Mechanism of salvianolic acid B neuroprotection against ischemia/reperfusion induced cerebral injury

Fan, Yong; Luo, Qianping; Wei, Jingjing; Lin, Ren; Lin, Lili; Li, Yongkun; Chen, Zhaorong; Lin, Wei; Chen, Qi

doi:10.1016/j.brainres.2017.11.027

Cited by 78 publications

(51 citation statements)

References 41 publications

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“…There are also two main components of DHI: salvianolic acid B and p-coumaric acid. Fan et al found that salvianolic acid B has neuroprotective effect on brain injury induced by ischemia-reperfusion injury in rats by reducing the generation of free radicals, and which may be an effective clinical candidate treatment (Fan et al, 2018). During the research, Sakamula et al found that pretreatment with p-coumaric acid can significantly reduce malondialdehyde levels, whole cerebral infarct volume, and hippocampal neuron death, and increase catalase and superoxide dismutase activities, eventually producing neuroprotective effect (Sakamula and Thong-asa, 2018).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway

et al. 2020

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Many traditional Chinese medicines, including Danhong injection (DHI), can be used to treat cerebral ischemia-reperfusion injury and have neuroprotective effects on the brain; however, few studies have explored the mechanism by which this effect is generated. In this study, we investigated the neuroprotective effect of DHI against cerebral ischemia-reperfusion injury mediated via the PI3K-Akt signaling pathway. After establishing the model of middle cerebral artery occlusion (MCAO), 60 male Sprague-Dawley rats were allocated to six groups as follows: sham, MCAO, DHI (MCAO + DHI), LY294002 (MCAO + LY294002 [PI3K-Akt pathway specific inhibitor]), DHI + LY294002 (MCAO + DHI + LY294002), and NMDP + LY294002 (MCAO + NMDP [nimodipine] + LY294002). Hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to evaluate the pathological changes of brain tissue and the degree of neuronal apoptosis. Real-time quantitative polymerase chain reaction (qRT-PCR), western blot analysis and enzyme-linked immunosorbent assays were used to measure the expression of Bad, Bax, Bcl-2, Bim, P53, MDM2, Akt, PI3K, p-Akt, p-PI3K, and Cyt-C. Compared with the MCAO group, brain tissue cell apoptosis was significantly reduced in the DHI group, and the brain function score was significantly improved. In addition, the expression of pro-apoptotic factors (Bad, Bax, and Bim) was significantly downregulated in the DHI group, while expression of the anti-apoptotic factor Bcl-2 was significantly upregulated, and expression of the apoptotic gene p53 was also significantly attenuated. Moreover, this neuroprotective effect was attenuated by the PI3K-Akt signaling pathway inhibitor (LY294002). Thus, our results confirmed the neuroprotective effects of DHI in rats with ischemia-reperfusion injury and indicate that these effects on the brain are partly generated by activation of the PI3K-Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway

et al. 2020

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“…Previous studies have shown that administration of either DSS, HSYA, SAB, or SAA resulted in distinct mechanisms of protection against cerebral I/R damage, such reduction of inflammation and oxidative stress (Sun et al, 2010;Fan et al, 2017;Xu et al, 2017). The BBB is a dynamic interface between the blood and the brain parenchyma (Sifat et al, 2017;Jiang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Hydroxysafflor yellow A (HSYA) is a bioactive component of the dried flower of Honghua ( Figure 1) (Hui et al, 2018). Studies have shown that DSS, SAA, SAB, and HSYA have therapeutic effects on cardiovascular and CVDs, through anti-inflammatory, anti-oxidative activities, etc (Fan et al, 2017;Feng et al, 2017;Xu et al, 2017;Sun et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Comparative Pharmacokinetics of Hydrophilic Components in Salvia miltiorrhiza Bge. and Carthamus tinctorius L. in Rats That Underwent Cerebral Ischemia Reperfusion Using an HPLC-DAD Method

Zhao

Chen

et al. 2020

Front. Pharmacol.

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Background: In China, the combination of herb Salvia miltiorrhiza Bge. (Danshen) and Carthamus tinctorius L. (Honghua) is an effective treatment for stroke. A previous study showed that the combination of four herbal components: danshensu (DSS), hydroxysafflor yellow A (HSYA), salvianolic acid A (SAA), and salvianolic acid B (SAB) was effective for treatment of cerebral ischemia-reperfusion (I/R) injury in rats. However, the pharmacokinetic characteristics of this formula require further investigation. The present study investigated the pharmacokinetic differences between each component of in two formulas in cerebral I/R injury rats. The influencing factors may affect the compatibility of components were analyzed.Methods: Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO). Rats that underwent MCAO were randomly divided into two groups and administered treatments through the tail vein. Blood samples were collected at predetermined time points following administration. The concentrations of DSS, HSYA, SAB, and SAA in rat plasma were determined using HPLC-DAD, and the main pharmacokinetic parameters were calculated. Pharmacokinetic parameters were calculated using DAS 3.2.6 software and SPSS 23.0 statistical analysis software.Results: Our results showed that DSS, HSYA, SAB, and SAA in MCAO model rats had statistically significant differences in two formulas. For DSS and SAA, pharmacokinetic parameters with statistically significant differences including AUC (0−t) , AUMC (0−t) , MRT (0−t) , VRT (0−t) , t 1/2z , V z , CL z , and C max (P < 0.01). For HSYA, significant differences in the parameters including AUC (0−t) , AUMC (0−t) , MRT (0−t) , VRT (0−t) (P < 0.01), CL z and C max (P < 0.05). Conclusion:The difference in pharmacokinetic parameters in response to each component may have been due to differences in the dosages of the components (HSYA, SAA, SAB) and the compatibility of components. Meanwhile, there were many Frontiers in Pharmacology | www.frontiersin.org January 2020 | Volume 10 | Article 1598 1

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“…We examined the neuroprotective roles of LE in an in vivo rat model of the middle cerebral artery occlusion (MCAO) and reperfusion. We assessed the neurological deficits using the modified Bederson score [ 32 ] and extracted the brain to measure the severity of infarctions in experimental groups. We assessed the changes in protein and mRNA expression of distinct genes related to cell survival, Wnt/β-catenin signaling pathway and inflammation.…”

Section: Introductionmentioning

confidence: 99%

Lipid Emulsion Improves Functional Recovery in an Animal Model of Stroke

Tanioka

Park

et al. 2020

IJMS

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Stroke is a life-threatening condition that leads to the death of many people around the world. Reperfusion injury after ischemic stroke is a recurrent problem associated with various surgical procedures that involve the removal of blockages in the brain arteries. Lipid emulsion was recently shown to attenuate ischemic reperfusion injury in the heart and to protect the brain from excitotoxicity. However, investigations on the protective mechanisms of lipid emulsion against ischemia in the brain are still lacking. This study aimed to determine the neuroprotective effects of lipid emulsion in an in vivo rat model of ischemic reperfusion injury through middle cerebral artery occlusion (MCAO). Under sodium pentobarbital anesthesia, rats were subjected to MCAO surgery and were administered with lipid emulsion through intra-arterial injection during reperfusion. The experimental animals were assessed for neurological deficit wherein the brains were extracted at 24 h after reperfusion for triphenyltetrazolium chloride staining, immunoblotting and qPCR. Neuroprotection was found to be dosage-dependent and the rats treated with 20% lipid emulsion had significantly decreased infarction volumes and lower Bederson scores. Phosphorylation of Akt and glycogen synthase kinase 3-β (GSK3-β) were increased in the 20% lipid-emulsion treated group. The Wnt-associated signals showed a marked increase with a concomitant decrease in signals of inflammatory markers in the group treated with 20% lipid emulsion. The protective effects of lipid emulsion and survival-related expression of genes such as Akt, GSK-3β, Wnt1 and β-catenin were reversed by the intra-peritoneal administration of XAV939 through the inhibition of the Wnt/β-catenin signaling pathway. These results suggest that lipid emulsion has neuroprotective effects against ischemic reperfusion injury in the brain through the modulation of the Wnt signaling pathway and may provide potential insights for the development of therapeutic targets.

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Mechanism of salvianolic acid B neuroprotection against ischemia/reperfusion induced cerebral injury

Cited by 78 publications

References 41 publications

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway

Neuroprotective Effect of Danhong Injection on Cerebral Ischemia-Reperfusion Injury in Rats by Activation of the PI3K-Akt Pathway

Comparative Pharmacokinetics of Hydrophilic Components in Salvia miltiorrhiza Bge. and Carthamus tinctorius L. in Rats That Underwent Cerebral Ischemia Reperfusion Using an HPLC-DAD Method

Lipid Emulsion Improves Functional Recovery in an Animal Model of Stroke

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