salvianolic-acid-B and Inflammation

Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which lacks effective treatment. Salviae Miltiorrhizae Radix Et Rhizoma is one of the key compatible traditional Chinese medicine in the prescription for the treatment of DN. Salvianolic acid B and tanshinone IIA are two monomer active components with high content and clear structure in Salvia miltiorrhiza, which can effectively improve early (DN), respectively.. To evaluate the compatible effect of salvianolic acid B and tanshinone IIA on early DN rats and elucidate the mechanism.. Early DN rats were induced by streptozotocin combined with high glucose and high fat diet, and intervened by salvianolic acid B, tanshinone IIA and their combinations. The pathological sections of kidney, liver and biochemical indexes were analyzed. Network pharmacology method was used to predict the possible mechanism. The mechanisms were elucidated by metabolomics, Elisa, and Western blot.. Given our analysis, salvianolic acid B and tanshinone IIA can synergistically regulate 24 h UTP, Urea and Scr and improve kidney damage in early DN rats. The metabolic abnormalities of early DN rats were improved by regulating the biosynthesis of saturated fatty acids, glycerol phospholipid metabolism, steroid biosynthesis, alanine, and arachidonic acid. Salvianolic acid B combined with tanshinone IIA at a mass ratio of 13.4:1 can significantly reduce kidney inflammation, up-regulate p-PI3K/PI3K and p-Akt/Akt and down-regulate p-NF-κB/NF-κB, which better than the single-used group and can be reversed by PI3K inhibitor LY294002.. Salvianolic acid B and tanshinone IIA can synergistically improve glucose and lipid disorders, liver and kidney damage, and resist kidney inflammation in early DN rats, and the mechanism may be related to regulating PI3K/Akt/NF-κB signaling pathway.

Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Glucose; Inflammation; Nephritis; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction

Autologous fat grafting is a common method for soft tissue defect repair. However, the high absorption rate of transplanted fat is currently a bottleneck in the process. Excessive inflammation is one of the main reasons for poor fat transplantation. Salvianolic acid B (Sal-B) is a herbal medicine that shows promise for improving the effectiveness of fat transplantation.. The aim of this study was to improve fat graft survival by injecting Sal-B into fat grafts locally.. In vivo, 0.2 mL of Coleman fat was transplanted into nude mice along with Sal-B. The grafts were evaluated by histologic analysis at 2, 4, and 12 weeks posttransplantation and by microcomputed tomography at 4 weeks posttransplantation. In vitro ribonucleic acid sequencing, cell proliferation assays, anti-inflammatory activity assays, molecular docking studies, and kinase activity assays were performed in RAW264.7 cells to detect the potential mechanism.. Sal-B significantly improved fat graft survival and attenuated adipose tissue fibrosis and inflammation. Sal-B also inhibited the polarization of M1 macrophages in fat grafts. In vitro, Sal-B inhibited the proliferation and activation of inflammatory pathways in RAW264.7 cells. In addition, Sal-B had an inhibitory effect on NF-κB (nuclear factor κ light polypeptide gene enhancer in B cells) signaling. This bioactivity of Sal-B may result from its selective binding to the kinase domain of the inhibitor of NF-κB kinase subunit β.. Sal-B could serve as a promising agent for improving the effect of fat transplantation by inhibiting the polarization of M1 macrophages through NF-κB signaling.

Topics: Animals; Inflammation; Macrophages; Mice; Mice, Nude; Molecular Docking Simulation; NF-kappa B; X-Ray Microtomography

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

Inflammation is critical in the pathophysiology of atherosclerosis (AS). The aim of this study was to investigate the protective effect of salvianolic acid B (Sal B) on AS and to explore the molecular mechanism of tumor necrosis factor-α (TNF-α)-induced damage in human umbilical vein endothelial cells (HUVECs).. In vivo studies, LDLR. The change in the weight of the mice over time was an indication that Sal B had an effect on weight gain.

Topics: Animals; Atherosclerosis; Cholesterol, LDL; Endothelial Cells; Humans; Inflammasomes; Inflammation; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Plaque, Atherosclerotic; Reactive Oxygen Species; Signal Transduction; Tumor Necrosis Factor-alpha

Topics: Animals; Antagomirs; Autophagy; Benzofurans; Glomerulonephritis, Membranous; Inflammation; Kidney; MicroRNAs; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Topics: Animals; Benzofurans; Inflammation; Mice; Myeloid Differentiation Factor 88; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; Oxidative Stress; Particulate Matter; Signal Transduction; Toll-Like Receptor 4

The root of Salvia miltiorrhiza f. alba (RSMA) (Lamiaceae) is used for the treatment of patients with thromboangiitis obliterans (TAO) in traditional Chinese medicine. Previously, a mixture of phenolic acids extracted from RSMA has shown significant protective effects on TAO rats.. This study investigates the inhibitory effects of salvianolic acid B on TAO induced by sodium laurate injection in rats to explore the effective constituents of RSMA in TAO treatment.. TAO rats were developed using injected sodium laurate. After treatment with ligustrazine hydrochloride (15 mg/kg) and various doses of salvianolic acid B (10, 20, 40 mg/kg) by tail intravenous injection, levels of thromboxane B. Salvianolic acid B significantly decreased the expressions of TXB. Salvianolic acid B has a protective effect on TAO rats. The mechanism may involve inhibition of thrombosis and TAO-associated inflammatory responses, which may explain the success of RSMA treatment of TAO in humans in traditional Chinese medical practice. Hence, it may be a potential drug for TAO treatment in conventional medicine.

Topics: Animals; Benzofurans; Humans; Inflammation; Lauric Acids; Male; Medicine, Chinese Traditional; Plant Roots; Rats; Rats, Wistar; Salvia miltiorrhiza; Thromboangiitis Obliterans; Thrombosis

Topics: Animals; Benzofurans; Cytokines; Inflammation; Intestines; Male; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Ischemic heart disease is a major cause of mortality and disability worldwide. Salvianolic acid B (Sal B) is one of the main water‑soluble components of Salvia miltiorrhiza Bge. Numerous studies have demonstrated that Sal B could exert significant anti‑inflammatory and cardiovascular protective effects; however, the underlying mechanisms remain unclear. To elucidate the association between myocardial ischemia and inflammation, and to develop effective protective drugs, a rat model of myocardial ischemia was induced using isoproterenol (ISO) and an inflammation model in H9C2 cells was induced with lipopolysaccharide + adenosine triphosphate. Both of these models were treated with different concentrations of Sal B (5, 10 and 15 mg/kg in vivo; 1, 5 and 25 µM in vitro). In vivo, the serum levels of creatine kinase isoenzyme MB, glutamic oxaloacetic transaminase and IL‑1β, the cardiac function and the mRNA expression levels of NLR family pyrin domain‑containing 3 (NLRP3) inflammasome components were evaluated using ELISAs, an electrocardiogram, hematoxylin and eosin staining and reverse transcription‑quantitative PCR, respectively. The results demonstrated that treatment with Sal B markedly alleviated the acute myocardial ischemic injury induced by hypodermic injection of ISO in rats. In vitro, the results of reactive oxygen species (ROS) detection, JC‑1 staining, western blotting and TUNEL assays showed that Sal B treatment significantly inhibited intracellular ROS production, increased the mitochondrial membrane potential, regulated the expression of mitophagy‑related proteins, inhibited the activation of the NLRP3 inflammasome and inhibited apoptosis in H9C2 cells. In conclusion, these findings indicated that Sal B exerted protective effects against myocardial ischemic injury by promoting mitophagy and maintaining mitochondrial function.

Topics: Animals; Apoptosis; Benzofurans; Cell Line; China; Disease Models, Animal; Inflammasomes; Inflammation; Ischemia; Lipopolysaccharides; Male; Mitophagy; Myocardial Ischemia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 4

The lack of inclusion of comorbidities in animal models of stroke may underlie the limited development of therapy in stroke. Previous studies in mice deficient of CD36, an immune receptor, indicated its contribution to stroke-induced inflammation and injury in hyperlipidemic conditions. The current study, therefore, tested whether pharmacological inhibition of CD36 provides neuroprotection in hyperlipidemic stroke. The hyperlipidemic mice subjected to stroke showed an exacerbation of infarct size and profound brain swelling. However, post-stroke treatment with CD36 inhibitors did not reduce, and in some cases worsened, acute stroke outcome, suggesting potential benefits of elevated CD36 in the post-stroke brain in a hyperlipidemic condition. On the other hand, chronic treatment of a CD36 inhibitor prior to stroke significantly reduced stroke-induced brain swelling. There was a trend toward infarct reduction, although it did not reach statistical significance. The observed benefit of preventative CD36 inhibition is in line with previously reported smaller infarct volume and swelling in CD36 KO mice. Thus, the current findings suggest that insights gained from the genetic models should be carefully considered before the implementation of pharmacological interventions, as a potential therapeutic strategy may depend on preventative treatment or a post-stroke acute treatment paradigm.

Topics: Animals; Apolipoproteins E; Benzofurans; Brain Edema; CD36 Antigens; Disease Models, Animal; Drug Administration Schedule; Drugs, Chinese Herbal; Hyperlipidemias; Inflammation; Male; Mice, Inbred C57BL; Mice, Knockout; Protective Agents; Stroke

Acute graft-versus-host disease (aGvHD) remains lethal, even after allogeneic hematopoietic stem cell transplantation. Inflammatory responses play an important role in aGvHD. Salvianolic acid B (Sal B) has been widely reported to have a major effect on the anti-inflammatory response, but these effects in an aGvHD model have never been reported. B6 donor splenocytes were transplanted into unirradiated BDF1 recipients and liver and serum were collected on day 14 after transplantation with or without Sal B administration. We measured the expression of pro-inflammatory cytokines and chemokines and other manifestations in aGvHD mice after Sal B treatment. Sal B ameliorated liver injury in aGvHD and promoted survival in mice. Sal B treatment resulted in decreased expression of pro-inflammatory cytokines and chemokines whose expressions in liver are normally elevated by aGvHD. Furthermore, Sal B treatment also enhanced PGC-1α expression in liver tissue and HO-1 expression in nonparenchymal cells. In addition, HO-1 inhibitor abrogated the improvement of survival rate of mice with aGvHD. These results indicated that the protective effect of Sal B relies on suppressing the inflammatory response phase in the aGvHD model, presumably by inducing HO-1. Taken together our data showed that Sal B ameliorates liver injury in aGvHD by decreasing inflammatory responses via upregulation of HO-1. It may provide a novel way to deal with this disease.

Topics: Acute Disease; Animals; Benzofurans; Disease Models, Animal; Gene Expression Regulation, Enzymologic; Graft vs Host Disease; Heme Oxygenase-1; Inflammation; Liver; Liver Diseases; Male; Membrane Proteins; Mice; Up-Regulation

BACKGROUND Salvianolic acid B (SB) is a major active phyto-component of the plant Radix Salvia miltiorrhiza, which is traditionally used to treat joint pain and arthritis. The present study examined the anti-rheumatoid arthritis efficacy of SB on collagen-induced rheumatoid arthritis (CIA) in a rat model. MATERIAL AND METHODS Forty-eight rats were divided into 4 groups: Control rats treated with saline (Group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type at the tail (Group II), and rats subjected to CIA and supplemented with either 20 or 40 mg/kg of SB for 28 days (group III or IV). RESULTS Paw swelling, edema, arthritis score, thymus and spleen indexes, and neutrophil infiltration were significantly decreased (p<0.01) by treatment with 20 or 40 mg/kg of SB. The levels of inflammatory cytokines (interleukin-1β, -6, and -17, and TNF-α) and anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) were markedly decreased (p<0.01), and those of antioxidant enzymes (SOD, CAT, and GSH) were significantly increased (p<0.01) in SB-treated rats. Administration with SB (20 or 40 mg/kg) resulted in lower phosphorylated IkB-a and NF-κB p65 protein levels and markedly downregulated IκB-a expression. Furthermore, CIA rats revealed the presence of highly diffused polymorphonuclear cells (PMNs) infiltration with eroded cartilage; however, these phenomena were considerably ameliorated by SB. CONCLUSIONS SB alleviates oxidative stress and inflammation in CIA rats, thus verifying its anti-rheumatoid arthritis property.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Benzofurans; Disease Models, Animal; Down-Regulation; Edema; Inflammation; Inflammation Mediators; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Transcription Factor RelA

Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

Topics: Animals; Benzofurans; Blood Urea Nitrogen; Creatinine; Drugs, Chinese Herbal; Inflammation; Kidney; Lipid Peroxidation; Male; Oxidative Stress; Peroxidase; Phosphatidylinositol 3-Kinases; Protective Agents; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction

Although accumulating evidence suggests that activated microglia are associated with deficits in neurogenesis and contribute to the physiopathology of major depressive disorder, the role of microglia in treating depression remains poorly understood. Our previous study showed that salvianolic acid (SalB) has the regulation of neuroinflammatory responses and antidepressant-like effects. Here, we hypothesized that SalB's therapeutic effects occur because it modulates microglial phenotypes that are associated with neurogenesis. To test this hypothesis, we treated CMS-exposed C57BL/6 mice with SalB (20mg/kg, intraperitoneally, once daily) for 3weeks and investigated microglial phenotypic profiles and hippocampal neurogenesis. The results showed that the SalB treatment skewed M1 microglial polarization toward M2 activation in the hippocampus and cortex and remedied CMS-induced deficits in hippocampal neurogenesis. SalB (40µM) inhibited LPS-stimulated microglial M1 activation as well as induced M2 activation in vitro, and the cultured microglia with the SalB treatment showed enhanced neural precursor cell proliferation, differentiation, and survival. SalB treatment also ameliorated the depressive-like behaviors of the CMS-treated mice in sucrose preference, forced swimming, and tail suspension tests. These findings suggest a possible antidepressive mechanism for anti-inflammatory agents that is correlated with microglial polarization and hippocampal neurogenesis and which may provide a new microglia-targeted strategy for depression therapy.

Topics: Animals; Benzofurans; Cerebral Cortex; Depression; Depressive Disorder; Hippocampus; Inflammation; Inflammation Mediators; Male; Mice, Inbred C57BL; Microglia; Neurogenesis; Phenotype; Stress, Psychological

Topics: Animals; Benzofurans; Cyclooxygenase 2; Diet, High-Fat; Dietary Supplements; Humans; Inflammation; Interleukin-10; Interleukin-6; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Plant Extracts; Salvia miltiorrhiza; Tumor Necrosis Factor-alpha

The NLRP3 inflammasome activation and neuroinflammation are known to be involved in the pathology of depression, whereas autophagy has multiple effects on immunity, which is partly mediated by the regulation of inflammasome and clearance of proinflammatory cytokines. Given the emerging evidence that autophagy dysfunction plays an essential role in depression, it is very likely that autophagy may interact with the inflammatory process in the development and treatment of depression. Salvianolic acid B (SalB), a naturally occurring compound extracted from Salvia miltiorrhiza, contains anti-inflammatory and antidepression properties and has recently been proven to modulate autophagy. In this study, we sought to investigate whether autophagy is involved in the inflammation-induced depression and the antidepressant effects of SalB.. The effects of prolonged lipopolysaccharide (LPS) treatment and SalB administration on behavioral changes, neuroinflammation, autophagic markers and NLRP3 activation in rat hippocampus were determined by using behavioral tests, real-time PCR analysis, western blot, and immunostaining.. Our data showed that periphery immune challenge by LPS for 2 weeks successfully induced the rats to a depression-like state, accompanied with enhanced expression of pro-inflammatory cytokines and NLRP3 inflammasome activation. Interestingly, autophagic markers, including Beclin-1, and the ratio of LC3II to LC3I were suppressed following prolonged LPS exposure. Meanwhile, co-treatment with SalB showed robust antidepressant effects and ameliorated the LPS-induced neuroinflammation. Additionally, SalB restored the compromised autophagy and overactivated NLRP3 inflammasome in LPS-treated rats.. Collectively, these data suggest that autophagy may interact with NLRP3 activation to contribute to the development of depression, whereas SalB can promote autophagy and induce the clearance of NLRP3, thereby resulting in neuroprotective and antidepressant actions.

Topics: Animals; Anti-Inflammatory Agents; Autophagy; Behavior, Animal; Benzofurans; Depression; Inflammasomes; Inflammation; Lipopolysaccharides; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley

Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases. In the present study, a rat model of transient middle cerebral artery occlusion (tMCAO) was established to investigate the neuroprotective effects and mechanisms of SAB treatment against focal cerebral I/R insult. The results showed that SAB treatment (3mg/kg, 6mg/kg and 12mg/kg, i.p.) dose-dependently decreased I/R-induced neurological deficits at 24, 48, and 72h after reperfusion and decreased plasma-soluble P-selectin and soluble CD40 ligand as early as 6h after onset of I/R insult. At 24h after reperfusion, SAB treatment significantly reduced neuronal and DNA damage in the hippocampal CA1 region and decreased neural cell loss in the ischemic core. The I/R-induced pro-inflammatory mediator mRNA and protein overexpression in the penumbra cortex, including ICAM-1, IL-1β, IL-6, IL-8, and MCP-1, were significantly inhibited by SAB in a dose-dependent manner. Further studies suggested SAB treatment attenuated CD40 expression and NF-κB activation, which involved NF-κB/p65 phosphorylation and IκBα phosphorylation and degradation. In conclusion, our findings indicated that the neuroprotective effects of SAB post cerebral I/R injury are associated with the inhibition of both platelets activation and production of pro-inflammatory mediators and the downregulation of the CD40/NF-κB pathway.

Topics: Animals; Benzofurans; Blood Platelets; Brain Ischemia; CA1 Region, Hippocampal; CD40 Antigens; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Inflammation; Male; Neuroimmunomodulation; Neuroprotective Agents; NF-kappa B; Platelet Activation; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury; Signal Transduction; Transcription Factor RelA

Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti-inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100μM) for 2h, then incubated with IL-1β (10ng/mL) for 24h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX-2, MMP-13, ADAMTS-5 and NF-κB-related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal-injection of either Sal B (25mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin-O-Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8weeks following the surgery. Sal B inhibited the over-production of NO and PGE2, while the elevated expression of INOS, COX-2, MMP-13 and ADAMTS-5 were reversed by Sal B in IL-1β-induced chondrocytes. In addition, IL-1β significantly induced phosphorylation of NF-κB signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL-1β-induced p65 nuclear translocation. In vivo, the cartilage in Sal B-treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cartilage; Chondrocytes; Cytokines; Disease Models, Animal; Humans; Inflammation; Interleukin-1beta; Male; Matrix Metalloproteinase 13; Menisci, Tibial; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide; Osteoarthritis; Phosphorylation; Signal Transduction

Salvianolic acid B (SAB) is a hydrophilic component isolated from the Chinese herb Salviae miltiorrhizae, which has been used clinically for the treatment of ischemic cardiovascular and cerebrovascular diseases. Platelets-mediated vascular inflammatory response contributes to the initiation and progression of atherosclerosis. In this paper, we focus on the modulating effects of SAB on the inflammatory reaction of endothelial cells triggered by activated platelets. Human umbilical vein endothelial cells (EA.hy926) were pretreated with SAB followed by co-culture with ADP-activated platelets. Adhesion of platelets to endothelial cells was observed by amorphological method. The activation of nuclear factor-kappa B was evaluated by NF-κB p65 nuclear translocation and the protein phosphorylation. A determination of the pro-inflammatory mediators (ICAM-1, IL-1β, IL-6, IL-8, MCP-1) mRNA and protein were also conducted. In addition, the inhibitory effects of SAB on platelets activation were also evaluated using a platelet aggregation assay and assessing the release level of soluble P-selectin. The results showed that SAB dose-dependently inhibited ADP- or α-thrombin-induced human platelets aggregation in platelet rich plasma (PRP) samples, and significantly decreased soluble P-selectin release from both agonists stimulated washed platelets. It was also found that pre-treatment with SAB reduced adhesion of ADP-activated platelets to EA.hy926 cells and inhibited NF-κB activation. In addition, SAB significantly suppressed pro-inflammatory mediators mRNA and protein in EA.hy926 cells in a dose-dependent manner. These results indicated that, in addition to its inhibitory effects on platelets activation, SAB was able to attenuate platelets-mediated inflammatory responses in endothelial cells even if the platelets had already been activated. This anti-inflammatory effect was related to the inhibition of NF-κB activation. Our findings suggest that SAB may be a potential candidate for the treatment of various atherosclerotic diseases.

Topics: Benzofurans; Blood Platelets; Cell Adhesion; Cells, Cultured; Coculture Techniques; Disease Progression; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Microscopy, Fluorescence; NF-kappa B; P-Selectin; Plant Preparations; Platelet Aggregation; RNA; Salvia

Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor. The infarct volume, neurological score and brain water content were assessed. In addition, levels of TNF-α and IL-1β in the brain tissues were detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1, Bcl-2 and Bax were detected by Western blot. The results suggested that SalB exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. SalB also exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-1β levels in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were abolished by EX527 treatment. In summary, our results demonstrate that SalB treatment attenuates brain injury induced by ischemic stoke via reducing apoptosis and inflammation through the activation of SIRT1 signaling.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzofurans; Brain; Brain Edema; Brain Ischemia; Carbazoles; Central Nervous System Agents; Disease Models, Animal; Infarction, Middle Cerebral Artery; Inflammation; Male; Neuroprotective Agents; Random Allocation; Rats, Sprague-Dawley; Severity of Illness Index; Sirtuin 1; Stroke; Treatment Outcome

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

Salvianolic acid B (Sal B) is a water-soluble compound found in the traditional Chinese medicine, Radix Salviae miltiorrhizae, and has been widely used to treat a variety of diseases in Asian cultures. Sal B was shown to inhibit apoptosis in many cell types, but its effect on hepatocyte apoptosis is unknown. In this study, we attempt to show that Sal B attenuates hepatocyte apoptosis and hepatic injury induced by lipopolysaccharide and D-galactosamine in mice. Sal B also inhibits apoptosis that is induced by the death receptor in the HL-7702 hepatocyte cell line. Apoptosis in vitro is determined by flow cytometry, DNA electrophoresis and high content screening assay. The antiapoptotic effect is generated by reducing the expression of tumor necrosis factor alpha receptor type 1, balancing the expression of Bcl-2 family members, decreasing the release of cytochrome C from the mitochondria into the cytosol and inhibiting activated Caspase-3. These findings suggest that Sal B can effectively inhibit hepatocyte apoptosis as well as the underlying mechanisms related to regulating mediators in death receptor and mitochondrial pathways.

Topics: Animals; Apoptosis; Benzofurans; Cell Line; DNA; DNA Fragmentation; Electrophoresis, Agar Gel; Flow Cytometry; Galactosamine; Hepatocytes; Humans; Inflammation; Lipopolysaccharides; Liver Diseases; Liver Function Tests; Male; Mice; Mitochondria; Receptors, Death Domain; Signal Transduction; Tumor Necrosis Factor-alpha