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Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.
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Realtime xCELLigence analysis (RTCA) is a new cell detection technology to continuously monitor, record and analyze a variety of information generated by cell activity. In drug research, it plays an important role in assessing myocardial toxicity and cell biological activity. Here, we first introduce the underlying mechanisms and characteristics of RTCA. Then we review the applications of RTCA in the research of myocardial toxicity and cell biological activity, to provides the fundamental baseline for understanding and exploiting RTCA. With the real-time, unlabeled, non-invasive, high throughput, and high accuracy features, RTCA not only promotes drug research and development, but also has a broad and good application prospect in other fields.
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Pharmaceutical PreparationsABSTRACT
OBJECTIVE:To study the effect and its possible mechanism of Xuezhiping capsule on blood lipid levels of high blood lipid model golden hamsters. METHODS:Golden hamsters were randomly divided into normal control group,model group, atorvastatin group (3 mg/kg),combination group (Xuezhiping capsule 1.3 g/kg+atorvastatin 1.5 mg/kg),Xuezhiping capsule low-dose,medium-dose,high-dose groups(Xuezhiping capsule 1.3,2.6,5.2 g/kg),10 in each group. Hamsters in normal control group received normal diet,the other groups were given high-fat diet to establish high blood lipid model. Then relevant drugs were intragastrically given 2 weeks later. Normal control group and model group were intragastrically given equal volume of distilled wa-ter,once a day,for 4 weeks. After last administration,blood lipid indexes(TG,TC,HDL-C,LDL-C,FFA),mRNA and protein expressions of lipid metabolism related genes (PPAR-α,CYP7A1,ACOX,SREBP-1c,ACC1) were detected. RESULTS:Com-pared with normal control group,serum contents of TC,TG,LDL-C,FFA in model group increased,HDL-C content decreased;PPAR-α,CYP7A1,ACOX mRNA and protein expressions were weakened,SREBP-1c,ACC1 mRNA and protein expressions were enhanced(P<0.05). Compared with model group,above-mentioned indexes were obviously improved in Xuezhiping capsule high-dose group,atorvastatin group and combination group (except for HDL-C in Xuezhiping capsule high-dose group)(P<0.05);TC,TG,FFA contents,and PPAR-α,CYP7A1,ACOX,ACC1 mRNA,and CYP7A1,SREBP-1c,ACC1 protein were obviously improved in Xuezhiping capsule medium-dose group(P<0.05);TC,TG contents,and PPAR-α mRNA,and CYP7A1, SREBP-1c protein were obviously improved in Xuezhiping capsule low-dose group (P<0.05). CONCLUSIONS:Xuezhiping cap-sule has a promising effect of lowering blood lipid,the mechanism may be related to activating PPAR-α and inhibiting SREBP-lc signaling pathway.
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Arsenic trioxide has a significantly positive effect on the treatment of acute promyelocyte leukemia( APL) , and it also has been proved that arsenic trioxide can protect against some other kinds of malignant tumors in recent years. However, with the further research about arsenic trioxide, the reports about car-diac toxicity of arsenic trioxide are increasing. Currently, the possible mechanisms of As2 O3-induced cardiotoxicity are mainly considered to be associated with changes in cardiac ion chan-nels, oxidative stress injury and apoptosis. Research advances on cardiac toxicity of arsenic trioxide and some ways of preven-tion are summarized.
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Aim To investigate the protective effect of Panax Notoginseng Saponins ( PNS ) on Aβ25-35-in-duced apoptosis in PC12 cells and molecular mecha-nism. Methods The cell viability of PC12 cells was detected by MTT assay. The levels of LDH leakage, ROS,MDA,Caspase-3 activity and antioxidant enzyme activities of SOD, CAT, and GSH-Px activity were de-termined by respective kits. The apoptosis of cells was decteced by Western blot. Results PNS could signifi-cantly inhibit the decrease of cell viability and LDH leakage, reduce the production of MDA and ROS( P<0. 01), increase the activity of SOD,CAT and GSH-Px ( P <0. 01 ) , and the mitochondrial membrane poten-tial, inhibit the activation of caspase-3 ( P <0. 01 ) in PC12 cells which were induced by Aβ25-35 . PNS could incrase nuclear Nrf2 and up-regulate HO-1 . The neu-roprotective of PNS could be inhibited by HO-1 inhibi-tor ZnPP. Conclusion PNS may inhibit Aβ25-35-in-duced oxidative stress and apoptosis in PC12 cells by activating Nrf2/HO-1 signaling pathway.
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Notch signaling, a highly conserved pathway, is wide-ly found in invertebrates and vertebrates. By mediating cell com-munication, it can regulate many physiological and pathological processes in various kinds of cells, including cell proliferation, differentiation and apoptosis in multi-cellular organism. Accu-mulating evidence shows that abnormality in Notch signaling is highly related to diabetes mellitus and its complications. Accord-ingly, this paper reviews the molecular basis of Notch signaling and the relations between its abnormal expression and diabetes mellitus, and focuses on the impact of key elements in the Notch signaling pathway on diabetic complications as well as correlative mechanisms.
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The damage of tissue increases dramatically after reperfusion of blood supply to ischemic tissues.Immune response is one of the key reasons of ischemia-reperfusion injury.Th1 /Th2 generally stays balanced in normal states.Under the envi-ronment of ischemia reperfusion,Th1 /Th2 shifting let Th1 domi-nant to mediate cellular immunity.Excessive immune reaction may cause cell apoptosis and tissue damage.Recent studies showed that induction of transferring Th1 dominant to Th2 domi-nant was feasible for the treatment of ischemia-reperfusion inju-ry.With the progress of modern drug development paradigm“multi-composition,multi-target”,Chinese medicine has advan-tages in treating complex diseases.This paper summarizes the research of the relationship between Th1 /Th2 imbalance and is-chemia-reperfusion injury,together with the prospects of tradi-tional Chinese medicine with multi-target effect in ischemia-reperfusion injury.
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Aim To investigate the protective effect of isorhamnetin on H9 C2 myocardial cell line and its mechanisms. Methods The toxicity and optimal pro-tective concentration of isorhamnetin were determined by MTT assay. The experimental subjects were divided into four groups:group N ( normal ) , group M ( mod-el) , group M + ISO ( model + isorhamnetin ) , and group ISO ( isorhamnetin only ) . Group M +ISO and ISO were pre-incubated with isorhamnetin for 12 hours while other groups with plain DMEM. Group M and M+ ISO were treated with 300μmol · L-1 H2 O2 for 4 hours after pre-incubation. Mitochondrial membrane potential depolarization of H9 C2 was measured by fluo-rescence microscope. Apoptotic rate and ROS produc-tion of injured myocardial cell line were detected using flow cytometry. The oxidative indictors were measured by spectrophotometry. The expressions of cytoplasmic cytochrome C, caspase-9, caspase-3, Bcl-2, Bax, Nrf2 and HO-1 were examined by Western blot. Result There was no difference in mitochondrial membrane potential depolarization, apoptotic rate, ROS produc-tion, oxidative indictors production and expressions of cytoplasmic cytochrome C, caspase-9,caspase-3, Bcl-2 , Bax between groups ISO and N ( P>0. 05 ) . Apop-totic rate, ROS production, expressions of cytoplasmic cytochrome C, caspase-9, caspase-3, Bax, MDA pro-duction of group M+ISO were significantly lower than those of group M ( P Nuclear translocation of Nrf2 and expression of HO-1 in myocardial cell line were increased with the prolonged isorhamnetin incubation time. Conclusion Isorham-netin could protect myocardial cell line against H2 O2-induced oxidative injury and apoptosis through the in- terruption of mitochondrial dependent apoptotic path-way and activation of Nrf2/ARE pathway.
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Myocardial ischemia/reperfusion injury ( MI/RI) is a pathophysiological phenomenon commonly seen during thromboly-sis, percutaneous transluminal coronary angioplasty ( PTCA ) , and coronary artery bypass grafting ( CABG ) . It is defined as restoration of blood flow to a previously ischemic region followed by complex pathological events leading to tissue injury greater than the original ischemic insult. Many experimental interven-tions have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The root of Panax notoginseng ( Burk. ) F. H. Chen ( PN) is one of the iconic herbs in traditional Chinese medicine. Traditional pharmacopeia recommended it among the most efficacious herbs for‘promoting blood circulation ’ and hemostasis. Inspired by this, in the last decade, a large number of modern investigators made substantial efforts to search the PN activities against a vari-ety of MIRI. The systematic review was performed according to the protecting drug of the MIRI development guidelines.
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[ ABSTRACT] AIM: To investigate the protective effect of mesenchymal stem cell ( MSC)-conditioned medium (MSCCM) on myocardial cell line H9c2 and its mechanism.METHODS:Verification of MSC was performed by flow cy-tometry analysis, followed by MTT assay to determine the optimal incubation time of MSCCM with myocardial cells.The cells were divided into 4 groups:normal ( N) group, model ( M) group, M+MSCCM group and MSCCM group.The cells in M+MSCCM group and MSCCM group were pre-incubated with MSCCM for 24 h.The cells in M group and M+MSCCM group were treated with 300 μmol/L H2 O2 for 4 h to imitate oxidative injury of myocardial cells.Mitochondrial membrane potential and apoptotic rate of injured myocardial cells were detected by flow cytometry.The ROS production was measured by fluorescence microscopy.The nuclear translocation of Nrf2 and expression of HO-1 was examined by Western blot.RE-SULTS:No difference of mitochondrial membrane potential, apoptotic rate or ROS production between MSCCM group and N group was observed (P>0.05).The mitochondrial membrane potential depolarization, apoptotic rate and ROS produc-tion in M+MSCCM group were significantly lower than those in M group ( P<0.01 ) .The nuclear translocation of Nrf2 and expression of HO-1 in the myocardial cells were increased with MSCCM incubation time prolonged.CONCLUSION:MSCCM protects the myocardial cells against oxidative injury induced by H2 O2 .The anti-oxidative mechanism would be as-sociated with the activation of Nrf2/ARE pathway.
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The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.
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Objective To study the chronic toxicity and its severity of a Chinese medicine, Anshen Bunao Liquid ( ABL) , in rats, provide the target organs and extent of reversibility of their adverse effects, determine its non-toxic dose, and to evaluate the safety of medication and provide reference for clinical trial dose and observation indexes.Methods Two hundred and forty healthy 6-week old Wistar rats ( male:female=1:1) were divided into low,middle, and high dose Anshen Bunao liquid groups (2.5, 5, 10 mL/kg),and solvent control group (distilled water 2 mL/100 g), with 60 rats in each group.The drug was orally administered to rats once a day and 6 days per week for 26 weeks.The general state, body mass and food intake were measured.By the end of 13 weeks, 26 weeks of experiment and 4-week recovery period after drug withdrawal, hematological and biochemical indexes were assayed, organ coefficients were determined, and histopathological observation was performed.Results Long-term continuous oral administration of Anshen Bunao liquid, the general state, behavior and gross appearance showed no significant abnormal changes.Compared with the control group, no significant differences in all checked items were found in the treatment groups.During 3 and 6 months, the size and location of organs,organ weight and organ coefficient had no obvious changes, with only non-significant increase of weight of some organs.All the organ coefficients of the animals in different groups were within normal range.Histopathology showed no obvious patho-logical and toxicological changes even in the high-dose drug treatment group, and no delayed toxicity occurred after with-drawal of drug administration.Conclusions The Chinese drug, Anshen Bunao liquid has no obvious toxicity and no de-layed toxicity after withdrawal of the drug in rats.It is expected that the planned dose in clinical use is a safe dose.
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Micro RNA (miRNA)were small RNAs encoded by the non-coding RNA genes,which functioned through degrada-tion of mRNA or inhibition of mRNA translation.The miRNA was involved in numerous biological processes,including cell proliferation,apoptosis,development and differentiation.And ectopic expression of miRNA could result in diseases,such as neoplastic hematologic disorder and solid tumor.miR-1 06b-25 cluster contained miR-1 06b,miR-93 and miR-25.These miR-NAs were correlated with the development of tumor.Therefore, we reviewed recent articles on the relationship of miR-1 06b-25 cluster with tumor.
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With the advanced development of information technology, there is a huge impact on various industries for the arrival of big data. In the biomedical field, innovative genome sequencing technology enables low-cost, high-throughput, and high-speed to become a reality, which leads to an explosive growth in data and also appeared in an urgent need to process those massive biological information. High performance computing (HPC) along with effective methods is one of the best ways to deal with the problem of big data in biomedical field which could serve the biomedical development best. We discussed the issues faced in biomedical big data processing and concluded that the bioinformatics is an indispensable component of biomedical technologies.
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In order to find the cardiotonic constituents of lateral roots of Aconitum carmichaelii Debx., the investigation was carried out. Silica gel column chromatography, Sephadex LH-20, medium-pressure MCI and reverse phase ODS column chromatography were used to separate the 90% EtOH extract of the lateral roots of Aconitum carmichaelii Debx. The structures of the isolated compounds have been identified by chemical properties and spectroscopic analyses. Ten compounds were isolated and their structures were elucidated as benzoic acid-5-hydroxy-2-benzoyl-amino methyl ester (1), honokiol (2), pinoresinol (3), salicylic acid (4), p-hydroxy-cinnamic acid (5), songorine (6), karakoline (7), mesaconitine (8), hypaconitine (9) and 14-benzoylhypaconitine (10), separetely. Compound 1 is a new compound and its structure has been established by NMR, HR-ESI-MS, UV, IR and X-Ray. Compound 2-5 are isolated from the lateral roots of Aconitum carmichaelii Debx. for the first time.
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This study is to report the study of protective effects of myricitrin against oxidative stress-induced apoptosis of vascular endothelial cells and the investigation of the possible mechanisms of action of myricitrin. The model of H2O2-induced apoptosis of vascular endothelial cells was used to determine the protective effects of myricitrin. The levels of LDH, MDA and the activities of SOD, NO were measured using the respective kits. The H2O2-induced apoptosis of vascular endothelial cells was detected using MTT reduction, TUNEL assay, JC-1 and ROS staining. The activation of Caspase-3 was also measured by fluorometry. The expression of apoptosis-related proteins was determined with Western blotting assay. Myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells in a time- and dose-dependent manner. The results show that myricitrin could attenuate H2O2-induced decrease in the activities of SOD (P < 0.01). Myricitrin could decrease the levels of LDH, MDA and increase cell viability and the mitochondrial membrane potential (P < 0.01). Myricitrin had protective effects in a dose-dependent manner between 32 micromol x L(-1) to 64 micromol x L(-1). Myricitrin pretreatment could attenuate H2O2-induced increase of p-ERK. Moreover, myricitrin pretreatment could up-regulate the expression of the anti-apoptotic protein Bcl-2, down-regulate the expression of the pro-apoptotic protein Bax, and decrease the expression of Caspase-3, 9. In conclusion, myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells. Myricitrin can enhance the activities of anti-oxidative enzymes and decrease the production of free radicals. The possible mechanisms of action of myricitrin are due to myricitrin-mediated inhibition of phosphorylation of the apoptosis signaling pathways-related kinase ERK, up-regulation of the expression of the anti-apoptotic protein, and down-regulation of the expression of the pro-apoptotic protein.
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<p><b>OBJECTIVE</b>To study the antioxidant activity in vitro of five flavonoids contained Hebei balmy chrysanthemum, luteolin, apigenin, acacetin, acacetin-7-O-beta-D-glucoside and acacetin-7-O-beta-D-glucoside and discuss the antioxidant mechanism of Hebei balmy chrysanthemum as well as the structure-activity relationship of antioxidant activity of flavonoids.</p><p><b>METHOD</b>UV-visible spectrophotometric method was used to determine the DPPH scavenging rate and anti-hemolysis activity of the five flavonoids. The inhibitions on lipid peroxidation in rat brain homogenate were evaluated by measuring the content of MDA, and detected by the TBA method. The effect on glutathione peroxidase (GSH-Px) in rat plasma was detected by GSH-Px kit.</p><p><b>RESULT</b>The flavonoids from Hebei balmy chrysanthemum showed better activity in scavenging DPPH radical, protecting RBC from hemolysis, inhibiting lipid peroxidation in rat brain homogenate, and increasing the activity of GSH-Px in rat plasma. The order of antioxidant efficacy was as follows: luteolin > luteolin-7-O-beta-D-glucoside > apigenin > acacetin > acacetin-7-O-beta-D-glucoside.</p><p><b>CONCLUSION</b>The antioxidant activity of Hebei balmy chrysanthemum is related to the effect of flavonoids in scavenging radical, inhibiting lipid peroxidation and increasing the activity of GSH-Px. And the antioxidant activity of flavonoids is related to the number and position of hydroxide radicals and the steric hindrance of glucoside.</p>
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Animals , Female , Male , Rats , Antioxidants , Chemistry , Pharmacology , Chrysanthemum , Chemistry , Flavonoids , Chemistry , Pharmacology , Lipid Peroxidation , Plant Extracts , Chemistry , Pharmacology , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
<p><b>OBJECTIVE</b>Through the paired comparison on the toxicity effect of Aconiti Lateralis Radix Praeparata of different compatibility proportion of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma, to observe the detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata.</p><p><b>METHOD</b>Paired comparison on the mouse acute toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the LD50. Paired comparison on the rat heart toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the TD50. We dilute medicated serum of Aconiti Lateralis Radix Praeparata, Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (3:1), Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (1: 1) into 5%, 10%, 20% solution with serum free DMEM, to survey the effect of different concentration of medicated serum to the pulsing rhythm of myocardial cell of original generation newborn rat, cell surviva rate and content of LDH in myocardial cells.</p><p><b>RESULT</b>LD50 and TD50 of Aconiti Lateralis Radix Praeparata can be increased after adding Glycyrrhizae Radix et Rhizoma Compared to the blank serum, medicated serum with Aconiti Lateralis Radix Praeparata can obviously increased the pulse rhythm of myocardial cell and the content of LDH (P < 0.05). The medicated serum with Aconiti Lateralis Radix Praeparata added different proportion of Glycyrrhizae Radix et Rhizoma can reduce the acceleration of myocardial cell's rhythm, which is induced by Aconiti Lateralis Radix Praeparata, and can reduce the content of LDH. With the increased ratio of Glycyrrhizae Radix et Rhizoma, the effect is stronger. But for the serum with different concerntration of Aconiti Lateralis Radix Praeparata or Aconiti Lateralis Radix Praeparata added Glycyrrhizae Radix et Rhizoma, there is no obvious effect to the cell survival.</p><p><b>CONCLUSION</b>Glycyrrhizae Radix et Rhizoma has the detoxication effect through increasing the ultimatetotaldosage of Aconiti Lateralis Radix Praeparata. The detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata is through restraining the increased rhythm of myocardial cell and protecting the myocardial cell.</p>
Subject(s)
Animals , Female , Male , Mice , Rats , Aconitum , Chemistry , Cells, Cultured , Chemistry, Pharmaceutical , Methods , Drug Interactions , Drugs, Chinese Herbal , Pharmacokinetics , Toxicity , Glycyrrhiza , Chemistry , Inactivation, Metabolic , Mice, Inbred ICR , Myocytes, Cardiac , Metabolism , Rats, Sprague-Dawley , Rhizome , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To study the protective effect and mechanism of salvianolic acid B on isolated heart ischemia/reperfusion injury in rats.</p><p><b>METHOD</b>Forty-eight SD rats were divided into 6 groups randomly(n = 8): the control group, the positive administration group (verapamil 150 microg x L(-1)), and high, middle and low-dose salvianolic acid B groups (10, 5, 2.5 mg x L(-1)). The myocardial ischemia/reperfusion injury model was established using the Langendorff method, re-perusing isolated working hearts for 30 min after ischemia for 25 min. A water-bag catheter was inserted in rat left atrium for recording the effect of salvianolic acid B on hemodynamics indexes-AST, LDH, SOD and MDA.</p><p><b>RESULT</b>Various group with different doses showed that salvianolic acid B decreased AST, release of LDH and formation of MDA and increased SOD activity.</p><p><b>CONCLUSION</b>Salvianolic acid B showed a protective effect on myocardial ischemia/reperfusion injury. Its mechanism may be related with improvement of cardiac contractility, cleaning of oxygen free radicals and reduction of lipid peroxidation.</p>