salvianolic-acid-a and Disease-Models--Animal

Both caffeic acid and 3,4-dihydroxyphenyllactic acid (danshensu) are synthesized through two distinct routs of the shikimic acid biosynthesis pathway. In many plants, especially the rosemary and sage family of Lamiaceae, these two compounds are joined through an ester linkage to form rosmarinic acid (RA). A further structural diversity of RA derivatives in some plants such as

Topics: Alkenes; Alzheimer Disease; Amyloid beta-Peptides; Animals; Cell Differentiation; Cinnamates; Dementia, Vascular; Depsides; Disease Models, Animal; Gene Expression Regulation; Humans; Lactates; Neural Stem Cells; Neurons; Neuroprotective Agents; Nootropic Agents; Polyphenols; Rosmarinic Acid; Stroke; tau Proteins

Radix

Topics: Acute Disease; Alkenes; Angiogenesis Inducing Agents; Animals; Disease Models, Animal; Drugs, Chinese Herbal; Female; Male; Myocardial Infarction; Polyphenols; Rats; Rats, Sprague-Dawley; Swine

Salvianolic acids possess anti-inflammatory properties. This study investigated the therapeutic effect of salvianolic acids on chronic mild stress (CMS)-induced depressive-like behaviors in rats and the involvement of toll-like receptor 4 (. Eighty male Sprague-Dawley rats were randomly subjected to CMS or non-CMS protocol for 6 weeks. Starting 3 weeks after CMS exposure, the rats in each group were administered saline, fluoxetine (positive control), salvianolic acids, or salvianolic acids + fluoxetine daily for 3 weeks. The body weight change, sucrose preference, and immobility duration in forced swimming were examined before and after drug treatment. The rats were sacrificed at 3 weeks after drug treatment. Quantitative real-time PCR was performed to measure the mRNA levels of. Compared with non-CMS rats, CMS rats had significantly reduced weight gains and sucrose preference, along with significantly increased immobility durations and elevated mRNA levels of. Thus, salvianolic acids alleviate depressive-like behaviors, possibly by suppressing

Topics: Animals; Disease Models, Animal; Fluoxetine; Hippocampus; Male; Myeloid Differentiation Factor 88; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stress, Psychological; Sucrose; Toll-Like Receptor 4; Weight Gain

Myofibroblasts activation intensively contributes to cardiac fibrosis with undefined mechanism. Salvianolic acid A (SAA) is a phenolic component derived from Salvia miltiorrhiza with antifibrotic potency. This study aimed to interrogate the inhibitory effects and underlying mechanism of SAA on myofibroblasts activation and cardiac fibrosis. Antifibrotic effects of SAA were evaluated in mouse myocardial infarction (MI) model and in vitro myofibroblasts activation model. Metabolic regulatory effects and mechanism of SAA were determined using bioenergetic analysis and cross-validated by multiple metabolic inhibitors and siRNA or plasmid targeting Ldha. Finally, Akt/GSK-3β-related upstream regulatory mechanisms were investigated by immunoblot, q-PCR, and cross-validated by specific inhibitors. SAA inhibited cardiac fibroblasts-to-myofibroblasts transition, suppressed collage matrix proteins expression, and effectively attenuated MI-induced collagen deposition and cardiac fibrosis. SAA attenuated myofibroblasts activation and cardiac fibrosis by inhibiting LDHA-driven abnormal aerobic glycolysis. Mechanistically, SAA inhibited Akt/GSK-3β axis and downregulated HIF-1α expression by promoting its degradation via a noncanonical route, and therefore restrained HIF-1α-triggered Ldha gene expression. SAA is an effective component for treating cardiac fibrosis by diminishing LDHA-driven glycolysis during myofibroblasts activation. Targeting metabolism of myofibroblasts might occupy a potential therapeutic strategy for cardiac fibrosis.

Topics: Animals; Disease Models, Animal; Fibrosis; Glycogen Synthase Kinase 3 beta; Glycolysis; Mice; Myocardial Infarction; Myofibroblasts; Proto-Oncogene Proteins c-akt; Signal Transduction

After cerebral ischemia/reperfusion injury, pro-inflammatory M1 and anti-inflammatory M2 phenotypes of microglia are involved in neuroinflammation, in which activation of NLRP3 inflammasome and subsequent pyroptosis play essential roles. Salvianolic Acids for Injection (SAFI) is Chinese medicine injection which composed of multiple phenolic acids extracted from Radix Salviae Miltiorrhizae, and has been reported to generate neuroprotective effects after cerebral ischemic insult in clinical and animal studies.. The present study was designed to investigate whether SAFI exerts neuroprotective effects by switching microglial phenotype and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia.. The middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) model in co-cultured primary neurons and primary microglia were utilized. The neuroprotective effect of SAFI was evaluated through measuring neurological deficit scores, neuropathological changes, inflammatory factors, cell phenotype markers, and related proteins of NLRP3 inflammasome/pyroptosis axis.. The results showed that SAFI treatment was able to: (1) produce a significant increase in neurological deficit scores and decrease in infarct volumes, and alleviate histological injury and neuronal apoptosis in cerebral cortex in MCAO/R model; (2) increase neuronal viability and reduce neuronal apoptosis in the OGD model; (3) reshape microglial polarization patterns from M1-like phenotype to M2-like phenotype; (4) inhibit the activation of the NLRP3 inflammasome and the expression of proteins related to NLRP3 inflammasome/pyroptosis axis in vivo and in vitro.. These findings indicate that SAFI exert neuroprotective effect, probably via reducing neuronal apoptosis, switching microglial phenotype from M1 towards M2, and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia.

Topics: Alkenes; Amino Acid Transport System ASC; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Brain Ischemia; Calcium-Binding Proteins; Caspase 1; Cell Survival; Cells, Cultured; Disease Models, Animal; Inflammasomes; Injections, Intraperitoneal; Interleukin-1beta; Intracellular Signaling Peptides and Proteins; Male; Microfilament Proteins; Microglia; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphate-Binding Proteins; Polyphenols; Pyroptosis; Rats, Sprague-Dawley; Reperfusion Injury

BACKGROUND A cardioprotective effect of salvianolic acid A (SalA) has been described, but it is unknown whether SalA can protect cardiomyocytes against doxorubicin (Dox)-induced cardiotoxicity. This study aimed to investigate whether SalA could inhibit Dox-induced apoptosis in H9C2 cells and to uncover the potential mechanism. MATERIAL AND METHODS H9C2 cardiomyocytes exposed to Dox were treated with SalA or not, and then cell viability, apoptosis, and the expression of nuclear factor-kappaB (NF-kappaB) signaling were detected by Cell Counting Kit-8, TUNEL staining, and western blot assays, respectively. Nuclear factor kappa B subunit 1 (NFKB1) was overexpressed in H9C2 cells, and then alterations in cell viability and apoptosis in H9C2 cells co-treated with Dox and SalA were investigated. RESULTS SalA (2, 10, and 50 μM) had no effect on H9C2 cell viability, while Dox reduced cell viability in a concentration-dependent manner. In addition, SalA rescued Dox-decreased cell viability. Dox also triggered apoptosis as evidenced by an increased ratio of TUNEL-positive cells, enhanced expression of pro-apoptotic proteins, and reduced expression of anti-apoptotic protein BCL-2, which were all partially blocked by SalA co-treatment. The proteins involved in NF-kappaB signaling including IkappaBalpha, IKKalpha, IKKß, and p65 were activated by Dox but inactivated by SalA co-treatment. Moreover, Dox increased NFKB1 mRNA and nuclear expression, which was blocked by SalA. NFKB1 could bind to plasmacytoma variant translocation 1 (PVT1) and upregulate PVT1 expression. Mechanistically, the overexpression of NFKB1 blocked the inhibitory effect of SalA on Dox-induced cell viability impairment and apoptosis. CONCLUSIONS We demonstrated that SalA may exert a protective effect against Dox-induced H9C2 injury and apoptosis via inhibition of NFKB1 expression, thereby downregulating lncRNA PVT1.

Topics: Animals; Caffeic Acids; Cardiotoxicity; Cells, Cultured; Disease Models, Animal; Down-Regulation; Doxorubicin; Lactates; Myocytes, Cardiac; NF-kappa B; Plasmacytoma; Rats; RNA, Long Noncoding; Signal Transduction

The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4'-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA.. The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Caffeic Acids; Cell Line, Tumor; Choroidal Neovascularization; Disease Models, Animal; Drug Liberation; Enzyme Inhibitors; Lactates; Mice; Mice, Inbred C57BL; Multifunctional Nanoparticles; Nanoparticles; Oligopeptides; Polyethylene Glycols; Polyethyleneimine; Proton Pump Inhibitors; Wound Healing

To investigate whether salvianolic acid B is able to enhance repair of degenerated intervertebral discs by mesenchymal stem cells (MSCs) through the promotion of MSC differentiation into nucleus pulposus cells in a nucleus-pulposus-like environment and by enhancing the trophic effect of MSCs on residual nucleus pulposus cells (mediated by transforming growth factor-β1).. Successful intervertebral disc degeneration models, established by aspiration of the nucleus pulposus in New Zealand white rabbits, were randomly divided into eight groups: Group A was treated with MSC transplantation. Group B was treated with MSC transplantation and salvianolic acid B, with the subgroups B1, B2, B3, and B4 receiving 0.01 mg/L, 0.1 mg/L, 1 mg/L, and 10 mg/L salvianolic acid B, respectively. Groups C and D were treated with phosphate buffer saline and sham graft, respectively. Group E was the normal control group. At the end of week 8, the type II collagen, proteoglycan, transforming growth factor-β1, and water contents in each group were examined by semi-quantitative immunohistochemistry, spectrophotometry, enzyme-linked immunosorbent assay, and magnetic resonance, respectively.. The content of type II collagen, proteoglycan, transforming growth factor-β1, and water in groups B3 and B4 were significantly higher than those in group A (. Salvianolic acid B (1 mg/L to 10 mg/L) plus MSC transplantation was more effective in repairing degenerated intervertebral discs than was stem cell transplantation alone.

Topics: Alkenes; Animals; Disease Models, Animal; Intervertebral Disc Degeneration; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nucleus Pulposus; Polyphenols; Rabbits; Regeneration

Salvia miltiorrhiza root has been used in Asian traditional medicine for the treatment of cardiovascular diseases, asthma, and other conditions. Salvianolic acid B from S. miltiorrhiza extracts has been shown to improve airway hyperresponsiveness. We investigated the effects of salvianolic acid A, tanshinone I, and tanshinone IIA from S. miltiorrhiza in allergic asthma by using rat RBL-2H3 mast cells and female Balb/c mice. Antigen-induced degranulation was assessed by measuring β-hexosaminidase activity in vitro. In addition, a murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of salvianolic acid A and tanshinone IIA. Tanshinone I and tanshinone IIA inhibited antigen-induced degranulation of mast cells, but salvianolic acid A did not. Administration of salvianolic acid A and tanshinone IIA decreased the number of immune cells, particularly eosinophils in allergic asthma-induced mice. Histological studies showed that salvianolic acid A and tanshinone IIA reduced mucin production and inflammation in the lungs. Administration of salvianolic acid A and tanshinone IIA reduced the expression and secretion of Th2 cytokines (IL-4 and IL-13) in the bronchoalveolar lavage fluid and lung tissues of mice with ovalbumin-induced allergic asthma. These findings provide evidence that salvianolic acid A and tanshinone IIA may be potential anti-allergic therapeutics.

Topics: Abietanes; Animals; Anti-Allergic Agents; beta-N-Acetylhexosaminidases; Caffeic Acids; Cell Degranulation; Cell Line; Cytokines; Disease Models, Animal; Female; Humans; Hypersensitivity; Lactates; Mast Cells; Mice; Mice, Inbred BALB C; Mucins; Rats; Salvia miltiorrhiza; Th2 Cells

Arsenic trioxide (ATO) has been verified as a breakthrough with respect to the management of acute promyelocytic leukemia (APL) in recent decades but associated with some serious adverse phenomena, particularly cardiac functional abnormalities. Salvianolic acid A (Sal A) is a major effective component in treating ATO-induced cardiotoxicity. Therefore, the objective of our study was to assess whether Sal A had protective effects by the regulation of calcium homeostasis and endoplasmic reticulum (ER) stress. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A via daily tail vein injections for two weeks. For the in vitro study, we detected the effects of ATO and/or Sal A in real time using adult rat ventricular myocytes (ARVMs) and an IonOptix MyoCam system. Our results showed that Sal A pretreatment alleviated cardiac dysfunction and Ca

Topics: Animals; Apoptosis; Arsenic Trioxide; Caffeic Acids; Calcium; Cardiotoxicity; Disease Models, Animal; Endoplasmic Reticulum Stress; Gene Expression Regulation; Homeostasis; Humans; Lactates; Leukemia, Promyelocytic, Acute; Mice; Myocytes, Cardiac; Rats; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases

To investigate the protective effects of salvianolic acid A (SAA) on renal damage in rats with chronic renal failure (CRF).. The five-sixth nephrectomy model of CRF was successfully established in group CRF (10 rats) and group CRF+SAA (10 rats). Ten rats were selected as sham-operated group (group S), in which only the capsules of both kidneys were removed. The rats in group CRF+SAA were intragastrically administrated with 10 mg/kg SAA for 8 weeks. The blood urine nitrogen (BUN), urine creatinine (Ucr), creatinine clearance rate (Ccr), and serum uperoxide dismutase (SOD) and malondialdehyde (MDA) were tested. The expressions of transforming growth factor-β1 (TGF-β1), bone morphogenetic protein 7 (BMP-7) and Smad6 protein in renal tissue were determined.. After treatment, compared with group CRF, in group CRF+SAA the BUN, Scr, serum MDA and kidney/body weight ratio were decreased, the Ccr and serum SOD were increased, the TGF-β1 protein expression level in renal tissue was decreased, and the BMP-7 and Smad6 protein levels were increased (all P < 0.05).. SAA can alleviate the renal damage in CRF rats through anti-oxidant stress, down-regulation of TGF-β1 signaling pathway and up-regulation of BMP-7/Smad6 signaling pathway.

Topics: Animals; Bone Morphogenetic Protein 7; Caffeic Acids; Disease Models, Animal; Down-Regulation; Kidney Failure, Chronic; Kidney Function Tests; Lactates; Male; Nephrectomy; Rats; Rats, Sprague-Dawley; Smad6 Protein; Transforming Growth Factor beta1; Up-Regulation

Salvianolic acid A (Sal A) has been shown to prevent and treat ischemic cardiovascular, as well as cerebral vascular diseases. However, little is known about Sal A in renal ischemia/reperfusion (I/R) injury. In this study, a renal I/R injury model in rats and a hypoxia/reoxygenation (H/R) model to damage proximal renal tubular cells (HK-2) were used to assess whether Sal A halts the development and progression of renal I/R injury. As compared with vehicle treatment, Sal A significantly attenuated kidney injury after renal I/R injury, accompanied by decreases in plasma creatinine, blood urea nitrogen levels, the number of apoptosis-positive tubular cells, and kidney oxidative stress. Sal A also activated phosphorylated protein kinase B (p-Akt) and phosphorylated-mammalian target of rapamycin (p-mTOR) compared with vehicle-treated I/R injury rats. In H/R-injured HK-2 cells, Sal A can reduce the levels of reactive oxygen species in a dose-related manner. Similar to the results from in vivo experiments, in vitro Sal A also increased the protein expression of phosphorylated-eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) compared with vehicle. Furthermore, the cytoprotective activity of Sal A was inhibited by LY294002 and rapamycin. These findings indicate that Sal A can ameliorate renal I/R injury and promote tubular cell survival partly via the Akt/mTOR/4EBP1pathway. Sal A could be a candidate compound to prevent ischemic tissue damage.

Topics: Acute Kidney Injury; Alkenes; Animals; Apoptosis; Biomarkers; Blood Urea Nitrogen; Carrier Proteins; Cell Line; Creatinine; Cytoprotection; Disease Models, Animal; Humans; Intracellular Signaling Peptides and Proteins; Kidney; Male; Oxidative Stress; Phosphoproteins; Phosphorylation; Polyphenols; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Renal Agents; Reperfusion Injury; Signal Transduction; TOR Serine-Threonine Kinases

Delayed fracture union is a significant clinical challenge in orthopedic practice. There are few non-surgical therapeutic options for this pathology. To address this challenge, we have developed a bone-targeting liposome (BTL) formulation of salvianic acid A (SAA), a potent bone anabolic agent, for improved treatment of delayed fracture union. Using pyrophosphorylated cholesterol as the targeting ligand, the liposome formulation (SAA-BTL) has demonstrated strong affinity to hydroxyapatite in vitro, and to bones in vivo. Locally administered SAA-BTL was found to significantly improve fracture callus formation and micro-architecture with accelerated mineralization rate in callus when compared to the dose equivalent SAA, non-targeting SAA liposome (SAA-NTL) or no treatment on a prednisone-induced delayed fracture union mouse model. Biomechanical analyses further validated the potent therapeutic efficacy of SAA-BTL. These results support SAA-BTL formulation, as a promising therapeutic candidate, to be further developed into an effective and safe clinical treatment for delayed bone fracture union.

Topics: Animals; Anti-Inflammatory Agents; Caffeic Acids; Cholesterol; Disease Models, Animal; Drug Compounding; Female; Fracture Healing; Fractures, Bone; Lactates; Liposomes; Mice; Osteogenesis; Prednisone; Proton Pump Inhibitors

Topics: Alkenes; Animals; Antigens, CD; Astragalus Plant; Brain; Brain Edema; Cadherins; Carotid Artery Thrombosis; Cell Adhesion Molecules; Cerebrovascular Circulation; Claudin-5; Collagen Type IV; Disease Models, Animal; Drug Combinations; Drugs, Chinese Herbal; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex IV; Intracranial Hemorrhages; Laminin; Male; Mice; Occludin; Panax notoginseng; Polyphenols; Receptors, Cell Surface; Reperfusion Injury; Saponins; Tissue Plasminogen Activator; Zonula Occludens-1 Protein

Salvianolic acid A (SAA), a water-soluble phenolic acid isolated from the root of Dan Shen, displays distinct antioxidant activity and effectiveness in protection against cerebral ischemia/reperfusion (I/R) damage. However, whether SAA can enter the central nervous system and exert its protective effects by directly targeting brain tissue remains unclear. In this study, we evaluated the cerebral protection of SAA in rats subjected to transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. The rats were treated with SAA (5, 10 mg/kg, iv) when the reperfusion was performed. SAA administration significantly decreased cerebral infarct area and the brain water content, attenuated the neurological deficit and pathology, and enhanced the anti-inflammatory and antioxidant capacity in tMCAO rats. The concentration of SAA in the plasma and brain was detected using LC-MS/MS. A pharmacokinetic study revealed that the circulatory system exposure to SAA was equivalent in the sham controls and I/R rats, but the brain exposure to SAA was significantly higher in the I/R rats than in the sham controls (fold change of 9.17), suggesting that the enhanced exposure to SAA contributed to its cerebral protective effect. Using a GC/MS-based metabolomic platform, metabolites in the serum and brain tissue were extracted and profiled. According to the metabolomic pattern of the tissue data, SAA administration significantly modulated the I/R-caused perturbation of metabolism in the brain to a greater extent than that in the serum, demonstrating that SAA worked at the brain tissue level rather than the whole circulation system. In conclusion, a larger amount of SAA enters the central nervous system in ischemia/reperfusion rats to facilitate its protective and regulatory effects on the perturbed metabolism.

Topics: Animals; Biological Availability; Brain; Caffeic Acids; Chromatography, Liquid; Cytoprotection; Disease Models, Animal; Gas Chromatography-Mass Spectrometry; Infarction, Middle Cerebral Artery; Injections, Intravenous; Lactates; Male; Metabolomics; Neuroprotective Agents; Rats, Sprague-Dawley; Reperfusion Injury; Tandem Mass Spectrometry

The purpose of this study is to develop a new method of preparing salvianolic acid extracts (SAE) water-in-oil-in-water (W/O/W) multiple emulsion (ME). SAE injection is used in the treatment of brain infarct and promotion of blood circulation in China. However, the injection is not convenient, and the oral preparation has poor bioavailability. Hence, a new preparation that is convenient and stable with good biological availability is required. SAE ME was prepared by two-step emulsification method. Combined with single-factor investigation and orthogonal test, the embedding rate and centrifugal retention rate were taken as the comprehensive indexes to optimize the formulation of SAE ME. The ME size was tested by laser particle size analyzer. The pharmacokinetic studies were conducted in Sprague-Dawley rats with HPLC-MS/MS method. The blood coagulation and hemorheology tests were conducted to assess the effect of preparation in rats. The best preparation technique for SAE ME is by the use of trospium chloride; SAE represent 12% of water in the phase, lipophilic emulsifier hydrophilic lipophilic balance value=4.3, lipophilic emulsifier is 20% of the oil phase. The median diameter of particle is (0.608±0.05) µm and the C

Topics: Administration, Oral; Alkenes; Animals; Biological Availability; Brain Infarction; Chromatography, High Pressure Liquid; Disease Models, Animal; Drug Compounding; Emulsifying Agents; Emulsions; Hematologic Diseases; Hemorheology; Humans; Hydrophobic and Hydrophilic Interactions; Injections, Intravenous; Male; Oils; Particle Size; Polyphenols; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Water

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Topics: Animals; Caffeic Acids; Capillary Permeability; Cardiovascular Agents; Caveolin 1; Cullin Proteins; Disease Models, Animal; Drug Evaluation, Preclinical; Heme Oxygenase (Decyclizing); Hypoxia; Lactates; Male; MicroRNAs; Motor Activity; Neuroprotective Agents; NF-E2-Related Factor 2; Random Allocation; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Tight Junctions; Zonula Occludens-1 Protein

Inflammatory reactions induced by microglia in the brain play crucial roles in ischemia/reperfusion (I/R) cerebral injuries. Microglia activation has been shown to be closely related to TLR4/NF-κB signal pathways. Salvianolic acids for injection (SAFI) have been used in clinical practice to treat ischemic stroke with reported neuroprotective effects; however, the underlying mechanisms are still uncertain.. First, we studied the effect of SAFI on inflammatory responses in LPS-stimulated BV-2 microglia. Then, to discover whether the beneficial in vitro effects of SAFI lead to in vivo therapeutic effects, an MCAO (Middle cerebral artery occlusion) rat model was further employed to elucidate the probable mechanism of SAFI in treating ischemic stroke. Rats in the SAFI group were given SAFI (23 or 46mg/kg) before I/R injury.. The results showed that SAFI treatment significantly decreased neuroinflammation and the infarction volume compared with the vehicle group. Activation of microglia cells was reduced, and TLR4/NF-κB signals, which were markedly inhibited by SAFI treatment in ischemic hemisphere, were accompanied by reduced expression and release of cytokines IL-1β and IL-6.. This study provides evidence that SAFI effectively protects the brain after cerebral ischemia, which may be caused by attenuating inflammation in microglia.

Topics: Alkenes; Animals; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-1beta; Interleukin-6; Male; Microglia; Neuroprotective Agents; NF-kappa B; Polyphenols; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Stroke; Toll-Like Receptor 4

Salvianolic acid A (SAA), one of the major active water-soluble salvianolic acids of traditional Chinese medicine Salvia miltiorrhiza Bunge, has been reported to be effective on anti-myocardial ischemia, anti-oxidation and anti-thrombus. This study aimed to investigate appropriate administration route on dogs with acute myocardial ischemia(AMI). Twenty-four dogs were randomized into four groups (n=6), model, oral administration of SAA (8 mg•kg⁻¹), intravenous administration of SAA (4 mg•kg⁻¹), intravenous administration of Herbesser(0.5 mg•kg⁻¹) as positive drug group. AMI model was established by ligating left anterior descending coronary arteries(LAD) of dogs. Changes of ST segment were determined by epicardial electrocardiogram(ECG), coronary blood flow (CBF) and myocardial oxygen consumption were measured by ultrasonic Doppler flow meter, serum creatine kinase (CK) and lactate dehydrogenase (LDH) were observed by fully automatic biochemical analyser. Myocardial infarct size was assessed by nitro blue tetrazolium (NBT) staining. Both oral and intravenous administration of SAA reduced the myocardial infarct area/left ventricle area significantly [(16.73±6.52)% and (13.19±2.38)%, compared with (24.35±4.89)% in model group, P<0.01). Oral administration of SAA improved the ECG performance of Σ-ST from 30-190 min after ischemia (P<0.05-0.01), while intravenous SAA had a rapid onset (10-190 min after ischemia, P<0.05-0.01). Compared with model group, oral and intravenous SAA both decreased serum CK and LDH significantly (P<0.05-0.01), while the difference of intravenous administration is more significant. SAA protects myocardium in canine experimental myocardial infarction models. Intravenous administration of SAA alleviates myocardial infarction with greater significance than oral route.

Topics: Animals; Caffeic Acids; Coronary Vessels; Disease Models, Animal; Dogs; Drugs, Chinese Herbal; Electrocardiography; Humans; L-Lactate Dehydrogenase; Lactates; Male; Myocardial Infarction; Myocardium; Salvia miltiorrhiza

To establish the beneficial effects of salvianolic acid and fluoxetine on the improvement of cognitive function and amelioration of depression-like symptoms of rats with chronic stress-induced depression.. Ninety-nine male Sprague-Dawley rats were randomly divided into 5 groups--a control group with no stress challenge and 4 chronic stress groups. Rats assigned to chronic stress groups were exposed to stress for 3 weeks, and then were given placebo, fluoxetine (20 mg/kg), salvianolic acid (40 mg/kg), or combined fluoxetine and salvianolic acid. Body weight of each rat was recorded throughout the study. Sucrose preference test and water maze experiment were performed after chronic stress challenge and after drug treatment to assess the effect of drug treatments on depressive-like symptoms and cognitive function. The sucrose preference test was also performed before chronic stress exposure for baseline measurement.. Exposure of rats to chronic stress for 3 weeks significantly reduced body weight and sucrose preference values compared with the no stress control. The water maze experiment showed that chronic stress impaired the spatial learning of rats as well. Treatment of stress-challenged rats with fluoxetine and fluoxetine combined with salvianolic acid resulted in shorter training latency and longer time spent in the target quadrant during the exploration stage of the water maze experiment compared with placebo treatment. Effect of the combined regimen was found more obvious.. Combination therapy of salvianolic acid and fluoxetine could alleviate depression-like symptoms and cognitive deficit induced by chronic stress.

Topics: Alkenes; Animals; Antidepressive Agents, Second-Generation; Chronic Disease; Cognition Disorders; Depressive Disorder; Disease Models, Animal; Drug Therapy, Combination; Fluoxetine; Male; Maze Learning; Polyphenols; Rats; Rats, Sprague-Dawley; Stress, Psychological

Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by compromising the activation of GSK3β and p25/Cdk5, which in turn upregulated β-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SalA blocks inflammatory responses by impairing NF-κB signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SalA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3β/Cdk5 activity to enhance the expression levels of β-catenin/DCX and Bcl-2 for neuroprotection.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; beta Catenin; Blood-Brain Barrier; Brain Ischemia; Brain-Derived Neurotrophic Factor; Caffeic Acids; Cyclin-Dependent Kinase 5; Disease Models, Animal; Doublecortin Domain Proteins; Doublecortin Protein; Drug Administration Schedule; Gene Expression Regulation; Glycogen Synthase Kinase 3 beta; Injections, Intravenous; Lactates; Male; Mice; Mice, Inbred ICR; Microtubule-Associated Proteins; Neurogenesis; Neuropeptides; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Signal Transduction; Stroke; Survival Analysis; Transcription Factor RelA

Carbon monoxide (CO) poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP) occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA) on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct), plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA) levels in red blood cells (RBCs). These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

Topics: Alkenes; Animals; Brain Injuries; Carbon Monoxide; Carbon Monoxide Poisoning; Disease Models, Animal; Erythrocytes; Hematocrit; Hemorheology; Hippocampus; Humans; Malondialdehyde; Mannitol; Neurotoxicity Syndromes; Polyphenols; Rats

The CC chemokine ligand-20 (CCL-20)/macrophage inflammatory protein-3α has been seen as one of the most important chemokines and played a key role in atherogenesis, but the mechanism that underlies the regulation of CCL-20 has not been established clearly yet. The aim of this study was to investigate the influence of salvianolic acid A (SAA) on the expression of CCL-20 in macrophages and ApoE-deficient (ApoE) mice.. The expression of CCL-20 was detected both at protein and messenger RNA levels in RAW264.7 cells. We validated the result in ApoE mice that were intraperitoneally injected with SAA. Phosphorylation of p38 mitogen-activated protein kinase was detected with Western blot, and inhibitor of p38 was used to investigate the mechanism of regulation of CCL-20. Hematoxylin and eosin and Oil-Red-O staining were used to evaluate the atherosclerotic lesions and lipid accumulation in ApoE mice. Immunohistochemical analysis was used to detect the expressions of CCL-20 and CCR6 in the atherosclerotic lesions. Immunofluorescent analysis was used to certify the origination of CCL-20.. Recombinant tumor necrosis factor-α (TNF-α) upregulated CCL-20 production in dose- and time-dependent manners in RAW264.7 cells. The activity of TNF-α-induced CCL-20 production seemed to be significantly suppressed by SAA. Using p38 mitogen-activated protein kinase inhibitor, we found that p38 mediated the effects of TNF-α- and SAA-induced CCL-20 expression changes. In addition, immunohistochemical analysis of aortic root of ApoE mice also demonstrated that the expressions of CCL-20 and CCR6 were both downregulated significantly with SAA treatment. Furthermore, treatment of SAA inhibited the progression of the atherosclerotic plaques and lipid accumulation.. These results demonstrate that TNF-α increased but SAA suppressed CCL-20 production significantly via a novel mechanism.

Topics: Animals; Anti-Inflammatory Agents; Apolipoproteins E; Atherosclerosis; Blotting, Western; Caffeic Acids; Cell Line; Chemokine CCL20; Disease Models, Animal; Dose-Response Relationship, Drug; Lactates; Lipid Metabolism; Macrophages; Mice, Inbred C57BL; Mice, Knockout; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Sinus of Valsalva; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation

Aortic aneurysm (AA) is a life-threatening vascular disease in defect of effective pharmaceutical therapy. Matrix metalloproteinase-9 (MMP-9) is implicated in the development of chronic vascular diseases including aneurysm, but the effective MMP-9 inhibitors are far from development. To develop new candidate for AA therapy, we evaluated the efficiency of salvianolic acid A (SalA), a novel MMP-9 inhibitor, on AA progression in a mouse model and characterized the mechanism of action. SalA is a water soluble compound of the herbal drug Rhizoma Salviae miltiorrhizae (Danshen) which in China is widely used for the treatment of hypertension, coronary artery diseases and myocardial infarction. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. SalA showed selectivity on gelatinase (MMP-2 and MMP-9) than on collagenase (MMP-8 and MMP-13) in vitro, and specificity on MMP-9 than MMP-2 in vivo. Aortic aneurysm was induced by angiotension II (AngII) in apolipoprotein E-deficient (ApoE(-/-)) mice. Aortic structure was evaluated by hematoxylin and eosin, picrosirius red, orein stain. Macrophage infiltration was detected by immunohistochemistry in vivo and transwell in vitro. Comparing with doxycycline (Dox), a well-known MMPs inhibitor, SalA showed similar efficiency against AA progression. SalA significantly decreased aortic diameter and aneurysm severity, ameliorated integrity of vascular structure, inhibited elastin fragmentation and macrophage infiltration. Furthermore, SalA showed greater safety than Dox based on hepatotoxicity evaluation. Our results demonstrated that SalA held great potential for AA therapy.

Topics: Angiotensin II; Animals; Aorta; Aortic Aneurysm; Apolipoproteins E; Caffeic Acids; Cell Line, Tumor; Cell Movement; Cell Survival; Disease Models, Animal; Lactates; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Salvia miltiorrhiza

: This study aimed to investigate the effects of salvianolic acid A (Sal A) on the time course of plasma and tissue dimethylarginine levels after myocardial infarction (MI) induced by left coronary artery ligation. The rats were assigned to 4 groups: Sham, MI, and MI treated with Sal A (1 or 5 mg/kg). The results showed that plasma symmetric dimethylarginine and asymmetric dimethylarginine (ADMA) levels separately reached the peak at the first and second day after MI. Dimethylarginine dimethylaminohydrolase (DDAH) activity in the heart was remarkably inhibited on the initial 2 days. Sal A restored DDAH activity in the heart and decreased the elevated plasma ADMA levels. ADMA concentrations in the heart and liver were significantly increased after MI, which could also be reduced by Sal A. In addition, Sal A showed regulating effects on symmetric dimethylarginine levels in the liver and also in the ischemic zone of heart. In conclusion, the variations of dimethylarginines in plasma and tissues were induced by the inhibition of DDAH activity and their leakage in the infarct zone after MI. Sal A exerted beneficial effects in MI by decreasing plasma and tissue dimethylarginine levels via restoring DDAH activity.

Topics: Amidohydrolases; Animals; Arginine; Caffeic Acids; Chromatography, High Pressure Liquid; Creatinine; Disease Models, Animal; Heart Ventricles; Kidney; Lactates; Liver; Male; Myocardial Infarction; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Salvia miltiorrhiza and Panax notoginseng are popularly used traditional Chinese medicine for cardiovascular disorders and they are often used in the form of combination. However, mechanisms of their cardioprotective effects were still not clear. In the present study, the protective effects of salvianolic acids (SA), notoginsengnosides (NG) and combination of SA and NG (CSN) against rat cardiac ischemia-reperfusion injury were checked and the protein expression profiles of heart tissues were examined to search their possible protein targets.. The cardioprotective effects of SA, NG and CSN were checked in a rat model of ischemia-reperfusion (IR) by temporarily occluding coronary artery for 20 min followed by reperfusion. Rats were grouped into sham-operation group, IR group, IR+SA group, IR+NG group and IR+CSN group. The plasma creatine kinase (CK) activities were measured using commercial kit and the percentages of infarcted area in total ventricle tissue were calculated after nitroblue-tetrazolium (N-BT) staining of heart tissue slices. Two-dimensional protein electrophoresis (2-DE) was used to check the protein expression profiles of heart tissues. Then, proteins differentially expressed between IR group and sham-operation group were identified using matrix assisted laser desorption ionization-time of flight-mass spectrometry/mass spectrometry (MALDI-TOF MS/MS). The regulative effects of SA, NG and CSN on these IR-related proteins were analyzed.. Treatments including SA, NG and CSN all showed cardioprotective effects against ischemia-reperfusion injury and CSN exhibited to be the best. Eighteen proteins involved in IR injury were found. These proteins are involved in pathways including energy metabolism, lipid metabolism, muscle contraction, heat shock stress, cell survival and proliferation. The regulation of these proteins by SA, NG or CSN suggested possible protein targets in their cardioprotective effects.. SA and NG showed both similarity and difference in their protein targets involved in cardioprotective effects. The capability of CSN to regulate both protein targets of SA and NG might be the basis of CSN to show cardioprotective effects better than that of SA or NG.

Topics: Alkenes; Animals; Creatine Kinase; Disease Models, Animal; Drugs, Chinese Herbal; Electrophoresis, Gel, Two-Dimensional; Male; Medicine, Chinese Traditional; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Panax notoginseng; Plants, Medicinal; Polyphenols; Proteomics; Rats; Rats, Wistar; Salvia miltiorrhiza; Saponins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors

Salvianolic acid (SAL) and tanshinone (TAN) are major hydrophilic and lipophilic compounds, respectively, from one herbal medicine, Danshen, which has been widely and successfully used for treating cardiovascular diseases in Asian countries. Because few studies have reported different molecular mechanisms between the different compounds in same herb, we investigate if separate molecular pathways are involved in cardioprotective effect by different active components of Danshen.. We used an acute myocardial infarction (MI) model to compare the cardioprotective effects of SAL and TAN in rats. Both infarct size and echocardiographic response were evaluated at 3, 7, 14 and 28 days after surgery. Genes involved in ischemic injury and in responses to SAL or TAN treatment in ischemic hearts were identified by microarray analysis and verified by quantitative real-time RT-PCR.. Results showed that both SAL and TAN delay the development of ischemia by decreasing infarct size and improving systolic function post MI. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated different kinetics and gene expression profiles by SAL and TAN. SAL acts in a later period after ischemia, and its effect is probably mediated by downregulation of genes involved in oxidative stress, certain G-protein coupled receptor activities and apoptosis. On the other hand, TAN acts relatively early after ischemic injury and its effect is at least in part mediated by inhibition of intracellular calcium, cell adhesion and alternative complement pathway. Strikingly, we found that TAN, a recently identified member of selective estrogen receptor modifier (SERM), indeed regulates genes known to be involved in estrogen metabolism post MI.. Although both SAL and TAN contribute to the cardioprotective effect of Danshen, there are significant mechanistic and temporal differences between the two: TAN acts at an early stage after ischemic injury mainly by inhibition of intracellular calcium and cell adhesion pathways whereas SAL acts mainly by down-regulating apoptosis.

Topics: Abietanes; Animals; Apoptosis; Caffeic Acids; Calcium; Cardiovascular Agents; Cell Adhesion; Complement Pathway, Alternative; Disease Models, Animal; Drugs, Chinese Herbal; Estrogens; Gene Expression Regulation; Heart; Lactates; Male; Microarray Analysis; Myocardial Infarction; Oxidative Stress; Phenanthrolines; Phytotherapy; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Salvia miltiorrhiza; Selective Estrogen Receptor Modulators; Signal Transduction; Systole

Excitatory amino acid toxicity, oxidative stress, intracellular calcium overload, as well as inflammation and apoptosis are involved in the pathological process after cerebral ischemic reperfusion injury. Picrodide 2 could inhibit neuronal apoptosis and play anti-oxidant and anti-inflammation role in cerebral ischemia/reperfusion injuries, but the exact mechanism is not very clear. This study aims to explore the anti-inflammation mechanism of picroside 2 in cerebral ischemic reperfusion injury in rats.. The middle cerebral artery occlusion reperfusion models were established with intraluminal thread methods in 90 adult healthy female Wistar rats. Picroside 2 and salvianic acid A sodium were respectively injected from tail vein at the dosage of 10 mg/kg for treatment. The neurobehavioral function was evaluated with Bederson's test and the cerebral infarction volume was observed with tetrazolium chloride (TTC) staining. The apoptotic cells were counted by in situ terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The immunohistochemistry stain was used to determine the expressions of toll-like receptor 4 (TLR4), nuclear transcription factor kappaB (NFkappaB) and tumor necrosis factor alpha (TNFalpha). The concentrations of TLR4, NFkappaB and TNFalpha in brain tissue were determined by enzyme linked immunosorbent assay (ELISA).. After cerebral ischemic reperfusion, the rats showed neurobehavioral function deficit and cerebral infarction in the ischemic hemisphere. The number of apoptotic cells, the expressions and the concentrations in brain tissue of TLR4, NFkappaB and TNFalpha in ischemia control group increased significantly than those in the sham operative group (P < 0.01). Compared with the ischemia control group, the neurobehavioral scores, the infarction volumes, the apoptotic cells, the expressions and concentrations in brain tissue of TLR4, NFkappaB and TNFalpha were obviously decreased both in the picroside 2 and salvianic acid A sodium groups (P < 0.01). There was no statistical difference between the two treatment groups in above indexes (P > 0.05).. Picroside 2 could down-regulate the expressions of TLR4, NFkappaB and TNFalpha to inhibit apoptosis and inflammation induced by cerebral ischemic reperfusion injury and improve the neurobehavioral function of rats.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Brain; Brain Ischemia; Caffeic Acids; Cinnamates; Disease Models, Animal; Encephalitis; Female; Glucosides; Infarction, Middle Cerebral Artery; Iridoid Glucosides; Lactates; Neuropsychological Tests; NF-kappa B; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury; Toll-Like Receptor 4; Treatment Outcome; Tumor Necrosis Factor-alpha

Oxidative stress induced by overproduction of reactive oxygen species (ROS) plays an important role in hypoxia/reoxygenation (H/R) injury. In the present study, effects of salvianolic acid A (1) on heart H/R injury through its antioxidant activity were examined, using a molecule-based ROS scavenging system and cardiomyocyte model of H/R injury, as well as isolated rat heart model. As a result, 1 showed a potent antioxidant activity, scavenging all of the tested ROS and DPPH (2,2-diphenyl-1-picrylhydrazyl). The antioxidant effect of 1 was also observed in cardiomyocytes exposed to H/R. Compound 1 remarkably decreased dihydroethidium and dichlorofluorescein fluorescence and increased cell viability and mitochondrial membrane potential, ΔΨ(m), when compared to the H/R group. In isolated rat hearts exposed to H/R, 1 markedly increased the coronary flow, the peak of pressure development and the valley of pressure development, and significantly reduced the left ventricular end diastolic pressure when compared to the H/R group. These results suggested that 1 had significant protective effects against H/R-induced myocardial injury through its antioxidant activity.

Topics: Animals; Biphenyl Compounds; Caffeic Acids; Cardiotonic Agents; Disease Models, Animal; Heart; Hypoxia; Lactates; Molecular Structure; Myocytes, Cardiac; Oxidative Stress; Picrates; Rats; Reactive Oxygen Species

The present study was to investigate the protective effects of salvianolic acids (SA) on deformability of red blood cells (RBCs) and its mechanism during the development of acute lung injury (ALI) induced by oleic acid (OA) in rabbits. 32 rabbits were randomized into four groups, normal control group, OA-treated group (0.15 ml/kg), SA-treated group and OA+SA treated group. The blood samples were collected at 0, 10, 30, 60, 90, 120 and 180 min after OA injection. The RBC deformation index, Orientation index and small deformation index were measured by ektacytometry. The concentration of malondialdehyde (MDA) in RBCs was detected by the assay kit. Meanwhile, the pulmonary pathological examination and the blood gas analysis were also performed. The results showed that the deformation index, orientation index and small deformation index decreased during the early phase of ALI, while the concentration of MDA in RBCs increased during the course. Pre-treatment with SA increased the deformability and orientability of RBC significantly and decreased the concentration of MDA in RBCs compared with OA group. Meanwhile, the hypoxia and pulmonary pathological damage were much improved. These results suggest that there were erythrocyte deformability changes in the early phase of ALI. SA has the protective effects on erythrocyte deformability during the development of ALI induced by OA, which might be due to its antioxidant effect. These results are valid in rabbits and in a model of ARDS, it would be interesting to see the effects of SA in patients.

Topics: Acute Disease; Animals; Benzofurans; Blood Gas Analysis; Caffeic Acids; Disease Models, Animal; Erythrocyte Deformability; Lactates; Lung Injury; Male; Oleic Acid; Rabbits; Respiratory Distress Syndrome; Time Factors

Salvianolic acid A, a depside from the roots of Salvia miltiorrhiza, inhibited pig gastric H+,K(+)-ATPase and pNPPase with 50% inhibition values (IC50) of 5.2 x 10(-7) M and 1.7 x 10(-6) M, respectively. Kinetic studies revealed that the inhibition patterns induced by salvianolic acid A were competitive with respect to ATP and noncompetitive with respect to K+. Salvianolic acid A (25 mg/kg, i.p.) significantly inhibited acid secretion in pylorus-ligated rats. At the same dose it also showed a significant reduction in the formation of gastric lesion induced by water immersion and restraint stress. These results suggest that salvianolic acid A shows antisecretory and antiulcer activity by inhibiting the gastric H+,K(+)-ATPase.

Topics: Adenosine Triphosphatases; Animals; Anti-Ulcer Agents; Caffeic Acids; Depsides; Disease Models, Animal; Drugs, Chinese Herbal; Gastric Acid; Gastric Mucosa; H(+)-K(+)-Exchanging ATPase; Hydroxybenzoates; In Vitro Techniques; Kinetics; Lactates; Male; Molecular Structure; Rats; Rats, Inbred Strains; Stomach Ulcer; Swine