Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation

Zhang, Wen; Song, Junke; Zhang, Xue; Zhou, Qimeng; He, Guorong; Xu, Xiaona; Yan, Rong; Zhou, Wenxia; Du, Guanhua

doi:10.1016/s1875-5364(18)30046-3

Cited by 33 publications

(33 citation statements)

References 36 publications

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“…What's more, according to the recent pharmacological studies, SalA and SalB have shown potential therapeutic approaches against ischemic diseases. SalA alleviated I/R-induced rat brain damage partially via the suppression of FoxO3a/Bim signaling and the downregulation of MMP-9 activity [39,62,63]. SalA also showed antimyocardial I/R damage effects as a consequence of the downregulation of platelet activation and inflammation in rats [41,64].…”

Section: Mediators Of Inflammationmentioning

confidence: 88%

“…As reported by chemistry research, effective compounds of Danshen are mainly summarized into two categories: lipophilic diterpenoids and watersoluble phenolic acids. The phenolic acids have been identified as natural cardiovascular and cerebrovascular protectants with a variety of pharmacological functions, such as anti-inflammation, antiplatelet aggregation, and antioxidation [36][37][38][39][40][41][42]. These phenolic acids have been accounted for most of the biological activities of Danshen, especially the beneficial impact on ischemia/reperfusion (I/R) damage [43].…”

Section: Introductionmentioning

confidence: 99%

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Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response

Zhang

Song

Wan

et al. 2020

Mediators of Inflammation

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Inflammatory response participates in the overall pathophysiological process of stroke. It is a promising strategy to develop antistroke drugs targeting inflammation. This study is aimed at investigating the therapeutic effect and anti-inflammatory mechanism of salvianolic acid D (SalD) against cerebral ischemia/reperfusion (I/R) injury. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established, and an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was established in PC12 cells. Neurological deficit score, cerebral infarction, and edema were studied in vivo. Cell viability was achieved using the MTT method in vitro. The Bax, Bcl-2, cytochrome c, HMGB1, TLR4, TRAF6, NF-κB p65, p-NF-κB p65, and cleaved caspase-3 and -9 were tested via the Western blot method. Cytokines and cytokine mRNA, including TNF-α, IL-1β, and IL-6, were studied via ELISA and PCR methods. The translocation of HMGB1 and NF-κB were studied by immunofluorescence assay. The HMGB1/NeuN, HMGB1/GFAP, and HMGB1/Iba1 double staining was carried out to observe the localization of HMGB1 in different cells. Results showed that SalD alleviated neurological impairment, decreased cerebral infarction, and reduced edema in I/R rats. SalD improved OGD/R-downregulated PC12 cell viability. SalD also promoted Bcl-2 expression and suppressed Bax, cytochrome c, and cleaved caspase-3 and -9 expression. SalD decreased the intensity of TLR4, MyD88, and TRAF6 proteins both in vivo and in vitro, and significantly inhibited the NF-κB nuclear translocation induced by I/R and OGD/R. What’s more, SalD inhibited HMGB1 cytoplasmic translocation in neurons, astrocytes, and microglia in both the cortex and hippocampus regions of I/R rats. In conclusion, SalD can alleviate I/R-induced cerebral injury in rats and increase the PC12 cell viability affected by OGD/R. The anti-inflammatory mechanism of SalD might result from the decreased nuclear-to-cytoplasmic translocation of HMGB1 and the inhibition on its downstream TLR4/MyD88/NF-κB signaling.

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Section: Mediators Of Inflammationmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response

Zhang

Song

Wan

et al. 2020

Mediators of Inflammation

Self Cite

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“…11 Accumulating evidence suggests that this multi-component cardiovascular herbal medicine has pleiotropic effects including anti-inflammation, anti-oxidation, anti-thrombosis, lipid lowering, and improvement of endothelial function. 12,13 Previous studies have shown that there are many microRNAs (miRNAs) unique to Salvia miltiorrhiza, and these miRNAs regulate the biosynthesis of major medicinal components and development and responses to abiotic stress. 14 However, it is still unclear whether miRNAs derived from Salvia miltiorrhiza, as the effective components, participate in the regulation of cardiovascular diseases, especially autophagy and inflammation.…”

Section: Introductionmentioning

confidence: 99%

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Qin

Zheng

Yang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Among then, SAB has been proved to improve mitochondrial function and play a neuroprotective role [60]. SAA can also participate in the protection and repair of the blood-brain barrier (BBB) [61]. Therefore, the CL 1 and CL 2 value of SAB in the plasma of the model group increased and the t 1/2α value of SAA decreased compared with the normal group.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

Ying

et al. 2019

Eur J Drug Metab Pharmacokinet

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Background and Objective Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. Methods Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. Results The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration-time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. Conclusion Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood-brain barrier during cerebral ischemia-reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

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Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation

Cited by 33 publications

References 36 publications

Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response

Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

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