory pain. Biol Pharm Bull 34: 1163–1169.
47. Poeckel D, Greiner C, Verhoff M, Rau O, Tausch L, Hornig C et al. (2008). Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes. Biochem Pharmacol 76: 91–97.
48. Raal A, Orav A, Arak E (2007). Composition of the essential oil of Salvia officinalis L. from various European countries. Nat Prod Res 21: 406–411.
49. Rackham A, Ford-Hutchinson AW (1983). Inflammation and pain sensitivity: effects of leukotrienes D4, B4 and prostaglandin E1 in the rat paw. Prostaglandins 25: 193–203.
50. Ramirez P, Garcia-Risco MR, Santoyo S, Senorans FJ, Ibanez E, Reglero G (2006). Isolation of functional ingredients from rosemary by preparative-supercritical fluid chromatography (Prep-SFC). J Pharm Biomed Anal 41: 1606–1613.
51. Randall LO, Selitto JJ (1957). A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther 111: 409–419.
52. Rates SMK (2001). Plants as source of drugs. Toxicon 39: 603–613.
53. Rau O, Wurglics M, Paulke A, Zitzkowski J, Meindl N, Bock A et al. (2006). Carnosic acid and carnosol, phenolic diterpene compounds of the labiate herbs rosemary and sage, are activators of the human peroxisome proliferator-activated receptor gamma. Planta Med 72: 881–887.
54. Rauf A, Khan R, Raza M, Khan H, Pervez S, De Feo V et al. (2015). Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf In silico predictive study on its mechanistic effect. Fitoterapia 103: 129–135.
55. Rodrigues MRA, Kanazawa LKS, das Neves TLM, da Silva CF, Horst H, Pizzolatti MG et al. (2012). Antinociceptive and anti-inflammatory potential of extract and isolated compounds from the leaves of Salvia officinalis in mice. J Ethnopharmacol 139: 519–526.
56. Salminen A, Lehtonen M, Suuronen T, Kaarniranta K, Huuskonen J (2008). Terpenoids: natural inhibitors of NF-kappaB signaling with anti-inflammatory and anticancer potential. Cell Mol Life Sci 65: 2979–2999.
57. Samuelsson B, Morgenstern R, Jakobsson PJ (2007). Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 59: 207–224.
58. Schaible AM, Koeberle A, Northoff H, Lawrenz B, Weinigel C, Barz D et al. (2013a). High capacity for leukotriene biosynthesis in peripheral blood during pregnancy. Prostaglandins Leukot Essent Fatty Acids 89: 245–255.
59. Schaible AM, Traber H, Temml V, Noha SM, Filosa R, Peduto A et al. (2013b). Potent inhibition of human 5-lipoxygenase and microsomal prostaglandin E(2) synthase-1 by the anti-carcinogenic and anti-inflammatory agent embelin. Biochem Pharmacol 86: 476–486.
60. Senorans FJ, Ibanez E, Cavero S, Tabera J, Reglero G (2000). Liquid chromatographic-mass spectrometric analysis of supercritical-fluid extracts of rosemary plants. J Chromatogr 870: 491–499.
61. Serhan CN (2014). Pro-resolving lipid mediators are leads for resolution physiology. Nature 510: 92–101.
62. Sherman W, Beard HS, Farid R (2006a). Use of an induced fit receptor structure in virtual screening. Chem Biol Drug Des 67: 83–84.
63. Sherman W, Day T, Jacobson MP, Friesner RA, Farid R (2006b). Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem 49: 534–553.
64. Shibata M, Ohkubo T, Takahashi H, Inoki R (1989). Modified formalin test - characteristic biphasic pain response. Pain 38: 347–352.
65. Sjogren T, Nord J, Ek M, Johansson P, Liu G, Geschwindner S (2013). Crystal structure of microsomal prostaglandin E-2 synthase provides insight into diversity in the MAPEG superfamily. Proc Natl Acad Sci U S A 110: 3806–3811.
66. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SPH et al. (2016). The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucleic Acids Res 44 (Database Issue): D1054–D1068.
67. Subbaramaiah K, Cole PA, Dannenberg AJ (2002). Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and -independent mechanisms. Cancer Res 62: 2522–2530.
68. Terracciano S, Lauro G, Strocchia M, Fischer K, Werz O, Riccio R et al. (2015). Structural Insights for the optimization of dihydropyrimidin-2(1H)-one based mPGES-1 inhibitors. ACS Med Chem Lett 6: 187–191.
69. Thoren S, Weinander R, Saha S, Jegerschold C, Pettersson PL, Samuelsson B et al. (2003). Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination. J Biol Chem 278: 22199–22209.
70. Villa C, Trucchi B, Bertoli A, Pistelli L, Parodi A, Bassi AM et al. (2009). Int J Cosmet Sci 31: 55–61.
71. Yu YM, Lin HC, Chang WC (2008). Carnosic acid prevents the migration of human aortic smooth muscle cells by inhibiting the activation and expression of matrix metalloproteinase-9. Br J Nutr 100: 731–738.
72. Zhang Y, Smuts JP, Dodbiba E, Rangarajan R, Lang JC, Armstrong DW (2012). Degradation study of carnosic acid, carnosol, rosmarinic acid, and rosemary extract (Rosmarinus officinalis L.) assessed using HPLC. J Agric Food Chem 60: 9305–9314.
73. Zhao H, Garg G, Zhao J, Moroni E, Girgis A, Franco LS et al. (2015). Design, synthesis and biological evaluation of biphenylamide derivatives as Hsp90 C-terminal inhibitors. Eur J Med Chem 89: 442–466.
74. Zhao H, Moroni E, Colombo G, Blagg BS (2014). Identification of a new scaffold for hsp90 C-terminal inhibition. ACS Meed Chem Lett 5: 84–88.