salvianolic-acid-B and Brain-Injuries

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated immuno-inflammatory response plays a critical role in exacerbating early brain injury (EBI) after subarachnoid hemorrhage (SAH). Salvianolic acid B (SalB) has previously been shown to suppress neuroinflammatory responses in many disorders. Meanwhile, a previous study has demonstrated that SalB mitigated oxidative damage and neuronal degeneration in a prechiasmatic injection model of SAH. However, the therapeutic potential of SalB on immuno-inflammatory responses after SAH remains unclear. In the present study, we explored the therapeutic effects of SalB on neuroinflammatory responses in an endovascular perforation SAH model. We observed that SalB ameliorated SAH-induced functional deficits. Additionally, SalB significantly mitigated microglial activation, pro-inflammatory cytokines release, and neuronal injury. Mechanistically, SalB inhibited NLRP3 inflammasome activation and increased sirtuin 1 (SIRT1) expression after SAH. Administration of EX527, an inhibitor of SIRT1, abrogated the anti-inflammatory effects of SalB against SAH and further induced NLRP3 inflammasome activation. In contrast, MCC950, a potent and selective NLRP3 inflammasome inhibitor, reversed the detrimental effects of SIRT1 inhibition by EX527 on EBI. These results indicated that SalB effectively repressed neuroinflammatory responses and neuronal damage after SAH. The action of SalB appeared to be mediated by blocking NLRP3 inflammasome and promoting SIRT1 signaling.

Topics: Animals; Brain Injuries; Inflammasomes; Inflammation; Neuroinflammatory Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Sirtuin 1; Subarachnoid Hemorrhage

Mesenchymal stem cells (MSCs) and Salvianolic acid B (SAB) are known to exert potent anti-inflammatory and anti-oxidative properties. But the effect of SAB and MSCs combination treatment on the cerebral ischemia/reperfusion injury (CI/RI) is not clear.. After the CI/RI animal model established, rats were administered with MSCs and SAB individually or combination treatment. To evaluate the therapeutic potential, behavioral tests, TTC staining, Hematoxylin-eosin (HE) staining, and immunofluorescence assays were performed to evaluate the neuroprotection and endogenous neurogenesis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the anti-apoptosis and anti-inflammatory effect. Meanwhile, the expression of the TLR4/NF-ĸB/MYD88 signal pathway-related proteins was evaluated by Western blot.. MSCs and SAB individually or combination treatment have protective effect in CI/RI rats. More importantly, the rats with the combination treatment showed a better behavioral recovery, neurogenesis and smaller infarct size compared with the rats administered with MSCs or SAB individually. Further research showed that the combination treatment decreased CI/RI induced inflammatory cytokines and oxidative stress, including inhibiting the production of IL-1β, IL-6, TNF-α, decreasing the levels of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD). In addition, the neuroprotection effect of SAB and MSCs combination was achieved through the regulation of TLR4/NF-κB/MyD88 signaling pathway related proteins, including inhibition the protein levels of TLR4, MYD88, p-NF-κB p65, TRAF6-and action of SIRT1 in brain tissues.. The present study indicated that the MSCs and SAB combination treatment had better protective effect against rat ischemic brain injury. The combination of SAB and MSCs may provide a potent and promising strategy for the treatment of ischemic stroke and is worthy for further development.

Topics: Animals; Anti-Inflammatory Agents; Brain Injuries; Brain Ischemia; Mesenchymal Stem Cells; Myeloid Differentiation Factor 88; NF-kappa B; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Toll-Like Receptor 4

The purpose of this study was to evaluate the cerebral protection of salvianolic acid B (Sal B) against cerebral I/R injury and investigate the underlying mechanism. As shown by 2,3,5-Triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI) analyses, Sal B significantly reduced cerebral infarct size, and accompanied with improved neurobehavioral functions as indicated by the modified Bederson score and Longa five-point scale. Sal B decreased the production of reactive oxygen species (p < .05, n = 10). The data of Western blotting and reverse transcription quantitative real time polymerase chain reaction (qRT-PCR) analyses showed that the expression of GFAP, Iba1, IL-1β, IL-6, TNF-α and Cleaved-caspase 3 was significantly reduced by Sal B in I/R injured brain tissues as compared to corresponding controls (p < .05, n = 10). Over activation of astrocytes and microglia were inhibited by Sal B as shown by immunostaining of GFAP and Iba 1. These data suggest that Sal B has neural protective effects against I/R-induced cerebral injury and could be an effective candidate for further development of clinical therapy.

Topics: Animals; Benzofurans; Brain Injuries; Calcium-Binding Proteins; Caspase 3; Cerebral Infarction; Cytokines; Disease Models, Animal; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins; Neuroprotective Agents; Reperfusion

Salvianolic acid B (SalB), a bioactive compound isolated from the Chinese medicinal herb Danshen, has been shown to exert various anti-oxidative and anti-inflammatory activities in in vitro and in vivo studies. Here, we investigated the protective effects of SalB on traumatic brain injury (TBI) in mice. When administered within 2 h after TBI onset, SalB (25 mg/kg) reduced brain edema, lesion volume and motor functional deficits, and improved spatial learning and memory abilities. Moreover, SalB treatment inhibited the neutrophil infiltration and microglial activation at 48 h after TBI. Enzyme-linked immunosorbent assay (ELISA) for brain tissue homogenates was performed at 24 h after TBI to evaluate the expression of inflammation-related cytokines. The results showed that SalB suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1β, whereas enhanced the expression of anti-inflammatory cytokines IL-10 and TGF-β1. All of these findings extended the protective role of SalB in the model of TBI and suggested that these protective effects might be associated with its anti-inflammatory activities. Thus SalB may have therapeutic potential for patients with TBI and perhaps other forms of acute brain injury.

Topics: Animals; Benzofurans; Brain Edema; Brain Injuries; Inflammation; Interleukin-10; Interleukin-1beta; Learning; Male; Memory; Mice; Mice, Inbred C57BL; Molecular Structure; Space Perception; Tumor Necrosis Factor-alpha