1.LC/MS guided approach to discovering nephroprotective substances from Huangkui capsule.
Tingting MA ; Yi WANG ; Xiaoqian CHEN ; Xiaoping ZHAO
Journal of Zhejiang University. Medical sciences 2017;46(1):66-73
To discover the nephroprotective substances from Huangkui capsule.The components of Huangkui capsule were isolated by preparative liquid chromatography, and the active components were screened by LC/MS and identified. The adriamycine-injured HK-2 cells were treated with various active components with different concentrations, and the malonaldehyde (MDA) content, adenosine triphosphate (ATP) level and mitochondrial oxygen consumption rate were measured to verify the protective activity of the compounds.Four active components in Huangkui capsule were identified to exert nephroprotective effects. Fifteen flavanoids from these four components were tentatively identified by LC/MS, and hyperin, myricetin, quercetin, rutin and isoquercetin were confirmed. Hyperin, myricetin quercetin and rutin showed dose-dependent protective effects on injured HK-2 cells. Espacially, hyperin significantly reduced MDA content, quercetin and rutin significantly increased ATP level, and myricetin significantly increased mitochondrial oxygen consumption rate.Hyperin, myricetin, querctein and rutin might be the potential nephroprotective compounds in Huangkui capsule, their effects may be related to the inhibition of lipid peroxidation and the alleviation of mitochondrial damage.
Abelmoschus
;
chemistry
;
drug effects
;
Adenosine Triphosphate
;
metabolism
;
Cell Line, Transformed
;
Chromatography, Liquid
;
Doxorubicin
;
Drugs, Chinese Herbal
;
Epithelial Cells
;
drug effects
;
Flavonoids
;
pharmacology
;
Kidney Diseases
;
chemically induced
;
drug therapy
;
prevention & control
;
Kidney Tubules, Proximal
;
drug effects
;
Lipid Peroxidation
;
drug effects
;
Malondialdehyde
;
metabolism
;
Mass Spectrometry
;
Mitochondria
;
drug effects
;
Oxygen Consumption
;
drug effects
;
Protective Agents
;
chemistry
;
pharmacology
;
Quercetin
;
analogs & derivatives
;
pharmacology
;
Rutin
;
pharmacology
2.Effects of different surfactant administrations on cerebral autoregulation in preterm infants with respiratory distress syndrome.
Xu-Fang LI ; Ting-Ting CHENG ; Rui-Lian GUAN ; Hong LIANG ; Wei-Neng LU ; Jing-Hua ZHANG ; Mei-Yi LIU ; Xin YU ; Jun LIANG ; Li SUN ; Lian ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(6):801-805
To treat respiratory distress syndrome, surfactant is currently delivered via less invasive surfactant administration (LISA) or INtubation SURfactant Extubation (INSURE). The aim of this study was to compare the effect of the two delivery methods of surfactant on cerebral autoregulation. Near infrared spectroscopy monitoring was carried out to detect cerebral oxygen saturation (ScO), and the mean arterial blood pressure (MABP) was simultaneously recorded. Of 44 preterm infants included, the surfactant was administrated to 22 via LISA and 22 via INSURE. The clinical characteristics, treatments and outcomes of the infants showed no significant differences between the two groups. The correlation coefficient of ScOand MABP (r) 5 min before administration was similar in the two groups. During surfactant administration, rincreased in both groups (0.44±0.10 to 0.54±0.12 in LISA, 0.45±0.11 to 0.69±0.09 in INSURE). In the first and second 5 min after instillation, rwas not significantly different from baseline in the LISA group, but increased in the first 5 min after instillation (0.59±0.13, P=0.000 compared with the baseline in the same group) and recovered in the second 5 min after instillation (0.48±0.10, P=0.321) in the INSURE group. There were significant differences in the change rates of rbetween the two groups during and after surfactant administration. Our results suggest that cerebral autoregulation may be affected transiently by surfactant administration. The effect duration of LISA is shorter than that of INSURE (<5 min in LISA vs. 5-10 min in INSURE).
Administration, Intranasal
;
adverse effects
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Brain
;
metabolism
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Female
;
Homeostasis
;
Humans
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Infant, Newborn
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Infant, Premature
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Intubation
;
adverse effects
;
Male
;
Oxygen Consumption
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Pulmonary Surfactants
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administration & dosage
;
therapeutic use
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Respiratory Distress Syndrome, Newborn
;
drug therapy
;
therapy
3.Effect of nitrogen supply on biomass accumulating and root respiration dynamic changing of Glycyrrhiza uralensis.
Pei-Jun GUO ; Guo-Feng WU ; Wen-Lan LIU ; Yu-Ling FAN ; Guang-Li NIU ; Guang-Ming WU ; Zhi-Rong SUN
China Journal of Chinese Materia Medica 2014;39(9):1584-1588
This paper aimed to study the effect nitrogen supplying on biomass accumulation and root respiration dynamic change of Glycyrrhiza uralensis and reveal the metabolic pathway of root respiration impact the biomass accumulating of G. uralensis. Six groups of one-year-old G. uralensis were fertilized with total nutrition containing various nitrogen concentration (0, 0.5, 1, 2, 4, 8 mmol x L(-1)) every week. At the end of every month, from June to October, the volume respiration rate and biomass of different classes of root samples were determined, and the correlation between root respiration and biomass was analyzed. The results indicated a negative correlation between volume respiration rate and biomass, nitrogen supply significantly affected both root respiration and biomass of G. uralensis by reducing root respiration and increasing root biomass. Under 8 mmol x L(-1) nitrogen supplying, there existed the optimal inhibition of root respiration, which has increased biomass of G. uralensis.
Biomass
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Dose-Response Relationship, Drug
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Glycyrrhiza uralensis
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drug effects
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growth & development
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metabolism
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Kinetics
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Nitrogen
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pharmacology
;
Oxygen Consumption
;
drug effects
;
Plant Roots
;
drug effects
;
metabolism
;
Seasons
;
Time Factors
4.Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1.
Woochul CHANG ; Chang Youn LEE ; Jun Hee PARK ; Moon Seo PARK ; Lee So MAENG ; Chee Soon YOON ; Min Young LEE ; Ki Chul HWANG ; Yong An CHUNG
Journal of Veterinary Science 2013;14(1):69-76
The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1alpha activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1alpha. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1alpha expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1alpha was important for MSC survival under hypoxic conditions.
Cell Survival
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Cobalt
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Gene Expression Regulation/*physiology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
;
Mesenchymal Stromal Cells/drug effects/metabolism/*physiology
;
MicroRNAs/*metabolism
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Oxygen/pharmacology
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*Oxygen Consumption
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RNA, Small Interfering/metabolism
5.Bisphenol A Impairs Mitochondrial Function in the Liver at Doses below the No Observed Adverse Effect Level.
Min Kyong MOON ; Min Joo KIM ; In Kyung JUNG ; Young Do KOO ; Hwa Young ANN ; Kwan Jae LEE ; Soon Hee KIM ; Yeo Cho YOON ; Bong Jun CHO ; Kyong Soo PARK ; Hak C JANG ; Young Joo PARK
Journal of Korean Medical Science 2012;27(6):644-652
Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.05 and 1.2 mg/kg body weight/day, were administered intraperitoneally for 5 days to mice. Both treatments impaired the structure of the hepatic mitochondria, although oxygen consumption rate and expression of the respiratory complex decreased only at the higher dose. The hepatic levels of malondialdehyde (MDA), a naturally occurring product of lipid peroxidation, increased, while the expression of glutathione peroxidase 3 (GPx3) decreased, after BPA treatment. The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) also increased. In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential. In conclusion, doses of BPA below the NOAEL induce mitochondrial dysfunction in the liver, and this is associated with an increase in oxidative stress and inflammation.
Adenosine Triphosphate/metabolism
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Animals
;
Glutathione Peroxidase/metabolism
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Hep G2 Cells
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Humans
;
Inflammation/chemically induced/metabolism/pathology
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Injections, Intraperitoneal
;
Interleukin-6/metabolism
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Lipid Peroxidation/drug effects
;
Liver/*drug effects/metabolism/pathology
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Male
;
Malondialdehyde/metabolism
;
Membrane Potential, Mitochondrial/drug effects
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Mice
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Mice, Inbred C57BL
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Mitochondria/drug effects/*metabolism
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Oxidative Stress/drug effects
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Oxygen Consumption/drug effects
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Phenols/*toxicity
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Tumor Necrosis Factor-alpha/metabolism
6.Effects of Tiangou Jiangya capsule on hypertension and hemodynamics in anaesthetized dogs.
Yujie LI ; Qing YANG ; Xiaogang WENG ; Ying CHEN ; Shuyuan ZHOU ; Dan LI ; Xiaoxin ZHU
China Journal of Chinese Materia Medica 2011;36(23):3338-3343
OBJECTIVETo evaluate the effects of Tiangou Jiangya capsule on blood pressure and hemodynamics in anesthetized Beagle dogs.
METHODAnesthetized dogs were divided into five groups: Tiangou Jiangya capsule 3-dose groups as 1.6, 3.2, 6.4 g x kg(-1), positive control group was giving captopril, negative control was giving 0.5% CMC-Na, duodenal administration. The blood pressure and hemodynamic changes were observed.
RESULTThe systolic blood pressure of middle-dose Tiangou Jiangya capsule group was significantly reduced at 30 min after administration. The systolic blood pressure (SAP) and diastolic blood pressure (DAP) of high-dose group of Tiangou Jiangya capsule was significantly reduced at 15 min to 90 min after administration. High-dose Tiangou Jiangya capsule can also significantly reduce cardiac work (LVW) and total peripheral resistance (TPR). Tiangou Jiangya capsule had no significant effect on the other hemodynamic parameters and myocardial oxygen consumption.
CONCLUSIONTiangou Jiangya capsule has a significant effect on reducing blood pressure, which is related to the reducing total peripheral resistance and reducing cardiac work. The result can provide a reference to further clarify the Tiangou Jiangya capsule mechanism on reducing blood pressure.
Animals ; Antihypertensive Agents ; administration & dosage ; pharmacology ; therapeutic use ; Benzyl Alcohols ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Disease Models, Animal ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Flavonoids ; pharmacology ; therapeutic use ; Furans ; pharmacology ; therapeutic use ; Glucosides ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Hypertension ; drug therapy ; Lignans ; pharmacology ; therapeutic use ; Male ; Oxygen Consumption ; drug effects ; Vascular Resistance ; drug effects
7.Influence of lyophilized Radix Astragali powder injection on hemodynamics of dogs with myocardial ischemia.
Congxun JIANG ; Xi GU ; Li LI ; Hua XIAO ; Yi ZOU ; Xu HAN ; Fangju YANG
Journal of Biomedical Engineering 2010;27(1):75-79
In order to observe the influence of lyophilized Radix Astragali powder injection on hemodynamics and myocardial consumption of oxygen of dogs with myocardial ischemia, we establised the myocardial ischemia model by ligating the anterior descending branch of left coronary artery of 5 mongrel dogs. Then the drugs were administered intravenously, and the hemodynamic parameters and myocardial consumption of oxygen of the dogs were measured. All the Radix Astragali groups and Radix Salviae Miltiorrhizae Group (RSMG) showed significantly decreased heart rate (HR), diastolic blood pressure (DBP), mean arterial pressure (MAP) of dogs with myocardial ischemia in 5-30 min after drug administration (P < 0.05-0.01). All the Radix Astragali groups and the RSMG showed significantly lowered left ventricular end-diastolic pressure (LVEDP) of the dogs in 10 min-4 h after drug administration (P < 0.05-0.01). All the Radix Astragali groups displayed significantly increased maximum contraction velocity (+dp/dt(max)) of the dogs in 10 min after drug administration (P < 0.05-0.01). All the Radix Astragali groups and the RSMG displayed significantly increased cardiac output (CO) in 10 min-4 h after drug administration, in which the High Dose Group (HDG) of Radix Astragali displayed the highest statistical significance (P < 0.01). All the Radix Astragali groups and the RSMG exhibited significantly decreased peripheral resistance (TPR) and increased coronary blood flow (CBF) in 10 min-4 h after drug administration (P < 0.05-0.01). HDG showed significantly decreased myocardial work (MW) in 5 min-30 min after drug administration (P < 0.05-0.01). HDG and MDG exhibited significantly decreased oxygen uptake rate of the myocardium (MVo2) in 30 min-3 h after drug administration(P < 0.05-0.01). In summary, the lyophilized Radix Astragali powder injection can significantly benefit all the indexes and strengthen the heart function of the dogs with myocardial ischemia.
Animals
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Astragalus membranaceus
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chemistry
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Dogs
;
Female
;
Freeze Drying
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Hemodynamics
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Injections
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Male
;
Myocardial Ischemia
;
drug therapy
;
metabolism
;
physiopathology
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Oxygen Consumption
;
drug effects
;
Plant Extracts
;
isolation & purification
;
pharmacology
;
Plant Roots
;
chemistry
;
Powders
8.Effect of heart tablets on cardiac hemodynamics and myocardial oxygen consumption in anesthetized dogs.
China Journal of Chinese Materia Medica 2010;35(18):2480-2487
OBJECTIVETo observe the pharmacological effects of Heart tablets on cardiac function and its mechanism, the effects on cardiac hemodynamics and myocardial oxygen consumption in anesthetized dogs were observed.
METHODObserve the effect of Heart tablets on coronary blood flow, cardiac output, myocardial oxygen consumption and other indicators in normal anesthetized dogs.
RESULTThe Heart tablets can increase femoral arterial blood pressure, while no effect is found on the heart rate, standard II ECG PR interval, QRS interval, QT interval, T wave and other parameters. The tablets can expand coronary artery and peripheral vessel, increase coronary blood flow, lower coronary resistance and increase cardiac blood supply capacity, improve left ventricular function, ameliorate cardiovascular adaptability, increase dp/dt(max), enhance myocardial activity and have a positive regulatory role in heart. At the meantime raise the cardiac output and stroke volume were raised, so that blood pressure can be increased, while the total peripheral resistance was decreased. The coronary vein sinus oxygen content were significantly increased and myocardial oxygen consumption index and myocardial oxygen utilization were reduced.
CONCLUSIONThe tablets can adjust and improve the cardiovascular system.
Anesthesia ; Animals ; Blood Pressure ; drug effects ; Coronary Disease ; drug therapy ; metabolism ; physiopathology ; Disease Models, Animal ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Heart ; drug effects ; physiopathology ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Humans ; Male ; Myocardium ; metabolism ; Oxygen Consumption ; drug effects ; Random Allocation ; Tablets
9.Antiangiogenic therapy: a novel approach to overcome tumor hypoxia.
Chinese Journal of Cancer 2010;29(8):715-720
Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The growth and metastasis of solid tumors rely on blood vessels. Antiangiogenic agents mainly target tumor blood vessels, and radiation therapy mainly targets tumor cells. Combination of antiangiogenic treatment and radiation exhibits synergistic effect, which improves the response of tumors to radiation therapy. The mechanisms of interaction between antiangiogenic agents and ionizing radiation are complex and involve interactions between tumor cells and tumor microenvironment, including tumor oxygenation, stroma, and vasculature. The original mechanism of antiangiogenesis is to induce ischemia and hypoxia in tumors, thereby, "starve" the tumors. However, recently, emerging data suggest that antiangiogenic agents could reduce the proportion of hypoxic cells through normalizing tumor vasculature, decreasing oxygen consumption, and other mechanisms. The use of antiangiogenic agents provides a new approach to overcome the hypoxia problem, and ultimately improves the efficacy of radiation therapy. In this review, we discuss tumor hypoxia, tumor angiogenesis and its regulation, mechanisms of antiangiogenic therapy combined with radiation therapy, and how antiangiogenic therapy overcomes tumor hypoxia.
Angiogenesis Inhibitors
;
pharmacology
;
therapeutic use
;
Animals
;
Antibodies, Monoclonal
;
pharmacology
;
therapeutic use
;
Antibodies, Monoclonal, Humanized
;
pharmacology
;
therapeutic use
;
Apoptosis
;
drug effects
;
Bevacizumab
;
Cell Hypoxia
;
drug effects
;
Combined Modality Therapy
;
Endostatins
;
pharmacology
;
therapeutic use
;
Humans
;
Neoplasms
;
blood supply
;
drug therapy
;
metabolism
;
radiotherapy
;
Neovascularization, Pathologic
;
drug therapy
;
Oxygen Consumption
;
drug effects
;
radiation effects
10.COLD and HOT nature of Coptis & Evodia and their prescriptions investigated with diet restriction/cold-water swimming mice models.
Yong-shen REN ; Jia-bo WANG ; Yan-ling ZHAO ; Ping ZHANG ; Hai-ping ZHAO ; Xue-ru ZHANG ; Can-ping ZHOU ; Xiao-he XIAO ; Cheng JIN
Acta Pharmaceutica Sinica 2009;44(11):1221-1227
To establish a new method to evaluate the COLD and HOT nature of Coptis & Evodia and their prescriptions Zuojinwan and Fanzuojinwan. Physical models of mice were established by diet restriction with cold-water swimming (weak model, WM) and fed with high protein animal feeds (strong model, SM). An instrument with cold and hot pads was used to investigate the variation of temperature tropism among SM and WM groups of mice affected by drugs. Meanwhile, the oxygen consumption and activity of adenosine triphosphatase (ATPase) were detected, in order to investigate the mechanism of energy metabolism which might be affected by these drugs. The results showed that the drug effects gradually changed in an order of "Coptis-->Zuojinwan--> Fanzuojinwan-->Evodia". In detail, Coptis increased the remaining rate (RR) of mice on hot pad, decreased oxygen consumption and ATPase activity (n=6, P < 0.01 or P < 0.05), while Evodia performed inversely; which indicated the COLD nature of Coptis and HOT nature of Evodia, and confirmed with their traditional definition in medicinal works. In conclusion, the methods applied in this work, can objectively and directly express the nature disparity between the two herbs and predict the tendency of changes of the nature of their combination, which brings a new approach in investigation of the nature theory of traditional Chinese medicine.
Animals
;
Body Temperature
;
Cold Temperature
;
Coptis
;
chemistry
;
Diet
;
Drug Combinations
;
Drugs, Chinese Herbal
;
isolation & purification
;
pharmacology
;
Evodia
;
chemistry
;
Hot Temperature
;
Medicine, Chinese Traditional
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Mice
;
Oxygen Consumption
;
drug effects
;
Plants, Medicinal
;
chemistry
;
Sodium-Potassium-Exchanging ATPase
;
metabolism
;
Swimming
;
Tropism

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