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
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
OBJECTIVE: To investigate the effective ingredients of Danshen(Radix Salviae Miltiorrhizae) and Honghua(Flos Carthami)(Danhong) on protective properties towards neonatal rat hippocampal neurons under hypoxia condition...OBJECTIVE: To investigate the effective ingredients of Danshen(Radix Salviae Miltiorrhizae) and Honghua(Flos Carthami)(Danhong) on protective properties towards neonatal rat hippocampal neurons under hypoxia condition.METHODS: Primary culture of neonatal rat hippocampal neurons was used to model hypoxia damage on the hippocampus. Methyl thiazolyl tetrazolium(MTT) assay and preliminary experiments were conducted to identify the four effective ingredients of Danhong, along with the injection of positive drug onto hippocampal neurons at a non-toxic dosage level. The cultured cells were randomly divided into 12 groups: the normal group, model group,positive drug control group and nine compatibility groups of the four effective ingredients. Different test methods were applied to determine lactate dehydrogenasein(LDH), total superoxide dismutase(T-SOD), malondialdehyde(MDA), 6-keto prostaglandin F_(la)(6-keto-PGF_(1 a)), thromboxane B_2(TXB_2),mitochondrial membrane potential(MMP), free calcium ions concentration([Ca^(2 +)]i) and early onsetcell apoptosis.RESULTS: Different compatibility groups could inhibit the content of LDH and intracellular calcium overload, increase activity in T-SOD, decrease level of MDA and TXB2, improve level of 6-keto-PGF1 aand MMP, and prevent the early onset cell apoptosis.CONCLUSION: The compatibility of four effective ingredients of Danhong had protective effect toward hippocampi hypoxia. The mechanism might be related to inhibit oxidative stress damage and cell apoptosis, resist thrombosis, and reduce the intracellular calcium ion of overload.展开更多
The protective effects for hepatocytes of Salviae miltiorrhiza and Paeonia lactiflora in ex-perimental rat models of liver damage were observed. Pathological changes in light and electron micro-scopies and plasma fibr...The protective effects for hepatocytes of Salviae miltiorrhiza and Paeonia lactiflora in ex-perimental rat models of liver damage were observed. Pathological changes in light and electron micro-scopies and plasma fibronectin level alterations of liver injury in rats, revealed that Salviae miltiorrhizacould induce the increase of plasma fibronectin level in rats, thus improved phagocytosis of the reticuloen-dothelial system and opsonin activity, preventing the liver from immunologic damage, protecting hepato-cytes and promoting regeneration. Similar but weaker actions were observed in Paeoniae lactiflora.展开更多
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.
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Supported by National Natural Science Foundation of China:Biological Foundation Research Related to Ischemic Stroke in Qi Deficiency and Blood Stasis Syndrome Based on Drug Metabolism and Biological Effects of Buyang Huanwu Decotion and Its Associated Prescriptions(No.81630105)Effect of Danhong Injection on Cerebral Ischemia Reperfusion Injury in Rats Mediated by Aldose Reductase(No.81673639)+3 种基金Zhejiang Provincial Natural Science Foundation of China:Mechanism of the Component Compatibility of Salvia Miltiorrhiza and Safflower against Cerebral Ischemic Injury Based on the Association of PK-PD(No.LZ17H270001)Zhejiang Provincial Program for the health leading talentsBasic public welfare research project of Zhejiang Province:Investigation and Application of Optimization of Chinese Traditional Medicine Extraction Process Based on Genetic Algorithm-neural Network Approach(No.LGN18A010001)Scientific Research Foundation of Zhejiang Chinese Medicine University:Mechanism of Danhong Injection against Cerebral Ischemic Injury Based on Pharmacokinetic Efficacy(PK-PD)Relationship(No.2017ZZ09)
文摘OBJECTIVE: To investigate the effective ingredients of Danshen(Radix Salviae Miltiorrhizae) and Honghua(Flos Carthami)(Danhong) on protective properties towards neonatal rat hippocampal neurons under hypoxia condition.METHODS: Primary culture of neonatal rat hippocampal neurons was used to model hypoxia damage on the hippocampus. Methyl thiazolyl tetrazolium(MTT) assay and preliminary experiments were conducted to identify the four effective ingredients of Danhong, along with the injection of positive drug onto hippocampal neurons at a non-toxic dosage level. The cultured cells were randomly divided into 12 groups: the normal group, model group,positive drug control group and nine compatibility groups of the four effective ingredients. Different test methods were applied to determine lactate dehydrogenasein(LDH), total superoxide dismutase(T-SOD), malondialdehyde(MDA), 6-keto prostaglandin F_(la)(6-keto-PGF_(1 a)), thromboxane B_2(TXB_2),mitochondrial membrane potential(MMP), free calcium ions concentration([Ca^(2 +)]i) and early onsetcell apoptosis.RESULTS: Different compatibility groups could inhibit the content of LDH and intracellular calcium overload, increase activity in T-SOD, decrease level of MDA and TXB2, improve level of 6-keto-PGF1 aand MMP, and prevent the early onset cell apoptosis.CONCLUSION: The compatibility of four effective ingredients of Danhong had protective effect toward hippocampi hypoxia. The mechanism might be related to inhibit oxidative stress damage and cell apoptosis, resist thrombosis, and reduce the intracellular calcium ion of overload.
文摘The protective effects for hepatocytes of Salviae miltiorrhiza and Paeonia lactiflora in ex-perimental rat models of liver damage were observed. Pathological changes in light and electron micro-scopies and plasma fibronectin level alterations of liver injury in rats, revealed that Salviae miltiorrhizacould induce the increase of plasma fibronectin level in rats, thus improved phagocytosis of the reticuloen-dothelial system and opsonin activity, preventing the liver from immunologic damage, protecting hepato-cytes and promoting regeneration. Similar but weaker actions were observed in Paeoniae lactiflora.
