BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
OBJECTIVE: To investigate the efficacy of administration of tanshinone Ⅱ A(TSA) combined with mesenchymal stem cells(MSCs) for the treatment of learning and memory impairment caused by vascular dementia(Va D) and to ...OBJECTIVE: To investigate the efficacy of administration of tanshinone Ⅱ A(TSA) combined with mesenchymal stem cells(MSCs) for the treatment of learning and memory impairment caused by vascular dementia(Va D) and to determine the underlying mechanism.METHODS: Modified four-vessel occlusion was used to establish a Va D model in rats, and their spatial learning and memory capacity was assessed by the Morris water maze. The rats were randomized into MSCs, TSA, MSCs combined with TSA, vehicle and sham groups. Histological changes were determined by hematoxylin and eosin staining, and the hippocampal neuron apoptosis ratio was assessed by flow cytometry. Western blotting was performed to detect Bcl-2 and Bax expression. The reactive oxidative species(ROS) levels and the activity of total superoxide dismutase(T-SOD), an antioxidant enzyme in the rat hippocampus, were determined.RESULTS: TSA combined with MSCs treatment administered by intravenous injection in the tail significantly attenuated cognitive deficits in the Va D model compared with the vehicle group(P < 0.01),and its protective effect on cognitive function was greater than that obtained by treatment with MSCs or TSA alone. Furthermore, TSA combined with MSCs treatment achieved synergistic effects in suppressing neuronal apoptosis in the rat hippocampus caused by global brain ischemia via up-regulating the expression of Bcl-2, an anti-apoptosis protein, and decreasing the expression of Bax, a pro-apoptotic protein. In addition, TSA combined with MSCs treatment attenuated ROS production and enhanced T-SOD activity in the rat hippocampus, and the antioxidant effect was greater than that of treatment with MSCs or TSA alone.CONCLUSION: TSA combined with MSCs treatment improved the spatial learning and memory capacity in a Va D model via suppressing neuronal apoptosis and antioxidant activity in the hippocampus, and this improvement was greater with combined treatment than with treatment with MSCs or TSA alone.展开更多
Objective:To assess whether an adjunctive therapy of Sodium Tanshinone ⅡA Sulfonate Injection(STS)is effective and safe in improving clinical outcomes in patients with coronary heart disease(CHD).Methods:A literature...Objective:To assess whether an adjunctive therapy of Sodium Tanshinone ⅡA Sulfonate Injection(STS)is effective and safe in improving clinical outcomes in patients with coronary heart disease(CHD).Methods:A literature search was conducted through PubMed,the Cochrane Library,Knowledge Infrastructure Databases(CNKI),Chinese Biomedical Literature Database(SinoMed),Chinese Science and Technology Periodical Database(VIP)and Wanfang Database up to August 2017.Randomized controlled trials(RCTs)comparing STS with placebo or no additional treatments on the basis of standard conventional medicine therapies were included.The outcomes were all-cause mortality,major acute cardiovascular events(MACEs),cardiac function and inflammatory factors.The risk of bias assessment according to the Cochrane Handbook was used to evaluate the methodological quality of the included trials.Revman 5.3 software was used for data analyses.Results:A total of 22 RCTs involving 1,873 participants were included.All of the trials used STS as adjunctive treatment to standard conventional medicine therapy.Due to the poor quality of methodologies of most trials,only limited evidence showed that a combination of STS with percutaneous coronary intervention(PCI)or thrombolytic therapy(TT)might be more effective on reduction of all cause death rate than TT alone[risk ratio(RR)0.25,95% confidence interval(CI)0.07 to 0.87]or PCI alone(RR 0.42,95%CI 0.04 to 4.36).The results of 6 trials comparing STS plus TT with TT alone showed that the addition of STS significantly reduced the incidence of cardiac shock(RR 0.35,95%CI 0.14 to 0.86),heart failure(RR 0.41,95% CI 0.20 to 0.83)and arrhythmia(RR 0.21,95%CI 0.12 to 0.46).STS combined with TT also showed a superior effect on cardiac function and inflammatory factor.No severe adverse event was reported related to STS.Conclusions:As an adjunctive therapy,STS combined with standard conventional medicine seems to be more effective on all-cause mortality or MACEs than conventional medicine treatment alone with less side effects.However,we cannot make a firm conclusion due to low quality of inclusion trials.Well-designed trials with high methodological quality are needed to validate the effect of STS for CHD patients.展开更多
Objective: Acute lung injury(ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone ⅡA(Tan-ⅡA) is the major constituent of S...Objective: Acute lung injury(ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone ⅡA(Tan-ⅡA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-ⅡA on ALI.Methods: A murine model of lipopolysaccharide(LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-ⅡA were investigated using in vivo and in vitro ALI models. Tan-ⅡA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-ⅡA function.Results: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-ⅡA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-ⅡA treatment. An in vitro assay also confirmed that including the Tan-ⅡA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-ⅡA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-ⅡA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.Conclusion: This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-ⅡA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.展开更多
This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues ...This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley (SD) rats by the trypsin digestion and differential adhesion method. The cells were treated with 5 ng/mL TGF-β1 alone or pretreated with TSNⅡA at different concentrations (10–5 mol/L, 10–4 mol/L). Immunocytochemistry was used for cell identification, RT-PCR for detection of the mRNA expression of connective tissue growth factor (CTGF) and collagen type Ⅰ (COLⅠ), Western blotting for detection of the protein expression of Smad7 and Smad3, and immunohistochemistry and immunofluorescence staining for detection of the protein expression of phosphorylated Smad3 (p-Smad3), CTGF and COLⅠ. The results showed that TGF-β1 induced the expression of CTGF, COLⅠ, p-Smad3 and Smad7 in a time-dependent manner. The mRNA expression of CTGF and COLⅠ was significantly increased 24 h after TGF-β1 stimulation (P<0.01 for all). The protein expression of p-Smad3 and Smad7 reached a peak 1 h after TGF-β1 stimulation, much higher than the baseline level (P<0.01 for all). Pretreatment with high concentration of TSNⅡA resulted in a decrease in the expression of p-Smad3, CTGF and COLⅠ (P<0.01). The protein expression of Smad7 was substantially upregulated after pretreatment with two concentrations of TSNⅡA as compared with that at 2h post TGF-β1 stimulation (P<0.05 for low concentration of TSNⅡA; P<0.01 for high concentration of TSNⅡA). It was concluded that TSNⅡA may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the TGF-β1-induced phosphorylation of Smad3 and partially blocking the TGF-β1-Smads signaling pathway.展开更多
Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cul...Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cultured neonate rat were cultured in medium with 200 μmol/L H2O2, and the medium was supplemented with tanshinone ⅡA (1 × 10-4 mol/L) in advance for 24 h. PHB in myocardial cells was knocked down by RNA interference, and the expression level of PHB was determined by Western blotting analysis. Flow cytometric analysis was used to detect apoptosis rate, intracellular calcium concentration ([Ca2+]i), and mitochondrial membrane potential (MMP). Results H2O2-mediated cell apoptosis resulted in activation of PHB, increasing of [Ca2+]i, and decreasing of MMP. Tanshinone ⅡA profoundly inhibited myocardial cell apoptosis induced by H2O2, decreased [Ca2+]i, and increased MMP. Specific silence of PHB by siRNA down-regulated the expression level of PHB, increased apoptosis rate and [Ca2+]i, and decreased MMP. Conclusion The results demonstrate that tanshinone ⅡA could attenuate apoptosis induced by H2O2, and the activation of PHB induced by H2O2 is the major regulatory pathway of cyto-protective gene expression against oxidative stress.展开更多
Objective:Hypertrophic scars(HS)are a variety of skin tissue fibrosis disease that occurs in human skin,the effective therapeutic method of which is still inaccessible up to now.As a bioactive constituent of a well-kn...Objective:Hypertrophic scars(HS)are a variety of skin tissue fibrosis disease that occurs in human skin,the effective therapeutic method of which is still inaccessible up to now.As a bioactive constituent of a well-known medical plant,Salvia miltiorrhiza(Danshen in Chinese),tanshinone Ⅱ_(A)(TSA)is reported to inhibit cell proliferation in HS.Therefore,the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site.The possible mechanism of action in suppressing HS was studied using human skin fibroblasts(HSF).Methods:Tanshinone Ⅱ_(A) self-dissolving microneedles(TSA-MN)was prepared using a negative mold casting method.The prescription process of microneedle was optimized by Box-Behnken effect surface method.Different media were selected to investigate the ability of transdermal absorption and in vitro release.Furthermore,according to Cell Counting Kit-8(CCK8)method as well as the Western blot method,the effect of TSA-MN on the biological characteristics of HSF was investigated.Results:With remarkable slow release effect and dermal retention,the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms.Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro,which plays a significant role in down-regulating the secretion of transforming growth factor-β1(TGF-β1)in HSF and increasing the expression level of Smad7.Conclusion:The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars,with a stable dermal retention effect after process optimization.展开更多
TanshinoneⅡA(TanⅡA)is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen(Radix Salviae Miltiorrhizae)that has various pharmacological properties,inclu...TanshinoneⅡA(TanⅡA)is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen(Radix Salviae Miltiorrhizae)that has various pharmacological properties,including anti-inflammatory,antibacterial,and antioxidative effects.Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection.Recently,increasing attention has been paid to sepsis-induced dysfunction of the intestine,cardiovascular system,lungs,kidneys,liver,and other organs.Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory,anti-apoptotic and regulatory effects on multiple signalling pathways.The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.展开更多
以人自发性永生化角质形成细胞系(Ha Ca T)细胞为材料,通过CCK8和蛋白印迹法分别测定不同剂量长波紫外线(ultraviolet A,UVA)、不同浓度丹参酮ⅡA(tanshinoneⅡA,TSⅡA),以及UVA和TSⅡA共同作用下的细胞活力和促分裂素原活化蛋白激酶(mi...以人自发性永生化角质形成细胞系(Ha Ca T)细胞为材料,通过CCK8和蛋白印迹法分别测定不同剂量长波紫外线(ultraviolet A,UVA)、不同浓度丹参酮ⅡA(tanshinoneⅡA,TSⅡA),以及UVA和TSⅡA共同作用下的细胞活力和促分裂素原活化蛋白激酶(mitogenactivated protein kinase,MAPK)信号通路蛋白(p38,JNK和Erk)磷酸化水平.结果表明:在10 J/cm2的UVA照射下,细胞活力为对照组的70%左右,在20 J/cm2的UVA照射下,细胞活力仅为对照组的55%左右;低浓度的TSⅡA在正常情况下对细胞活力无影响,高浓度(85μmol/L)TSⅡA处理组的细胞活力约为对照组的70%左右.与TSⅡA或UVA单独处理相比,二者共同作用下细胞活力大大降低且差异极其显著.UVA照射提高了MAPK信号通路中的p38和JNK磷酸化水平,但是对Erk磷酸化水平没有影响;而TSⅡA可以显著提高低辐射剂量(2 J/cm2)UVA诱导下的p38和JNK的磷酸化水平.这说明UVA促进Ha Ca T细胞凋亡是通过提高p38和JNK磷酸化水平来实现的;而TSⅡA可以提高p38和JNK磷酸化水平,进一步加速UVA诱导的Ha Ca T细胞凋亡.展开更多
OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatom...OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.展开更多
OBJECTIVE: To investigate the efficacy and safety of Sodium tanshinone ⅡA sulfonate(STS) plus the conventional treatment on acute myocardial infarction(AMI) patients.METHODS: We searched several electrical databases ...OBJECTIVE: To investigate the efficacy and safety of Sodium tanshinone ⅡA sulfonate(STS) plus the conventional treatment on acute myocardial infarction(AMI) patients.METHODS: We searched several electrical databases and hand searched several Chinese medical journals up to January 2019. Randomized controlled trials(RCTs) comparing STS plus conventional treatment with conventional treatment were retrieved.Study screening, data extraction, quality assessment, and data analysis were conducted in accordance with the Cochrane standards.RESULTS: Sixteen trials involving 1383 people were included. The Meta-analysis showed STS combined with conventional treatment was a better treatment option than conventional treatment alone in reducing the risk of mortality, heart failure, arrhythmia and shock. In addition, STS was associated with improvement in left ventricular ejection fraction(LVEF) and left ventricular end diastolic dimension(LVEDD). No significant difference of STS was found on recurrent angina and recurrent AMI. However,the safety of STS remained uncertain for limited data.CONCLUSION: Compared with conventional treatment alone, STS combined with conventional treatment may provide more benefits for patients with AMI. Due to the fact that the overall quality of all included trials is generally low, further large-scale high quality trials are warranted.展开更多
The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced by the abdominal aorta partial coarctation were investigated.Rat models of myocardial hype...The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced by the abdominal aorta partial coarctation were investigated.Rat models of myocardial hypertrophy were established by using abdom-inal aorta partial coarctation method.Forty-eight rats were randomly divided into sham group(S group),model group(M group),valsartan treatment group(X group),low-dose tanshinone treatment group(LD group),medium-dose tanshinone treatment group(MD group),and high-dose tanshinone treatment group(HD group)(n=8 in each group).Left ventricular mass index(LVMI),left ventri-cular posterior wall(LVPW),and septal thickness(IVS)were detected by high frequency ultrasonography.Myocardialfiber diameter(MFD)was examined by Hematoxylin-Eosin(HE)staining,and the contents of phosphorylated protein kinase B(p-Akt)and p-Gsk3βin myocardium were assayed by Western blot.The results showed that compared with S group,the values of LVMI,LVPW,IVS and MFD were increased in other groups(P<0.05),and the contents of p-Akt,and p-Gsk3βwere also increased in other groups.As compared with MD group,the values of LVMI,LVPW,IVS and MFD were decreased in all treatment groups(P<0.05),and the contents of p-Akt,and p-Gsk3βwere also decreased in all treatment groups.However,there were no significant differences among LD,MD,and HD groups(P>0.05),and there were no significant differences between X group and tanshinone treatment groups(P>0.05).It was suggested that tanshinone II A could prevent myocardial hypertrophy by its action on the Akt signaling pathway.展开更多
Objective To select the strains which can produce tanshinone ⅡA like its host plant Salvia miltiorrhiza bung.Methods A total of 50 strains of endophytic fungi were isolated from healthy,living and symptomless tissues...Objective To select the strains which can produce tanshinone ⅡA like its host plant Salvia miltiorrhiza bung.Methods A total of 50 strains of endophytic fungi were isolated from healthy,living and symptomless tissues of Salvia miltiorrhiza bung,among which 29 strains were obtained from the root,14 from the stem,3 from the leaf,3 from the flower and 1 from the seed.Their antimicrobial activities against nine different bacteria,including both Gram-negative and Gram-positive bacteria,were measured by Oxford plate agar diffusion bioassay.Results Our data showed that all but four strains had significant antibacterial activities on at least one indicator bacterium to some extent,and five strains(DR1,DR4,DR16,DR18 and DF2)manifested quite prominent antibacterial activities against certain pathogenic bacteria.In some degree,it might indicate that this endophytic fungus isolated from the tissues of Salvia miltiorrhiza bung has a potential value as a natural antibacterial medicine as well.Thin layer chromatography(TLC)and high-performance liquid chromatography(HPLC)were carried out to test selected strains,both inside and outside of the cell to see if any strain can produce tanshinone ⅡA.The result showed that extracts from three strains,labeled as DR12(outside cell),DR21(inside cell)and DF3(inside cell),had a component with the same Rf value in TLC assay as that of authentic tanshinone ⅡA.The extract from DR12(outside cell)and DR21(inside cell)had a peak at retention time identical to that of authentic tanshinone ⅡA in HPLC.Conclusion The fungi appear to produce the bioactive compound tanshinone ⅡA,and they could be used to produce tanshinone ⅡA by fermentation.It provides a new way to synthesize this natural medicine.展开更多
Objective To optimize the preparation of the Naoxueling capsules.Methods To optimize the extraction of the Naoxueling prescription successively with alcohol and water,several principal ingredients in the final extract...Objective To optimize the preparation of the Naoxueling capsules.Methods To optimize the extraction of the Naoxueling prescription successively with alcohol and water,several principal ingredients in the final extracts were evaluated and data were analyzed by the orthogonal test.The capsule-molding process was investigated by measuring the angle of repose and the moisture absorption percentage.Results The optimum process of the alcohol extraction was the refluxing of herbs first in twelve-fold volume of 75% ethanol for 2 h,then in eight-fold volume of 75% ethanol for 1.5 h,and finally in seven-fold volume of 75% ethanol for 0.5 h.Meanwhile,the best water extraction was performed by boiling samples in twelve-fold amount of water for 2 h followed by another 1 h in eight-fold amount of water.To mold the capsule,the appropriate ratio of micro-powder to dextrin was 20:1.Conclusion The preparation technology of the Naoxueling capsules is reasonable and feasible,which provides evidences for the industrial manufacture.展开更多
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
基金Supported by the National Natural Science Foundation-funded Project: Melanin Nanoparticles Promote the Survival of Mesenchymal Stem Cells in Ischemic Conditions and Enhance Their Therapeutic Effect on Ischemic Stroke via up-regulating the Expression of Iduna (No. 81801361)。
文摘OBJECTIVE: To investigate the efficacy of administration of tanshinone Ⅱ A(TSA) combined with mesenchymal stem cells(MSCs) for the treatment of learning and memory impairment caused by vascular dementia(Va D) and to determine the underlying mechanism.METHODS: Modified four-vessel occlusion was used to establish a Va D model in rats, and their spatial learning and memory capacity was assessed by the Morris water maze. The rats were randomized into MSCs, TSA, MSCs combined with TSA, vehicle and sham groups. Histological changes were determined by hematoxylin and eosin staining, and the hippocampal neuron apoptosis ratio was assessed by flow cytometry. Western blotting was performed to detect Bcl-2 and Bax expression. The reactive oxidative species(ROS) levels and the activity of total superoxide dismutase(T-SOD), an antioxidant enzyme in the rat hippocampus, were determined.RESULTS: TSA combined with MSCs treatment administered by intravenous injection in the tail significantly attenuated cognitive deficits in the Va D model compared with the vehicle group(P < 0.01),and its protective effect on cognitive function was greater than that obtained by treatment with MSCs or TSA alone. Furthermore, TSA combined with MSCs treatment achieved synergistic effects in suppressing neuronal apoptosis in the rat hippocampus caused by global brain ischemia via up-regulating the expression of Bcl-2, an anti-apoptosis protein, and decreasing the expression of Bax, a pro-apoptotic protein. In addition, TSA combined with MSCs treatment attenuated ROS production and enhanced T-SOD activity in the rat hippocampus, and the antioxidant effect was greater than that of treatment with MSCs or TSA alone.CONCLUSION: TSA combined with MSCs treatment improved the spatial learning and memory capacity in a Va D model via suppressing neuronal apoptosis and antioxidant activity in the hippocampus, and this improvement was greater with combined treatment than with treatment with MSCs or TSA alone.
基金Supported by the Twelve Five-Year Plan of China(No.2013BAI02B01)the National Traditional Chinese Medicine Clinical Research Center Project(No.2015ZSC02)
文摘Objective:To assess whether an adjunctive therapy of Sodium Tanshinone ⅡA Sulfonate Injection(STS)is effective and safe in improving clinical outcomes in patients with coronary heart disease(CHD).Methods:A literature search was conducted through PubMed,the Cochrane Library,Knowledge Infrastructure Databases(CNKI),Chinese Biomedical Literature Database(SinoMed),Chinese Science and Technology Periodical Database(VIP)and Wanfang Database up to August 2017.Randomized controlled trials(RCTs)comparing STS with placebo or no additional treatments on the basis of standard conventional medicine therapies were included.The outcomes were all-cause mortality,major acute cardiovascular events(MACEs),cardiac function and inflammatory factors.The risk of bias assessment according to the Cochrane Handbook was used to evaluate the methodological quality of the included trials.Revman 5.3 software was used for data analyses.Results:A total of 22 RCTs involving 1,873 participants were included.All of the trials used STS as adjunctive treatment to standard conventional medicine therapy.Due to the poor quality of methodologies of most trials,only limited evidence showed that a combination of STS with percutaneous coronary intervention(PCI)or thrombolytic therapy(TT)might be more effective on reduction of all cause death rate than TT alone[risk ratio(RR)0.25,95% confidence interval(CI)0.07 to 0.87]or PCI alone(RR 0.42,95%CI 0.04 to 4.36).The results of 6 trials comparing STS plus TT with TT alone showed that the addition of STS significantly reduced the incidence of cardiac shock(RR 0.35,95%CI 0.14 to 0.86),heart failure(RR 0.41,95% CI 0.20 to 0.83)and arrhythmia(RR 0.21,95%CI 0.12 to 0.46).STS combined with TT also showed a superior effect on cardiac function and inflammatory factor.No severe adverse event was reported related to STS.Conclusions:As an adjunctive therapy,STS combined with standard conventional medicine seems to be more effective on all-cause mortality or MACEs than conventional medicine treatment alone with less side effects.However,we cannot make a firm conclusion due to low quality of inclusion trials.Well-designed trials with high methodological quality are needed to validate the effect of STS for CHD patients.
基金supported by National Natural Science Foundation of China (No. 81570020 and 82170033)Natural Science Foundation of Shanghai (21ZR1479200)Shanghai Changhai Hospital Scientific Research Fund (2019SLZ002, 2019YXK018, CHJG2019029 and CHPY2021A05)。
文摘Objective: Acute lung injury(ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone ⅡA(Tan-ⅡA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-ⅡA on ALI.Methods: A murine model of lipopolysaccharide(LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-ⅡA were investigated using in vivo and in vitro ALI models. Tan-ⅡA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-ⅡA function.Results: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-ⅡA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-ⅡA treatment. An in vitro assay also confirmed that including the Tan-ⅡA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-ⅡA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-ⅡA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.Conclusion: This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-ⅡA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
基金supported by a grant from the Natural Science Foundation of Hubei Province of China(Nos.2009CDB092,2007ABA272)
文摘This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley (SD) rats by the trypsin digestion and differential adhesion method. The cells were treated with 5 ng/mL TGF-β1 alone or pretreated with TSNⅡA at different concentrations (10–5 mol/L, 10–4 mol/L). Immunocytochemistry was used for cell identification, RT-PCR for detection of the mRNA expression of connective tissue growth factor (CTGF) and collagen type Ⅰ (COLⅠ), Western blotting for detection of the protein expression of Smad7 and Smad3, and immunohistochemistry and immunofluorescence staining for detection of the protein expression of phosphorylated Smad3 (p-Smad3), CTGF and COLⅠ. The results showed that TGF-β1 induced the expression of CTGF, COLⅠ, p-Smad3 and Smad7 in a time-dependent manner. The mRNA expression of CTGF and COLⅠ was significantly increased 24 h after TGF-β1 stimulation (P<0.01 for all). The protein expression of p-Smad3 and Smad7 reached a peak 1 h after TGF-β1 stimulation, much higher than the baseline level (P<0.01 for all). Pretreatment with high concentration of TSNⅡA resulted in a decrease in the expression of p-Smad3, CTGF and COLⅠ (P<0.01). The protein expression of Smad7 was substantially upregulated after pretreatment with two concentrations of TSNⅡA as compared with that at 2h post TGF-β1 stimulation (P<0.05 for low concentration of TSNⅡA; P<0.01 for high concentration of TSNⅡA). It was concluded that TSNⅡA may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the TGF-β1-induced phosphorylation of Smad3 and partially blocking the TGF-β1-Smads signaling pathway.
基金National Natural Sciences Foundation of China (30572435)
文摘Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cultured neonate rat were cultured in medium with 200 μmol/L H2O2, and the medium was supplemented with tanshinone ⅡA (1 × 10-4 mol/L) in advance for 24 h. PHB in myocardial cells was knocked down by RNA interference, and the expression level of PHB was determined by Western blotting analysis. Flow cytometric analysis was used to detect apoptosis rate, intracellular calcium concentration ([Ca2+]i), and mitochondrial membrane potential (MMP). Results H2O2-mediated cell apoptosis resulted in activation of PHB, increasing of [Ca2+]i, and decreasing of MMP. Tanshinone ⅡA profoundly inhibited myocardial cell apoptosis induced by H2O2, decreased [Ca2+]i, and increased MMP. Specific silence of PHB by siRNA down-regulated the expression level of PHB, increased apoptosis rate and [Ca2+]i, and decreased MMP. Conclusion The results demonstrate that tanshinone ⅡA could attenuate apoptosis induced by H2O2, and the activation of PHB induced by H2O2 is the major regulatory pathway of cyto-protective gene expression against oxidative stress.
基金supported by the National Natural Science Foundation of China(No.82173982,2021)the Guangdong Natural Science Project(No.2018A0303130234)Excellent Young Teachers Training Project in Higher Education of Guangdong(No.YQ2015099).
文摘Objective:Hypertrophic scars(HS)are a variety of skin tissue fibrosis disease that occurs in human skin,the effective therapeutic method of which is still inaccessible up to now.As a bioactive constituent of a well-known medical plant,Salvia miltiorrhiza(Danshen in Chinese),tanshinone Ⅱ_(A)(TSA)is reported to inhibit cell proliferation in HS.Therefore,the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site.The possible mechanism of action in suppressing HS was studied using human skin fibroblasts(HSF).Methods:Tanshinone Ⅱ_(A) self-dissolving microneedles(TSA-MN)was prepared using a negative mold casting method.The prescription process of microneedle was optimized by Box-Behnken effect surface method.Different media were selected to investigate the ability of transdermal absorption and in vitro release.Furthermore,according to Cell Counting Kit-8(CCK8)method as well as the Western blot method,the effect of TSA-MN on the biological characteristics of HSF was investigated.Results:With remarkable slow release effect and dermal retention,the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms.Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro,which plays a significant role in down-regulating the secretion of transforming growth factor-β1(TGF-β1)in HSF and increasing the expression level of Smad7.Conclusion:The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars,with a stable dermal retention effect after process optimization.
基金Natural Science Foundation of Hubei Province:Mechanism of Degenerative Aortic Valve Calcification Induced by Inflammatory Responses in Valvular Interstitial Cells(No.2020CFB577)。
文摘TanshinoneⅡA(TanⅡA)is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen(Radix Salviae Miltiorrhizae)that has various pharmacological properties,including anti-inflammatory,antibacterial,and antioxidative effects.Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection.Recently,increasing attention has been paid to sepsis-induced dysfunction of the intestine,cardiovascular system,lungs,kidneys,liver,and other organs.Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory,anti-apoptotic and regulatory effects on multiple signalling pathways.The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.
文摘以人自发性永生化角质形成细胞系(Ha Ca T)细胞为材料,通过CCK8和蛋白印迹法分别测定不同剂量长波紫外线(ultraviolet A,UVA)、不同浓度丹参酮ⅡA(tanshinoneⅡA,TSⅡA),以及UVA和TSⅡA共同作用下的细胞活力和促分裂素原活化蛋白激酶(mitogenactivated protein kinase,MAPK)信号通路蛋白(p38,JNK和Erk)磷酸化水平.结果表明:在10 J/cm2的UVA照射下,细胞活力为对照组的70%左右,在20 J/cm2的UVA照射下,细胞活力仅为对照组的55%左右;低浓度的TSⅡA在正常情况下对细胞活力无影响,高浓度(85μmol/L)TSⅡA处理组的细胞活力约为对照组的70%左右.与TSⅡA或UVA单独处理相比,二者共同作用下细胞活力大大降低且差异极其显著.UVA照射提高了MAPK信号通路中的p38和JNK磷酸化水平,但是对Erk磷酸化水平没有影响;而TSⅡA可以显著提高低辐射剂量(2 J/cm2)UVA诱导下的p38和JNK的磷酸化水平.这说明UVA促进Ha Ca T细胞凋亡是通过提高p38和JNK磷酸化水平来实现的;而TSⅡA可以提高p38和JNK磷酸化水平,进一步加速UVA诱导的Ha Ca T细胞凋亡.
基金Supported by National Natural Science Foundation of China(CN):Vascular Normalization by Huoxuehuayu medicine Induces decrease of the Interstitial Fluid and Improves Drug Penetration in Tumors(No.81202784)
文摘OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.
基金Supported by Project of Administration of Traditional Chinese Medicine of Guangdong Province Clinical Study of the Effect of TanshinoneⅡA Sodium Sulfonate on Coronary Microcirculation in Patients with Acute Coronary Syndrome(No. 20181126)Project of Special Clinical Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine Clinical Study of the Effect of TanshinoneⅡA Sodium Sulfonate on Coronary Microcirculation in Patients with Acute Coronary Syndrome (No.YN2018QL06)Project of Department of Education of Guangdong Province Acute Myocardial Infarction Chinese Medicine Prevention and Treatment Team (No. 2020KT1207)。
文摘OBJECTIVE: To investigate the efficacy and safety of Sodium tanshinone ⅡA sulfonate(STS) plus the conventional treatment on acute myocardial infarction(AMI) patients.METHODS: We searched several electrical databases and hand searched several Chinese medical journals up to January 2019. Randomized controlled trials(RCTs) comparing STS plus conventional treatment with conventional treatment were retrieved.Study screening, data extraction, quality assessment, and data analysis were conducted in accordance with the Cochrane standards.RESULTS: Sixteen trials involving 1383 people were included. The Meta-analysis showed STS combined with conventional treatment was a better treatment option than conventional treatment alone in reducing the risk of mortality, heart failure, arrhythmia and shock. In addition, STS was associated with improvement in left ventricular ejection fraction(LVEF) and left ventricular end diastolic dimension(LVEDD). No significant difference of STS was found on recurrent angina and recurrent AMI. However,the safety of STS remained uncertain for limited data.CONCLUSION: Compared with conventional treatment alone, STS combined with conventional treatment may provide more benefits for patients with AMI. Due to the fact that the overall quality of all included trials is generally low, further large-scale high quality trials are warranted.
基金supported by the National Natural Science Foundation of China(Grant No.30500657).
文摘The effects of tanshinone II A on cell signal transduction system protein kinase B in rats with myocardial hypertrophy induced by the abdominal aorta partial coarctation were investigated.Rat models of myocardial hypertrophy were established by using abdom-inal aorta partial coarctation method.Forty-eight rats were randomly divided into sham group(S group),model group(M group),valsartan treatment group(X group),low-dose tanshinone treatment group(LD group),medium-dose tanshinone treatment group(MD group),and high-dose tanshinone treatment group(HD group)(n=8 in each group).Left ventricular mass index(LVMI),left ventri-cular posterior wall(LVPW),and septal thickness(IVS)were detected by high frequency ultrasonography.Myocardialfiber diameter(MFD)was examined by Hematoxylin-Eosin(HE)staining,and the contents of phosphorylated protein kinase B(p-Akt)and p-Gsk3βin myocardium were assayed by Western blot.The results showed that compared with S group,the values of LVMI,LVPW,IVS and MFD were increased in other groups(P<0.05),and the contents of p-Akt,and p-Gsk3βwere also increased in other groups.As compared with MD group,the values of LVMI,LVPW,IVS and MFD were decreased in all treatment groups(P<0.05),and the contents of p-Akt,and p-Gsk3βwere also decreased in all treatment groups.However,there were no significant differences among LD,MD,and HD groups(P>0.05),and there were no significant differences between X group and tanshinone treatment groups(P>0.05).It was suggested that tanshinone II A could prevent myocardial hypertrophy by its action on the Akt signaling pathway.
基金supported by the sub-project of Key Projects in the National Science & Technology Pillar Program(2006BA106A-04)
文摘Objective To select the strains which can produce tanshinone ⅡA like its host plant Salvia miltiorrhiza bung.Methods A total of 50 strains of endophytic fungi were isolated from healthy,living and symptomless tissues of Salvia miltiorrhiza bung,among which 29 strains were obtained from the root,14 from the stem,3 from the leaf,3 from the flower and 1 from the seed.Their antimicrobial activities against nine different bacteria,including both Gram-negative and Gram-positive bacteria,were measured by Oxford plate agar diffusion bioassay.Results Our data showed that all but four strains had significant antibacterial activities on at least one indicator bacterium to some extent,and five strains(DR1,DR4,DR16,DR18 and DF2)manifested quite prominent antibacterial activities against certain pathogenic bacteria.In some degree,it might indicate that this endophytic fungus isolated from the tissues of Salvia miltiorrhiza bung has a potential value as a natural antibacterial medicine as well.Thin layer chromatography(TLC)and high-performance liquid chromatography(HPLC)were carried out to test selected strains,both inside and outside of the cell to see if any strain can produce tanshinone ⅡA.The result showed that extracts from three strains,labeled as DR12(outside cell),DR21(inside cell)and DF3(inside cell),had a component with the same Rf value in TLC assay as that of authentic tanshinone ⅡA.The extract from DR12(outside cell)and DR21(inside cell)had a peak at retention time identical to that of authentic tanshinone ⅡA in HPLC.Conclusion The fungi appear to produce the bioactive compound tanshinone ⅡA,and they could be used to produce tanshinone ⅡA by fermentation.It provides a new way to synthesize this natural medicine.
基金Hunan Natural Science Foundation (2009FJ3209)Changsha Science and Technology Plan (K0902033-31)
文摘Objective To optimize the preparation of the Naoxueling capsules.Methods To optimize the extraction of the Naoxueling prescription successively with alcohol and water,several principal ingredients in the final extracts were evaluated and data were analyzed by the orthogonal test.The capsule-molding process was investigated by measuring the angle of repose and the moisture absorption percentage.Results The optimum process of the alcohol extraction was the refluxing of herbs first in twelve-fold volume of 75% ethanol for 2 h,then in eight-fold volume of 75% ethanol for 1.5 h,and finally in seven-fold volume of 75% ethanol for 0.5 h.Meanwhile,the best water extraction was performed by boiling samples in twelve-fold amount of water for 2 h followed by another 1 h in eight-fold amount of water.To mold the capsule,the appropriate ratio of micro-powder to dextrin was 20:1.Conclusion The preparation technology of the Naoxueling capsules is reasonable and feasible,which provides evidences for the industrial manufacture.
