The emerging role of signal transducer and activator of transcription 3 in cerebral ischemic and hemorrhagic stroke

Liang, Zhenxing; Wu, Guiling; Fan, Chongxi; Xu, Jing; Jiang, Shuai; Yan, Xiaolong; Di, Shouyin; Ma, Zhiqiang; Hu, Wei; Yang, Yang

doi:10.1016/j.pneurobio.2015.11.001

Cited by 83 publications

(57 citation statements)

References 148 publications

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“…Aging 36 is the result of biological events that progressively and irreversibly compromise the function of vital organs. The related pathophysiological changes include cancer, [37][38][39] cardiovascular diseases, [40][41][42] neurological diseases, [43][44][45] metabolic syndrome, [46][47][48] and motor system diseases. 20 Osteoporosis is a debilitating chronic bone disease accompanied by increased bone loss and a high risk of fracture and is F I G U R E 1 Signaling network of osteogenesis and osteolysis.…”

Section: Melatonin Maintains Metabolic Homeostasis In Bonementioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

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111

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Melatonin is a signal molecule that modulates the biological circadian rhythms of vertebrates. Melatonin deficiency is thought to be associated with several disorders, including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating evidence has also indicated that melatonin may be involved in the homeostasis of bone metabolism. Age‐related reductions in melatonin are considered to be critical factors in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve as a biomarker for the early detection and prevention of osteoporosis. Compared to conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin both suppresses bone loss and promotes new bone formation. Mechanistically, by activating melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin to promote osteogenesis while inhibiting the receptor activator of NF‐kB ligand (RANKL) pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone metabolism, we hypothesize that melatonin may be a novel remedy for the prevention and clinical treatment of osteoporosis.

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Section: Melatonin Maintains Metabolic Homeostasis In Bonementioning

confidence: 99%

Melatonin: Another avenue for treating osteoporosis?

Tian

Jiang

et al. 2019

Journal of Pineal Research

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111

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“…Subsequently, APLNR may be downregulated by apelin reduction (Wang et al, 2009). In addition, inflammatory responses may be implicated in the regulation of apelin and APLNR expression mediated by STAT3, as it directly regulates the promoter activity of the apelin gene (Han et al, 2008; Liang et al, 2016). Interestingly, STAT3 is only activated during the reperfusion phase but not the ischemic phase.…”

Section: Temporal Expression Of Apelin/aplnr In Ischemic Strokementioning

confidence: 99%

Temporal Expression of Apelin/Apelin Receptor in Ischemic Stroke and its Therapeutic Potential

Wang

Zhou

et al. 2017

Front. Mol. Neurosci.

114

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Stroke is one of the leading causes of death and disability worldwide, and ischemic stroke accounts for approximately 87% of cases. Improving post-stroke recovery is a major challenge in stroke treatment. Accumulated evidence indicates that the apelinergic system, consisting of apelin and apelin receptor (APLNR), is temporally dysregulated in ischemic stroke. Moreover, the apelinergic system plays a pivotal role in post-stroke recovery by inhibiting neuronal apoptosis and facilitating angiogenesis through various molecular pathways. In this review article, we summarize the temporal expression of apelin and APLNR in ischemic stroke and the mechanisms of their dysregulation. In addition, the protective role of the apelinergic system in ischemic stroke and the underlying mechanisms of its protective effects are discussed. Furthermore, critical issues in activating the apelinergic system as a potential therapy will also be discussed. The aim of this review article is to shed light on exploiting the activation of the apelinergic system to treat ischemic stroke.

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“…In any event, incensol and, with the exception of 1e and 1c, also its esters and analogues showed only marginal, if any, activity on TNFα-induced NF-κB activation (IC 50 > 50 μM), casting doubts on the involvement of NF-κB in the in vivo activity of IA against neuroinflammation. On the other hand, incensol (1a), but not IA (1b), showed potent inhibitory activity on IL-6-induced STAT3 activation (IC 50 = 15.8 ± 2.88 μM), and, given the relevance of STAT3 in neuro-inflammation, 25 it does not seem unrealistic to assume its involvements, secondary to enzymatic deacetylation, in the in vivo neuroprotective activity of IA (1b). The nonanoate and the phenylacetate esters of incensol (1c and 1e, respectively) showed a significant inhibitory activity on NF-κB activation (Table 1), an interesting observation, since, unlike most NF-κB inhibitors, these compounds are devoid of electrophilicity and redox properties.…”

Section: Journal Of Natural Productsmentioning

confidence: 95%

“…The in vivo evaluation of the neuroprotective activity of the phenolic monoterpene carvacrol to demonstrate the druggability of TRPV3 by small molecules gave unclear results due to the low potency of this agonist and its pleiotropic profile of activity. 25 Cembrane ligands such as IA (1b) and serratol (2) qualify as better probes because of their higher potency and, at least for IA and possibly also for serratol, selectivity within the TRP ion channel family and should be …”

Section: Journal Of Natural Productsmentioning

confidence: 99%

Neuroactive and Anti-inflammatory Frankincense Cembranes: A Structure–Activity Study

et al. 2016

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An expeditious isolation method for the cembrane diterpene alcohols incensol (1a) and serratol (2) has been developed from respectively African and Indian frankincense. The two native alcohols and a series of semisynthetic derivatives of incensol were evaluated for transient receptor potential vanilloid 3 (TRPV3) activation and the inhibition of NF-κB, the putative molecular targets underlying the psychotropic and anti-inflammatory activities of incensol acetate (IA, 1b). Serratol (2) was the most potent TRPV3 activator, outperforming by 2 orders of magnitude the reference agonist thymol and by 1 order of magnitude incensol acetate (1b). Acylation, epimerization, and oxidation did not significantly improve the affinity of incensol for TRPV3, while NF-κB inhibition, marginal for both natural alcohols, could be improved by esterification of incensol (1a) with lipophilic acids. Interestingly, incensol (1a) but not IA (1b) was a potent inhibitor of STAT3, raising the possibility that hydrolysis to incensol (1a) might be involved in the in vivo biological activity of IA (1b). Serratol was not amenable to chemical modification, but some marine cembranoids related to the frankincense diterpenoids showed a certain degree of TRPV3-activating properties, qualifying the aliphatic macrocyclic cembrane skeleton as a selective chemotype to explore the pharmacology of TRPV3, a thermo-TRP otherwise resistant to modulation by small molecules.

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The emerging role of signal transducer and activator of transcription 3 in cerebral ischemic and hemorrhagic stroke

Cited by 83 publications

References 148 publications

Melatonin: Another avenue for treating osteoporosis?

Melatonin: Another avenue for treating osteoporosis?

Temporal Expression of Apelin/Apelin Receptor in Ischemic Stroke and its Therapeutic Potential

Neuroactive and Anti-inflammatory Frankincense Cembranes: A Structure–Activity Study

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