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Aquaporin is a membrane channel protein widely expressed in body tissues, which can control the input and output of water in cells. AQPs are differentially expressed in different cardiovascular tissues and participate in water transmembrane transport, cell migration, metabolism, inflammatory response, etc. The aberrant expression of AQPs highly correlates with the onset of ischemic heart disease, myocardial ischemia-reperfusion injury, heart failure, etc. Despite much attention to the regulatory role of AQPs in the cardiovascular system, the translation of AQPs into clinical application still faces many challenges, including clarification of the localization of AQPs in the cardiovascular system and mechanisms mediating cardiovascular pathophysiology, as well as the development of cardiovascular-specific AQPs modulators.Therefore, in this study, we comprehensively reviewed the critical roles of AQP family proteins in maintaining cardiovascular homeostasis and described the underlying mechanisms by which AQPs mediated the outcomes of cardiovascular diseases. Meanwhile, AQPs serve as important therapeutic targets, which provide a wide range of opportunities to investigate the mechanisms of cardiovascular diseases and the treatment of those diseases.
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Acuaporinas , Enfermedades Cardiovasculares , Acuaporinas/metabolismo , Transporte Biológico , Corazón , Humanos , AguaRESUMEN
Objectives: Licoflavone A (LA) is a natural flavonoid compound derived from the root of Glycyrrhiza. This study investigated the antitumor effect and underlying molecular mechanisms of LA against gastric cancer (GC) in vitro and in vivo. Materials and Methods: A CCK8 assay was used to measure the antiproliferative activity of LA in human GC SGC-7901, MKN-45, MGC-803 cells, and human GES-1 cells. Target prediction and protein-protein interaction (PPI) analysis were used to identify the potential molecular targets of LA. The binding pattern of LA to VEGFR-2 was analyzed by molecular docking and molecular dynamic (MD). The affinity of LA for VEGFR-2 was determined by microscale thermophoresis (MST). The protein tyrosine kinase activity of VEGFR-2 in the presence of LA was determined by an enzyme activity test. The effect of LA on the proliferation of VEGF-stimulated MKN-45 cells was measured with CCK8 assays, clone formation assays, and 3D microsphere models. Hoechst 33342 staining, FCM, MMP, and WB assays were used to investigate the ability of LA to block cell cycle and promote apoptosis of VEGF-stimulated MKN-45 cells. Transwell matrix assays were used to measure migration and invasion, and WB assays were used to measure EMT. Results: LA inhibited the proliferation of SGC-7901, MKN-45, and MGC-803 cells and VEGF-stimulated MKN-45 cells. VEGFR-2 was identified as the target of LA. LA could also block cell cycle, induce apoptosis, and inhibit migration, invasion, and EMT of VEGF-stimulated MKN-45 cells. Functional analyses further revealed that the cytotoxic effect of LA on VEGF-stimulated MKN-45 cells potentially involved the PI3K/AKT and MEK/ERK signaling pathways. Conclusions: This study demonstrates that LA has anti-GC potency in vitro and in vivo. LA affects the proliferation, cycle, apoptosis, migration, invasion, and EMT by targeting VEGFR-2 and blocks the PI3K/AKT and MEK/ERK signaling pathways in VEGF-stimulated MKN-45 cells.
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OBJECTIVES: Bellidifolin (BEL) is one type of tetraoxygenated xanthone that is particularly found in Swertia and Gentiana (Gentianaceae). Despite its broad range of pharmacological activities, it is still unclear whether BEL could be used for lung cancer treatment. Hence, we presently demonstrate the roles of BEL towards the proliferative inhibition of the prototypical A549 lung cancer cells. MATERIALS AND METHODS: The antiproliferative activity of BEL was initially verified by cellular experiments. A network pharmacology method was then pursued to assess BEL potential molecular targets from the platform for pharmacological analysis of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease enrichment of potential targets and construction of compound-target-disease network maps were performed based on a total of 20 diseases. Two core targets related to the BEL-mediated effect in A549 cells were obtained by importing potential targets into a protein-protein interaction database (STRING) and also analyzing respective data of related targets into this database. Last, these core targets were examined by in vitro analysis and molecular docking. RESULTS: CCK8 assays indicated that treatment with 50-100 µm BEL had an inhibitory effect on the proliferation of human A549 lung cancer cells, whereas this effect was time- and concentration-dependent. As control, treatment with 50-100 µm BEL did not inhibit the proliferation of normal lung epithelial cells (BEAS-2b cell line). H&E staining of BEL-treated A549 cells showed that, upon an increase of drug concentration, nuclear condensation and fragmentation were largely observed. Cell cycle analysis showed that in vitro treatment with 75-100 µm BEL could block A549 cells in S and G2 phases. Western blot analyses showed that after 72 hours of BEL treatment, the level of caspase-8/3 in A549 cells increased, and the level of PARP1 decreased in a dose-dependent manner. Network pharmacology analysis also indicated that lung cancer was the major disease susceptible to BEL treatment. At the same time, STAT3 and COX-2 were identified as two core targets of BEL in lung cancer treatment. Functional analyses further revealed that the cytotoxicity effect of BEL in A549 cells potentially involved the STAT3/COX-2 pathway. Moreover, molecular docking analysis indicated that BEL structure properly matches with COX-2 and STAT3 in space shape, thus illustrating the putative molecular mechanism of BEL's anticancer effect. CONCLUSIONS: Based on a series of in vitro analyses, network pharmacology, and molecular docking, the potential mechanism involving the antiproliferative and cytotoxic effects of BEL in lung cancer cells was investigated. Our study may help providing some theoretical basis for the discovery of novel phytotherapy drugs applicable for the treatment of lung cancer.
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ObjectiveTo investigate the effects of licoflavone A on the proliferation and glycolysis of gastric cancer cells in the hypoxic environment. MethodHuman gastric cancer AGS cells were classified into five groups： Normoxia， hypoxia， and low-， medium-， and high-dose （25， 50， 100 μmol·L-1， respectively） licoflavone A. The cells in other groups except the normoxia group were cultured in the environment with 5% O2 for 48 h. The cell counting kit-8 （CCK-8） and colony formation assay were employed to examine the proliferation of AGS cells. Cell migration was detected by the scratch assay. The protein and mRNA levels of hypoxia-inducible factor 1-alpha （HIF-1α）， glucose transporter 1 （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and hexokinase Ⅱ （HK2） in AGS cells were measured by Western blotting and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. The corresponding kits were used to determine glucose uptake and HK activity. ResultThe CCK-8 results showed that compared with the hypoxia group， the high- and medium-dose licoflavone A groups showed decreased proliferation rate of AGS cells at the time point of 24 h （P<0.01） and all the licoflavone A groups demonstrated decreased proliferation rate at the time point of 48 h （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased number of clone formation of AGS cells （P<0.01）， which was decreased after the treatment with licoflavone A at high， medium， and low doses （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased migration of AGS cells （P<0.01）， which was attenuated by the high， medium， and low doses of licoflavone A （P<0.01）. Compared with the normoxia group， the hypoxia group showed up-regulated mRNA levels of GLUT1， LDHA， PKM2， and HK2 （P<0.05， P<0.01）. Compared with those in the hypoxia group， the mRNA levels of GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group， GLUT1， LDHA， and HK2 in the medium-dose licoflavone A group， and HK2 in the low-dose licoflavone A group were down-regulated （P<0.05， P<0.01）. The protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the hypoxia group were higher than those in the normoxia group （P<0.05， P<0.01）. Compared with those in the hypoxia group， the protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group and HK2 in the medium- and low-dose licoflavone A groups were down-regulated （P<0.05， P<0.01）. The glucose uptake and HK activity were elevated in the hypoxia group compared with those in the normoxia group （P<0.01）. Compared with the hypoxia group， high-dose licoflavone A decreased the glucose uptake and HK activity， and medium-dose licoflavone A decreased the HK activity （P<0.01）. ConclusionLicoflavone A inhibits the proliferation of AGS cells under hypoxic conditions by regulating glycolysis in gastric cancer.
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The pathological manifestations of neurodegenerative diseases， such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis， are abnormal protein aggregation and accumulation， microglia activation， and mitochondrial dysfunction， which eventually lead to the gradual loss of neuronal structure or function and deteriorate over time. These pathological processes are related to the production of reactive oxygen species （ROS）， which can cause oxidative stress and damage proteins， lipids， and DNA， leading to cell and tissue injuries. The Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is the main mechanism to maintain the redox balance of the body and defend against oxidative stress injury. Nrf2 activates the expression of a series of antioxidant genes related to ARE through the dissociation of Keap1 and nuclear transfer in the cytoplasm to protect the body from oxidative damage. Therefore， the discovery and study of the Keap1/Nrf2/ARE signaling pathway activator is of great significance for the prevention and treatment of neurodegenerative diseases. Because of the remarkable biological activity and slight side effects， natural products are a treasure trove for new drug research and development. Studies have shown that a variety of natural products can activate the Keap1/Nrf2/ARE signaling pathway and play a neuroprotective role. According to the structural characteristics， natural products can be divided into flavonoids， terpenoids， volatile oils， polyphenols， and phenylpropanoids. This study summarized the underlying mechanism of the Keap1/Nrf2/ARE signaling pathway in regulating diseases and reviewed the research progress on natural products based on this signaling pathway in neuroprotection to provide references for the development of clinical drugs for the prevention and treatment of neurodegenerative diseases.
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Acute lung injury (ALI) is a common clinical critical respiratory disease. At present, the mechanism of the disease has not been fully elucidated, there is a lack of specific drugs in clinical practice and the mortality rate is high, which is a difficult problem in the medical field. In recent years, traditional Chinese medicine has exerted its unique advantages and efficacy in the prevention and treatment of ALI, which has aroused the attention of domestic and foreign scholars. Based on the theory of "Wei Qi Ying Xue", this paper discusses the current research status of prevention and treatment of ALI by traditional Chinese medicine, and analyzes its pathogenesis, clinical manifestations and corresponding analysis with TCM syndrome. According to the angle of "Wei Qi Ying Xue", the progress of syndrome differentiation and treatment is highly consistent with immune response, inflammatory response, oxidative stress and apoptosis, in order to find new ideas and medication for the prevention and treatment of ALI with integrated traditional Chinese and Western medicine.
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Malignant tumors of digestive system are highly prevalent malignant tumors that seriously threaten human health around the world. At present, the curative efficacy and prognosis of traditional treatment methods cannot reach the expectation, so it is urgent to find new targets for cancer treatment and realize targeted therapy for tumors. Abnormal energy metabolism in tumor cells is regarded as a hallmark of cancer, and malignant tumor cells absorb glucose through aerobic glycolysis pathway, and obtain a small amount of energy and produce lactate under the catalysis of a series of enzymes. Lactate dehydrogenase A (Lactate dehydrogenase A, LDHA), as a key enzyme in the aerobic glycolysis pathway of tumor cells, plays an important role in the metabolic changes of tumor cells. Studies have demonstrated that LDHA has high expression characteristics in a variety of tumor cells,and its high expression in clinic is often related to the poor prognosis and high metastasis rate of tumors, which is expected to be a new target for cancer therapy. This article reviews the role of LDHA in the development of digestive system tumors and the research progress of related drugs.
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ObjectiveTo observe the effect of Huangqi Baihe granules on the hypoxia-inducible factor 1α （HIF-1α）/nuclear factor-κB （NF-κB）/NOD-like receptor hot protein domain related protein 3 （NLRP3） signaling pathway in a rat model of high altitude hypoxia. MethodSixty male SPF SD rats were randomly divided into blank group， model group， dexamethasone group （5 mg·kg-1）， and high， middle， and low-dose groups of Huangqi Baihe granules （4.1， 2.05， 1.025 g·kg-1）. Among them， each Chinese medicine group was administrated orally for continuously 14 d， once a day， and the dexamethasone group was injected intraperitoneally for continuously 3 d as the positive control group. On the 15th d， the model group， dexamethasone group， and high， middle， and low dose groups of Huangqi Baihe granules were exposed to the simulated high altitude， low pressure， and low oxygen environment in the animal low-pressure simulation cabin， and the exposure lasted for 3 d. Blood was collected from the abdominal aorta and serum was separated， and the brain tissue was taken after being killed. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in rat serum. Western blot was used to detect HIF-1α， NLRP3， phosphorylated nuclear factor-κB （p-NF-κB）， NF-κB， desquamation D （GSDMD）， and cysteine aspartate-specitis protein-1（Caspase-1） in rats of each group. The mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultThe results of HE staining showed that as compared with the normal group， the pathological sections of brain tissues in the model group showed that pyramidal cells were loosely arranged and distributed in disorder， with different sizes. Compared with the model group， the pathological changes in pyramidal cells in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules were reduced. The results of ELISA showed that as compared with the normal group， the content of TNF-α， IL-6， and IL-1β in the serum of rats in the model group was significantly higher （P<0.01）. Compared with the model group， the content of TNF-α， IL-6， and IL-1β in the serum of rats in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules decreased significantly （P<0.05， P<0.01）. The results of Western blot showed that as compared with the normal group， the relative protein expression levels of HIF-1α， NLRP3， p-NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly higher （P<0.01）. As compared with the model group， the relative expressions of HIF-1α， NLRP3， p-NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group and the high-dose group of Huangqi Baihe granules were significantly decreased （P<0.05， P<0.01）. The relative protein expression levels of HIF-1α， NLRP3， p-NF-κB p65， and Caspase-1 in the brain tissue of rats in the middle-dose group of Huangqi Baihe granules decreased significantly （P<0.01）， and the relative protein expression of HIF-1α in the brain tissue of rats in the low-dose group of Huangqi Baihe granules was reduced （P<0.05）. The Real-time PCR analysis showed that as compared with the normal group， the mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly increased （P<0.01）. As compared with the model group， the mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group were significantly decreased （P<0.01）. The mRNA expression levels of HIF-1α， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the high-dose group of Huangqi Baihe granules decreased significantly （P<0.01）. The mRNA expression levels of HIF-1α， NLRP3， and Caspase-1in the brain tissue of rats in the middle-dose group of Huangqi granules decreased （P<0.05， P<0.01）. ConclusionThe protective effect of Huangqi Baihe granules on acute brain injury in low-pressure hypoxic rats may be related to the HIF-1α/NF-κB/NLRP3 signaling pathway.
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ObjectiveTo investigate the protective effect of Guiqi Baizhu prescription combined with oxaliplatin on the intestinal barrier of tumor-bearing mice with gastric cancer by regulating downstream aquaporin 3 （AQP3） and aquaporin 4 （AQP4） through the vasoactive intestinal peptide （VIP）/cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA） signaling pathway. MethodThe gastric cancer cell lines MFC with a density of 1×107/mL were prepared into cell suspension. The tumor-bearing mouse model of gastric cancer was established by inoculating 0.2 mL cell suspension under the right axilla of mice. After successful modeling， mice were randomly divided into 5 groups， namely， model group， oxaliplatin group （10 mg·kg-1）， and high， medium， and low-dose oxaliplatin + Guiqi Baizhu prescription groups （17.68， 8.84， 4.42 g·kg-1）， with 10 mice in each group， and the remaining 10 mice were set as a blank group. Mice in each group were treated with Chinese medicine， oxaliplatin， or normal saline by gavage or intraperitoneal injection for 14 d. The next day after the last dose， blood was taken from the eyeball to separate serum and take colonic samples. Hematoxylin-eosin （HE） staining was used to observe the changes in tissue morphology. The content of D-lactate acid （D-LA） and diamine oxidase （DAO） in the serum was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of VIP， cAMP， PKA， AQP3， and AQP4 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed edema in the colonic submucosa， disordered arrangement of intestinal glands in the mucosal layer， loss of goblet cells， infiltration of inflammatory cells， and villus shedding. However， there were different degrees of improvement in each administration group. As compared with the blank group， the serum levels of DAO and D-LA in the model group were significantly increased （P<0.01）. As compared with the model group， the levels of DAO and D-LA in the high-dose oxaliplatin + Guiqi Baizhu prescription group and the level of D-LA in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were decreased （P<0.05， P<0.01）. As compared with the oxaliplatin group， the levels of D-LA in the high and medium-dose oxaliplatin + Guiqi Baizhu prescription groups were decreased （P<0.05）， and the levels of DAO and D-LA in other administration groups were decreased as well， but the difference had no statistical significance. As compared with the blank group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in the model group were significantly decreased （P<0.05， P<0.01）. As compared with the model group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in each administration group were increased， and those in the high-dose oxaliplatin + Guiqi Baizhu prescription group were significantly increased （P<0.05， P<0.01）， while the protein expression level of cAMP in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）. As compared with the oxaliplatin group， the protein expression levels of cAMP in the high-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）， and the mRNA and protein expressions of these indexes in the other groups were also increased but the differences were not statistically significant. ConclusionGuiqi Baizhu prescription combined with oxaliplatin can regulate AQP3 and AQP4 through the VIP/cAMP/PKA signaling pathway to protect the intestinal barrier of tumor-bearing mice with gastric cancer.
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OBJECTIVE：To compare the protective effects of different effective components of Astragali radix against DNA damage of human bone marrow mesenchymal stem cells （BMSCs）induced by ionizing radiation. METHODS ：2 Gy X-rays were used to directly irradiate BMSCs to establish a radiation model. CCK- 8 method was used to detect the effects of different mass concentrations（25，50，75，100 μg/mL）of astragalus polysaccharide ，astragalus saponin and astragalus flavonoids for 1 day before radiation + 1 to 5 days after radiation on the proliferation of BMSCs. The dose concentration and the duration of intervention after radiation were selected. The irradiated BMSCs were divided into radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group. The last three groups were treated with appropriate dosage of corresponding drugs before and 2 days after radiation ，and a blank groupwas set for comparison. Cytoplasmic division arrest qq.com micronucleus method was used to detect micronucleus cell rate and cell micronucleus rate after appropriate time of was used to detect th e number of 53BP1 foci in cells after appropriare time of intervention following radiation ；the number of 53BP1 foci were compared among different time points （0.5，2，12，24 h）. RESULTS ：Compared with blank group ，OD values of BMSCs were decreased significantly in radiation group （P＜0.05 or P＜0.01）. Compared with radiation group ，the OD values of BMSCs were significantly increased when 50 μ g/mL astragalus polysaccharide，astragalus saponin and astragalus flavonoids continuously intervened radiation for 2-3 days，there was significant difference in other groups at some time point （P＜0.05 or P＜ 0.01）. After consideration ，drug concentration was determined to be 50 μg/mL，and the continuous intervention time was 2 days after radiation. Compared with blank group ，the micronucleus cell rate and cell micronucleus rate of radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group increased significantly ，and the number of 53BP1 focus cluster in radiation group and astragalus polysaccharide group increased significantly （P＜0.01）. Compared with radiation group and astragalus flavonoids group ，the micronucleus cell rate ，cell micronucleus rate and the number of 53BP1 focus cluster （continued intervention for 0.5，2，12 h）in the astragalus polysaccharide group and astragalus saponin group were significantly reduced，and the micronucleus cell rate and cell micronucleus rate in the astragalus polysaccharide group were significantly lower than astragalus saponin group （P＜0.05）. 53BP1 focus cluster could not be detected 24 h later （P＜0.05）. CONCLUSIONS ： Astragalus polysaccharide and astragalus saponin both have protective effects on BMSCs DNA damage induced by radiation ，and the protective effect of astragalus polysaccharide is better than that of astragalus saponin ；astragalus flavonoids has no protective effect on radiation-induced DNA damage.
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Objective To improve the preparation method of rat model of acute myocardial ischemia reperfusion injury(MI/RI), to make a comprehensive evaluation and to lay a good model foundation for following MI/RI research. Methods Thirty-six clean grade Wistar rats were randomly divided into 3 groups: normal group without intervention of the left anterior descending coronary artery (LAD), sham operation group with only wearing thread but no ligation of the coronary artery, and ischemia reperfusion group, with ligation of the LAD for 30 min and reperfusion for 120 min. Rats after anesthesia had continuous ECG recording, and tracheostomy for mechanical auxiliary ventilation. Thoracotomy and LAD intervention were carried out on the rats, and then the rat models were comprehensively evaluated by electrocardiography, detection of myocardial enzyme content, determination of the infarct size, and pathological examination of the myocardium. Results The electrocardiogram of the MI/RI group showed obvious ST-T dynamic changes. The level of CK-MB in the MI/RI group was significantly increased at 2 h after surgery. Compared with the sham group, the infarct size of the MI/RI group was significantly increased, with evident degeneration and necrosis of cardiomyocytes and extensive inflammatory cell infiltration in the myocardium. Conclusions The improved modeling method not only reduced the difficulties of operation, but has also successfully established the rat model of MI/RI, providing a good foundation for further MI/RI research.
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To study the effect of Astragalus polysaccharide (APS) on adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) cultured in hypoxic environment. The optimal APS concentration, which could promote the proliferation of BMSCs, was screened by methyl thiazolyl tetrazolium method. The concentration was used to intervene in BMSCs-induced by adipogenic differentiation fluid growing in different oxygen concentrations (3%, 6%, 10% and 20%). The formation of lipid droplets in the BMSCs-intervened was observed by oil red O staining under the optical microscope. The mRNA and protein levels of the lipid relating genes peroxisome proliferator activated receptor gamma 2 (PPAR-γ₂) and lipoprotein lipase (LPL) were detected by Real-time PCR and Western blotting, respectively. The results showed that, comparing with the control group, 40 μg/mL APS could significantly promote the proliferation of BMSCs under low oxygen concentration. A large amount of lipid droplets existed in BMSCs growing in the adipogenic inducing fluid containing 40 μg/mL APS and the hypoxic environment, and the protein and mRNA levels of PPAR-γ₂ and LPL also raised. It was worth noting that the phenomenon was more significant in 10% oxygen concentration, and the difference was statistically significant (P<0.05). 40 μg/mL APS had effect on promoting the proliferation and adipogenic differentiation of BMSCs cultured in hypoxic environment, and the effect was related to the concentration of oxygen of BMSCs-cultured.
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Objective To investigate the protective effects of Angelicae Sinensis Radix and Angelicae Sinensis Radix polysaccharides on immune function injury induced by X rays in SD rats. Methods Forty SD rats were randomly divided into control group, model group, Angelicae Sinensis Radix Decoction group, Angelicae Sinensis Radix polysaccharide group and positive medicine group. After routine feeding for 14 day, each administration group was given relevant medicine for gavage, while control group and model group were given the same amount of distilled water for gavage, once a day for 7 d. From the 8th day, except for the control group, the rats in the rest of groups were subjected to whole-body X ray irradiation, continuous exposure to 2 d; the total absorbed dose was 6 Gy. The rats were killed by femoral artery after irradiate 3 d. The WBC count, RBC, HGB, and PLT in peripheral blood were observed by blood routine test; the number of nucleated cells in the bone marrow was observed by nucleated cell count method; the pathological changes of spleen were observed by HE staining under microscope; the contents of IFN-γ and IL-4 in serum were detected by ELISA. Results Compared with the control group, the spleen index WBC, number of bone marrow nucleated cells and serum contents of IL-4 and IFN-γ in model group was significantly lower (P<0.05), The contents of RBC and HGB increased (P<0.05). Compared with the model group, WBC, number of bone marrow nucleated cells, and the contents of IL-4 and IFN-γ in serum of each administration group increased significantly (P<0.05); RBC and HGB decreased significantly (P<0.05). Conclusion Angelicae Sinensis Radix and Angelicae Sinensis Radix polysaccharides have protective effects on the immune function injure induced by X ray in SD rats.
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Objective To discuss the protective effects ofGuiqi YiyuanOintment on damages caused by heavy ion radiation induced bystander effects; To explore the possible mechanism.Methods Totally 42 Wistar male rats were randomly divided into blank control group, pure radiation group andGuiqi Yiyuan Ointment group. TheGuiqi Yiyuan Ointment group was givenGuiqi Yiyuan Ointment by gavage for two weeks in advance. Later the right lungs of the rats in the pure radiation group andGuiqi Yiyuan Ointment group were radiated once by 2 Gy12C6+, while the blank control group received no radiation. 6, 12, 24 h after radiation all groups of rats were executed. Peripheral hemogram and the levels of IL-6, TGF-β1 and IL-1β in serum of the rats were examined. The changes of lung tissue pathology morphology in the rats were observed by HE staining.Results Compared with the blank control group, the contents of IL-6, TGF-β1 and IL-1β in serum of the pure radiation group increased obviously at 12 h after radiation (P<0.01), and the amount of leukocyte, erythrocyte, blood platelet and hemoglobin distinctly declined at 12 h after radiation (P<0.01); HE staining showed that the alveolar wall was thickened at 24 h after radiation, and there were exudate and inflammatory cell infiltration in the alveolar cavity. Compare with the pure radiation group at 12 h after radiation, the levels of IL-6, TGF-β1 and IL-1β inGuiqi Yiyuan Ointment group decreased significantly at 12 h after radiation (P<0.01). Indexes of blood routine significantly increased (P<0.01), and the pathological changes of lung tissue in rats improved (P<0.01). ConclusionGuiqi Yiyuan Ointment can protect damages caused by heavy ion radiation induced bystander effects.
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Objective To investigate the mechanism of Guiqiyiyuan Ointment (GO) for preventing and treating 12C6+ beam radiation induced lung and kidney bystander effect to provide a new strategy for prevention and treatment of clinical radiation injury. Methods Sixty healthy male Wistar rats were randomly and equally divided into 3 groups: NC group, SR group (simple radiation 2ml/kg), GO group(GO 2ml/kg intragastric administration for 7 days). The right side of the lung was modeled by 12C6+beam radiation. After modeling, the rats were killed at 48h. The left lung, left and right kidney tissues were taken from the rats. The DNA methylation rate was detected by ELISA assay, pathological changes were observed by HE staining, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were detected by immunohistochemistry. Results Compared with the NC group, the level of DNA methylation was decreased significantly (P<0.01), the left lung showed inflammation, no abnormal finding was seen in the left and right kidneys, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly increased in the SR group (P<0.01). Compared with the SR group, the level of DNA methylation was increased significantly (P<0.01), the left lung inflammation became better, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly decreased in the GO group (P<0.01). Dnmt1, Dnmt3a and Dnmt3b proteins were expressed in the cytoplasms of bronchial and renal tubular epithelial cells in all the groups. The NC group presented as light brown-brown staining, showing a weak positive expression, the SR group as brown-brown staining, showing astrong positive expression, and the GO group as light brown-brown staining, showing a moderate positive expression. Conclusion The GO can reduce the bystander effect caused by 12C6+ beam radiation, and its mechanism is related to improving the level of DNA methylation.
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Objective To investigate the effects of Astragalus polysaccharide (APS) on damage of keratinocytes in ultraviolet B (UVB) radiation skin in HaCaT cells; To preliminarily explore its mechanism of action.Methods HaCaT cells were treated by UVB irradiated for modeling. Blank control group, model group, UVB irradiation group and low-, medium- and high-dose APS interventional groups were set up. Each medication group was given relevant medicine. MTT assay was used to determine the cell activity; GSH-Px, CAT, SOD activity and MDA content were detected by biochemical colorimetric method; contents of TNF-α and IL-6 were detected by ELISA.Results Compared with the control group, the contents of SOD, CAT and GSH-Px in the model group decreased significantly, while the contents of MDA, TNF-α and IL-6 increased significantly (P<0.05); compared with the mode group, the contents of SOD, CAT and GSH-Px in the medication groups increased significantly, while the contents of MDA, TNF-α and IL-6 were reduced significantly (P<0.01).Conclusion APS can reduce the oxidative stress injury of UVB to HaCaT cells to some extent.
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Objective To observe the molecular mechanism of adaptive response of the kidney and skeleton and brain issues in the high altitude hypoxia; To discuss the unity of yin and yang oscillation relationship of kidney and brain marrow.Methods SPF KM mice were randomly divided into control group and model group according to random number table method. Mice in the model group were exposed to high altitude hypoxia cabin for successive 21 d. On the 22nd day, mice got out of the cabin and their body weight was measured, and then they were put to death through eyeball blood sampling. The activities of lactic LDH and Na+-K+-ATPase in brain tissue were detected by spectrophotometric colorimetry. The PFK activities of brain and skeletal muscle were detected by ELISA. Meanwhile the contents of EPO and EPOR in the kidney were measured by ELISA. The mRNA expressions of HIF-1α and AQP-4 in brain were assessed by RT-PCR. At the same time, the protein expressions of HIF-1α and AQP-1 in brain and the protein expression of Mb in skeletal muscle were detected by Western blot.Results Compared with the normal group, the LDH and PFK in brain tissue and the content of EPO in kidney tissue were all raised in the model group(P<0.05). Meanwhile the mRNA expressions of HIF-1α and AQP-4 and the protein expressions of HIF-1α and AQP-1 in brain were all increased in the mice from the model group; the activities of PFK and the protein expression of Mb in skeletal muscle were also raised in the model group. But the activity of Na+-K+-ATPase in brain tissue and the content of EPOR in kidney tissue both decreased in the model group (P<0.05,P<0.01).Conclusion Adaptive response and the unity of yin and yang oscillation relationship between kidney, skeleton and brain tissue happen in high altitude hypoxia.
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Objective To observe the effects of Radix Hedysari on collagen area, hyaluronic acid (HA) and laminin (LN) of lung tissues in rat with pulmonary interstitial fibrosis; To investigate the mechanism and screen the best active ingredients in Radix Hedysari.Methods Totally 144 SPF Wistar rats were randomly divided into control group, model group, metacortandracin group, and Radix Hedysari polysaccharide, flavone and saponin groups were set as high-, medium-, and low-dose groups. Pulmonary interstitial fibrosis models were set up by dropping bleomycin into air tube of rats. All groups were taken corresponding medicine with appropriate dose daily on day 2 after models were established for 28 days. Collagen fibrils in lung tissue were observed by Masson dying and contents of HA and LN in lung tissue of rats in each group were detected by radioimmunoassay.Results Compared with the model group, pulmonary alveoli in Radix Hedysari flavone high-, medium-, and low-dose groups and Radix Hedysari polysaccharide low-dose group were relieved obviously; collagenous fiber area in Radix Hedysari flavone low-dose group, Radix Hedysari polysaccharide medium-dose group, and Radix Hedysari saponin low-dose group decreased obviously. Compared with the model group, the content of HA in Radix Hedysari polysaccharide high-dose group, Radix Hedysari flavone high-, medium-, and low-dose groups, and Radix Hedysari saponin high-dose group decreased obviously; the content of LN in Radix Hedysari polysaccharide high-dose group, Radix Hedysari flavone medium- and low-dose groups, and Radix Hedysari saponin medium- and low-dose groups decreased obviously. Conclusion Polysaccharide, flavone and saponin of Radix Hedysari have the abilities to alleviate inflammation of pulmonary alveoli, inhibit proliferation and deposition of collagen fibrils, and reduce the contents of HA and LA in lung tissue. Among these active ingredients, flavone has the best effect.
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Objective To explore the intervention effect of active fraction of Angelica Sinensis Radix in mice under high altitude hypoxia condition. Methods Totally 72 healthy SPF mice were randomly divided into control group (K), model group (M), Rhodiola rosea group, and active fraction of Angelica Sinensis Radix groups (B, C, X). The mice were administerted corresponding treatment by gavage for 21 days. Control mice were given normal saline in same volume. From the 8th day, all mice excepted control mice were exposed to high altitude hypoxia cabin after 0.5 hour gavage treament. On the 22nd day, after got out of the cabin and their body weight were measured, mice were put to death through eyeball blood sampling to prepare splenic lymphocyte suspension. The proliferation and transformation capacities of lymphocyte cell and killing activity of NK cells were detected by MTT. The content of IL-2 in the serum of mice in each group were detected by ELISA. Results Compared with the control group, the body weight of mice, the proliferation and transformation capacities of lymphocyte cell, the killing activity of NK cells, and the content of IL-2 were all significantly decreased (P<0.05, P<0.01). Experiment tests showed that the proliferation and transformation abilities of lymphocyte cell and the killing activity of NK cells were all increased in the mice of group B, C, and X compared with those of the model group (P<0.05, P<0.01). The stimulate index of lymphocyte cell was raised after X intervention compared with those of the model group (P<0.05). The content of IL-2 in the serum was enhanced after intervention of active fraction C and X of Angelica Sinensis Radix compared with those of the model group (P<0.05, P<0.01). Conclusion Active fraction of Angelica Sinensis Radix shows increasing immunological function of mice exposed to hypoxia.
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Objective To investigate the effects of volatile oil of Fructus Evodia, mustar d oil and total anthraquinone in Rheum on the transcutaneous permeability of paeoniflorin. Methods Using intelligent transdermal diffusion cell and excised mice skin in vitro as transdermal barrier, the kinetics parameters such as cumulative permeation quantity, permeation rate and permeation lagged time of the three kinds of penetration enhancers on paeoniflorin were determined by HPLC in 12 hours. Results The penetration rate of volatile oil of Fructus Evodia, mustard oil and total anthraquinone in Rheum were 8.188 6, 3.411 7, 1.230 3 μg/(cm2?h), respectively, the enhancement ratios were 22.6, 9.40, 3.40, respectively, and the permeation lagged times were 0.93, 0.51, 0.83 h, respectively. Conclusion Three penetration enhancers all can enhance previously percutaneous absorption of paeoniflorin, which provides reference for the selection of the penetration enhancers of transdermal delivery.