Issue
Assessment of the anti-inflammatory, analgesic and sedative effects of oleuropein from Olea europaea L
Corresponding Author(s) : Zhiming Zhou
Cellular and Molecular Biology,
Vol. 65 No. 1: Issue 1
Abstract
More and more studies show that inflammation, pain and insomnia have become the main common diseases. Effective treatments of inflammation, pain and insomnia have become an issue of primary concern in clinical practice. Oleuropein (OLE), the main phenolic component of Mediterranean extra virgin olive oil, has shown many pharmacological properties. In the present study, the anti-inflammatory effect of OLE was firstly evaluated using RAW264.7 macrophages subjected to stimulation with lipopolysaccharide (LPSC). The results obtained revealed that OLE caused significant and dose-dependent downregulation of nitric (NO), COX-2, inducible NO synthase iNOS, and the inflammation-associated cytokines IL-6 and TNF-α. From the mechanism, the expression of COX-2, cytokines IL-6 and TNF-α OLE is closely related to analgesic and sedation effect. Further evaluations showed significant analgesic and sedative effects of OLE in tail-flick test and sedation test conducted in SD rats in vivo. All these results indicate that OLE has anti-inflammatory, analgesic and sedative effects both in vitro and in vivo.
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- Lönnqvist PA, Ecoffey C, Bosenberg A, Suresh S, Ivani G. The European society of regional anesthesia and pain therapy and the American society of regional anesthesia and pain medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us? Reg Anesth Pain Med 2018; 43: 211.
- Gupta A, Bah M. NSAIDs in the Treatment of Postoperative Pain. Curr Pain Headache Rep 2016; 20: 62.
- Wong SH, Chan FKL. Adverse Effects of NSAIDs in the Gastrointestinal Tract: Risk Factors of Gastrointestinal Toxicity with NSAIDs. Springer International Publishing; 2016.
- Shoaib M, Shah SWA, Ali N, Shah I, Ullah S, Ghias M, et al. Scientific investigation of crude alkaloids from medicinal plants for the management of pain. BMC Complement Altern Med 2016; 16: 1-8.
- Singh H, Bhushan S, Arora R, Singh BH, Arora S, Singh B. Alternative treatment strategies for neuropathic pain: Role of Indian medicinal plants and compounds of plant origin-A review. Biomed Pharmacother 2017; 92: 634.
- Morin CM, Beaulieubonneau S, Ivers H, Vallières A, Guay B, Savard J, et al. Speed and trajectory of changes of insomnia symptoms during acute treatment with cognitive–behavioral therapy, singly and combined with medication. Sleep Med 2014; 15: 701-707.
- Prather AA, Vogelzangs N, Penninx BW. Sleep duration, insomnia, and markers of systemic inflammation: results from the Netherlands Study of Depression and Anxiety (NESDA). J Psychiatr Res 2015; 60: 95-102.
- Buford UJ, Nemeroff CB. Current treatment options for insomnia. Drugs Today 2012; 48: 415-423.
- Wang ZJ, Liu JF. The Molecular Basis of Insomnia: Implication for Therapeutic Approaches. Drug Dev Res 2016; 77: 427-436.
- Beck TC, Garcia-Trevino JA, Ramirez BA. Hypnotics and Sedatives. Side Effects Drugs Annual 2017.
- Leri M, Nosi D, Natalello A, Porcari R, Ramazzotti M, Chiti F, et al. The polyphenol Oleuropein aglycone hinders the growth of toxic transthyretin amyloid assemblies. J Nutr Biochem 2016; 30: 153-166.
- Rigacci S, Miceli C, Nediani C, Berti A, Cascella R, Pantano D, et al. Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight. Oncotarget 2015; 6: 35344-35357.
- Barbaro B, Toietta G, Maggio R, Arciello M, Tarocchi M, Galli A, et al. Effects of the Olive-Derived Polyphenol Oleuropein on Human Health. Int J Mol Sci 2014; 15: 18508-18524.
- Fotakis G, Timbrell JA. In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 2006; 160: 171-177.
- Carroll FI, Ma W, Deng L, Navarro HA, Damaj MI, Martin BR. Synthesis, Nicotinic Acetylcholine Receptor Binding, and Antinociceptive Properties of 3"²-(Substituted Phenyl)epibatidine Analogues. Nicotinic Partial Agonists⊥. J Med Chem 2014; 57: 836-848.
- Mimura M, Namiki A, Kishi R, Ikeda T, Miyake H. Antagonistic effect of physostigmine on ketamine-induced anesthesia. Psychopharmacol 1990; 102: 399-403.
- Tomioka H, Shimizu T, Sato K, Sano C, Kamei T, Emori M, et al. Comparative roles of macrophages and NK cells in the host innate resistance of mice to Mycobacterium fortuitum infection. J Infect 2004; 48: 74-80.
- Jiang CY, Wang W, Tang JX, Yuan ZR. The adipocytokine resistin stimulates the production of proinflammatory cytokines TNF-α and IL-6 in pancreatic acinar cells via NF-κB activation. J Endocrinol Invest 2013; 36: 986-992.
- Oxide N. Nitric oxide (NO) is a gas with diverse biological activities produced from arginine by NO synthases. It is capable of interacting with a number of molecules, most notably superoxide, forming peroxynitrite, which, in turn, can mediate bactericidal or. Nitric Oxide Synthase 1997.
- Singh S, Gupta AK. Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies. Cancer Chemotherapy Pharmacol 2011; 67: 1211-1224.
- Zhang ZJ, Cheang LC, Wang MW, Lee SM. Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish. Int J Mol Med 2011; 27: 195.
- Rajeswari SR, Gowda TM, Kumar TA, Thimmasetty J, Mehta DS. An appraisal of innovative meloxicam mucoadhesive films for periodontal postsurgical pain control: A double-blinded, randomized clinical trial of effectiveness. Contemp Clin Dent 2015; 6: 299-304.
- Varga H, Pardutz A, Vamos E, Plangar I, Egyud E, Tajti J, et al. Cox-2 inhibitor attenuates NO-induced nNOS in rat caudal trigeminal nucleus. Headache 2010; 47: 1319-1325.
- Charrad R, Berraí¯es A, Hamdi B, Ammar J, Hamzaoui K, Hamzaoui A. Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A. Immunobiology 2016; 221: 182.
- Xue X, Piao JH, Nakajima A, Sakon-Komazawa S, Kojima Y, Mori K, et al. Tumor Necrosis Factor α (TNFα) Induces the Unfolded Protein Response (UPR) in a Reactive Oxygen Species (ROS)-dependent Fashion, and the UPR Counteracts ROS Accumulation by TNFα. J Biol Chem 2005; 280: 33917-33925.
- Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101: 311-320.
- Möller B, Villiger PM. Inhibition of IL-1, IL-6, and TNF-α in immune-mediated inflammatory diseases. Springer Semin Immunopathol 2006; 27: 391-408.
References
Lönnqvist PA, Ecoffey C, Bosenberg A, Suresh S, Ivani G. The European society of regional anesthesia and pain therapy and the American society of regional anesthesia and pain medicine joint committee practice advisory on controversial topics in pediatric regional anesthesia I and II: what do they tell us? Reg Anesth Pain Med 2018; 43: 211.
Gupta A, Bah M. NSAIDs in the Treatment of Postoperative Pain. Curr Pain Headache Rep 2016; 20: 62.
Wong SH, Chan FKL. Adverse Effects of NSAIDs in the Gastrointestinal Tract: Risk Factors of Gastrointestinal Toxicity with NSAIDs. Springer International Publishing; 2016.
Shoaib M, Shah SWA, Ali N, Shah I, Ullah S, Ghias M, et al. Scientific investigation of crude alkaloids from medicinal plants for the management of pain. BMC Complement Altern Med 2016; 16: 1-8.
Singh H, Bhushan S, Arora R, Singh BH, Arora S, Singh B. Alternative treatment strategies for neuropathic pain: Role of Indian medicinal plants and compounds of plant origin-A review. Biomed Pharmacother 2017; 92: 634.
Morin CM, Beaulieubonneau S, Ivers H, Vallières A, Guay B, Savard J, et al. Speed and trajectory of changes of insomnia symptoms during acute treatment with cognitive–behavioral therapy, singly and combined with medication. Sleep Med 2014; 15: 701-707.
Prather AA, Vogelzangs N, Penninx BW. Sleep duration, insomnia, and markers of systemic inflammation: results from the Netherlands Study of Depression and Anxiety (NESDA). J Psychiatr Res 2015; 60: 95-102.
Buford UJ, Nemeroff CB. Current treatment options for insomnia. Drugs Today 2012; 48: 415-423.
Wang ZJ, Liu JF. The Molecular Basis of Insomnia: Implication for Therapeutic Approaches. Drug Dev Res 2016; 77: 427-436.
Beck TC, Garcia-Trevino JA, Ramirez BA. Hypnotics and Sedatives. Side Effects Drugs Annual 2017.
Leri M, Nosi D, Natalello A, Porcari R, Ramazzotti M, Chiti F, et al. The polyphenol Oleuropein aglycone hinders the growth of toxic transthyretin amyloid assemblies. J Nutr Biochem 2016; 30: 153-166.
Rigacci S, Miceli C, Nediani C, Berti A, Cascella R, Pantano D, et al. Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight. Oncotarget 2015; 6: 35344-35357.
Barbaro B, Toietta G, Maggio R, Arciello M, Tarocchi M, Galli A, et al. Effects of the Olive-Derived Polyphenol Oleuropein on Human Health. Int J Mol Sci 2014; 15: 18508-18524.
Fotakis G, Timbrell JA. In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 2006; 160: 171-177.
Carroll FI, Ma W, Deng L, Navarro HA, Damaj MI, Martin BR. Synthesis, Nicotinic Acetylcholine Receptor Binding, and Antinociceptive Properties of 3"²-(Substituted Phenyl)epibatidine Analogues. Nicotinic Partial Agonists⊥. J Med Chem 2014; 57: 836-848.
Mimura M, Namiki A, Kishi R, Ikeda T, Miyake H. Antagonistic effect of physostigmine on ketamine-induced anesthesia. Psychopharmacol 1990; 102: 399-403.
Tomioka H, Shimizu T, Sato K, Sano C, Kamei T, Emori M, et al. Comparative roles of macrophages and NK cells in the host innate resistance of mice to Mycobacterium fortuitum infection. J Infect 2004; 48: 74-80.
Jiang CY, Wang W, Tang JX, Yuan ZR. The adipocytokine resistin stimulates the production of proinflammatory cytokines TNF-α and IL-6 in pancreatic acinar cells via NF-κB activation. J Endocrinol Invest 2013; 36: 986-992.
Oxide N. Nitric oxide (NO) is a gas with diverse biological activities produced from arginine by NO synthases. It is capable of interacting with a number of molecules, most notably superoxide, forming peroxynitrite, which, in turn, can mediate bactericidal or. Nitric Oxide Synthase 1997.
Singh S, Gupta AK. Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies. Cancer Chemotherapy Pharmacol 2011; 67: 1211-1224.
Zhang ZJ, Cheang LC, Wang MW, Lee SM. Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish. Int J Mol Med 2011; 27: 195.
Rajeswari SR, Gowda TM, Kumar TA, Thimmasetty J, Mehta DS. An appraisal of innovative meloxicam mucoadhesive films for periodontal postsurgical pain control: A double-blinded, randomized clinical trial of effectiveness. Contemp Clin Dent 2015; 6: 299-304.
Varga H, Pardutz A, Vamos E, Plangar I, Egyud E, Tajti J, et al. Cox-2 inhibitor attenuates NO-induced nNOS in rat caudal trigeminal nucleus. Headache 2010; 47: 1319-1325.
Charrad R, Berraí¯es A, Hamdi B, Ammar J, Hamzaoui K, Hamzaoui A. Anti-inflammatory activity of IL-37 in asthmatic children: Correlation with inflammatory cytokines TNF-α, IL-β, IL-6 and IL-17A. Immunobiology 2016; 221: 182.
Xue X, Piao JH, Nakajima A, Sakon-Komazawa S, Kojima Y, Mori K, et al. Tumor Necrosis Factor α (TNFα) Induces the Unfolded Protein Response (UPR) in a Reactive Oxygen Species (ROS)-dependent Fashion, and the UPR Counteracts ROS Accumulation by TNFα. J Biol Chem 2005; 280: 33917-33925.
Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 1998; 101: 311-320.
Möller B, Villiger PM. Inhibition of IL-1, IL-6, and TNF-α in immune-mediated inflammatory diseases. Springer Semin Immunopathol 2006; 27: 391-408.