Heme oxygenase-1 dependant pathway contributes to protection by tetramethylpyrazine against chronic hypoxic injury on medulla oblongata in rats

Ding, Yan; Hou, Xuefei; Chen, Li; Zhou, Hua; Gong, Yanju; Dai, Liqun; Zheng, Yu

doi:10.1016/j.jns.2015.12.026

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…Among the major functional subunits of NADPH oxidase involved in the pathogenesis of stroke, NOX2 is one of the most important members mediating cerebral ischemic injury [ 31 ]. Consistent with the antioxidative roles of L-carnitine [ 4 ] and TMP [ 32 ], we found that LR134 and LR143 reduced NOX2 expression together with superoxide production. An increasing number of evidence have indicated that activation of the immune system as a result of disturbances in the redox state of cells seems to contribute to brain damage.…”

Section: Discussionsupporting

confidence: 87%

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Wang

Zhou

Wei

et al. 2017

Oxidative Medicine and Cellular Longevity

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Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.

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Section: Discussionsupporting

confidence: 87%

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Wang

Zhou

Wei

et al. 2017

Oxidative Medicine and Cellular Longevity

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show abstract

“…For example, SnPP abolished the baicalein-, tetramethylpyrazine- and cepharanthine-mediated protection against ischaemia/reperfusion injury in various models. 22,62,63 Future studies with CAPE should involve SnPP to reveal the role of HO1 in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…8 In turn, HO1 activates the cellular defence mechanisms against oxidative stress, 19 including superoxide dismutase (SOD), catalase (CAT) and glutathione S -transferase (GST) expression. 20 In support of this mechanism, Nrf2 21 and HO1 22,23 regulate SOD expression.…”

Section: Introductionmentioning

confidence: 87%

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

et al. 2019

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Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.

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Tetramethylpyrazine attenuates carbon tetrachloride-caused liver injury and fibrogenesis and reduces hepatic angiogenesis in rats

Zhao

Zhang

Qian

et al. 2017

Biomedicine & Pharmacotherapy

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Heme oxygenase-1 dependant pathway contributes to protection by tetramethylpyrazine against chronic hypoxic injury on medulla oblongata in rats

Cited by 6 publications

References 37 publications

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

Tetramethylpyrazine attenuates carbon tetrachloride-caused liver injury and fibrogenesis and reduces hepatic angiogenesis in rats

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