Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

Chen, Hansen; Chen, Xi; Li, Wenting; Shen, Jiangang

doi:10.1038/aps.2018.27

Cited by 60 publications

(29 citation statements)

References 208 publications

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“…With respect to ischemic stroke, several natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide, chlorogenic acid, lutein, and lycopene, have shown potential for targeting the RNS/CAV1/MMP signaling pathway (see the review in [212] and references therein).…”

Section: Future Perspectivesmentioning

confidence: 99%

Role of Caveolin-1 in Diabetes and Its Complications

Haddad

Madhoun

Nizam

et al. 2020

Oxidative Medicine and Cellular Longevity

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It is estimated that in 2017 there were 451 million people with diabetes worldwide. These figures are expected to increase to 693 million by 2045; thus, innovative preventative programs and treatments are a necessity to fight this escalating pandemic disorder. Caveolin-1 (CAV1), an integral membrane protein, is the principal component of caveolae in membranes and is involved in multiple cellular functions such as endocytosis, cholesterol homeostasis, signal transduction, and mechanoprotection. Previous studies demonstrated that CAV1 is critical for insulin receptor-mediated signaling, insulin secretion, and potentially the development of insulin resistance. Here, we summarize the recent progress on the role of CAV1 in diabetes and diabetic complications.

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Section: Future Perspectivesmentioning

confidence: 99%

Role of Caveolin-1 in Diabetes and Its Complications

Haddad

Madhoun

Nizam

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Nitric oxide (NO) is an important second messenger with multiple functions involved in the control of vasomotor tone, vascular homeostasis, neuronal, and immunological functions [16]. Low concentration of NO considered as protective to brain vasculature by inducing vasodilatation and improving blood flow to penumbra [17,18]. However, during the ischemia-reperfusion stage, the activation of iNOS leads to the excessive release of NO, which causes the reaction of NO to superoxide (O2-) generating peroxynitrite radicals (ONOO-) and exacerbation of brain ischemia-and reperfusion-injury damage [17,[19][20][21].…”

Section: Discussionmentioning

confidence: 99%

“…Low concentration of NO considered as protective to brain vasculature by inducing vasodilatation and improving blood flow to penumbra [17,18]. However, during the ischemia-reperfusion stage, the activation of iNOS leads to the excessive release of NO, which causes the reaction of NO to superoxide (O2-) generating peroxynitrite radicals (ONOO-) and exacerbation of brain ischemia-and reperfusion-injury damage [17,[19][20][21]. ANP down-regulated the level of brain tissue and serum, suggest that ANP could also inhibit NO generation, decrease the negative effect of NO to nerve system.…”

Section: Discussionmentioning

confidence: 99%

Discussion on rationality of administration of Angong Niuhuang Pills from pharmacological and toxicological perspectives

Chen¹,

Chai²,

He³

et al. 2020

Preprint

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Background: Investigate the different treatment course of ANP from pharmacology and toxicology to provide scientific basis for clinic use. Method: In pharmacology study, cerebral ischemia-reperfusion model was made; rats were divided into six groups, Sham, model, aspirin 25 mg/kg, ANP 270 mg/kg (1 day, 4 days and 7 days) groups. Rats were fed for 30 days. Neurological function, cerebral infraction volume, brain histopathology, cytokines were detected; in toxicology study, rats were divided into four groups, normal control, ANP (550, 1640, 4910 mg/kg) group. ANP was daily administered by gavage for 30 days. Detection indicators included appearance, behavior, excrement character, food-intake, body weight, hematological parameters, etc. In addition, biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP were also detected. Result: In pharmacology study, compared with model group, the neurological function scores of ANP 270mg/kg (1 day, 4 days and 7 days) were decreased (P<0.11 or P<0.05); the volume of ANP 270mg/kg (1 day and 7 days) were decreased (P<0.05); the R value of ANP 270mg/kg (1 day, 4 days and 7 days) groups were decreased (P<0.11 or P<0.05); the serum content of IL-1β, TNFα and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P< 0.05); the brain content of IL-1β and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P<0.05). In toxicology study, no mortality, ophthalmic abnormalities were identified. Compared with normal control group, body weights were significantly lower in ANP 4910 mg/kg group; TBA was significantly increased in ANP 4910mg/kg group; liver organ coefficient of female rats of ANP 4910 mg/kg group was increased (P < 0.05); kidney organ coefficient of male rats of ANP 1640mg/kg, 4910 mg/kg groups were increased (P < 0.05), these all recovered after drug withdraw for 8 weeks. Conclusion: The effect of ANP 270 mg/kg (7 days) was much better than ANP (1 day and 4 days). ANP 550mg/kg is non toxicity dose. So, ANP is taken one pill peer day for 7 days is safety and effective, it can be used as the scientific basis for clinic use.

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“…Nitric oxide (NO) is an important second messenger with multiple functions involved in the control of vasomotor tone, vascular homeostasis, neuronal, and immunological functions [16]. Low concentration of NO considered as protective to brain vasculature by inducing vasodilatation and improving blood flow to penumbra [17,18]. However, during the ischemia-reperfusion stage, the activation of iNOS leads to the excessive release of NO, which causes the reaction of NO to superoxide (O 2-) generating peroxynitrite radicals (ONOO -) and exacerbation of brain ischemia and reperfusion injury damage [17,[19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

Chen¹,

Chai²,

He³

et al. 2020

Preprint

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Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

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Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

Cited by 60 publications

References 208 publications

Role of Caveolin-1 in Diabetes and Its Complications

Role of Caveolin-1 in Diabetes and Its Complications

Discussion on rationality of administration of Angong Niuhuang Pills from pharmacological and toxicological perspectives

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

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