Objective:Tanshinone ⅡA,one of the most abundant liposoluble components isolated from the traditional Chinese medicine Salvia miltiorrhiza,exhibits significant biological activities in anti-inflammatory,antibacterial...Objective:Tanshinone ⅡA,one of the most abundant liposoluble components isolated from the traditional Chinese medicine Salvia miltiorrhiza,exhibits significant biological activities in anti-inflammatory,antibacterial,and antitumor eff ects.This study aims to systematically explore the mechanism of Tanshinone ⅡA through bioinformatics.Methods:We utilized the TCMSP database to retrieve the oral bioavailability(OB)and drug-likeness(DL)of Tanshinone ⅡA.The gene chip numbered GSE85871 was downloaded from the GEO database,and diff erential genes were analyzed using R language to identify potential targets of Tanshinone ⅡA.After obtaining these targets,GO analysis and KEGG pathway analysis were performed using the DAVID 6.8 database.Diseases related to Tanshinone ⅡA were explored through the CTD database.Finally,Cytoscape was employed to construct a visual network of multiple targets,pathways,and diseases associated with Tanshinone ⅡA.Results:Tanshinone ⅡA demonstrated good drug effi cacy with an OB value of 49.89%and a DL value of 0.4.A total of 132 potential targets were identifi ed,primarily exhibiting gene co-expression and physical interaction in the PPI network.These targets were enriched in biological processes and pathways such as ovarian steroidogenesis,cell cycle,and steroid hormone biosynthesis.Tanshinone ⅡA was found to be relevant in the treatment of diseases including breast tumors,hypertension,atherosclerosis,gliomas,vascular system injuries,left ventricular hypertrophy,leukemia,and hearing loss.Conclusion:Utilizing bioinformatics approaches,we systematically analyzed the possible molecular mechanisms of Tanshinone ⅡA,providing potential targets and insights into its pharmacological mechanisms and treatment strategies.展开更多
Total tanshinones are lipophilic active constituents extracted from Salvia miltiorrhiza Bge.Tanshinone ⅡA and cryptotanshinone are the major components in total tanshinones.However, the bioavailability of both compou...Total tanshinones are lipophilic active constituents extracted from Salvia miltiorrhiza Bge.Tanshinone ⅡA and cryptotanshinone are the major components in total tanshinones.However, the bioavailability of both compounds is low due to poor water solubility. To enhance the solubility and dissolution rate of tanshinone ⅡA, cryptotanshinone and total tanshinones,three common used hydrophilic carriers including PEG 6000, poloxamer 188 and PVP K30 were used to prepare the solid dispersions at different ratios, respectively. The solid dispersions were characterised by scanning electron microscopy(SEM), differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR). The results of powder X-ray diffraction confirmed the microcrystal state of total tanshinones in solid dispersions and no chemical interaction between total tanshinones and carriers was observed in FTIR spectra. The solubility and dissolution rate of tanshinone ⅡA and cryptotanshinone were significantly increased in all solid dispersions. Regarding tanshinone ⅡA, the solubility and dissolution rate of in solid dispersions prepared with poloxamer 188 were significantly higher than that with PEG 6000 and PVP K30. The higher solubility and dissolution rate of cryptotanshinone were obtained in solid dispersion of PVP K30 than that of PEG 6000 solid dispersions but no significant difference from poloxamer 188 solid dispersions. The results indicate that the superior carrier for preparation of tanshinone ⅡA and total tanshinones solid dispersions is poloxamer 188, and that for cryptotanshinone is PVP K30.展开更多
[Objective]The aim was to extract tanshinone from Salvia miltiorrhiza Bge. dregs and to determine tanshinone components. [Method]Organic solvent method was adopted to extract tanshinone from S. miltiorrhiza dregs and ...[Objective]The aim was to extract tanshinone from Salvia miltiorrhiza Bge. dregs and to determine tanshinone components. [Method]Organic solvent method was adopted to extract tanshinone from S. miltiorrhiza dregs and TLC was used to determine the optimum extraction solvent. The components of tanshinone were measured with HPLC. [Result]Ether was the best solvent to extract tanshinone from S. miltiorrhiza dregs. After water immersion,dry dregs of S. miltiorrhiza and Panax notoginseng were extracted with ethanol to obtain fat-soluble extracts. Then with ether as the solvent for Soxhlet extraction,the yield of crude tanshinone was 2.17%. The HPLC detection showed that the contents of tanshinone Ⅱ A,methylene tanshinquinone,cryptotanshinone,tanshinone Ⅰ were 3.62%,1.02%,2.56%,2.75% respectively. [Conclusion]The components of tanshinone in S. miltiorrhiza dregs were basically the same as tanshinone in medicine S. miltiorrhiza. S. miltiorrhiza dregs could be used as a kind of tanshinone resource,which has the value of development and utilization.展开更多
Tanshinone ⅡA（TSⅡA） is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion（MIR） injury.However,the cardioprotect...Tanshinone ⅡA（TSⅡA） is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion（MIR） injury.However,the cardioprotective effects of TSⅡA as well as its clinical use were limited due to its poor water solubility.The objective of this study was to evaluate whether Tanshinone ⅡA derivative（TD）,a new water soluble compound synthesized by TSⅡA and N-Methyl-D-Glucamine,had protective effects on MIR injury and what the related mechanism was.The cardioprotective effects of TD were evaluated and compared with TSⅡA in a rat MIR model.The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase（LDH） and malondialdehyde（MDA）,decreasing expression of nuclear factor-κ-gene binding（NF-κB） and upregulating expression of heme oxygenase（HO-1）,but having no effect on the content of total superoxide dismutase（T-SOD） and m RNA expression of superoxide dismutase（SOD-1）.Thus,our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses.展开更多
Danshen,the dried roots and rhizomes of Salvia miltiorrhiza Bunge(S.miltiorrhiza),is widely used in the treatment of cardiovascular and cerebrovascular diseases.Tanshinones,the bioactive compounds from Danshen,exhibit...Danshen,the dried roots and rhizomes of Salvia miltiorrhiza Bunge(S.miltiorrhiza),is widely used in the treatment of cardiovascular and cerebrovascular diseases.Tanshinones,the bioactive compounds from Danshen,exhibit a wide spectrum of pharmacological properties,suggesting their potential for future therapeutic applications.Tanshinone biosynthesis is a complex process involving at least six P450 enzymes that have been identified and characterized,most of which belong to the CYP76 and CYP71 families.In this study,CYP81C16,a member of the CYP71 clan,was identified in S.miltiorrhiza.An in vitro assay revealed that it could catalyze the hydroxylation of four para-quinone-type tanshinones,namely neocryptotanshinone,deoxyneocryptotanshinone,and danshenxinkuns A and B.SmCYP81C16 emerged as a potential broad-spectrum oxidase targeting the C-18 position of para-quinone-type tanshinones with an impressive relative conversion rate exceeding 90%.Kinetic evaluations and in vivo assays underscored its highest affinity towards neocryptotanshinone among the tested substrates.The overexpression of SmCYP81C16 promoted the accumulation of(iso)tanshinone in hairy root lines.The characterization of SmCYP81C16 in this study accentuates its potential as a pivotal tool in the biotechnological production of tanshinones,either through microbial or plant metabolic engineering.展开更多
Danshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine （TCM） for treatment of various diseases. Tanshinone IIA （TSA） is one of the main active components of Danshen, w...Danshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine （TCM） for treatment of various diseases. Tanshinone IIA （TSA） is one of the main active components of Danshen, which has multiple bioactivities. This article reviews the research progress of TSA in the treatment of cardiovascular disease, anti-inflammatory and immune, anti-tumor, liver protection, neuroprotection. It provides more ideas for the clinical application of TSA and the development of drug resistance.展开更多
The reaction of cryptotanshinone and tanshinone IIA with several biogenic amine metabolites involved in the pathogenic pathways of HE were investigated and eight 1,2,3,4- tetrahydrophenanthrene derivatives, 2-6 and 8-...The reaction of cryptotanshinone and tanshinone IIA with several biogenic amine metabolites involved in the pathogenic pathways of HE were investigated and eight 1,2,3,4- tetrahydrophenanthrene derivatives, 2-6 and 8-10, were obtained. The probable mechanism on reaction was discussed.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
Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate(STS) is a water-soluble derivative of Tanshinone IIA(TA), a main a...Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate(STS) is a water-soluble derivative of Tanshinone IIA(TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein(CRP), procalcitonin(PCT), cardiac troponin Ⅰ(cTn-Ⅰ), cardiac troponin T(cTn-T), and brain natriuretic peptide(BNP) in cecal ligation and puncture(CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10) and high mobility group protein B1(HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose(15 mg×kg–1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30%(P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.展开更多
TanshinoneⅡA,extracted from Salvia miltiorrhiza Bunge,exerts neuroprotective effects through its anti-inflammatory,anti-oxidative and anti-apoptotic properties.This study intravenously injected tanshinoneⅡA 20 mg/kg...TanshinoneⅡA,extracted from Salvia miltiorrhiza Bunge,exerts neuroprotective effects through its anti-inflammatory,anti-oxidative and anti-apoptotic properties.This study intravenously injected tanshinoneⅡA 20 mg/kg into rat models of spinal cord injury for 7 consecutive days.Results showed that tanshinoneⅡA could reduce the inflammation,edema as well as compensatory thickening of the bladder tissue,improve urodynamic parameters,attenuate secondary injury,and promote spinal cord regeneration.The number of hypertrophic and apoptotic dorsal root ganglion(L6–S1)cells was less after treatment with tanshinoneⅡA.The effects of tanshinoneⅡA were similar to intravenous injection of 30 mg/kg methylprednisolone.These findings suggested that tanshinoneⅡA improved functional recovery after spinal cord injury-induced lower urinary tract dysfunction by remodeling the spinal pathway involved in lower urinary tract control.展开更多
This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate(STS) in healthy volunteers and coronary heart disease(CHD) patients in order to identify significant covariates for the pharm...This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate(STS) in healthy volunteers and coronary heart disease(CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance(CL) of STS in CHD patients with total bilirubin(TBIL) level of 10 μmol×L^(–1) was 48.7 L×h^(–1) with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L×h^(–1). Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.展开更多
Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue isch...Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone lla, 0.5 hour prior to model establishment. Results showed that Tanshinone Ila promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone Ila, compared with positive control Danshen injection.展开更多
Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hyp...Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hypoxia,cerebral ischemia and alzheimer’s disease,etc.In the treatment of cerebrovascular diseases,borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs,especially to the brain.The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA(TS IIA),salvianolic acid B(SAB)and ginsenoside Rg1 in FDP.Male healthy Sprague-Dawley(SD)rats were given Danshen extracts,Sanqi extracts(Panax notoginseng saponins)or simultaneously administered Danshen extracts,Sanqi extracts and borneol.Plasma and brain samples were collected at different points in time.The concentration of TS IIA,SAB and Rg1 was determined by UPLC-MS/MS method.The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software.In comparison with Danshen and Sanqi alone,there were significant differences in pharmacokinetic parameters of TS IIA,SAB and Rg1,and the brain distribution of SAB and TS IIA when Danshen,Sanqi and borneol were administrated together.Borneol statistically significant shortened tmax of TS IIA,SAB and Rg1 in plasma and brain,increased the bioavaiability of Rg1,inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain.These results indicated that borneol could affect the multiple targets components and produce synergistic effects.Through accelerating the intestinal absorption and brain distribution,borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.展开更多
This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts(CFs) and its potential mechanism, as well as whether sodium tanshinone ⅡA sulfonate(STS) has protective effect on CFs and it...This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts(CFs) and its potential mechanism, as well as whether sodium tanshinone ⅡA sulfonate(STS) has protective effect on CFs and its possible mechanism. Our data demonstrated that X-rays inhibited cell growth and increased oxidative stress in CFs, and STS mitigated X-ray-induced injury. Enzyme-linked immuno-sorbent assay showed that X-rays increased the levels of secreted angiotensin Ⅱ(Ang Ⅱ) and brain natriuretic peptide(BNP). STS inhibited the X-ray-induced increases in Ang Ⅱ and BNP release. Apoptosis and cell cycle of CFs were analyzed using flow cytometry. X-rays induced apoptosis in CFs, whereas STS inhibited apoptosis in CFs after X-ray irradiation. X-rays induced S-phase cell cycle arrest in CFs, which could be reversed by STS. X-rays increased the expression of phosphorylated-P38/P38,cleaved caspase-3 and caspase-3 as well as decreased the expression of phosphorylated extracellular signal-regulated kinase 1/2(ERK1/2)/ERK 1/2 and B cell lymphoma 2(Bcl-2)/Bcl-2 associated X protein(BAX) in CFs, as shown by Western blotting. STS mitigated the X-ray radiation-induced expression changes of these proteins. In conclusion, our results demonstrated that STS may potentially be developed as a medical countermeasure to mitigate radiation-induced cardiac damage.展开更多
To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of ...To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with high-dose TSN Ⅱ A was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN ⅡA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.展开更多
OBJECTIVE:To identify the active anti-tumor constituents in the extract from Danshen(Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.METHODS:First,we introduced a two-step counter-cu...OBJECTIVE:To identify the active anti-tumor constituents in the extract from Danshen(Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.METHODS:First,we introduced a two-step counter-current chromatography to extract the therapeutically active diterpenoid,tanshinone from Danshen(Radix Salviae Miltiorrhizae).The cholecystokinin(CCK-8) method was used to evaluate the inhibitory effect of diterpenoid tanshinone in liver cancer QGY-7703,lung cancer PC9,lung cancer A549,gastric cancer MKN-45,gastric cancer HGC-27,colon cancer HCT116,myeloma cell U266/RPMI8226,and human breast cancer MCF-7 in vitro.Fluorescence staining was used to observe the cytotoxicity ofditerpenoid tanshinone on PC9 cells.The Western blot was used to detect apoptosis-related protein poly ADP-ribose polymerase(PARP),cysteinyl aspartate specific proteinase3/9(caspase3/9),and cleaved-cysteinyl aspartate specific proteinase3/9(cleaved-caspase3/9).The endoplasmic reticulum stress-related activating transcription factor 4(ATF4),phosphorylated eukaryotic initiation factor 2α(p-e IF2α),and phosphorylated jun amino-terminal kinase(p-JNK),and caspase-12 were also analyzed using the Western blot.RESULTS:Diterpenoid tanshinone inhibited the nine human tumor cell lines,with an IC50 of4.37-29 μg/m L,with the PC9 and MCF-7 displaying the lowest values.Fluorescence staining showed a lethal effect of diterpenoid tanshinone on PC9 cells.The Western blot showed that the expression of caspase3/9 protein and ATF-4 protein decreased gradually.However,the PARP,cleaved-caspase 3/9and the expression of p-e IF2 α,P-JNK,and caspase-12 increased gradually,in a dose-dependent fashion.CONCLUSION:We successfully introduced a two-step counter-current chromatography method to extract diterpenoid tanshinone,and demonstrated its antitumor activity.Diterpenoid tanshinone can induce apoptosis in nine human cancer cell lines.展开更多
AIM To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and vari...AIM To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation was detected.RESULTS The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid. Flow cytometric assay demonstrated that S phase cells decreased and G0/G1 phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly increased.CONCLUSION Tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.展开更多
Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidatio...Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidation stress of myocardial cells. Methods: Primary cultured neonate rat myocardial cells were cultured with TSN (1×10-4 mol/L) for 24 hours, and then the medium was supplemented with 200 μmol/L hydrogen peroxide for 2 h to initiate myocardial cell oxidative stress injury. PHB in myocardial cells was knocked down by small interfering RNA (siRNA), and the expression level of PHB was determined by western blot analysis. Flow cytometry was used to detect the apoptosis rate, intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP). Results: The PHB expression, [Ca2+]i and the apoptotic rate significantly increased, and the MMP significantly decreased in the oxidative stress group compared with the control. The PHB expression, apoptosis rate and [Ca2+]i decreased, and MMP increased significantly in the TSN group compared with the oxidative stress group. Compared with the siRNA negative control group, the PHB expression level in myocardial cells was down-regulated, and the apoptosis rate and [Ca2+]i increased, and MMP decreased significantly in the siRNA group. Conclusion: TSN can reduce PHB expression in oxidative stress-injured myocardial cells hence protecting the myocardial cells.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
The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocyte...The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction （RT-PCR）. It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly （P〈0.01）. After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group （P〈0.01）. After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group （P〈0.05）. After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ （P〈0.05 or P〈0.01）. It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.展开更多
文摘Objective:Tanshinone ⅡA,one of the most abundant liposoluble components isolated from the traditional Chinese medicine Salvia miltiorrhiza,exhibits significant biological activities in anti-inflammatory,antibacterial,and antitumor eff ects.This study aims to systematically explore the mechanism of Tanshinone ⅡA through bioinformatics.Methods:We utilized the TCMSP database to retrieve the oral bioavailability(OB)and drug-likeness(DL)of Tanshinone ⅡA.The gene chip numbered GSE85871 was downloaded from the GEO database,and diff erential genes were analyzed using R language to identify potential targets of Tanshinone ⅡA.After obtaining these targets,GO analysis and KEGG pathway analysis were performed using the DAVID 6.8 database.Diseases related to Tanshinone ⅡA were explored through the CTD database.Finally,Cytoscape was employed to construct a visual network of multiple targets,pathways,and diseases associated with Tanshinone ⅡA.Results:Tanshinone ⅡA demonstrated good drug effi cacy with an OB value of 49.89%and a DL value of 0.4.A total of 132 potential targets were identifi ed,primarily exhibiting gene co-expression and physical interaction in the PPI network.These targets were enriched in biological processes and pathways such as ovarian steroidogenesis,cell cycle,and steroid hormone biosynthesis.Tanshinone ⅡA was found to be relevant in the treatment of diseases including breast tumors,hypertension,atherosclerosis,gliomas,vascular system injuries,left ventricular hypertrophy,leukemia,and hearing loss.Conclusion:Utilizing bioinformatics approaches,we systematically analyzed the possible molecular mechanisms of Tanshinone ⅡA,providing potential targets and insights into its pharmacological mechanisms and treatment strategies.
文摘Total tanshinones are lipophilic active constituents extracted from Salvia miltiorrhiza Bge.Tanshinone ⅡA and cryptotanshinone are the major components in total tanshinones.However, the bioavailability of both compounds is low due to poor water solubility. To enhance the solubility and dissolution rate of tanshinone ⅡA, cryptotanshinone and total tanshinones,three common used hydrophilic carriers including PEG 6000, poloxamer 188 and PVP K30 were used to prepare the solid dispersions at different ratios, respectively. The solid dispersions were characterised by scanning electron microscopy(SEM), differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR). The results of powder X-ray diffraction confirmed the microcrystal state of total tanshinones in solid dispersions and no chemical interaction between total tanshinones and carriers was observed in FTIR spectra. The solubility and dissolution rate of tanshinone ⅡA and cryptotanshinone were significantly increased in all solid dispersions. Regarding tanshinone ⅡA, the solubility and dissolution rate of in solid dispersions prepared with poloxamer 188 were significantly higher than that with PEG 6000 and PVP K30. The higher solubility and dissolution rate of cryptotanshinone were obtained in solid dispersion of PVP K30 than that of PEG 6000 solid dispersions but no significant difference from poloxamer 188 solid dispersions. The results indicate that the superior carrier for preparation of tanshinone ⅡA and total tanshinones solid dispersions is poloxamer 188, and that for cryptotanshinone is PVP K30.
基金Supported by National Natural Science Foundation of China(30470055)Innovation Team Project of Liaoning Education Department (2007T006)~~
文摘[Objective]The aim was to extract tanshinone from Salvia miltiorrhiza Bge. dregs and to determine tanshinone components. [Method]Organic solvent method was adopted to extract tanshinone from S. miltiorrhiza dregs and TLC was used to determine the optimum extraction solvent. The components of tanshinone were measured with HPLC. [Result]Ether was the best solvent to extract tanshinone from S. miltiorrhiza dregs. After water immersion,dry dregs of S. miltiorrhiza and Panax notoginseng were extracted with ethanol to obtain fat-soluble extracts. Then with ether as the solvent for Soxhlet extraction,the yield of crude tanshinone was 2.17%. The HPLC detection showed that the contents of tanshinone Ⅱ A,methylene tanshinquinone,cryptotanshinone,tanshinone Ⅰ were 3.62%,1.02%,2.56%,2.75% respectively. [Conclusion]The components of tanshinone in S. miltiorrhiza dregs were basically the same as tanshinone in medicine S. miltiorrhiza. S. miltiorrhiza dregs could be used as a kind of tanshinone resource,which has the value of development and utilization.
基金The National Natural Science Foundation of China(Grant No.81360054)
文摘Tanshinone ⅡA（TSⅡA） is the major bioactive constituent of Salvia miltiorrhiza Bunge,a Chinese herbal medicine,which has protective effects on myocardial ischemia/reperfusion（MIR） injury.However,the cardioprotective effects of TSⅡA as well as its clinical use were limited due to its poor water solubility.The objective of this study was to evaluate whether Tanshinone ⅡA derivative（TD）,a new water soluble compound synthesized by TSⅡA and N-Methyl-D-Glucamine,had protective effects on MIR injury and what the related mechanism was.The cardioprotective effects of TD were evaluated and compared with TSⅡA in a rat MIR model.The results show that pretreatment with TD significantly alleviated inflammatory infiltration and exhibited antioxidant effect in MIR injury by reducing the activity of lactate dehydrogenase（LDH） and malondialdehyde（MDA）,decreasing expression of nuclear factor-κ-gene binding（NF-κB） and upregulating expression of heme oxygenase（HO-1）,but having no effect on the content of total superoxide dismutase（T-SOD） and m RNA expression of superoxide dismutase（SOD-1）.Thus,our study reveals that TD exerted significant protective effects on MIR injury through attenuating oxidative stress and inflammatory responses.
基金This work was supported by the National Key R&D Program of China(Nos.2020YFA0908000,2018YFA0900600)the National Natural Science Foundation of China(Nos.82003904,81822046)+4 种基金the Fundamental Research Funds for the Central public welfare research institutes(No.ZZ13-YQ-083)a Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021A04110)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202005)a key project at central government level(the ability to establish sustainable use of valuable Chinese medicine resources2060302,China).
文摘Danshen,the dried roots and rhizomes of Salvia miltiorrhiza Bunge(S.miltiorrhiza),is widely used in the treatment of cardiovascular and cerebrovascular diseases.Tanshinones,the bioactive compounds from Danshen,exhibit a wide spectrum of pharmacological properties,suggesting their potential for future therapeutic applications.Tanshinone biosynthesis is a complex process involving at least six P450 enzymes that have been identified and characterized,most of which belong to the CYP76 and CYP71 families.In this study,CYP81C16,a member of the CYP71 clan,was identified in S.miltiorrhiza.An in vitro assay revealed that it could catalyze the hydroxylation of four para-quinone-type tanshinones,namely neocryptotanshinone,deoxyneocryptotanshinone,and danshenxinkuns A and B.SmCYP81C16 emerged as a potential broad-spectrum oxidase targeting the C-18 position of para-quinone-type tanshinones with an impressive relative conversion rate exceeding 90%.Kinetic evaluations and in vivo assays underscored its highest affinity towards neocryptotanshinone among the tested substrates.The overexpression of SmCYP81C16 promoted the accumulation of(iso)tanshinone in hairy root lines.The characterization of SmCYP81C16 in this study accentuates its potential as a pivotal tool in the biotechnological production of tanshinones,either through microbial or plant metabolic engineering.
文摘Danshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine （TCM） for treatment of various diseases. Tanshinone IIA （TSA） is one of the main active components of Danshen, which has multiple bioactivities. This article reviews the research progress of TSA in the treatment of cardiovascular disease, anti-inflammatory and immune, anti-tumor, liver protection, neuroprotection. It provides more ideas for the clinical application of TSA and the development of drug resistance.
基金The program is sponsored by the Guangzhou City Science Foundation(2000-Z-021-01)Guangdong Provincial Science Foundation(2KM04103S).
文摘The reaction of cryptotanshinone and tanshinone IIA with several biogenic amine metabolites involved in the pathogenic pathways of HE were investigated and eight 1,2,3,4- tetrahydrophenanthrene derivatives, 2-6 and 8-10, were obtained. The probable mechanism on reaction was discussed.
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.
文摘Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate(STS) is a water-soluble derivative of Tanshinone IIA(TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein(CRP), procalcitonin(PCT), cardiac troponin Ⅰ(cTn-Ⅰ), cardiac troponin T(cTn-T), and brain natriuretic peptide(BNP) in cecal ligation and puncture(CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-10(IL-10) and high mobility group protein B1(HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose(15 mg×kg–1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30%(P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
基金supported by the China Postdoctoral Science Foundation,No.2015M581120
文摘TanshinoneⅡA,extracted from Salvia miltiorrhiza Bunge,exerts neuroprotective effects through its anti-inflammatory,anti-oxidative and anti-apoptotic properties.This study intravenously injected tanshinoneⅡA 20 mg/kg into rat models of spinal cord injury for 7 consecutive days.Results showed that tanshinoneⅡA could reduce the inflammation,edema as well as compensatory thickening of the bladder tissue,improve urodynamic parameters,attenuate secondary injury,and promote spinal cord regeneration.The number of hypertrophic and apoptotic dorsal root ganglion(L6–S1)cells was less after treatment with tanshinoneⅡA.The effects of tanshinoneⅡA were similar to intravenous injection of 30 mg/kg methylprednisolone.These findings suggested that tanshinoneⅡA improved functional recovery after spinal cord injury-induced lower urinary tract dysfunction by remodeling the spinal pathway involved in lower urinary tract control.
基金supported by the Science and Technology Commission of Shanghai Municipality(12DZ1930300,12DZ1930302,12DZ1930303)the Weak Discipline Construction Project(No.2016ZB0301–01)the 2016 Key Clinical Program of Clinical Pharmacy of Shanghai Municipal Commission of Health and Family Planning.cdh3
文摘This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate(STS) in healthy volunteers and coronary heart disease(CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance(CL) of STS in CHD patients with total bilirubin(TBIL) level of 10 μmol×L^(–1) was 48.7 L×h^(–1) with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L×h^(–1). Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.
基金supported by the National Natural Science Foundation of China,No.30973765New Century Excellent Talents Program,No. NECT-09-0013the Foundationfor Doctors,Ministry of Education,No.20113519110001
文摘Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone lla, 0.5 hour prior to model establishment. Results showed that Tanshinone Ila promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone Ila, compared with positive control Danshen injection.
基金the Natural Science Foundation of Hunan Province(Nos.2017JJ2338 and 2020JJ4860)the National Key Specialty Construction Project of Clinical Pharmacy(No.2013-5).
文摘Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hypoxia,cerebral ischemia and alzheimer’s disease,etc.In the treatment of cerebrovascular diseases,borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs,especially to the brain.The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA(TS IIA),salvianolic acid B(SAB)and ginsenoside Rg1 in FDP.Male healthy Sprague-Dawley(SD)rats were given Danshen extracts,Sanqi extracts(Panax notoginseng saponins)or simultaneously administered Danshen extracts,Sanqi extracts and borneol.Plasma and brain samples were collected at different points in time.The concentration of TS IIA,SAB and Rg1 was determined by UPLC-MS/MS method.The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software.In comparison with Danshen and Sanqi alone,there were significant differences in pharmacokinetic parameters of TS IIA,SAB and Rg1,and the brain distribution of SAB and TS IIA when Danshen,Sanqi and borneol were administrated together.Borneol statistically significant shortened tmax of TS IIA,SAB and Rg1 in plasma and brain,increased the bioavaiability of Rg1,inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain.These results indicated that borneol could affect the multiple targets components and produce synergistic effects.Through accelerating the intestinal absorption and brain distribution,borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.
基金the National Natural Science Foundation of China(No.81860047)the Postdoctoral Science Foundation of China(No.22019M653474)。
文摘This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts(CFs) and its potential mechanism, as well as whether sodium tanshinone ⅡA sulfonate(STS) has protective effect on CFs and its possible mechanism. Our data demonstrated that X-rays inhibited cell growth and increased oxidative stress in CFs, and STS mitigated X-ray-induced injury. Enzyme-linked immuno-sorbent assay showed that X-rays increased the levels of secreted angiotensin Ⅱ(Ang Ⅱ) and brain natriuretic peptide(BNP). STS inhibited the X-ray-induced increases in Ang Ⅱ and BNP release. Apoptosis and cell cycle of CFs were analyzed using flow cytometry. X-rays induced apoptosis in CFs, whereas STS inhibited apoptosis in CFs after X-ray irradiation. X-rays induced S-phase cell cycle arrest in CFs, which could be reversed by STS. X-rays increased the expression of phosphorylated-P38/P38,cleaved caspase-3 and caspase-3 as well as decreased the expression of phosphorylated extracellular signal-regulated kinase 1/2(ERK1/2)/ERK 1/2 and B cell lymphoma 2(Bcl-2)/Bcl-2 associated X protein(BAX) in CFs, as shown by Western blotting. STS mitigated the X-ray radiation-induced expression changes of these proteins. In conclusion, our results demonstrated that STS may potentially be developed as a medical countermeasure to mitigate radiation-induced cardiac damage.
基金supported by a grant from the National Natural Science Foundation of China(No.30500657)
文摘To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with high-dose TSN Ⅱ A was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN ⅡA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.
基金Supported by Key Projects of Zhejiang Province Science and Technology(Arsenic Trioxide Injection Associate with Tanshinone Treat the Hepatocarcinoma of Qi-Stagnancy and Blood Stasis,No.2012C13017-1)the Specialized Research Foundation for the Doctoral Program of Higher Education of China(the Mechanism of Jak-STAT3 Signaling Transduction in Anti-Hepatocarcinoma Associated with Arsenic Trioxide and Cryptotanshinone,No.20123322110001)
文摘OBJECTIVE:To identify the active anti-tumor constituents in the extract from Danshen(Radix Salviae Miltiorrhizae) and investigate the mechanisms underlying the actions.METHODS:First,we introduced a two-step counter-current chromatography to extract the therapeutically active diterpenoid,tanshinone from Danshen(Radix Salviae Miltiorrhizae).The cholecystokinin(CCK-8) method was used to evaluate the inhibitory effect of diterpenoid tanshinone in liver cancer QGY-7703,lung cancer PC9,lung cancer A549,gastric cancer MKN-45,gastric cancer HGC-27,colon cancer HCT116,myeloma cell U266/RPMI8226,and human breast cancer MCF-7 in vitro.Fluorescence staining was used to observe the cytotoxicity ofditerpenoid tanshinone on PC9 cells.The Western blot was used to detect apoptosis-related protein poly ADP-ribose polymerase(PARP),cysteinyl aspartate specific proteinase3/9(caspase3/9),and cleaved-cysteinyl aspartate specific proteinase3/9(cleaved-caspase3/9).The endoplasmic reticulum stress-related activating transcription factor 4(ATF4),phosphorylated eukaryotic initiation factor 2α(p-e IF2α),and phosphorylated jun amino-terminal kinase(p-JNK),and caspase-12 were also analyzed using the Western blot.RESULTS:Diterpenoid tanshinone inhibited the nine human tumor cell lines,with an IC50 of4.37-29 μg/m L,with the PC9 and MCF-7 displaying the lowest values.Fluorescence staining showed a lethal effect of diterpenoid tanshinone on PC9 cells.The Western blot showed that the expression of caspase3/9 protein and ATF-4 protein decreased gradually.However,the PARP,cleaved-caspase 3/9and the expression of p-e IF2 α,P-JNK,and caspase-12 increased gradually,in a dose-dependent fashion.CONCLUSION:We successfully introduced a two-step counter-current chromatography method to extract diterpenoid tanshinone,and demonstrated its antitumor activity.Diterpenoid tanshinone can induce apoptosis in nine human cancer cell lines.
基金卫生部科研项目,Grant of China Medical Board of New York,INC。
文摘AIM To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation was detected.RESULTS The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid. Flow cytometric assay demonstrated that S phase cells decreased and G0/G1 phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly increased.CONCLUSION Tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30572435)
文摘Objective:To investigate the protective action of tanshinone IIA (TSN) on myocardial apoptosis induced by hydrogen peroxide (H2O2) and its effect on prohibitin (PHB) expression to probe the role of PHB in the oxidation stress of myocardial cells. Methods: Primary cultured neonate rat myocardial cells were cultured with TSN (1×10-4 mol/L) for 24 hours, and then the medium was supplemented with 200 μmol/L hydrogen peroxide for 2 h to initiate myocardial cell oxidative stress injury. PHB in myocardial cells was knocked down by small interfering RNA (siRNA), and the expression level of PHB was determined by western blot analysis. Flow cytometry was used to detect the apoptosis rate, intracellular calcium ion concentration ([Ca2+]i) and mitochondrial membrane potential (MMP). Results: The PHB expression, [Ca2+]i and the apoptotic rate significantly increased, and the MMP significantly decreased in the oxidative stress group compared with the control. The PHB expression, apoptosis rate and [Ca2+]i decreased, and MMP increased significantly in the TSN group compared with the oxidative stress group. Compared with the siRNA negative control group, the PHB expression level in myocardial cells was down-regulated, and the apoptosis rate and [Ca2+]i increased, and MMP decreased significantly in the siRNA group. Conclusion: TSN can reduce PHB expression in oxidative stress-injured myocardial cells hence protecting the myocardial cells.
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a grant from National Natural Sciences Foundation of China (No. 30500657)
文摘The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction （RT-PCR）. It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly （P〈0.01）. After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group （P〈0.01）. After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group （P〈0.05）. After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ （P〈0.05 or P〈0.01）. It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.
