Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Whar...Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton＇ s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton＇ s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton＇ s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy （EM）, and laser scanning confocal microscopy （LSCM） . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction （RT-PCR）.Results MSCs in the Wharton＇ s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease （GVHD）-related cells. Treatment with Salvia mihiorrhiza caused Wharton＇ s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament （NF） and glial fibrillary acidic protein （GFAP）. It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharto展开更多
Objective To investigate the differentiation of bone marrow stromal cells （BMSC） into neuron-like cells and to explore their potential use for neural transplantation. Methods BMSC from rats and adult humans were cul...Objective To investigate the differentiation of bone marrow stromal cells （BMSC） into neuron-like cells and to explore their potential use for neural transplantation. Methods BMSC from rats and adult humans were cultured in serum-containing media. Salvia miltiorrhiza was used to induce human BMSC （hBMSC） to differentiate. BMSC were identified with immunocytochemistry. Semi-quantitative RT-PCR was used to examine mRNA expression of neurofilamentl （NF1）, nestin and neuron-specific enolase （NSE） in rat BMSC （rBMSC）. Rat BMSC labelled by Hoschst33258 were transplanted into striatum of rats to trace migration and distribution. Results rBMSC expressed NSE, NFI and nestin mRNA, and NF1 mRNA and expression was increased with induction of Salvia miltiorrhiza. A small number of hBMSC were stained by anti-nestin, anti-GFAP and anti-S 100. Salvia miltiorrhiza could induce hBMSC to differentiate into neuron-like cells. Some differentiated neuron-like cells, that expressed NSE, beta-tubulin and NF-200, showed typical neuron morphology, but some neuron-like cells also expressed alpha smooth muscle protein, making their neuron identification complicated, rBMSC could migrate and adapted in the host brains after being transplanted. Conclusion Bone marrow stromal cells could express phenotypes of neurons, and Salvia milliorrhiza could induce hBMSC to differentiate into neuron-like cells, If BMSC could be converted into neurons instead of mesenchymal derivatives, they would be an abundant and accessible cellular source to treat a variety of neurological diseases.展开更多
Chemical studies on nine Salvia species yielded various polyphenolic acids. Eleven of them were depsides of R (+) β (3,4 dihydroxyphenyl) lactic acid and a caffeic acid derivative or caffeic acid dimer. Except th...Chemical studies on nine Salvia species yielded various polyphenolic acids. Eleven of them were depsides of R (+) β (3,4 dihydroxyphenyl) lactic acid and a caffeic acid derivative or caffeic acid dimer. Except the two known depsides, rosmarinic acid and lithospermic acid, this type of depsides has not been isolated from other plant materials before, so they were named salvianolic acid A, B, C, D, E, H, I, J and isosalvianolic acid C. Salvianolic acid F, G and przewalskinic acid A were new polyphenolic acids. Pharmacological studies of these polyphenolic acids showed potent antioxidant activities. The effects of these components in protecting against brain and heart damage have been studied.展开更多
Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper(b...Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper(bZIP) proteins regulate plant secondary metabolism, growth and developmental processes. However, the b ZIP transcription factors involved in tanshinone biosynthesis are unknown.Here, we conducted the first genome-wide survey of the b ZIP gene family and analyzed the phylogeny,gene structure, additional conserved motifs and alternative splicing events in S. miltiorrhiza. A total of 70 Smb ZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in Arabidopsis. Moreover, seventeen Smb ZIP genes underwent alternative splicing events. According to the transcriptomic data, the Smb ZIP genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of b ZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag^+ treatment via quantitative real-time polymerase chain reaction(qRT-PCR), we concluded that Smb ZIP7 and Smb ZIP20 potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate Smb ZIP genes, which have the potential to increase tanshinone production.展开更多
Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sha...Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results:The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions:Both dexamethasone and Salvia miltiorrhiza can reduce the inflammat展开更多
AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 eac...AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.展开更多
4-Coumarate ： coenzyme A Ilgase （4CL） Is one of the key enzymes In phenylpropanoid metabolism leading to series of phenollcs, Including water-soluble phenolic acids, which are important compounds determining the me...4-Coumarate ： coenzyme A Ilgase （4CL） Is one of the key enzymes In phenylpropanoid metabolism leading to series of phenollcs, Including water-soluble phenolic acids, which are important compounds determining the medicinal quality of Danshen （Salvia miltiorrhiza Bunge）, a traditional Chinese medicinal herb. To Investigate the function of 4CL in the biosynthesis of water-soluble phenolic acid in Danshen, we have cloned two cDNAs （Sm4CL1 and Sm4CL2） encoding divergent 4CL members by applying nested reverse transcrlptlon-polymerase chain reaction （RT-PCR） with degenerate primers followed by 5′/3′rapid amplification of cDNA ends （RACE） （Note, these sequence data have been submitted to the GenBank database under accession numbers AY237163 and AY237164）. Either of the coding regions was inserted into a pRSET vector and a kinetic assay was performed with purified recombinant proteins. The substrate utilization profile of Sm4CL1 was distinct from that of Sm4CL2. The Km values of Sm4CL1 and Sm4CL2 to 4-coumarlc acid were （72.20±4.10） and （6.50±1.45） μmol/L, respectively. These results, In conjunction with Northern blotting and other information, imply that Sm4CL2 may play an Important role in the biosynthesis of watersoluble phenolic compounds, whereas Sm4CL1 may play a minor role in the pathway. Southern blotting analysis suggested that both Sm4CL1 and Sm4CL2 genes are present as a single copy and are located at different sites In the genome.展开更多
BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the pre...BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the present study was to determine the effects of Salvia miltiorrhiza on intestinal mi- croflora, endotoxemia, and bacterial translocation in rats with hepatic I/R injury. METHODS: Sprague-Dawley rats in specific pathogen free grade were divided into 3 groups: group I(n =6) for sham operation: groups ( n = 7) for liver ische- mia for 20 minutes and reperfusion for 22 hours. Group was also pretreated with 4 ml/day of Salvia miltiorrhiza solu- tion (250 mg/kg) by daily gavage for 7 days. The levels of serum alanine aminotransferase (ALT), aspartate amino- transferase (AST), malondialdehyde ( MDA) and supero- xide dismutase ( SOD ) in liver tissues, serum endotoxin, intestinal bacterial counts, intestinal mucosal histology and bacterial translocation were studied. RESULTS: The levels of ALT, AST, plasma endotoxin and MDA in liver tissues were decreased more markedly in group (57.57 ± 18.08 U/L, 147.57 ±40.84 U/L, 0.42 ± 0.144 EU/ml and 0. 52 ±0.19 nmol/mg-prot respectively) in group 295.9±216.92 U/L, 0.80± 0.262 EU/ml and 0.72±0.12 nmol/mg-prot; P <0.05-0.01 respectively). Liver SOD activity was increased more sig- nificantly in group (318.47±64.62 U/mg-prot) than in group U/mg-prot, P<0.05). The counts of Bifidobacteria and Bacteroides increased more significantly in group than in group but were similar to those in group I. Bacterial translocation to the kidney in group was 50% (5/10), whereas no bacterial translocation to the kidney occurred in the other two groups (P <0. 01). Ileal mucosal structure was markedly ameliorated in group as compared with group CONCLUSIONS: Salviae miltiorrhiza could partially restore intestinal microflora balance, improve intestinal mucosal integrity, and reduce bacterial translocation and plasma en- dotoxin in rats with hepatic ischemia/reperfusion injury.展开更多
The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion gen...The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion generation by xanthine─xanthine oxidase system. It was also demonstrated that six components( 100 μmol/L) prevented H_2O_2─induced hemolysis and MDA fonnation in mouse erythrocytes.The effects of Sal A, Sal B, Sal C and Ros A were dose dependent. In Langendorff rat heart, pretreatment with Sal A 20μmol/L significantly prevented MDA production induced by 30 min reoxygenation after 45 min anoxia.The results indicated that there were also other potent antioxidant componentts in Salvia milliorrhiza besides Dphl and Pal. The protection of Sal A against myocardial anoxiareoxygenation inury may be mainly ascribed to its oxygen free radical scavenging activity.展开更多
SQUAMOSA promoter binding protein-likes （SPLs） are plant-specific transcription factors playing vital regulatory roles in plant growth and development. There is no information about SPLs in Salvia miltiorrhiza （Dan...SQUAMOSA promoter binding protein-likes （SPLs） are plant-specific transcription factors playing vital regulatory roles in plant growth and development. There is no information about SPLs in Salvia miltiorrhiza （Danshen）, a significant medicinal plant widely used in Traditional Chinese medicine （TCM） for＆gt;1,700 years and an emerging model plant for TCM studies. Through genome-wide identification and subsequent molecular cloning, we identified a total 15 SmSPLs with divergent sequence features, gene structures, and motifs. Comparative analysis showed sequence conservation between SmSPLs and their Arabidopsis counterparts. A phylogenetic tree clusters SmSPLs into six groups. Many of the motifs identified commonly exist in a group/subgroup, implying their functional redundancy. Eight SmSPLs were predicted and experimental y validated to be targets of miR156/157. SmSPLs were differen-tial y expressed in various tissues of S. milltiorrhiza. The expression of miR156/157-targeted SmSPLs was increased with＆amp;nbsp;the maturation of S. miltiorrhiza, whereas the expression of miR156/157 was decreased, confirming the regulatory roles of miR156/157 in SmSPLs and suggesting the functions of SmSPLs in S. miltiorrhiza development. The expression of miR156/157 was negatively correlated with miR172 during the maturation of S. miltiorrhiza. The results indicate the significance and complexity of SmSPL-, miR156-, and miR172-mediated regula-tion of developmental timing in S. miltiorrhiza.展开更多
Objective: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection（SML） on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2...Objective: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection（SML） on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2（NDRG2, a tumor suppressor gene）. Methods: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×10;cells/mL and cultured for 24 h followed by the application of different concentrations of SML（1, 2, 4 and 8 μL/mL）. Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot. Results: With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h（P<0.05）. With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected. Conclusion: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.展开更多
OBJECTIVE: To undertake a systematic review and network meta-analysis(NMA) to compare the effectiveness among the different regimens of Salvia miltiorrhiza injection classes(SMICs) for unstable angina pectoris(UAP) tr...OBJECTIVE: To undertake a systematic review and network meta-analysis(NMA) to compare the effectiveness among the different regimens of Salvia miltiorrhiza injection classes(SMICs) for unstable angina pectoris(UAP) treatment.METHODS: A systematic retrieval was conducted in several literature databases to identify randomized controlled trials focusing on the different regimens of SMICs for UAP treatment until January2016. The quality assessment was accomplished according to the Cochrane risk of bias tool. Pair-wise meta-analyses were carried out by Rev Man 5.3. A random-effects model of NMA was used to compare the different regimens of SMICs with regard to efficacy by STATA 13.0.RESULTS: A total of 111 studies involving 10 500patients were included in the NMA. The methodological quality of included studies was not high.Current evidence shows that salvianolate(SI) is the optimal treatment for UAP in improving the total efficacy against UAP. Guanxingning(GXN) is the optimal treatment for UAP for improving the total effectiveness of electrocardiography.CONCLUSION: SMICs have advantages in preventing cardiovascular events. GXN, SI, and Danhong had the greatest probability of being the best treatment in the total efficacy against UAP and for improving the total effectiveness of electrocardiography.展开更多
AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid indu...AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.展开更多
文摘Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton＇ s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton＇ s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton＇ s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy （EM）, and laser scanning confocal microscopy （LSCM） . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction （RT-PCR）.Results MSCs in the Wharton＇ s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease （GVHD）-related cells. Treatment with Salvia mihiorrhiza caused Wharton＇ s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament （NF） and glial fibrillary acidic protein （GFAP）. It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharto
基金This work was supported by Natural Science Foundation of Guangdong Province (No. 012452, No. 020001).
文摘Objective To investigate the differentiation of bone marrow stromal cells （BMSC） into neuron-like cells and to explore their potential use for neural transplantation. Methods BMSC from rats and adult humans were cultured in serum-containing media. Salvia miltiorrhiza was used to induce human BMSC （hBMSC） to differentiate. BMSC were identified with immunocytochemistry. Semi-quantitative RT-PCR was used to examine mRNA expression of neurofilamentl （NF1）, nestin and neuron-specific enolase （NSE） in rat BMSC （rBMSC）. Rat BMSC labelled by Hoschst33258 were transplanted into striatum of rats to trace migration and distribution. Results rBMSC expressed NSE, NFI and nestin mRNA, and NF1 mRNA and expression was increased with induction of Salvia miltiorrhiza. A small number of hBMSC were stained by anti-nestin, anti-GFAP and anti-S 100. Salvia miltiorrhiza could induce hBMSC to differentiate into neuron-like cells. Some differentiated neuron-like cells, that expressed NSE, beta-tubulin and NF-200, showed typical neuron morphology, but some neuron-like cells also expressed alpha smooth muscle protein, making their neuron identification complicated, rBMSC could migrate and adapted in the host brains after being transplanted. Conclusion Bone marrow stromal cells could express phenotypes of neurons, and Salvia milliorrhiza could induce hBMSC to differentiate into neuron-like cells, If BMSC could be converted into neurons instead of mesenchymal derivatives, they would be an abundant and accessible cellular source to treat a variety of neurological diseases.
文摘Chemical studies on nine Salvia species yielded various polyphenolic acids. Eleven of them were depsides of R (+) β (3,4 dihydroxyphenyl) lactic acid and a caffeic acid derivative or caffeic acid dimer. Except the two known depsides, rosmarinic acid and lithospermic acid, this type of depsides has not been isolated from other plant materials before, so they were named salvianolic acid A, B, C, D, E, H, I, J and isosalvianolic acid C. Salvianolic acid F, G and przewalskinic acid A were new polyphenolic acids. Pharmacological studies of these polyphenolic acids showed potent antioxidant activities. The effects of these components in protecting against brain and heart damage have been studied.
基金supported by the National Natural Science Foundation (Grant No.81573398)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences (CIFMS,2016-I2M-3–016)
文摘Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper(bZIP) proteins regulate plant secondary metabolism, growth and developmental processes. However, the b ZIP transcription factors involved in tanshinone biosynthesis are unknown.Here, we conducted the first genome-wide survey of the b ZIP gene family and analyzed the phylogeny,gene structure, additional conserved motifs and alternative splicing events in S. miltiorrhiza. A total of 70 Smb ZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in Arabidopsis. Moreover, seventeen Smb ZIP genes underwent alternative splicing events. According to the transcriptomic data, the Smb ZIP genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of b ZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag^+ treatment via quantitative real-time polymerase chain reaction(qRT-PCR), we concluded that Smb ZIP7 and Smb ZIP20 potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate Smb ZIP genes, which have the potential to increase tanshinone production.
基金Project (No. 2010382) supported by the Foundation for the Excellent Middle-Aged and Talented Young Persons of Zhejiang Province"151", China
文摘Objective:To investigate the protective effects and mechanisms of action of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis (SAP). Methods:The rats were divided into sham-operated, model control, dexamethasone treated, and Salvia miltiorrhiza treated groups. At 3, 6, and 12 h after operation, the mortality rate of different groups, pathological changes, Bcl-2-associated X protein (Bax) and nuclear factor-κB (NF-κB) protein expression levels in multiple organs (the pancreas, liver, kidneys, and lungs), toll-like receptor 4 (TLR-4) protein levels (only in the liver), intercellular adhesion molecule 1 (ICAM-1) protein levels (only in the lung), and terminal deoxynucleotidy transferase mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining expression levels, as well as the serum contents of amylase, glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), and creatinine (CREA) were observed. Results:The mortality rate of the dexamethasone treated group was significantly lower than that of the model control group (P<0.05). The pathological changes in multiple organs in the two treated groups were relieved to different degrees (P<0.05 and P<0.01, respectively), the expression levels of Bax and NF-κB proteins, and apoptotic indexes of multiple organs were reduced (P<0.05 and P<0.01, respectively). The contents of amylase, GPT, GOT, BUN, and CREA in the two treated groups were significantly lower than those in model control groups (P<0.05 and P<0.01, respectively). The expression level of ICAM-1 protein in the lungs (at 3 and 12 h) in the dexamethasone treated group was significantly lower than that in the Salvia miltiorrhiza treated group (P<0.05). The serum contents of CREA (at 12 h) and BUN (at 6 h) of the Salvia miltiorrhiza treated group were significantly lower than those in the dexamethasone treated group (P<0.05). Conclusions:Both dexamethasone and Salvia miltiorrhiza can reduce the inflammat
基金Supported by Production of New Medicine Program of Ministry of Science and Technology of the People's Republic of China,No.2008ZX09401
文摘AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.
基金Supported by the National Natural Science Foundation of China （30300447）.The authors thank Dr Chen Yongning （China Innovation Centre for Drug Development, HK） for useful suggestions and support. The authors also thank to Dr Fanya Zeng and Miss Charis Chan （Department of Zoology, University of Hong Kong） for technical assistance.
文摘4-Coumarate ： coenzyme A Ilgase （4CL） Is one of the key enzymes In phenylpropanoid metabolism leading to series of phenollcs, Including water-soluble phenolic acids, which are important compounds determining the medicinal quality of Danshen （Salvia miltiorrhiza Bunge）, a traditional Chinese medicinal herb. To Investigate the function of 4CL in the biosynthesis of water-soluble phenolic acid in Danshen, we have cloned two cDNAs （Sm4CL1 and Sm4CL2） encoding divergent 4CL members by applying nested reverse transcrlptlon-polymerase chain reaction （RT-PCR） with degenerate primers followed by 5′/3′rapid amplification of cDNA ends （RACE） （Note, these sequence data have been submitted to the GenBank database under accession numbers AY237163 and AY237164）. Either of the coding regions was inserted into a pRSET vector and a kinetic assay was performed with purified recombinant proteins. The substrate utilization profile of Sm4CL1 was distinct from that of Sm4CL2. The Km values of Sm4CL1 and Sm4CL2 to 4-coumarlc acid were （72.20±4.10） and （6.50±1.45） μmol/L, respectively. These results, In conjunction with Northern blotting and other information, imply that Sm4CL2 may play an Important role in the biosynthesis of watersoluble phenolic compounds, whereas Sm4CL1 may play a minor role in the pathway. Southern blotting analysis suggested that both Sm4CL1 and Sm4CL2 genes are present as a single copy and are located at different sites In the genome.
基金This study was supported by grants from the NationalBasic Research Program (973) of China ( No. 2003CB515506),Postdoctoral Fund of China (20040350233), and Research Grantawarded by the First Affiliated Hospital, Zhejiang UniversitySchool of Medicine, Hangzhou, China.
文摘BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the present study was to determine the effects of Salvia miltiorrhiza on intestinal mi- croflora, endotoxemia, and bacterial translocation in rats with hepatic I/R injury. METHODS: Sprague-Dawley rats in specific pathogen free grade were divided into 3 groups: group I(n =6) for sham operation: groups ( n = 7) for liver ische- mia for 20 minutes and reperfusion for 22 hours. Group was also pretreated with 4 ml/day of Salvia miltiorrhiza solu- tion (250 mg/kg) by daily gavage for 7 days. The levels of serum alanine aminotransferase (ALT), aspartate amino- transferase (AST), malondialdehyde ( MDA) and supero- xide dismutase ( SOD ) in liver tissues, serum endotoxin, intestinal bacterial counts, intestinal mucosal histology and bacterial translocation were studied. RESULTS: The levels of ALT, AST, plasma endotoxin and MDA in liver tissues were decreased more markedly in group (57.57 ± 18.08 U/L, 147.57 ±40.84 U/L, 0.42 ± 0.144 EU/ml and 0. 52 ±0.19 nmol/mg-prot respectively) in group 295.9±216.92 U/L, 0.80± 0.262 EU/ml and 0.72±0.12 nmol/mg-prot; P <0.05-0.01 respectively). Liver SOD activity was increased more sig- nificantly in group (318.47±64.62 U/mg-prot) than in group U/mg-prot, P<0.05). The counts of Bifidobacteria and Bacteroides increased more significantly in group than in group but were similar to those in group I. Bacterial translocation to the kidney in group was 50% (5/10), whereas no bacterial translocation to the kidney occurred in the other two groups (P <0. 01). Ileal mucosal structure was markedly ameliorated in group as compared with group CONCLUSIONS: Salviae miltiorrhiza could partially restore intestinal microflora balance, improve intestinal mucosal integrity, and reduce bacterial translocation and plasma en- dotoxin in rats with hepatic ischemia/reperfusion injury.
文摘The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion generation by xanthine─xanthine oxidase system. It was also demonstrated that six components( 100 μmol/L) prevented H_2O_2─induced hemolysis and MDA fonnation in mouse erythrocytes.The effects of Sal A, Sal B, Sal C and Ros A were dose dependent. In Langendorff rat heart, pretreatment with Sal A 20μmol/L significantly prevented MDA production induced by 30 min reoxygenation after 45 min anoxia.The results indicated that there were also other potent antioxidant componentts in Salvia milliorrhiza besides Dphl and Pal. The protection of Sal A against myocardial anoxiareoxygenation inury may be mainly ascribed to its oxygen free radical scavenging activity.
基金supported by grants from the Beijing Natural Science Foundation(Grant No.5112026 to S.L.)the Major Scientific and Technological Special Project for Significant New Drugs Creation(Grant No.2012ZX09301002-001-031 to S.L.)+2 种基金the Research Fund for the Doctoral Program of Higher Education of China(20111106110033 to S.L.)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT,Grant No.IRT1150)the Program for Xiehe Scholars in Chinese Academy of Medical Sciences&Peking Union Medical College(to S.L.)
文摘SQUAMOSA promoter binding protein-likes （SPLs） are plant-specific transcription factors playing vital regulatory roles in plant growth and development. There is no information about SPLs in Salvia miltiorrhiza （Danshen）, a significant medicinal plant widely used in Traditional Chinese medicine （TCM） for＆gt;1,700 years and an emerging model plant for TCM studies. Through genome-wide identification and subsequent molecular cloning, we identified a total 15 SmSPLs with divergent sequence features, gene structures, and motifs. Comparative analysis showed sequence conservation between SmSPLs and their Arabidopsis counterparts. A phylogenetic tree clusters SmSPLs into six groups. Many of the motifs identified commonly exist in a group/subgroup, implying their functional redundancy. Eight SmSPLs were predicted and experimental y validated to be targets of miR156/157. SmSPLs were differen-tial y expressed in various tissues of S. milltiorrhiza. The expression of miR156/157-targeted SmSPLs was increased with＆amp;nbsp;the maturation of S. miltiorrhiza, whereas the expression of miR156/157 was decreased, confirming the regulatory roles of miR156/157 in SmSPLs and suggesting the functions of SmSPLs in S. miltiorrhiza development. The expression of miR156/157 was negatively correlated with miR172 during the maturation of S. miltiorrhiza. The results indicate the significance and complexity of SmSPL-, miR156-, and miR172-mediated regula-tion of developmental timing in S. miltiorrhiza.
基金Supported by the National Natural Science Foundation of China(No.81272490 and 81100764)
文摘Objective: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection（SML） on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2（NDRG2, a tumor suppressor gene）. Methods: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×10;cells/mL and cultured for 24 h followed by the application of different concentrations of SML（1, 2, 4 and 8 μL/mL）. Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and β-catenin were measured by Western blot. Results: With the exception of the 1 and 2 μL/mL concentrations, 4 and 8 μL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h（P<0.05）. With the exception of the 1 and 2 μL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of β-catenin was unaffected. Conclusion: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.
基金Supported by National Natural Science Foundation of China:Study on the Key Influencing Factors of Anaphylaxis in Traditional Chinese Medicine Injection(No.81473547)Multi-dimensional Clinical Evaluation Model of Salvia Injection for the Treatment of Unstable Angina Pectoris(No.81673829)
文摘OBJECTIVE: To undertake a systematic review and network meta-analysis(NMA) to compare the effectiveness among the different regimens of Salvia miltiorrhiza injection classes(SMICs) for unstable angina pectoris(UAP) treatment.METHODS: A systematic retrieval was conducted in several literature databases to identify randomized controlled trials focusing on the different regimens of SMICs for UAP treatment until January2016. The quality assessment was accomplished according to the Cochrane risk of bias tool. Pair-wise meta-analyses were carried out by Rev Man 5.3. A random-effects model of NMA was used to compare the different regimens of SMICs with regard to efficacy by STATA 13.0.RESULTS: A total of 111 studies involving 10 500patients were included in the NMA. The methodological quality of included studies was not high.Current evidence shows that salvianolate(SI) is the optimal treatment for UAP in improving the total efficacy against UAP. Guanxingning(GXN) is the optimal treatment for UAP for improving the total effectiveness of electrocardiography.CONCLUSION: SMICs have advantages in preventing cardiovascular events. GXN, SI, and Danhong had the greatest probability of being the best treatment in the total efficacy against UAP and for improving the total effectiveness of electrocardiography.
文摘AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.
