Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway

Wang, Lu; Fu, Yuanbo; Liu, Yi; Yang, Nana; Ma, Si‐Ming; Wang, Xuerui; Huang, Jin; Shi, Guang‐Xia; Yang, Jing‐Wen; Liu, Cun‐Zhi

doi:10.1016/j.brainres.2022.147926

Cited by 6 publications

(5 citation statements)

References 46 publications

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“…In the ischemic lesion of the mouse middle cerebral artery occlusion model, the mAChRs, such as M3 was upregulated in the microglia in the ischemic lesion; meanwhile, a protective role of M3-mAChR activation was shown in myocardial injury and motor coordination of microglia and monocytes (Costa et al, 2021). Suppression of M2-mAChR by moxibustion or the receptor antagonist methotramine hemihydrate attenuated the neurogenic detrusor overactivity in spinal cord injury (Wang et al, 2022). Rather different from the activation of mAChRs, however, in the present study, we found that downregulation of M2-and M4-mAChRs by AT3, and M2and M4-mAChR inhibitors attenuated the H/R-induced cell apoptosis, showing a protective effect of AT3 and M2-and M4-mAChRs antagonists against the H/R injury of hCMEC/ D3 cells.…”

Section: Discussionmentioning

confidence: 97%

Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

JIANG,

SHEN,

et al. 2023

BIOCELL

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Background: Anisodine hydrobromide (AT3), an anti-cholinergic agent, could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury. Endothelial dysfunction can be caused by hypoxia/reoxygenation (H/R) via oxidative stress and metabolic alterations. The present study investigated whether AT3 regulates the production of nitric oxide (NO) and reactive oxygen species (ROS), and the HIF-1α pathway via regulation of muscarinic acetylcholine receptors (mAChRs) in brain microvascular endothelial cells after H/R exposure. Methods: Under H/R conditions, hCMEC/D3 cerebral microvascular endothelial cells were treated with AT3. Specific inhibitors of M2-and M4-mAChRs were used to explore the mechanism by which AT3 influences oxidative stress in endothelial cells. Then, mAChRs expression was detected by western blotting and NO production was detected by Greiss reaction. The intracellular ROS level was measured using DCFH-DA probes. The expression of hypoxia-inducible transcription factor 1α (HIF-1α) was also detected. Results: While H/R induced the expression of M2-and M4-mAChRs, AT3 suppressed the H/R-upregulated M2-and M4-mAChRs. H/R also induced the production of NO, ROS, and apoptosis. AT3 and M4-mAChR inhibitors inhibited the H/R-induced production of NO and ROS and apoptosis. HIF-1α was induced by H/R, but was suppressed by AT3. Conclusion: Thus, the in vitro evidence shows that AT3 protects against H/R injury in cerebral microvascular endothelial cells via inhibition of HIF-1α, NO and ROS, predominantly through the downregulation of M4-mAChR. The findings offer novel understandings regarding AT3-mediated attenuation of endothelial cell apoptosis and cerebral ischemia/ reperfusion injury.

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Section: Discussionmentioning

confidence: 97%

Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

JIANG,

SHEN,

et al. 2023

BIOCELL

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“…There is a growing incidence in clinical settings of SCI, a serious disorder of the central nervous system. For the treatment and rehabilitation of SCI, TCM has been widely used, [ 32 ] including acupuncture, [ 33 ] moxibustion, [ 34 ] and Chinese herbal medicine. [ 35 ] Mechanisms of TCM for SCI involve the inhibition of inflammation, [ 36 ] lipid peroxidation, [ 37 ] neuronal cell death, [ 38 ] improvement of microcirculation, [ 39 ] and promotion of axonal regeneration, [ 40 ] with interactions and interrelations between multiple molecular mechanisms that promote functional recovery after SCI.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Valeriana Jatamansi Jones for the treatment of spinal cord injury based on network pharmacology and molecular docking

Wang,

Lu,

Xiao

et al. 2023

Medicine

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Spinal cord injury (SCI) is characterized by high rates of disability and death. Valeriana jatamansi Jones (VJJ), a Chinese herbal medicine, has been identified to improve motor function recovery in rats with SCI. The study aimed to analyze the potential molecular mechanisms of action of VJJ in the treatment of SCI. The main ingredients of VJJ were obtained from the literature and the SwissADME platform was used to screen the active ingredients. The Swiss TargetPrediction platform was used to predict the targets of VJJ, and the targets of SCI were obtained from the GeneCards and OMIM databases. The intersecting genes were considered potential targets of VJJ in SCI. The protein–protein interaction network was constructed using the STRING database and the hub genes of VJJ for SCI treatment were screened according to their degree values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape database. Cytoscape software was used to construct the “herb-ingredient-target-pathway” network. Preliminary validation was performed using molecular docking via Auto Dock Vina software. A total of 56 active ingredients of VJJ, mainly iridoids, were identified. There were 1493 GO items (P < .01) and 173 signaling pathways (P < .01) obtained from GO and Kyoto Encyclopedia of Genes and Genomes enrichment, including the phosphoinositide-3-kinase (PI3K)–protein kinase B (Akt) signaling pathway, hypoxia-inducible factor 1 signaling pathway, and tumor necrosis factor signaling pathway. Molecular docking revealed that 12 hub genes enriched in the PI3K/Akt signaling pathway had a high binding affinity for the active ingredient of VJJ. VJJ may exert its therapeutic effects on SCI through the iridoid fraction, acting on signal transducer and activator of transcription 3, CASP3, AKT1, tumor necrosis factor, mammalian target of rapamycin, interleukin 6, and other hub genes, which may be related to the PI3K/Akt signaling pathway.

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“…M3 receptor plays a direct contractile role, while M2 receptor plays an indirect mediating role [ 36 , 37 ]. Based on the cholinergic pathway, one study designed controlled experiments with M receptor agonists and M2 receptor blockers, and moxibustion significantly inhibited the expression of M2, but not M3, in the bladder detrusor muscle of neurogenic detrusor overactivity (NDO) rats [ 38 ]. Furthermore, a large number of experimental studies have also confirmed the regulatory effect of various Chinese herbal extracts on smooth muscle M receptor, which has been reviewed in detail [ 39 ].…”

Section: Mechanisms Of Tcm In Oabmentioning

confidence: 99%

“…In the experiment of TCM formula Suo-Quan-Wan intervention in diabetic OAB model mice, the experiment showed that SQW could directly act on the bladder to improve the bladder function, rather than change the hyperglycemic status of mice and the mechanism may be that SQW inhibits ATP vesicle transport by down-regulating the expression levels of myosin Va and SLC17A9 in detrusor muscle [ 46 ]. Some researchers used moxibustion to intervene NDO rats, and the results showed that moxibustion could reduce the content of ATP in bladder mucosa, increase the content of NO in bladder mucous membrane, and reduce the expression of P2X3 receptor protein and mRNA in DO rats, thus improving bladder function [ 38 ]. In addition, Ba-Wei-Di-Huang-Wan, a Chinese medicine prescription, can improve CYP-induced persistent DO by inhibiting the overexpression of P2X2, P2X3, M2 and M3 receptor proteins in the mucosa, and the overexpression of M2 and M3 receptor proteins in detrusor muscle [ 47 ].…”

Section: Mechanisms Of Tcm In Oabmentioning

confidence: 99%

“…There is still a lack of K + channel openers with bladder specificity, and in the future, the use of bladder-specific K + channel openers may replace current first-line pharmacotherapy [ 67 ]. There is increasing evidence that TCM can inhibit the involuntary contraction of the bladder urine storage period without affecting the contraction of the detrusor muscle during the bladder urination period, which is similar to the effect of K + channel openers [ 38 , 45 ]. Therefore, we believe that K + channel may be one of the important targets for TCM treatment of OAB.…”

Section: Mechanisms Of Tcm In Oabmentioning

confidence: 99%

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Mechanism of traditional Chinese medicine in treating overactive bladder

Liao

et al. 2022

Int Urol Nephrol

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Overactive bladder syndrome (OAB) has made increasing progress in mechanism and treatment research. Traditional Chinese medicine (TCM) is a common complementary therapy for OAB, and it has been found to be effective. However, the intervention mechanism of TCM in the treatment of OAB is still unclear. The aim of this review is to consolidate the current knowledge about the mechanism of TCM: acupuncture, moxibustion, herbs in treating OAB, and the animal models of OAB commonly used in TCM. Finally, we put forward the dilemma of TCM treatment of OAB and discussed the insufficiency and future direction of TCM treatment of OAB.

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Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway

Cited by 6 publications

References 46 publications

Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

Mechanism of Valeriana Jatamansi Jones for the treatment of spinal cord injury based on network pharmacology and molecular docking

Mechanism of traditional Chinese medicine in treating overactive bladder

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