ABSTRACT
Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).
ABSTRACT
OBJECTIVE: To investigate the effect of electroacupuncture combined with thunder-fire moxibustion on urodynamics in patients with neurogenic bladder (NB) after spinal cord injury(SCI). METHODS: A total of 60 patients with NB after SCI were divided into control group and observation group using a random number table, with 30 patients in each group. Bladder management protocol was performed for both groups. The patients in the control group were given electroacupuncture at Shangliao (BL31), Zhongliao (BL33), Xialiao (BL34), and Ciliao (BL32) at both sides, and those in the observation group were given thunder-fire moxibustion as mild-warm moxibustion at Yaoyangguan (GV3), Mingmen (CV4), Qihai (CV6), Guanyuan (CV4), and Zhongji (CV3) in addition to the treatment in the control group; electroacupuncture or moxibustion was performed for 20 min each time, once a day, with 10 times as one course of treatment, and both groups were treated for 3 courses. Number of times of voluntary urination, maximum single urine volume, and number of times of urethral catheterization were recorded at 3 d before and after treatment; maximum urinary flow rate during urination, maximum bladder capacity during urination, bladder pressure during the bladder filling period, and residual urine volume were recorded before and after treatment, and bladder compliance was calculated; clinical outcome was evaluated for both groups. RESULTS: After treatment, both groups had significant reductions in the numbers of times of urination and urethral catheterization (P<0.05) and a significant increase in maximum single urine volume (P<0.05), and the observation group had significantly better results than the control group (P<0.05). After treatment, both groups had significant reductions in residual urine volume and bladder pressure during the bladder filling period, and the observation group had significantly greater reductions than the control group (P<0.05); both groups had significant increases in bladder compliance, maximum bladder capacity during urination, and maximum urinary flow rate during urination, and the observation group had significantly higher values than the control group (P<0.05). The observation group had a significantly higher response rate than the control group ï¼»90.00% (27/30) vs 63.33% (19/30), P<0.05ï¼½. CONCLUSION: Thunder-fire moxibustion combined with electroacupuncture can effectively improve bladder urodynamics and has a marked clinical effect in patients with NB after SCI.
Subject(s)
Electroacupuncture , Moxibustion , Spinal Cord Injuries , Urinary Bladder, Neurogenic , Humans , Spinal Cord Injuries/therapy , Urinary Bladder, Neurogenic/etiology , Urinary Bladder, Neurogenic/therapy , UrodynamicsABSTRACT
Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii. Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B (16) and trioxacarcin G (20), together with known gutingimycin (12), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.
Subject(s)
Actinobacteria/genetics , Anti-Bacterial Agents/pharmacology , Wetlands , Animals , Anti-Bacterial Agents/chemistry , Aquatic Organisms , China , Drug Evaluation, Preclinical , Metabolomics , Microbial Sensitivity TestsABSTRACT
Clematis florida is widely used in She Ethnopharmacy in China owing to its significant anti-inflammatory activities. This study aimed to investigate the anti-inflammatory effect of the active fraction of C. florida (CFAF) in an arthritis animal model and its possible mechanism. Pre-inflammatory cytokine levels were examined by ELISA. CFAF can significantly improve the symptoms of arthritis such as paw swelling, arthritic index, and histological condition in AA rat. CFAF can also reduce levels of IL-1ß, TNF-α and IL-6. Further studies showed that triterpene saponins from CFAF induced anti-inflammatory activity inhibited inflammatory mediators by blocking JAK/STAT signalling pathways in the LPS-treated macrophages.
Subject(s)
Clematis , Saponins , Triterpenes , Animals , Anti-Inflammatory Agents/pharmacology , Cytokines , Female , Plant Extracts , Rats , Saponins/pharmacology , Triterpenes/pharmacologyABSTRACT
Since the outbreak of Corona Virus Disease 2019 (COVID-19) in Hubei province, the epidemic scale has increased rapidly, and no effective antiviral drug therapy has been identified yet. This study aimed to evaluate the adjuvant efficacy of Natural Herbal Medicine (NHM) combined with Western medicine in the treatment of COVID-19. We performed a retrospective, 1:1 matched, case-control study of the first cohort of hospitalized COVID-19-confirmed cases (January 17, 2020 to January 28, 2020). A total of 22 of the 36 confirmed patients were included in this study, split into two groups of 11: the NHM group (NHM combined standard Western medicine treatment) and control group (standard Western medicine treatment alone). All patients received appropriate supportive care and regular clinical and laboratory monitoring. Main evaluation indicators included improvement of clinical symptoms such as fever, cough and diarrhea after hospitalization; pathogen nucleic acid test result of respiratory tract and fecal specimens of the patient after hospitalization, and change of chest CT examination after hospitalization. The duration of fever in the NHM group ([Formula: see text] days) was significantly shorter than that in the control group ([Formula: see text] days) ([Formula: see text]). During the whole hospitalization period, the number of cases with diarrhea in the NHM group (two cases) was less than that in the control group (eight cases) ([Formula: see text]). Compared with the control group ([Formula: see text]), the duration for improvement (DI) of chest CT in the NHM group ([Formula: see text]) was significantly shorter ([Formula: see text]). Our results suggest that NHM could improve the clinical symptoms of COVID-19 patients and may be effective in treating COVID-19; thus, a larger, prospective, randomized, controlled clinical trial should be conducted to further evaluate the adjuvant efficacy of NHM in the treatment of COVID-19.
Subject(s)
Coronavirus Infections/drug therapy , Phytotherapy/methods , Plant Preparations/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Aged , Betacoronavirus , COVID-19 , Case-Control Studies , China , Cohort Studies , Combined Modality Therapy , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Drugs, Chinese Herbal/therapeutic use , Female , Hospitalization , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
The processing of Mongolian medicine,which is called " mort harl" in Mongolian language,refers to a traditional processing technology to " tame" some toxic,aggressive,ineffective or inconvenient Mongolian medicines,so as to make it " compliant" to clinical needs. It is the summary of long-term experience in drug preparation by Mongolian medicine experts,one of the bridges for the dialectical unity of Mongolian medicine,the essential content in evaluation of the clinical efficacy of Mongolian medicine and the study of Mongolian medicine modernization,and also the important soft power carrier of " intangible cultural heritage" and " grassland culture" in Inner Mongolia autonomous region. In this study,the processing history,purpose,crafts,mechanism,processing standards and quality standards of Mongolian medicine were explained,and some suggestions were proposed for the problems of the Mongolian medicine processing and development: focus on the basic theory of Mongolian medicine and the clinical experience of Mongolian medicine in the development of traditional Mongolian medicine processing; strengthen the literature research on the processing method of Mongolian medicine; establish comprehensive and systematic Mongolian medicine concocts standards and quality standards; enhance the research and development of special processing equipment and process quality control instruments for Mongolian medicine; and strengthen the training of professional technicians,the protection of copyright in Mongolian medicine processing,and scientific research on Mongolian medicine processing. In the inheritance of the tradition,the latest achievements of modern scientific development can be also absorbed to provide reference for the further development of traditional Mongolian medicine processing technology.
Subject(s)
Medicine, Mongolian Traditional , China , Quality Control , Reference StandardsABSTRACT
The development of novel, efficient and nontoxic photosensitizers (PSs) is a challenging task for photodynamic therapy (PDT). In our previous study, corrole had been demonstrated to be a promising PS in PDT for cancer cells. In this paper, a novel electron-deficient flat phosphorus tris(ethoxycarbonyl) corrole (1-P) was synthesized and characterized. In vitro photodynamic activities and toxicity of 1-P in HepG2 xenograft tumours was evaluated by standard assay. The results shown 1-P displayed a potential efficient and low-toxic PS, which suggesting this kind of corrole is a powerful and promising antitumor PS for PDT. In addition, the potential anti-tumour mechanism study of 1-P was also investigated by the apoptosis antibody array, immunohistochemical and western blotting assay (WB) experiments, we found that the PDT activity of 1-P can degrade SIRT1 (an important deacetylase), and activate the Fas signal pathway to inhibit the growth of liver cancer cells.
Subject(s)
Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Mice , Phosphorus/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/toxicity , Porphyrins/pharmacology , Sirtuin 1/drug effects , Xenograft Model Antitumor Assays , fas Receptor/metabolismABSTRACT
One new indole-type alkaloid, α-L-rhamnopyranosyl-(1â6)-ß-D- glucopyranosyl 6-methoxy-3-indolecarbonate (1), together with three known alkaloids (2-4), one aromatic acid (5) and five known saponins (6-10), was isolated from the roots of Clematis florida var. plena. Their structures were established by NMR spectroscopic analysis and acid hydrolysis. In in vivo anti-inflammatory activity, n-butanol extract was found to be potent against ear edema in mice, with inhibition rate of 48.7% at a dose of 800 mg/kg. Furthermore, compounds 8 and 9 obtained from the n-butanol extract exhibited significant anti-inflammatory activities with inhibition rates of 50.9% and 54.7% at a dose of 200 mg/kg.
Subject(s)
Alkaloids/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Clematis/chemistry , Plant Roots/chemistry , Alkaloids/analysis , Animals , Edema/etiology , Florida , Hydrolysis , Indoles/isolation & purification , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Plant Extracts/pharmacology , Saponins/chemistry , Triterpenes/chemistryABSTRACT
Lomatogonium rotatum (L.) Fries, Gentianopsis barbata (Froel) Ma, and Gentianella acuta (Michx.) Hulten, the three kinds of Digeda-species Mongolian medicinal materials belonging to the family Gentianaceae, bad been widely used for the treatment of liver diseases. To analyze comparatively the content of swertiamarin and swertisin among these three kinds of Digeda-species Mongolian medicinal materials. HPLC method was applied for qualitative and quantitative analysis of swertiamarin and swertisin. The Phenomenex C18 (4.6 mm x 250 mm, 5 µm) was used, chromatographic methanol and water as mobile phase, the flow rate was 1.5 mL x min(-1) with UV detected at 237 nm, column oven temperature was 25 degrees C. Results showed that the contents of swertiamarin and swertisin were closely related the different species and producing areas. The content range of swertiamarin in L. rotatum from different habitats was 1.73% - 2.72%, 0.43% - 0.96% for the swertisin content; the content of swertiamarin in G. barbata from Alxa Left Banner was 0.38%, and the content of swertiamarin and swertisin in G. barbata from the others habitats and G. Acuta from different habitats were all detected qualitatively. The contents of swertiamarin and swertisin among these medicinal plants showed a significant difference due to the different species and producing areas. As a consequence, these medicinal plants should not be put together for clinical applications.
Subject(s)
Apigenin/analysis , Gentianaceae/chemistry , Iridoid Glucosides/analysis , Plant Extracts/analysis , Pyrones/analysis , Chromatography, High Pressure Liquid , Gentianaceae/classification , Gentianella/chemistry , Gentianella/classification , Medicine, Mongolian Traditional , MongoliaABSTRACT
BACKGROUND: No-reflow after emergency percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI) is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI. METHODS: A total of 219 patients (female 31, 14%) undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group (n = 108) and control group (n = 111), given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with aspirin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography (SPECT) to determine the infarct area. RESULTS: There was no statistical significance in sex, age, past history, chest pain, onset-to-reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, ß-blocker, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours ((-0.22 ± 0.18) mV vs. (-0.18 ± 0.16) mV, P = 0.0394), 12 hours ((-0.24 ± 0.18) mV vs. (-0.18 ± 0.15) mV, P = 0.0158) and 24 hours ((-0.27 ± 0.16) mV vs. (-0.20 ± 0.16) mV, P = 0.0021) reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour reperfusion (34.3% vs. 54.1%, P = 0.0031). The myocardial perfusion scores of 17 segments evaluated by static SPECT was improved significantly on day 7 and day 180 after STEMI in Tongxinluo group compared to the control group (0.61 ± 0.40 vs. 0.76 ± 0.42, P = 0.0109 and 0.51 ± 0.42 vs. 0.66 ± 0.43, P = 0.0115, respectively). There was no significant difference in severe adverse events between two groups. CONCLUSION: Tongxinluo as a kind of traditional Chinese medicine could reduce myocardial no-reflow and infarction area significantly after emergency PCI for STEMI with conventional medicine therapy.
Subject(s)
Coronary Circulation , Drugs, Chinese Herbal/therapeutic use , Myocardial Infarction/drug therapy , Acute Disease , Aged , Double-Blind Method , Electrocardiography , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Myocardial Infarction/physiopathology , Tomography, Emission-Computed, Single-PhotonABSTRACT
The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 µg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.
Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Drugs, Chinese Herbal/therapeutic use , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide Synthase Type III/metabolism , Signal Transduction/physiology , Animals , Creatine Kinase/blood , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacology , Isoquinolines/pharmacology , Models, Animal , Myocardial Reperfusion Injury/metabolism , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Sulfonamides/pharmacology , Swine , Swine, MiniatureABSTRACT
AIM: To investigate the mechanism by which galangin, a polyphenolic compound derived from medicinal herbs, induces apoptosis of hepatocellular carcinoma (HCC) cells. METHODS: The 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to measure cell viability. Apoptosis was evaluated by in situ uptake of propidium iodide and Hoechst 33258 and was then detected by fluorescence microscopy. Protein expressions were detected by Western blotting. To confirm the apoptotic pathway mediated by galangin, cells were transfected by bcl-2 gene to overexpress Bcl-2 or siRNA to down-regulate Bcl-2 expression. RESULTS: Galangin (46.25-370.0 micromol/L) exerted an anti-proliferative effect, induced apoptosis, and decreased mitochondrial membrane potential in a dose and time-dependent manner. Treatment with galangin induced apoptosis by translocating the pro-apoptotic protein Bax to the mitochondria, which released apoptosis-inducing factor and cytochrome c into the cytosol. Overexpression of Bcl-2 attenuated galangin-induced HepG2 cell apoptosis, while decreasing Bcl-2 expression enhanced galangin-induced cell apoptosis. CONCLUSION: Our data suggests that galangin mediates apoptosis through a mitochondrial pathway, and may be a potential chemotherapeutic drug for the treatment of HCC.
Subject(s)
Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor/drug effects , Flavonoids/pharmacology , Liver Neoplasms/pathology , Mitochondria/drug effects , Mutagens/pharmacology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor/metabolism , Cell Line, Tumor/pathology , Dose-Response Relationship, Drug , Flavonoids/therapeutic use , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Mutagens/therapeutic use , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
OBJECTIVE: To compare the clinical effect of acupuncture treatment and western medicine Carbamazepine for thalamic pain. METHODS: Crossover trial design was used, 11 cases diagnosed as thalamic pain were randomly divided into two groups according to the mini-unbalance-index method, group I (with 6 cases received acupuncture first and then western medicine) and group II (with 5 cases received western medicine first and then acupuncture). When the effects were evaluated, the two groups were named as acupuncture group and western medicine group, 11 cases in each group. The method of clearing away the heart fire, regulating the spirit, activating blood and relieving pain was adopted in acupuncture treatment, Ximen (PC 4), Yinxi (HT 6), Xuehai (SP 10) and Zhaohai (KI 6) were selected; the western medicine group was treated with oral administration of Carbamazepine, and one course as well as the eluting period were both 10 days. The effects were evaluated with visual analogue scale (VAS) and evaluation scale of Anderson Cancer Center pain in US (MD Pain Evaluation value) respectively. RESULTS: The VAS and MD value in two groups were obviously decreased after treatment (both P < 0.05), while there was no significant difference between two groups; the markedly effective rate of pain relieving in acupuncture group was 63.6% (7/11), which was higher than that of 36.4% (4/11) in western medicine group, but there was no significant difference between two groups. CONCLUSION: Acupuncture treatment of regulating spirit, activating blood and relieving pain has a better therapeutic effect for thalamic pain, and can reach to the same therapeutic effect with western medicine Carbamazepine.
Subject(s)
Acupuncture Therapy , Medicine, Chinese Traditional , Pain Management , Thalamus/physiopathology , Adult , Aged , Blood Circulation , Carbamazepine/therapeutic use , Cross-Over Studies , Female , Humans , Male , Middle Aged , Pain/physiopathology , Pain Measurement , SpiritualityABSTRACT
OBJECTIVE: To assess the effect of Tongxinluo on cytokines and myocardial no-reflow in early reperfusion of acute myocardial infarction (AMI). METHODS: Forty mini-swine were divided into five groups randomly, sham group, control group, low dose (0.1 g/kg), medium dose (0.2 g/kg) and high dose (0. 4 g/kg) group of Tongxinluo (which were administered 2 h before reperfusion), eight swine in each group. Animals except those in the sham group were subjected to 1.5 h of coronary occlusion followed by 3 h of reperfusion. Serum contents of P-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), interleukin 6 (IL-6) and interleukin 10 (IL-10), as well as myocardial contrast echocardiography (MCE) were evaluated at baseline, and after 1.5 h of AMI and 3 h of reperfusion. RESULTS: (1) Compared with that of the control group, high dose of Tongxinluo could reduce serum contents of P-selectin and ICAM-1 at 1.5 h of AMI (all P<0.05), and P-selectin, ICAM-1, VCAM-1, and IL-6 at 3 h of reperfusion significantly (all P< 0.05), accompanied by significantly elevated IL-10 (P<0.05). (2) Compared with that of control group, high dose of Tongxinluo could reduce no-reflow area at 3 h of reperfusion significantly [(6.59 +/- 1.73) cm2 vs (4.68 +/- 1.53) cm2, P<0.05]. CONCLUSION: High dose of Tongxinluo could effectively reduce serum contents of adhesion and pro-inflammatory cytokines, regulate anti-inflammatory factor levels, and attenuate no-reflow area in the early reperfusion of AMI. It thus provided experimental basis for its clinical application.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Myocardial Infarction/metabolism , Myocardial Reperfusion , Phytotherapy , Animals , Cytokines/metabolism , Intercellular Adhesion Molecule-1/metabolism , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , P-Selectin/metabolism , Swine , Swine, MiniatureABSTRACT
BACKGROUND: The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. METHODS: Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. RESULTS: Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. CONCLUSIONS: Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide/physiology , Animals , Antigens, CD/analysis , Blood Pressure/drug effects , Cadherins/analysis , Heart Rate/drug effects , Microscopy, Fluorescence , Myocardial Infarction/drug therapy , Myocardial Infarction/physiopathology , Myocardium/enzymology , Myocardium/pathology , Neutrophil Infiltration , Nitric Oxide Synthase/metabolism , Peroxidase/metabolism , Swine , Swine, MiniatureABSTRACT
OBJECTIVE: To assess the effects of tongxinluo on vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction. METHODS: Forty mini-swines were divided into five groups randomly, sham group, control group, low dose (0.1 g/kg), medium dose (0.2 g/kg) and high dose (0.4 g/kg) groups of Tongxinluo. It was administered at 2 hours pre-reperfusion. Animals except in sham group were subjected to 1.5 hour of coronary occlusion followed by 3 hours of reperfusion. Content of VE-cadherin, beta-catenin, matrix metalloproteinase (MMP)-2 and 9 in myocardium were evaluated; no-reflow area was examined with myocardial contrast echocardiography (MCE) at 1.5 hour of AMI and 3 hours of reperfusion. RESULTS: (1) Compared with that of normal myocardium, content of VE-cadherin and beta-catenin decreased in reperfusion and no-reflow myocardium while MMP-2 and 9 increased significantly (all P < 0.05); (2) Compared with that of control group, a high dose of Tongxinluo could increase significantly the content of VE-cadherin in both reperfusion and no-reflow myocardium, (22.2 +/- 3.2)% vs (32.0 +/- 3.9)% and (14.5 +/- 2.8)% vs (28.3 +/- 2.2)% respectively, beta-catenin, (20.5 +/- 3.5)% vs (27.3 +/- 2.9)% and (13.3 +/- 2.1)% vs (20.6 +/- 2.4)%, while reduce MMP-2, (48.3 +/- 4.1)% vs (29.4 +/- 3.5)% and (57.3 +/- 4.3)% vs (38.2 +/- 4.0)% respectively, MMP-9, (55.6 +/- 4.0)% vs (34.3 +/- 3.5)% and (62.4 +/- 4.8)% vs (44.4 +/- 4.1)%, all P < 0.05; (3) Compared with that of control group, a high dose of Tongxinluo could reduce significantly both no-reflow area, (6.6 +/- 1.7) cm2 vs (4.7 +/- 1.5) cm2, P < 0.05, and percentage (90.8 +/- 3.8)% vs (71.4 +/- 4.1)%, P < 0.05, at 3 hours of reperfusion. CONCLUSION: A high dose of tongxinluo could effectively maintain the integrity of vascular endothelium and attenuate no-reflow area in early reperfusion of acute myocardial infarction.
Subject(s)
Capillaries/pathology , Drugs, Chinese Herbal/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Phytotherapy , Animals , Drugs, Chinese Herbal/pharmacology , Endothelium, Vascular/drug effects , Female , Ischemic Preconditioning , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/pathology , Myocardium , Swine , Swine, MiniatureABSTRACT
OBJECTIVE: To investigate apoptosis of BEL-7402 cells induced by Galangin. METHODS: Cytotoxicity and cell viability were assayed by MT methods. Morphologic assessment of apoptosis was performed by fluorescence microscope, cell cycle and mitochondrial membrane potential were analyzed by flow cytometry, Caspases Activities were detected by chromogenic substrate assay. RESULTS: BEL-7402 cells treated with Galangin showed apparently cytotoxicity, IC50 of Galangin was 30.15 mg/L The growth curve showed that the ratio of growth decreased with the increasing of concentration of Galangin. The apoptosis appeared 24 hours after treated with 20-80 mg/L Galangin, morphologic changes included nuclear chromatin condensation and fluorescence strength was observed with fluorescence microscope. The activity of Caspase-9 attained to peak value at 6 h, while Caspase-6 activity was up to peak value at 12h and Caspase-3 activity attained to peak value at 18 h. CONCLUSION: Galangin may induce BEL-7402 cells apoptosis by mitochondrial pathway.
Subject(s)
Alpinia/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Flavonoids/pharmacology , Liver Neoplasms/pathology , Caspases/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Liver Neoplasms/metabolism , Membrane Potential, Mitochondrial/drug effects , Plants, Medicinal/chemistry , Rhizome/chemistryABSTRACT
In the present paper, the simultaneous determination of multi-components in Chinese herbal medicine was performed by artificial neural network-UV spectrometry. The interference of other components was eliminated by self-revising and self-simulation of the virtual component. The double ANN including training and simulation network was established, and the capabilities of self-recognition and self-studying were improved. Therefore, the prediction accuracy of multicomponent content was improved greatly in the complicated Chinese herbal medicine system. The contents of aesculin and aesculetin, which were extracted from 21 Cortex Fraxinis, were predicted. Comparing the results with those of HPLC, the prediction accuracy was more than 90% within the relative errors less than 10%. The measurement precisions of aesculin and aesculetin were 0. 37% and 1. 5% respectively.