Salvianic Acid A Research Articles

Enhanced Brain Targeting Delivery of Salvianic Acid Using Borneol as a Promoter of Blood/Brain Transport and Regulator of P-gp.

Borneol can enhance the blood-brain barrier (BBB) permeability of some drugs and suppress the efflux transport of P-glycoprotein (P-gp), which will contribute to the brain delivery of salvianic acid A (SAA). The study aimed to develop an approach to improve the brain targeting delivery of SAA with the aid of borneol. "Borneol" was involved in SAA via esterified prodrug SAA borneol ester (SBE) and combined administration (SAA-borneol, SAA-B). Subsequently, the blood-brain transport of SAA through brain/blood distribution and P-gp regulation via expression and function assay were investigated in rats. The SBE and SAA-B-treated group received a three-fold brain concentration and longer t1/2 and retention period of active SAA than that of SAA alone (20.18/13.82 min vs. 6.48 min; 18.30/17.42 min vs. 11.46 min). In addition, blood to brain transport of active SAA in SBE was altered in comparison to that of SAA-B, ultimately resulting in a better drug targeting index (9.93 vs. 3.63). Further studies revealed that SBE-induced downregulation of P-gp expression occurred at the later stage of administration (60 min, P < 0.01), but SBE always showed a more powerful drug transport activity across BBB represented by Kp value of rhodamine 123 than SAA-B (30, 60 min, P < 0.05). The comparative results indicate that SBE exhibits prominent efficiency on SAA's targeting delivery through improved blood/brain metabolic properties and sustained inhibitory effect of "borneol" on P-gp efflux. Therefore, prodrug modification can be applied as a more effective approach for brain delivery of SAA.

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

Potential Beneficial Effects of Salvianic Acid A and Salvianolic Acid B in Skin Whitening

Objective Natural product-derived biomaterials are highly desired as possible ingredients in cosmetics, as they are often safe and effective. Salvianic acid A (SAA) and salvianolic acid B (SAB) are the primary water-soluble ingredients of Salvia miltiorrhiza Bunge ( Lamiaceae). These compounds have extensive applications as both effective and biocompatible bioactive agents for the treatment of various diseases including cardiovascular disorders, liver ailments, and neuroprotection. This study aimed to evaluate the skin-whitening effects of SAA and SAB on co-cultured human melanoma A375 cells and human keratinocytes HaCaT cells, with the intention of investigating their potential as cosmetic ingredients. Methods First, we assessed the SAA and SAB's efficacy on cells proliferation using MTT assay, as well as their inhibition on intracellular tyrosinase (TYR) activity. Next, we evaluated their effects on the mRNA expression levels of TYR and its related proteins. Furthermore, the whitening efficacy of SAA and SAB was assessed by observing the decrease in melanin content in treated human amalignant melanoma A375 and human keratinocyte HaCaT cells. Results Both SAA and SAB inhibited the activity of TYR and decreased the mRNA expression of TYR-related proteins, thereby inhibiting melanin synthesis. Conclusion Our results suggest that both SAA and SAB can be applied as natural and novel cosmetics materials having a whitening function, which could be beneficial in the cosmeceutical industry.

ROS-Responsive Prodrug Micelle Co-Delivery System for Synergistic Antiatherosclerotic Therapy.

Tanshinone IIA (TS-IIA) and salvianic acid A (SAA) are the main pharmacological active constituents of Danshen, which exhibit potent effects on atherosclerosis. A combination of TS-IIA and SAA might exert a synergistic antiatherosclerotic effect. However, the opposite solubility profiles of TS-IIA and SAA might lead to difficulty in achieving a synergistic combined effect of the two active components. Therefore, in this work, we fabricated a ROS-responsive prodrug micelle for the codelivery of TS-IIA and SAA (TS-IIA-PM) by self-assembling amphiphilic block copolymer PEG5000-SAA/PLA10000-APBA. The amphiphilic polymer was characterized by 1H NMR, FTIR, and alizarin red S competition tests. The ROS responsiveness of TS-IIA-PM was evidenced by time-course monitoring of particle size and morphology changes and drug release behavior in the presence of 1 mM H2O2. We found TS-IIA-PM was stable according to its critical micelle concentration and the unchanged particle sizes in 10% FBS for 7 days. The results of in vitro and in vivo tests revealed that TS-IIA-PM was safe and biocompatible. Furthermore, it was observed that TS-IIA and prodrug micelle could produce synergistic antiatherosclerotic effect based on the results of the antioxidant study, which was further confirmed by a series of pharmocodynamics studies, such as in vitro DiI-oxLDL uptake study, oil red O staining, cholesterol efflux study, inflammatory cytokine analysis, in vivo CD68 immunostaining, and lipid disposition staining studies. Collectively, TS-IIA-PM holds great potential for the safe and efficient codelivery of TS-IIA and SAA for synergistic antiatherosclerosis.

Protective benefits of salvianic acid A against retinal iron overload by inhibition of ferroptosis

BackgroundBoth the accumulation of reactive oxygen species (ROS) and iron overload are significant variables that enhance the incidence of photoreceptor cell death and retinal degeneration. The discovery of ferroptosis, which is characterized by iron-dependent lipid peroxidation, has led to a new perspective on how retinal degeneration develops. As a natural phenolic acid, salvianic acid A (SAA) from Salvia miltiorrhiza has promise in treating eye diseases. The purpose of this research was to learn more about SAA and its function in the development of iron-overload-induced retinal degeneration. MethodsModels of iron overload in Kunming mice and the murine photoreceptor cell line 661 W were established, then the protective and antiferroptotic properties of SAA were assessed in vivo and in vitro. ResultsBiochemical and histopathological findings on the retina confirmed that SAA successfully alleviated retinal injury. In photoreceptor cells, iron overload caused cell death, mitochondrial dysfunction, ROS generation, and iron deposition. Salvianic acid A relieved lipid peroxidation and decreased iron accumulation by modulating Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, solute carrier family 7 member 11, and iron-metabolism-related proteins. The mitochondrial morphology suggests that the retinal protective effect of SAA is mediated via antiferroptotic action. ConclusionFerroptosis plays an important role in the pathogenesis of iron-overload-induced retinal degeneration. New roles of SAA in ferroptosis prevention via iron deposit inhibition, lipid peroxidation inhibition, and mitochondrial dysfunction reduction, were identified.

Efficient production of salvianic acid A from l-dihydroxyphenylalanine through a tri-enzyme cascade

Salvianic acid A (SAA), used for treating cardiovascular and cerebrovascular diseases, possesses several pharmacological properties. However, the current methods for the enzymatic synthesis of SAA show low efficiency. Here, we constructed a three-enzyme cascade pathway in Escherichia coli BL21 (DE3) to produce SAA from l-dihydroxyphenylalanine (L-DOPA). The phenylpyruvate reductase (LaPPR) from Lactobacillus sp. CGMCC 9967 is a rate-limiting enzyme in this process. Therefore, we employed a mechanism-guided protein engineering strategy to shorten the transfer distances of protons and hydrides, generating an optimal LaPPR mutant, LaPPRMu2 (H89M/H143D/P256C), with a 2.8-fold increase in specific activity and 9.3-time increase in kcat/Km value compared to that of the wild type. Introduction of the mutant LaPPRMu2 into the cascade pathway and the optimization of enzyme levels and transformation conditions allowed the obtainment of the highest SAA titer (82.6 g L−1) ever reported in vivo, good conversion rate (91.3%), excellent ee value (99%) and the highest productivity (6.9 g L−1 h−1) from 90 g L−1 L-DOPA in 12 h. This successful strategy provides a potential new method for the industrial production of SAA.Graphical

Production of Salvianic Acid A from l-DOPA via Biocatalytic Cascade Reactions.

Salvianic acid A (SAA), as the main bioactive component of the traditional Chinese herb Salvia miltiorrhiza, has important application value in the treatment of cardiovascular diseases. In this study, a two-step bioprocess for the preparation of SAA from l-DOPA was developed. In the first step, l-DOPA was transformed to 3,4-dihydroxyphenylalanine (DHPPA) using engineered Escherichia coli cells expressing membrane-bound L-amino acid deaminase from Proteus vulgaris. After that, the unpurified DHPPA was directly converted into SAA by permeabilized recombinant E. coli cells co-expressing d-lactate dehydrogenase from Pediococcus acidilactici and formate dehydrogenase from Mycobacterium vaccae N10. Under optimized conditions, 48.3 mM of SAA could be prepared from 50 mM of l-DOPA, with a yield of 96.6%. Therefore, the bioprocess developed here was not only environmentally friendly, but also exhibited excellent production efficiency and, thus, is promising for industrial SAA production.

A green and highly efficient method to deliver hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius for enhanced anti-atherosclerotic effect via metal-phenolic network

Salvia miltiorrhiza and Carthamus tinctorius are traditional Chinese medicines that have been widely used for the treatment of cardiovascular disease. Salvianic acid A (SAA), salvianic acid B (SAB), protocatechuic aldehyde (PCA) and hydroxysafflor yellow A (HSYA) are the major hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius, all of which have been documented as active compounds for the prevention and treatment of atherosclerosis (AS). However, high aqueous solubility, low permeability and poor stability properties of the four hydrophilic polyphenols might influence their bioavailability and thus hinder their clinical potential. In this work, we introduced a green and highly efficient method for the efficient delivery of the four hydrophilic components via metal-phenolic network. The four coordination polymers of SAA, SAB, PCA and HSYA were successfully fabricated, and confirmed by UV–vis, FTIR, XPS, ICP-MS and dynamic light scattering analysis. We found all of them displayed potent antioxidant activity, good biocompatibility and stability. Impressively, the four coordination polymers showed remarkably enhanced anti-atherosclerotic effect compared with free drugs. Collectively, metal-phenolic network-based coordination polymer might show great potential for safe and efficient delivery of the hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius for anti-atherosclerotic therapy.

Highly sensitive detection of salvianic acid a drug by a novel electrochemical sensor based on HKUST-1 loaded on three-dimensional graphene-MWCNT composite

HKUST-1, a kind of metal-organic framework (MOF) composed by Cu2+ and trimesic acid, loaded on reduced graphene oxide and multi-walled carbon nanotubes nanocomposite [HKUST-1 @ (RGO-MWCNT)] was successfully synthesized by a facile and simple route. Then, a highly sensitive non-enzymatic salvianic acid A (SAA) electrochemical sensor was fabricated by modifying HKUST-1 @ (RGO-MWCNT) on a glassy carbon electrode, taking full advantage of the synergistic effect between the redox catalytic capacity of Cu2+ and the electrical conductivity of carbon materials. The sensor showed a low limit of detection of 0.081 μM, limit of quantitation of 0.27 μM, high sensitivity of 509.6 μA/mM and a good relationship between reduction peak current and concentration of SAA from 2 to 4600 μM. Meanwhile, the sensor had the advantages of repeatability and stability. Finally, it was used to detect SAA in real samples with noteworthy electroanalytical performance. In short, the sensor has considerable potential for the electroanalysis of SAA. Moreover, the study provides a promising composite of MOF and carbon materials with potential application in the analysis of effective components of herbaceous medicinal plants.

Ameliorative effects and mechanisms of salvianic acid A on retinal iron overload in vivo and in vitro

Excessive iron can be accumulated in the retina and lead to retinal iron overload. Salvianic acid A (SAA) has a variety of pharmacologic effects, but there is only a limited understanding of its benefits for retinal iron overload. The aim of this study was to examine the protective effects and latent mechanisms of SAA on retinal iron overload. SAA reduced iron in the serum and retina, attenuated pathophysiological changes, and reduced retinal iron deposition in the retinas of iron-overloaded mice. It also reduced intracellular iron in ARPE-19 cells by regulating iron-handling proteins and chelating with iron. It also significantly inhibited cellular oxidative and inflammatory damage by increasing the nuclear translocation of nuclear erythroid 2-related factor 2 (Nrf2) while decreasing nuclear factor-kappa B (NF-κB), protecting the ARPE-19 cells from apoptosis by suppressing the Bax/Bcl-2 ratio, cytochrome c release, caspase activation, and poly ADP-ribose polymerase cleavage. The ability of SAA to inhibit apoptosis, increase nuclear Nrf2 expression, and decrease nuclear NF-κB expression was further confirmed in the retinas of iron-overloaded mice. This study demonstrates that SAA shows significant protective effects against retinal iron overload; its mechanisms might be associated with iron chelation; regulation of iron-handling proteins; and inhibition of oxidative stress, inflammation and apoptosis.

Salvianic Acid A Regulates High-Glucose-Treated Endothelial Progenitor Cell Dysfunction via the AKT/Endothelial Nitric Oxide Synthase (eNOS) Pathway.

BackgroundThe primary cause of death in patients with diabetes mellitus (DM) is diabetic macroangiopathy, a complication that related to the function and number of endothelial progenitor cells (EPCs). Salvianic acid A (SAA) is a water-soluble active ingredient of Salvia miltiorrhiza, a traditional Chinese medicine used to treat cardiovascular diseases. The purpose of this study was to explore the effects of SAA on the function of rat EPCs cultured in vitro in a high-glucose environment.Material/MethodsBone marrow-derived EPCs from 40 Sprague-Dawley rats were identified by fluorescence staining. Cell viability, apoptosis, tube formation, lactated dehydrogenase (LDH) release, and nitric oxide (NO) production were detected by 3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium bromide assay, flow cytometry, tube formation, LDH, and 3-amino,4-aminomethyl-2′,7′-difluorescein, and diacetate assays, respectively. The expression levels of proteins were examined by western blotting.ResultsCultured EPCs showed a cobblestone morphology and positive expression of Dil-ac-LDL and FITC-UEA-1. High glucose impaired cell viability. Different concentrations of SAA had no significant effect on EPC viability. SAA reduced the apoptosis rate and LDH release, but promoted tube formation, viability, and NO production in high-glucose-treated EPCs. The ratios of p-AKT/AKT and p-eNOS/eNOS in high-glucose-treated EPCs were elevated by SAA. Phosphoinositide 3-kinase inhibitor LY294002 blocked the rescue effects of SAA on high-glucose-treated EPCs.ConclusionsSAA protected EPCs against high-glucose-induced dysfunction via the AKT/eNOS pathway.

The enhanced protective effects of salvianic acid A: A functionalized nanoparticles against ischemic stroke through increasing the permeability of the blood-brain barrier

Ischemic stroke is the leading cause of disability and death worldwide. Currently, the only proven treatment for ischemic stroke is restoring the cerebral blood supply. In addition, some of the tissue is damaged during the subsequent reperfusion because of the overproduction of reactive oxygen species (ROS). Furthermore, antioxidant therapies have shown promise in preclinical studies for the treatment of ischemia-reperfusion injury. However, their therapeutic efficacy has been limited because of their low bioavailability in brain. To resolve this issue, we synthesized ROS-responsive, fan-shaped dendrimer nanoparticles (NPs) and conjugated them with a blood-brain barrier (BBB)-targeting peptide, COG1410, and salvianic acid A (SA), which is an effective antioxidant in ischemic stroke. The BBB targeting peptide acts as a ligand of the nanocarrier system and penetrates the BBB through the endocytosis of the ligand receptor. The results showed that T-SA-NPs not only target and accumulate in the infarct area, they also reduce over 2 times of the infarct area and reverse the behavioral deficits in MCAO mice, which illustrates that these NPs have an effective therapeutic effect on the ischemic stroke. In addition, these NPs had no toxicity in any organs of the body. Importantly, the present study provides an alternative strategy for delivering antioxidants to the brain and achieving targeted therapy of ischemic stroke.

Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down-regulating BRD4.

Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol‐induced liver injury and ameliorated ethanol‐induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol‐induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol‐induced HMGB1 release and inflammatory cytokine production in AML‐12 cells. Similarly, alcohol‐induced pro‐inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.

Potential mechanisms underlying the protective effects of salvianic acid A against atherosclerosis in vivo and vitro

Salvianic acid A (SAA) is an active water-soluble constituent derived from Salvia miltiorrhiza Bge that is used extensively in the treatment of angiocardiopathy in China. However, few reports have investigated the therapeutic effect and the underlying mechanisms of SAA on atherosclerosis (AS). This study examines the protective mechanisms of SAA on AS in vivo and in vitro. SAA treatment (3 and 10 mg/kg/d) prevented the progression of atherosclerotic lesions and decreased 58.2% and 72.8% of the lipid deposition in the aorta of high fat-diet-induced AS rat. Notably, SAA treatment ameliorated serum lipid abnormalities by decreasing 20.4% and 33.8% of triglyceride, 26.1% and 32.7% of total cholesterol, 36.0% and 57.3% of low-density lipoprotein-cholesterol levels and increasing 183.4% and 337.5% of high-density lipoprotein-cholesterol level in the serum of AS rat (all P < 0.05). SAA treatment lowered pro-inflammatory mediators including interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (all P < 0.05) by inhibiting the toll-like receptor 4/nuclear factor kappa B pathway. In addition, SAA treatment significantly decreased oxidative stress by increasing antioxidant enzymes activity, upregulating nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway and downregulated expression of p47phox and p22phox (all P < 0.05) in vivo. Furthermore, SAA (10−5 and 3 × 10−5 M) suppressed oxidized low-density lipoprotein-induced expression of lectin-like oxidized low-density lipoprotein receptor-1, the phosphorylation of nuclear factor kappa B (p65), ICAM-1 and VCAM-1 (all P < 0.05) and inhibited NADPH oxidase subunit 4-mediated reactive oxygen species generation in human umbilical vein endothelial cells. The experimental data verify the protective role of SAA in AS and the underlying mechanisms are strongly associated with the inhibition of oxidative stress, inflammation, and amelioration of endothelial dysfunction.

Copper (II)-ploy-L-histidine functionalized multi walled carbon nanotubes as efficient mimetic enzyme for sensitive electrochemical detection of salvianic acid A

In this work, carboxylated multi walled carbon nanotubes (CMWCNTs) were firstly prepared and functionalized with poly-L-histidine (PLH), which were then chelated with copper (II) ions to from the nanocomposites of Cu(II)-PLH-CMWCNTs. The nanocomposites could be exploited as an efficient mimic enzyme for sensitive electrochemical detection of salvianic acid A (SAA). Cu(II)-PLH-CMWCNTs owned good charge transfer property and excellent synergetic catalytic effect between the overoxidized imidazole groups and the copper redox-active units. Therefore, highly sensitive electrochemical response to SAA was achieved under optimum experimental conditions. A good linear relationship between differential pulse voltammetry (DPV) peak current and the SAA concentration was established in the range of 0.4–1000 μM. A low detection limit of 0.037 μM and a sensitivity of 0.27 μA μM−1 cm−2 were achieved. The developed biosensor also had advantages of good repeatability, stability and high selectivity, thus, it was successfully applied to the determination of SAA in real samples with satisfactory results, which may have great potential for further exploitation of electroanalysis applications.

Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice

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.

Cardiovascular Protective Effects of Salvianic Acid A on db/db Mice with Elevated Homocysteine Level.

The onsets of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in diabetics, especially in those with elevated homocysteine (Hcy), precede the development of cardiovascular (CV) events. Salvianic acid A (SAA) is a renowned Traditional Chinese Medicine (TCM) that has been applied in the treatment of cardiovascular disease for many decades. In this study, we aimed (1) to investigate the CV protective effects of SAA on ameliorating LVH and ED in db/db mice with elevated blood Hcy level and (2) to decipher whether the observed CV protective effects of SAA are associated with Hcy metabolism by modulating the methylation potential and redox status in the liver of the db/db mice with elevated blood Hcy level. Our results found that the administration of SAA could significantly slow down the build-up of left ventricular mass and ameliorate ED. Immunological assay analysis on the mouse liver tissue also indicated that SAA treatment on db/db mice with elevated Hcy was associated with reduced methylation potential but improved redox status. In conclusion, we revealed that SAA has the potential to protect against the hyperglycemia- and hyperhomocysteinemia-induced oxidative stress on diabetic mice via modulation in Hcy metabolism.

Salvianic acid A protects L-02 cells against γ-irradiation-induced apoptosis via the scavenging of reactive oxygen species

Salvianic acid A (SAA) is the main hydrophilic active ingredient of Salvia miltiorrhiza bunge, which has long been used to treat liver and heart disease in China. In the present study, we investigated the radioprotective effects of SAA against γ-radiation-induced apoptosis in cultured human embryo liver L-02 cells. The results demonstrated that SAA markedly inhibited γ-radiation induced apoptosis, decreased DNA damage, and increased the intracellular antioxidative ability of the L-02 cells. SAA exhibited radioprotection by decreasing the generation of reactive oxygen species, inhibiting the release of mitochondrial cytochrome C, blocking the activation of caspase-3, and down regulating the expression of Bax and P53 and up regulating the expression of Bcl-2. This indicated that SAA pretreatment inhibited the caspase-dependent mitochondria apoptosis pathway. The radioprotection of the SAA pretreatment was also evidenced by an increased survival ratio, maintaining the antioxidant enzyme levels in the liver, inhibition of oxidative stress, and relative low liver and renal toxicity compared with estriol exposure. In conclusion, SAA may be an effective radioprotector against γ-radiation induced apoptosis in L-02 cells and damage in mice, the antioxidant potency of SAA might be correlated with the beneficial radioprotectant effects observed.

Salvianic acid A inhibits lipopolysaccharide-induced apoptosis through regulating glutathione peroxidase activity and malondialdehyde level in vascular endothelial cells

Aim To find out the role of salvianic acid A (SAA) in the protection of vascular endothelial cells (VEC) and its possible mechanism in vitro. Methods The ingredient at various concentrations was added to human umbilical vein endothelial cells (HUVEC) treated with 0.5 μmol·L −1 lipopolysaccharide (LPS) for 24 h. Apoptotic morphological changes of cells were observed under inverted phase contrast microscope; the cell viability was quantified using MTT assay. Nuclear fragmentation of cells was observed under laser scanning confocal microcope after being stained with acridinorange. Cell cycle distribution was detected by flow-cytometry after being stained with propidium iodide (PI). The activities of glutathione peroxidase (GPH-PX) as well as maleic dialdehyde (MDA) level in cells were measured by spectrophotometric methods as described in the assay kits. Results Apoptotic morphological changes and the decrease of cell viability of these cells were obviously inhibited by SAA in a dose-dependent manner. Furthermore, the abnormal cell cycle distribution, the decrease of GSH-Px activity and the increase of MDA level induced by LPS were markedly reversed. Conclusion SAA exerts protective effect on VEC induced by LPS via an antioxidative mechanism.

Salvianic acid A protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity

1-methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Salvianic acid A (SA), isolated from the Chinese herbal medicine Salvia miltiorrhiza, is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the protective effects of SA on MPP(+)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Treatment of SH-SY5Y cells with MPP(+) caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, the increase in Bax/Bcl-2 ratio, and the activation of caspase-3. MPP(+) induced mitochondria dysfunction characterized by mitochondrial membrane potential loss and cytochrome c release. These phenotypes induced by MPP(+) were reversed by SA. Our results suggested that the protective effects of SA on MPP(+)-induced cytotoxicity may be ascribed to its antioxidative properties and anti-apoptotic activity via regulating the expression of Bcl-2 and Bax. These data indicated that SA might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.