Determination of Salvianolic Acid B in Yiqi Huayu Prescription by HPLC

[Objectives]To determine the content of salvianolic acid B in Yiqi Huayu Prescription by HPLC.[Methods]The chromatographic column was ZORBAX Eclipse Plus C 18(4.6 nm×250 nm,5μm);the mobile phase was acetonitrile-0.1%phosphoric acid(21:79),the detection wavelength was 286 nm,the column temperature was 30℃,and the flow rate was 1.0 mL/min.A method for determination of salvianolic acid B in Yiqi Huayu Prescription was established.[Results]The linear relationship of salvianolic acid B was good in the range of 0.0214-0.4064 mg/mL.The regression equation was Y=5995.98984 X-0.07332,r=0.9999.The average recovery rate was 98.88%(RSD=1.6%).[Conclusions]The method is reliable,accurate and specific,and can be used for the determination of salvianolic acid B in Yiqi Huayu Prescription.

Effect of salvianolic acid B-loaded mesoporous silica nanoparticles on myocardial ischemia-reperfusion injury

Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical application is limited by its low oral bioavailability and poor intestinal absorption.The exploration of its preparation and clinical applications has become a research hotspot in recent years.Methods:To determine whether mesoporous silica nanoparticles(MSNs)efficiently delivered SalB to the heart and SalB@MSNs-RhB reduced myocardial ischemia-reperfusion injury,we constructed a myocardial ischemia-reperfusion male rat model,hypoxia/reoxygenation cardiomyocytes,and treated them with SalB@MSNs-RhB.Results:SalB@MSNs-RhB showed improved bioavailability,therapeutic effect,heightened JAK2/STAT3-dependent pro-survival signaling,and antioxidant responses,thereby protecting cardiomyocytes from ischemia-reperfusion injury-induced oxidative stress and apoptosis.Conclusion:This use of SalB-loaded nanoparticles and investigation of their mechanism of action may provide a new strategy for treating cardiomyocytes.Thus,hypoxia/reoxygenation promotes the clinical application of SalB.

Effect and mechanism of salvianolic acid B on the myocardial ischemiareperfusion injury in rats

Objective:To investigate the effect of salvianolic acid B on rats with myocardial ischemiareperfusion injury.Methods:SD rats were randomly divided into five groups(n=10 in each group):A sham operation group,B ischemic reperfusion group model group,C low dose salvianolic acid B group,D median dose salvianolic acid B group,E high dose salvianolic acid B group.One hour after establishment of the myocardial ischemia-reperfusion model,the concentration and the apoptotic index of the plasma level of myocardial enzymes(CTnⅠ,CKMB),SOD,MDA,NO,ET were,measured.Heart tissues were obtained and micro-structural changes were observed.Results:Compared the model group,the plasma CTnⅠ,CK-MB,MDA and ET contents were significantly increased,NO,T-SOD contents were decreased in the treatment group(group C,D,and E)(P<0.05);compared with group E,the plasma CTnⅠ,CKMB,MDA and ET levels were increased,the NO,T-SOD levels were decreased in groups C and D(P<0.05).Infarct size was significantly reduced,and the myocardial ultrastructural changes were improved significantly in treatment group.Conclusions:Salvianolic acid B has a significant protective effect on myocardial ischemia-reperfusion injury.It can alleviate oxidative stress,reduce calcium overload,improve endothelial function and so on.

Effects of salvianolic acid B on liver mitochondria of rats with nonalcoholic steatohepatitis

AIM: To investigate the effects of salvianolic acid B(Sal B) on the morphological characteristics and functions of liver mitochondria of rats with nonalcoholic steatohepatitis(NASH).METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into three groups:(1) a normal group fed a normal diet;(2) an NASH model group; and(3) a Sal B-treated group fed a high-fat diet. Two rats from each group were executed at the end of the 12 th week to detect pathological changes. The rats in the Sal B-treated group were gavaged with 20 m L/kg Sal B(1 mg/m L) daily. The model group received an equal volume of distilled water as a control. At the end of the 24 th weekend, the remaining rats were executed. Serum biochemical parameters and liver histological characteristics were observed. Malondialdehyde(MDA) and superoxide dismutase(SOD) in the liver were determined. Protein expression of Cyt C and caspase-3 was determined by immunohistochemistry. The m RNA transcripts of mitofusin-2(Mfn2) and NF-κB in the liver tissue were detected by real-time PCR. Mitochondrial membrane potential was detected using a fluorescence spectrophotometer. Mitochondrial respiratory function was detected using a Clark oxygen electrode.RESULTS: The model group showed significantly higher ALT, AST, TG, TC and MDA but significantly lower SOD than the normal group. In the model group,the histological characteristics of inflammation and steatosis were also evident; mitochondrial swelling and crest were shortened or even disappeared. Cyt C(18.46 ± 1.21 vs 60.01 ± 3.43, P < 0.01) and caspase-3 protein expression(30.26 ± 2.56 vs 83.31 ± 5.12, P < 0.01) increased significantly. The m RNA expression of NF-κB increased(0.81 ± 0.02 vs 0.91 ± 0.03, P < 0.05), whereas the m RNA expression of Mfn2 decreased(1.65 ± 0.31 vs 0.83 ± 0.16, P < 0.05). Mitochondrial membrane potential also decreased and breathing of rats was weakened. Steatosis and inflammation degrees in the treatment group were significantly alleviated compared with those of the model group. In the treatment group, mitochondrial swelling was alleviated. Cyt C(60.01 ± 3.43 vs 30.52 ± 2.01, P < 0.01) and caspase-3 protein expression(83.31 ± 5.12 vs 40.15 ± 3.26, P < 0.01) significantly decreased. The m RNA expression of NF-κB also decreased(0.91 ± 0.03 vs 0.74 ± 0.02, P < 0.01), whereas the m RNA expression of Mfn2 increased(0.83 ± 0.16 vs 1.35 ± 0.23, P < 0.01). Mitochondrial membrane potential increased and respiratory function was enhanced. CONCLUSION: Sal B can treat NASH by protecting the morphological characteristics and functions of liver mitochondria, regulating lipid metabolism, controlling oxidative stress and lipid peroxidation and inhibiting apoptosis.

Effect of salvianolic acid B on Smad3 expression in hepatic stellate cells

BACKGROUND: Salvianolic acid B (SA-B), one of water soluble compounds derived from Radix salviae miltiorrhizae, had good action against liver fibrosis of patients with chro- nic hepatitis. Hepatic stellate cells (HSCs) is the cellular re- source for liver fibrogenesis, while transforming growth factor-β1 (TGF-β1) is most potent fibrogenic factor. In this study we investigated the mechanism of SA-B action against liver fibrosis relating to the interference with TGF- β1 signaling at HSC. METHODS: Hepatic stellate cells (HSCs) were isolated, cultured, and incubated with SA-B. The TGF-β1 content in the supernatant of subcultured HSCs was assayed with ELISA. Type I collagen and Smad3 protein in TGF-β1-sti- mulated primarily cultured HSCs for 4 days were detected by Western blot. RESULTS: TGF-β1 secreted in activated HSCs was more than in primary HSCs, and SA-B significantly decreased TGF-β1 secretion in activated HSCs. TGF-β1 increased the expression of type I collagen and Smad3 protein in d4 pri- mary HSCs, while SA-B inhibited their expression. CONCLUSIONS: SA-B inhibits TGF-β1 secretion in activa- ted HSCs and counteracts the expression of TGF-β1 stimu- lated type I collagen and Smad3. These actions are associat- ed with the effect of SA-B on liver fibrosis.

Salvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2 cells

BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.

Effects of salvianolic acid B on in vitro growth inhibition and apoptosis induction of retinoblastoma cells

AIM: To observe the effects of salvianolic add B (SalB) on in vitro growth inhibition and apoptosis induction of retinoblastoma HXO-RB44 cells. METHODS: The effects of SalB on the HXO-RB44 cells proliferation in vitro were observed by MTT colorimetric method. The morphological changes of apoptosis before and after the treatment of SalB were observed by Hoechst 33258 fluorescent staining method. Apoptosis rate and cell cycle changes of HXO-RB44 cells were detected by flow cytometer at 48 hours after treated by SalB. The expression changes of Caspase-3 protein in HXO-RB44 cells were detected by Western Blot. RESULTS: SalB significantly inhibited the growth of HXO-RB44 cells, while the inhibition was in a concentration-and time-dependent manner. The results of fluorescent staining method indicated that HXO-RB44 cells showed significant phenomenon of apoptosis including karyorrhexis, fragmentation and the formation of apoptotic bodies, etc. after 24, 48 and 72 hours co-culturing of SalB and HXO-RB44 cells. The results of flow cytometer showed that the apoptosis rate and the proportion of cells in S phase were gradually increased at 48 hours and 72 hours after treated by different concentrations of SalB. Western Blot strip showed that the expression of Caspase-3 protein in HXO-RB44 cells was gradually increased with the increase of the concentration of SalB. CONCLUSION: SalB can significantly affect on HXO-RB44 cells growth inhibition and apoptosis induction which may be achieved through the up-regulation of Caspase-3 expression and the induction of cell cycle arrest.

Salvianolic acid B protects hepatocytes from H2O2 injury by stabilizing the lysosomal membrane

AIM To investigate the capability of salvianolic acid B(Sal B) to protect hepatocytes from hydrogen peroxide(H_2O_2)/carbon tetrachloride(CCl_4)-induced lysosomal membrane permeabilization. METHODS Cell Counting Kit-8 assay was used to measure cell viability. Apoptosis and death were assayed through flow cytometry. Brd U incorporation was used to detect cell proliferation. Serum alanine aminotransferase activity and liver malondialdehyde(MDA) content were measured. Liver histopathological changes were evaluated using hematoxylin-eosin staining. Lysosomal membrane permeability was detected with Lyso Tracker Green-labeled probes and acridine orange staining. The levels of protein carbonyl content(PCC), cathepsins(Cat)B/D, and lysosome-associated membrane protein 1(LAMP1) were evaluated through western blotting. Cytosol Cat B activity analysis was performed with chemiluminescence detection. The m RNA level ofLAMP1 was evaluated through quantitative real-time polymerase chain reaction. RESULTS Results indicated that H_2O_2 induced cell injury/death. Sal B attenuated H_2O_2-induced cell apoptosis and death, restored the inhibition of proliferation, decreased the amount of PCC, and stabilized the lysosome membrane by increasing the LAMP1 protein level and antagonizing Cat B/D leakage into the cytosol. CCl_4 also triggered hepatocyte death. Furthermore, Sal B effectively rescued hepatocytes by increasing LAMP1 expression and by reducing lysosomal enzyme translocation to the cytosol.CONCLUSION Sal B protected mouse embryonic hepatocytes from H_2O_2/CCl_4-induced injury/death by stabilizing the lysosomal membrane.

Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.

Salvianolic acid B protects the myelin sheath around injured spinal cord axons

Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

Evaluation of pharmacokinetics and pharmacodynamics relationships for Salvianolic Acid B micro-porous osmotic pump pellets in angina pectoris rabbit

The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand White(NZW)rabbits,compared with those of SalB immediate-release pellets(SalB-IRPs).The SalB plasma concentrations and Superoxide dismutase levels(PD index)were recorded continuously at predetermined time interval after administration,and the related parameters were calculated by using Win-Nonlin software.The release profile of MPOPs was more sustained than that of IRPs.PK results indicated that the mean C_(max) was significantly lower,the SalB plasma concentrations were steadier,both area under concentration-time curve from 0 to 24 h(AUC_(0-24 h))and from 0 to infinity(AUC_(0-∞))were presented larger,and both the peak concentration time(T_(max))and mean residence time(MRT)were prolonged for MPOPs,as compared with those of IRPs.PD results suggested that peak drug effect(E_(max))was lower and the equilibration rate constant(k_(e0))between the central compartment and the effect compartment was higher of MPOPs vs.those of IRPs.PKePD relationships demonstrated that the effectconcentration-time(ECT)course of MPOPs was clockwise hysteresis loop,and that of IRPs was counter-clockwise hysteresis loop.Collectively,those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.

Neuroprotective effects of salvianolic acid B on secondary spinal cord damage

Salvianolic acid B （Sal B）, an effective ingredient of Danshen （salvia miltiorrhiza root）, has been shown to exhibit anti-oxidative and anti-inflammatory effects. The present study investigated whether Sal B has a neuroprotective effect on secondary spinal cord injury when administrated alone. In addition, the effects of Sal B on attenuating expression of tumor necrosis factor-α （TNF-α） following acute spinal cord injury were analyzed, as well as the effects of combined treatment of Sal B and etanercept. Immunohistochemical staining demonstrated that Sal B significantly reduced matrix metalloproteinase-1 and c-Fos expression at 24 hours after spinal cord injury, and decreased tissue edema was detected using the dry-wet weight method at 3 days after injury. In addition, Sal B significantly promoted recovery of motor function in rats. These effects were most significant at a dose of 20 mg/kg Sal B. At 24 hours after spinal cord injury, reverse transcription-polymerase chain reaction and western blot assay results showed that Sal B, etanercept, or the combination significantly suppressed increased TNF-α mRNA and protein expression, although the combination resulted in more significant outcomes. These results suggested that Sal B exerted neuroprotective effects against secondary spinal cord injury by reducing expression of matrix metalloproteinase-1, c-Fos, and TNF-α. Moreover, Sal B combined with etanercept resulted in more significant anti-inflammatory effects.

Interactions of acetylcholinesterase with salvianolic acid B and rosmarinic acid from Salvia miltiorhiza water extract investigated by NMR relaxation rate

In order to understand whether the ameliorating effect on old ages memory disorder by the root of Salvia miltiorhiza is related to the acetylcholinesterase （ACHE） inhibition, two main ingredients, salvianolic acid B （1） and rosmarinic acid （2）, which were isolated from S. miltiorhiza water extract, were investigated in vitro by NMR relaxation rate in this work. The results showed that the proton selective relaxation rates and the molecular rotational correlation time of proton pairs for compounds 1 and 2 increased significantly by adding of AChE in mixing solution. The study reveals that the two compounds might bind to the enzyme and have ACHE inhibitory effect, which could contribute to the ameliorating effect at some extent on old ages memory disorder.

Salvianolic acid B improves glucolipid metabolism by regulating adipogenic transcription factors in mice with diet-induced obesity

Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.

Application of on-line quality control for salvianolic acid B by near infrared spectroscopy

OBJECTIVE: To study and establish quality con-trol model of the Salvianolic Acid B by Near In-frared Spectroscopy (NIRS), and to realize on-line quality control of extracting and purifying proc-esses of industrial scale herbal product manu-facturing. METHOD: NIR chromatography was obtained from on-line NIR detection of extract-ing process and purifying process. HPLC analysis was carried out to determine the con-tents of salvianolic acid B. Partial Least Squares Regression (PLS) was used to establish the model between the information between NIRS and HPLC. RESULTS: For extracting model: the optimum Near Infrared (NIR) wavelength range was 9815- 5430cm-1, R=0.9784, RMSEC=0.258;for puri-fying model: the optimum NIR wavelength range was 9815-5430cm-1, R=0.9776, RMSEC=4.02. The average relative error was <5%. CONCLUSION: NIR technique is applicable for on-line quality control in production of salvianolic acid B.

Salvianolic acid A alleviates renal injury in systemic lupus erythematosus induced by pristane in BALB/c mice

OBJECTIVE To investigate the effects of salvianolic acid A(SAA)in systemic lupus erythematosus(SLE)induced by pristane in BALB/c mice,this study was performed.METHODS Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Micewere then treated with daily oral doses of SAA for 5months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E)and periodic acid-Schiff(PAS)staining.Western blot analysis of renal tissue was also employed.RESULTS SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.CONCLUSION The results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.

Protection of Salvianolic Acid B for Human Endothelial Cells Against Hydrogen Peroxide-Induced Oxidative Damage

Salvianolic acid B(Sal B) is an active component of traditional Chinese medicine Salvia miltiorrhiza and is used to treat vascular diseases. To better understand its mechanism, the antioxidant capacities of Sal B was evaluated with human endothelial cells under oxidative stress. Human endothelial cells were pretreated with Sal B for 12 h followed by hydrogen peroxide for another 12 h. Production of reactive oxygen species (ROS), activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and concentration of glu-tathione were measured. Protective effect of Sal B on the endothelial cells from hydrogen peroxide-induced damage was observed, and ROS production in the cells was found significantly inhibited. Sal B remarkably enhanced the activities of antioxidant enzymes SOD, CAT and GPX. Furthermore, Sal B up-regulated the intracellular glu-tathione concentration. The results indicate that Sal B protected endothelial cells from oxidative stress by improving the redox status of the cells through enhancing the antioxidant enzyme activities and increasing the reductive glu-tathione concentration after the oxidative challenge.

丹酚酸B通过SIRT1/PGC-1α通路对Aβ_(1-42)干预N2A细胞保护作用研究

目的观察沉默信息调节因子2相关酶1(SIRT1)/过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)的表达及检测活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量和线粒体膜电势,探讨丹酚酸B(SalB)减轻β淀粉样多肽1-42(Aβ1-42)干预小鼠来源神经瘤母细胞(N2A)后氧化应激损伤的作用及机制。方法使用10μM Aβ1-42寡聚体干预N2A细胞构建阿尔茨海默病(AD)细胞模型,使用40μM SalB干预细胞为对照组,模型组和SalB干预组。使用MTT法检测不同实验组细胞活力;DCFH-DA染色测定实验组细胞内ROS水平;ELISA法检测SOD,MDA水平;Western blot法和RTPCR法分别检测不同实验组SIRT1、PGC-1α蛋白和mRNA水平。结果与Aβ干预N2A细胞构建的模型组相比,SalB组处理后的模型组细胞活力显著升高(P<0.001),SalB组细胞中ROS水平显著下降(P<0.01),SOD水平显著上升(P<0.001),MDA生成显著减少(P<0.05),有效恢复线粒体膜电势(P<0.05)。另外,SalB处理后模型组细胞的SIRT1、PGC-1α蛋白和mRNA水平均升高。结论SalB可以显著降低Aβ干预N2A细胞后诱导的氧化应激反应,减少ROS产生及下调MDA水平,上调SOD水平,该神经保护作用可能与上调SIRT1/PGC-1α通路相关。

1例抗GABA_(B)R抗体相关脑炎的全程化药学监护和用药分析

1例67岁男性患者因“阵发性抽搐发作2周余”入院,诊断为抗γ-氨基丁酸B型受体(GABA_(B)R)抗体相关脑炎。入院后给予免疫治疗,治疗过程中出现癫痫持续状态、肺部感染、低蛋白血症、凝血功能异常等。临床药师结合患者病情,在免疫治疗方案的选择上给予甲泼尼龙联合静脉注射免疫球蛋白,在需要抗感染治疗时给予美罗培南(1 g q8h ivgtt);应用多烯磷脂酰胆碱护肝,给予氨溴索联合布地奈德改善肺功能,应用低分子量肝素钙预防血栓形成,对患者的营养和电解质平衡方面进行监护,给予患者全程化监护,最终患者病情好转出院。

丹酚酸B对肝损伤小鼠肠道菌群和短链脂肪酸代谢的影响

本研究旨在探讨丹酚酸B(salvianolic acid B,Sal B)对小鼠肝损伤的干预作用,以及对肠道菌群和短链脂肪酸(short-chain fatty acids,SCFAs)代谢的影响。通过皮下注射20%CCl 4溶液建立小鼠肝损伤模型,在造模的同时给予Sal B和阳性药2-脱氧-葡萄糖(2-deoxy-D-glucose)灌胃干预,干预结束后通过苏木素-伊红(hematoxylin-eosin,HE)、Masson、天狼星红染色观察小鼠肝脏病理变化;采用生化试剂盒检测血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)水平;运用16S rRNA测序技术检测小鼠肠道菌群结构变化;通过气相色谱法测定小鼠粪便中SCFAs的含量。结果显示,Sal B可以显著降低CCl 4诱导的肝损伤小鼠血清ALT、AST水平(P<0.001),并减轻肝组织病理损伤。测序结果显示,Sal B可以部分恢复肝损伤小鼠的肠道菌群结构,同时显著增加肠道中异丁酸、异戊酸、丙酸和戊酸的含量(P<0.001)。本实验揭示了Sal B可以减轻CCl 4所诱导的小鼠肝损伤,机制可能与其对肠道菌群和SCFAs紊乱的调节有关。