5 results on '"Meng-Yan Deng"'
Search Results
2. Lemairamin, isolated from the Zanthoxylum plants, alleviates pain hypersensitivity via spinal α7 nicotinic acetylcholine receptors
- Author
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Meng-Jing Zhao, Yong-Xiang Wang, Rana Muhammad Shoaib, Zi-Ying Wang, Evhy Apryani, Meng-Yan Deng, Qiao-Qiao Han, and Dong-Qing Wei
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Male ,Zanthoxylum ,0301 basic medicine ,Agonist ,alpha7 Nicotinic Acetylcholine Receptor ,medicine.drug_class ,Aconitine ,Biophysics ,Minocycline ,Pharmacology ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Formaldehyde ,Animals ,Medicine ,Rats, Wistar ,Molecular Biology ,Injections, Spinal ,Neuroinflammation ,Methyllycaconitine ,Acrylamides ,Analgesics ,Naloxone ,business.industry ,beta-Endorphin ,Antagonist ,Cancer Pain ,Cell Biology ,Interleukin-10 ,Rats ,Interleukin 10 ,030104 developmental biology ,Nociception ,Spinal Cord ,chemistry ,Hyperalgesia ,030220 oncology & carcinogenesis ,Neuropathic pain ,Neuralgia ,Female ,Microglia ,business ,medicine.drug - Abstract
Lemairamin (also known as wgx-50), is isolated from the pericarps of the Zanthoxylum plants. As an agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), it can reduce neuroinflammation in Alzheimer's disease. This study evaluated its antinociceptive effects in pain hypersensitivity and explored the underlying mechanisms. The data showed that subcutaneous lemairamin injection dose-dependently inhibited formalin-induced tonic pain but not acute nociception in mice and rats, while intrathecal lemairamin injection also dose-dependently produced mechanical antiallodynia in the ipsilateral hindpaws of neuropathic and bone cancer pain rats without affecting mechanical thresholds in the contralateral hindpaws. Multiple bi-daily lemairamin injections for 7 days did not induce mechanical antiallodynic tolerance in neuropathic rats. Moreover, the antinociceptive effects of lemairamin in formalin-induced tonic pain and mechanical antiallodynia in neuropathic pain were suppressed by the α7nAChR antagonist methyllycaconitine. In an α7nAChR antagonist-reversible manner, intrathecal lemairamin also stimulated spinal expression of IL-10 and β-endorphin, while lemairamin treatment induced IL-10 and β-endorphin expression in primary spinal microglial cells. In addition, intrathecal injection of a microglial activation inhibitor minocycline, anti-IL-10 antibody, anti-β-endorphin antiserum or μ-opioid receptor-preferred antagonist naloxone was all able to block lemairamin-induced mechanical antiallodynia in neuropathic pain. These data demonstrated that lemairamin could produce antinociception in pain hypersensitivity through the spinal IL-10/β-endorphin pathway following α7nAChR activation.
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- 2020
3. Microglial IL-10 and β-endorphin expression mediates gabapentinoids antineuropathic pain
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Meng-Yan Deng, Rana Muhammad Shoaib, Le Ma, Yong-Xiang Wang, Khalil Ali Ahmad, Muhammad Zaeem Ahsan, Evhy Apryani, and Xin-Yan Li
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0301 basic medicine ,Male ,Gabapentin ,Immunology ,Pregabalin ,Pharmacology ,03 medical and health sciences ,Behavioral Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Mirogabalin ,Medicine ,Animals ,Rats, Wistar ,Microglia ,Endocrine and Autonomic Systems ,business.industry ,beta-Endorphin ,Dynorphin A ,Spinal cord ,Interleukin-10 ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Allodynia ,chemistry ,Spinal Cord ,Hyperalgesia ,Neuropathic pain ,Neuralgia ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Gabapentinoids are recommended first-line treatments for neuropathic pain. They are neuronal voltage-dependent calcium channel α2δ-1 subunit ligands and have been suggested to attenuate neuropathic pain via interaction with neuronal α2δ-1 subunit. However, the current study revealed their microglial mechanisms underlying antineuropathic pain. Intrathecal injection of gabapentin, pregabalin and mirogabalin rapidly inhibited mechanical allodynia and thermal hyperalgesia, with projected ED50 values of 30.3, 6.2 and 1.5 µg (or 176.9, 38.9 and 7.2 nmol) and Emax values of 66%, 61% and 65% MPE respectively for mechanical allodynia. Intrathecal gabapentinoids stimulated spinal mRNA and protein expression of IL-10 and β-endorphin (but not dynorphin A) in neuropathic rats with the time point parallel to their inhibition of allodynia, which was observed in microglia but not astrocytes or neurons in spinal dorsal horns by using double immunofluorescence staining. Intrathecal gabapentin alleviated pain hypersensitivity in male/female neuropathic but not male sham rats, whereas it increased expression of spinal IL-10 and β-endorphin in male/female neuropathic and male sham rats. Treatment with gabapentin, pregabalin and mirogabalin specifically upregulated IL-10 and β-endorphin mRNA and protein expression in primary spinal microglial but not astrocytic or neuronal cells, with EC50 values of 41.3, 11.5 and 2.5 µM and 34.7, 13.3 and 2.8 µM respectively. Pretreatment with intrathecal microglial metabolic inhibitor minocycline, IL-10 antibody, β-endorphin antiserum or μ-opioid receptor antagonist CTAP (but not κ- or δ-opioid receptor antagonists) suppressed spinal gabapentinoids-inhibited mechanical allodynia. Immunofluorescence staining exhibited specific α2δ-1 expression in neurons but not microglia or astrocytes in the spinal dorsal horns or cultured primary spinal cells. Thus the results illustrate that gabapentinoids alleviate neuropathic pain through stimulating expression of spinal microglial IL-10 and consequent β-endorphin.
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- 2020
4. Thalidomide alleviates neuropathic pain through microglial IL-10/β-endorphin signaling pathway
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Meng-Yan Deng, Qiao-Qiao Han, Rana Muhammad Shoaib, Xin-Yan Li, Khalil Ali Ahmad, Yong-Xiang Wang, and Zi-Ying Wang
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Male ,(+)-Naloxone ,Pharmacology ,Biochemistry ,Proinflammatory cytokine ,medicine ,Animals ,Rats, Wistar ,Cells, Cultured ,Multiple myeloma ,Lenalidomide ,Dose-Response Relationship, Drug ,Microglia ,business.industry ,beta-Endorphin ,medicine.disease ,Pomalidomide ,Interleukin-10 ,Rats ,Thalidomide ,medicine.anatomical_structure ,Neuropathic pain ,Neuralgia ,business ,Immunosuppressive Agents ,Signal Transduction ,medicine.drug - Abstract
Thalidomide is an antiinflammatory, antiangiogenic and immunomodulatory agent which has been used for the treatment of erythema nodosum leprosum and multiple myeloma. It has also been employed in treating complex regional pain syndromes. The current study aimed to reveal the molecular mechanisms underlying thalidomide-induced pain antihypersensitive effects in neuropathic pain. Thalidomide gavage, but not its more potent analogs lenalidomide and pomalidomide, inhibited mechanical allodynia and thermal hyperalgesia in neuropathic pain rats induced by tight ligation of spinal nerves, with ED50 values of 44.9 and 23.5 mg/kg, and Emax values of 74% and 84% MPE respectively. Intrathecal injection of thalidomide also inhibited mechanical allodynia and thermal hyperalgesia in neuropathic pain. Treatment with thalidomide, lenalidomide and pomalidomide reduced peripheral nerve injury-induced proinflammatory cytokines (TNFα, IL-1β and IL-6) in the ipsilateral spinal cords of neuropathic rats and LPS-treated primary microglial cells. In contrast, treatment with thalidomide, but not lenalidomide or pomalidomide, stimulated spinal expressions of IL-10 and β-endorphin in neuropathic rats. Particularly, thalidomide specifically stimulated IL-10 and β-endorphin expressions in microglia but not astrocytes or neurons. Furthermore, pretreatment with the IL-10 antibody blocked upregulation of β-endorphin in neuropathic rats and cultured microglial cells, whereas it did not restore thalidomide-induced downregulation of proinflammatory cytokine expression. Importantly, pretreatment with intrathecal injection of the microglial metabolic inhibitor minocycline, IL-10 antibody, β-endorphin antiserum, and preferred or selective μ-opioid receptor antagonist naloxone or CTAP entirely blocked thalidomide gavage-induced mechanical antiallodynia. Our results demonstrate that thalidomide, but not lenalidomide or pomalidomide, alleviates neuropathic pain, which is mediated by upregulation of spinal microglial IL-10/β-endorphin expression, rather than downregulation of TNFα expression.
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- 2021
5. Cynandione A and PHA-543613 inhibit inflammation and stimulate macrophageal IL-10 expression following α7 nAChR activation
- Author
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Usman Ali, Meng-Yan Deng, Xin-Yan Li, Yong-Xiang Wang, Qiao-Qiao Han, and Hao Liu
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Male ,0301 basic medicine ,Quinuclidines ,alpha7 Nicotinic Acetylcholine Receptor ,Lipopolysaccharide ,Inflammation ,Pharmacology ,Biochemistry ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,STAT3 ,Cells, Cultured ,Methyllycaconitine ,Cynanchum ,Dose-Response Relationship, Drug ,biology ,Macrophages ,Biphenyl Compounds ,Interleukin ,Bridged Bicyclo Compounds, Heterocyclic ,Interleukin-10 ,Mice, Inbred C57BL ,Interleukin 10 ,RAW 264.7 Cells ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Tumor necrosis factor alpha ,Inflammation Mediators ,medicine.symptom - Abstract
Cynandione A, an acetophenone isolated from Cynanchum Wilfordii Radix, attenuates inflammation. The present study aimed to study the mechanisms underlying cynandione A-induced antiinflammation. Treatment with cynandione A and the specific α7 nicotinic acetylcholine receptor (α7 nAChR) agonist PHA-543613 remarkably reduced overexpression of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells and primary peritoneal macrophages, and endotoxemic mice. Both cynandione A and PHA-543613 also stimulated IL-10 expression in naïve and LPS-treated macrophages and endotoxemic mice. Cynandione A- and PHA-543613-inhibited proinflammatory cytokine expression was completely blocked by the α7 nAChR antagonist methyllycaconitine and the IL-10 antibody. The stimulatory effect of cynandione A and PHA-543613 on IL-10 expression were suppressed by methyllycaconitine and knockdown of α7 nAChRs using siRNA/α7 nAChR. Cynandione A significantly stimulated STAT3 phosphorylation, which was attenuated by methyllycaconitine and the IL-10 neutralizing antibody. The STAT3 activation inhibitor NSC74859 also blocked cynandione A-inhibited proinflammatory cytokine expression. Taken together, our results, for the first time, demonstrate that cynandione A and PHA-543613 inhibit inflammation through macrophageal α7 nAChR activation and subsequent IL-10 expression.
- Published
- 2021
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