ReferenceID 74
Morroniside, a secoiridoid glycoside from Cornus officinalis, attenuates neuropathic pain by activation of spinal glucagon-like peptide-1 receptors
Br J Pharmacol
BACKGROUND AND PURPOSE: Iridoid glycosides containing the double bond scaffold of cyclopentapyran are reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and exert anti-nociceptive and neurop
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- Reference Id
- 74
- Evidence Id
- 16664
- Core Evidence Id
- 16664
- Source Reference Id
- 126
- Herb2 Reference Id
- HBREF000281
- Subject Paper Key
- HBIN035768_28098360
- Pubmed Id
- 28098360
- Doi
- 10.1111/bph.13720
- Paper Title
- Morroniside, a secoiridoid glycoside from Cornus officinalis, attenuates neuropathic pain by activation of spinal glucagon-like peptide-1 receptors
- Paper Abstract
- BACKGROUND AND PURPOSE: Iridoid glycosides containing the double bond scaffold of cyclopentapyran are reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and exert anti-nociceptive and neuroprotective actions. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical secoiridoid containing a six-membered cyclic inner ether fragment. Here we investigated whether morroniside was an orthosteric GLP-1 receptor agonist and had anti-hypersensitivity activities in a model of neuropathic pain. EXPERIMENTAL APPROACH: We used a model of neuropathic pain, induced by tight ligation of L5/L6 spinal nerves in rats. Hydrogen peroxide-induced oxidative damage was also assayed in N9 microglial cells and human HEK293 cells stably expressing GLP-1 receptors. KEY RESULTS: Morroniside protected against hydrogen peroxide-induced oxidative damage in N9 microglial and HEK293 cells that expressed mouse or human GLP-1 receptors, but not in HEK293T cells without GLP-1 receptors. The GLP-1 receptor orthosteric antagonist exendin(9-39) also concentration-dependently shifted the concentration-protective response curves of morroniside and exenatide to the right without affecting maximal protection, with similar pA2 values. Furthermore, morroniside given by oral gavage or intrathecally in neuropathic rats dose-dependently attenuated mechanical allodynia, with comparable Emax values and ED50 s of 335 mg·kg-1 and 7.1 μg and completely blocked thermal hyperalgesia. Daily intrathecal injections of morroniside over 7 days did not induce anti-allodynic tolerance. Pretreatment with intrathecal exendin(9-39) completely blocked systemic and intrathecal morroniside-induced mechanical anti-allodynia. CONCLUSION AND IMPLICATIONS: Our data demonstrated that morroniside was an orthosteric agonist of GLP-1 receptors and produced antihypersensitivity in a neuropathic pain model by activation of spinal GLP-1 receptors.
- Journal
- Br J Pharmacol
- Publish Year
- 2017
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Morroniside, a secoiridoid glycoside from Cornus officinalis, attenuates neuropathic pain by activation of spinal glucagon-like peptide-1 receptors
- Bilingual Status
- semi_complete