Ononis spinosa alleviated capsaicin-induced mechanical allodynia in a rat model through transient receptor potential vanilloid 1 modulation
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Background: Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of Ononis spinosa (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action. Methods: Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 μg CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 μg O. spinosa methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between O. spinosa constituents and TRPV1 receptor. Results: The ipsilateral ipl injection of O. spinosa before CAPS injection increased PWT in rats at all time points. O. spinosa decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 μg 4-[3-Chloro-2-pyridinyl]- N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 μg butoxamine) attenuated the action of O. spinosa. Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1. Conclusions: O. spinosa alleviated CAPS-induced mechanical allodynia through 2 mechanisms: the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.
Abstract
Background: Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of Ononis spinosa (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action. Methods: Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 μg CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 μg O. spinosa methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between O. spinosa constituents and TRPV1 receptor. Results: The ipsilateral ipl injection of O. spinosa before CAPS injection increased PWT in rats at all time points. O. spinosa decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 μg 4-[3-Chloro-2-pyridinyl]- N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 μg butoxamine) attenuated the action of O. spinosa. Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1. Conclusions: O. spinosa alleviated CAPS-induced mechanical allodynia through 2 mechanisms: the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.
참고문헌 (38)
- Moran MM, "Targeting nociceptive transient receptor potential channels to treat chronic pain : current state of the field", Br J Pharmacol, 175, pp.2185~2203 (2018)
- Cavanaugh DJ, "Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons", J Neurosci, 31, pp.10119~10127 (2011)
- Gilchrist HD, "Enhanced withdrawal responses to heat and mechanical stimuli following intraplantar injection of capsaicin in rats", Pain, 67, pp.179~188 (1996)
- Caterina MJ, "The capsaicin receptor : a heat-activated ion channel in the pain pathway", Nature, 389, pp.816~824 (1997)
- Julius D, "TRP channels and pain", Annu Rev Cell Dev Biol, 29, pp.355~384 (2013)
- Alsalem M, "The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inf lammatory pain mechanisms", Br J Pharmacol, 168, pp.1961~1974 (2013)
- Wongrakpanich S, "A comprehensive review of non-steroidal antiinflammatory drug use in the elderly", Aging Dis, 9, pp.143~150 (2018)
- Al-Eisawi DMH, "Field guide to wild flowers of Jordan and neighbouring countries" (1998), Jordan Press Foundation
- Al-Snafi AE, "The traditional uses, constituents and pharmacological effects of Ononis spinosa", IOSR J Pharm, 10, pp.53~59 (2020)
- Yõlmaz BS, "Analgesic and hepatotoxic effects of Ononis spinosa L", Phytother Res, 20, pp.500~503 (2006)
- Ergene Öz B, "Wound healing and anti-inflammatory activity of some Ononis taxons", Biomed Pharmacother, 91, pp.1096~1105 (2017)
- Al-Khalil S, "A survey of plants used in Jordanian traditional medicine", Int J Pharmacogn, 33, pp.317~323 (1995)
- Jaffal SM, "Antinociceptive action of Ononis spinosa leaf extract in mouse pain models", Acta Pol Pharm, 76, pp.299~304 (2019)
- Lolignier S, "Mechanical allodynia", Pflugers Arch, 467, pp.133~139 (2015)
- Khasar SG, "Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors", J Neurophysiol, 81, pp.1104~1112 (1999)
- Nozadze I, "NSAIDs attenuate hyperalgesia induced by TRP channel activation", Data Brief, 6, pp.668~673 (2016)
- Ferrier J, "Assessment of mechanical allodynia in rats using the electronic von frey test", Bio Protoc, 6, pp.e1933~ (2016)
- Gao Y, "TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action", Nature, 534, pp.347~351 (2016)
- Walpole CS, "The discovery of capsazepine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin", J Med Chem, 37, pp.1942~1954 (1994)
- "Version 2018.1", 2018
- "Version 2002-2021", 2002
- Abbas MA, "Efficacy of extract from Ononis spinosa L. on ethanol-induced gastric ulcer in rats", J Tradit Chin Med, 41, pp.270~275 (2021)
- Fricker PC, "Automated drawing of structural molecular formulas under constraints", J Chem Inf Comput Sci, 44, pp.1065~1078 (2004)
- Stierand K, "Molecular complexes at a glance : automated generation of two-dimensional complex diagrams", Bioinformatics, 22, pp.1710~1716 (2006)
- Matsushita Y, "Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats", PLoS One, 13, pp.e0191032~ (2018)
- Filippi A, "Catecholamines reduce transient receptor potential vanilloid type 1 desensitization in cultured dorsal root ganglia neurons", J Physiol Pharmacol, 67, pp.843~850 (2016)
- Jeske NA, "A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1", Pain, 138, pp.604~616 (2008)
- Chakraborty S, "Presynaptic inhibition of transient receptor potential vanilloid type 1(TRPV1)receptors by noradrenaline in nociceptive neurons", J Physiol, 595, pp.2639~2660 (2017)
- Nackley AG, "Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2-and beta3-adrenergic receptors", Pain, 128, pp.199~208 (2007)
- Zhu L, "Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity", Sci Rep, 5, pp.16109~ (2015)
- Coutaux A, "Hyperalgesia and allodynia : peripheral mechanisms", Joint Bone Spine, 72, pp.359~371 (2005)
- Benarroch EE, "Dorsal horn circuitry : complexity and implications for mechanisms of neuropathic pain", Neurology, 86, pp.1060~1069 (2016)
- Al-Najjar BO, "Synthesis, molecular docking and antioxidant evaluation of benzylidene ketone derivatives", Jordan J Biol Sci, 11, pp.307~313 (2018)
- Benedec D, "Isoflavonoids from Glycyrrhiza sp. and Ononis spinosa", Farmacia, 60, pp.615~620 (2012)
- Peres MTLP, "Pharmaco-chemical criteria used in their isolation", Phytother Res, 12, pp.209~211 (1998)
- Lee CW, "Introduction of visceral pain model to test of visceral nociception in the rats", J Korean Pain Soc, 8, pp.25~30 (1995)
- Julius D, "Molecular mechanisms of nociception", Nature, 413, pp.203~210 (2001)
- Walker CIB, "Anti-nociceptive effect of stigmasterol in mouse models of acute and chronic pain", Naunyn Schmiedebergs Arch Pharmacol, 390, pp.1163~1172 (2017)
