ABSTRACT
ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L-1）， Coptidis Rhizoma group（B group， 38.4 g·L-1）， processed Euodiae Fructus group（C group， 5.88 g·L-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（Cmax） of Ber， Pal， Evo， and Rut were the highest and time to peak（tmax） were the lowest in the liver of A group. In plasma， the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group， tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver， compared with B-D groups， Cmax values of 5 representative components except Pae were elevated， AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t1/2） of each representative components in A group was elevated and tmax was decreased， and Cmax of each representative ingredient except Pal was decreased， AUC0-t values of Ber and Pal were increased， whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.
ABSTRACT
ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.
ABSTRACT
Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.
ABSTRACT
The clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile genome editing tool with high efficiency. A guide sequence of 20 nucleotides (nt) is commonly used in application of CRISPR/Cas9; however, the relationship between the length of the guide sequence and the efficiency of CRISPR/Cas9 in porcine cells is still not clear. To illustrate this issue, guide RNAs of different lengths targeting the EGFP gene were designed. Specifically, guide RNAs of 17 nt or longer were sufficient to direct the Cas9 protein to cleave target DNA sequences, while 15 nt or shorter guide RNAs had loss-of-function. Full-length guide RNAs complemented with mismatches also showed loss-of-function. When the shortened guide RNA and target DNA heteroduplex (gRNA:DNA heteroduplex) was blocked by mismatch, the CRISPR/Cas9 would be interfered with. These results suggested the length of the gRNA:DNA heteroduplex was a key factor for maintaining high efficiency of the CRISPR/Cas9 system rather than weak bonding between shortened guide RNA and Cas9 in porcine cells.
Subject(s)
Base Sequence , Complement System Proteins , CRISPR-Cas Systems , DNA , Genome , Nucleotides , SwineABSTRACT
The proliferation of tumor cells is regulated by a complex array of signaling pathways, among these signaling pathways,the programmed cell death. Autophagy and apoptosis are two types of programmed death. There are significant differences in their morphological and functional features, but they also have many links. Both apoptosis and autophagy are involved in activation,expression and regulation of a series of genes. By reviewing the research progress in recent years, this article will discuss the cellular regulation and molecular mechanisms of their related genes. Through summarizing the relationship between autophagy and apoptosis,it aims to get a better understanding of the mechanisms of autophagy and apoptosis in tumor progression,and looking at the perspectives for studies on the autophagy and apoptosis in tumor treatment.
ABSTRACT
Objective To explore the biological indicators of diagnosis and treatment of irritable bowel syndrome (IBS), and to explore the mechanism of action of a Chinese medicine Wuji Pill (WJW) on irritable bowel syndrome (IBS). Methods (1) Postinflammatory irritable bowel syndrome (PI-IBS) rat model was established by acetic acid plus restraint stress method . (2) The colonic motor ability of rats was evaluated by colon motility index (MI), the number of fecal particles discharged within 2 h, and the time of glass pellet discharge. (3) The formation of PI-IBS model rats and the therapeutic effect of WJW were observed. (4) The levels of calcitonin gene-related peptide (CGRP), motilin (MTL), neuropeptide Y (NPY), substance P (SP), somatostatin (SS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results (1) The rat PI-IBS model was successfully established. Compared with the normal group, the body weight of the model rats was decreased, the food intake decreased, the amount of feces increased, loose stools and amorphous soft stools appeared, voluntary movements decreased, colon motility index ( MI) significantly increased ( P ＜ 0. 05 ), the number of fecal particles discharged significantly increased ( P＜ 0. 05), and the glass pellet discharge time was significantly shortened ( P ＜ 0. 05). (2) WJW treatment for 7 days significantly improved a variety of symptoms. Compared with the normal control, the levels of CGRP, SS and VIP in the brain tissue of PI-IBS rats were significantly increased (P＜ 0. 05), and the NPY concentration was significantly decreased ( P ＜ 0. 05). However, the treatment with WJW significantly reduced CGRP, SS and VIP levels (P＜ 0. 05), and significantly increased the NPY concentration level (P ＜ 0. 05). (3) Compared with the normal control group, the levels of CCK, NPY, MTL, SS and VIP in colonic tissues of PI-IBS rats were significantly decreased (P＜ 0. 05), while WJW significantly increased the CCK and VIP levels. Conclusions WJW can be used to treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissues of IBS rats. These anomalous and adjustable brain-gut peptides may become a potential biomarker for the diagnosis and treatment of IBS.
ABSTRACT
Neurodegenerative diseases are threating our health seriously.Inflammation plays an important role in the initiation and development of neurodegenerative diseases, and its primary characteristics are the activation of microglia and the increasing level of inflammation cytokines.This review describes the relationship between neuroinflammation and several neurodegenerative diseases, and the models in vivo and in vitro.In addition, combining with traditional Chinese medicines knowledge of encephalopathy, we summarizes pharmacological effects and mechanisms of multiple herb extracts and monomer compounds in preventing the activation of microglia and inhibiting neuroinflammation, thus, to provide the basis for gradually revealing the related rules and characteristics of treating encephalopathy by traditional Chinese medicine, and improving the accuracy of the clinical drugs, as well as developing new drugs for the prevention and control of encephalopathy.
ABSTRACT
The fruit of Ziziphus jujuba was known as fine quality in the Shennong's Herbal. It is sweet in taste and mild in property with the effect of regulating the middle, invigorating the spleen, assisting twelve meridians, harmonizing stomach-qi, unclogging nine orifices, and moderating hundreds of herbs. In recent years, the efficacies of Ziziphus jujuba have been widely studied with considerable meaningful achievements. In this article, main research progresses in recent ten years were reviewed, which included resources, chemical components and pharmacological effects of Ziziphus jujuba. The research and development of medication, health care product and food with Ziziphus jujuba as its main ingredient were summarized for further references in related studies.
ABSTRACT
Atherosclerosis (As) is an important pathological basis of cardiovascular and cerebrovascular diseases. The pathogenesis studies of As have been a hot topic in the field of vascular biology research. The inflammation is known as a major participant in the development process of As. And monocyte-macrophage plays a central role in inflam-mation. In recent years, with the deepening research on inflammatory mechanisms, the As macrophage polarization is attracting researchers' attention. Under different environmental inductions, macrophages develop into M1 and M2 phenotypes. M1 macrophages (classical type), which can stimulate the secretion of pro-inflammatory cytokines, is generally considered as pro-inflammatory subtypes and can facilitate the progress of As. Whereas, M2 macrophages (alternative type), which can inhibit pro-inflammatory factor production, function as anti-inflammatory subtypes and likely to inhibit the progression of As. The mechanisms of As, macrophage polarization in As, and opportunities for herbal medicines will be summarized in this review.
ABSTRACT
The interactions between endothelial cells (EC) and smooth muscle cells (SMC) contribute to vascular physiological functions and also cause the occurrence and development of different kinds of diseases. Currently, EC-SMC co-culture model is the best way to study the interactions between the two kinds of cells. This article summarizes existing EC-SMC co-culture models and their effects on the structure and functions of the two kinds of cells. Microscopically speaking, it provides a basis for in-depth studies on their interactions as well as a reference for the establishment of in vitro EC-SMC co-culture system that is closer to organic physiology or pathology state.
Subject(s)
Animals , Humans , Coculture Techniques , Methods , Endothelial Cells , Cell Biology , Metabolism , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Cell Biology , MetabolismABSTRACT
To illustrate the compability rule of Jinlingizi powder, by investigating the effects of Jinlingzi Powder with different compatibility on the enzymatic activity of cytochrome P1 A2 (CYP1A2) from rat liver microsome. The different compability of Jinlingizi powder is designed, based on the orthogonal array L9 (3(4)). In vitro test, rat liver microsomes incubation system is applied to detect the 50% inhibitory concentraton of Jinlingzi powder with different compatibility to cytochrome P1A2 (CYP1A2) enzyme. In vivo experiments, rats is treated orally with the different compability of Jinlingizi powder for 5 days, then be injected with probe drug phenacetin. The biosample from liver tissue is obtained by microdialysis probe, then analysisd by HPLC. The concentration-time data are modulated by software WinNonlin. IC50 data show no significant inhibitory activty to cytochrome P1 A2. Acetaminophen and phenacetin PK parameters indicate that the different compability of Jinlingizi powder can modulate the CYP 1A2 mediated metabolism, which is associate with the compatibility of Jinlingzi powder.
Subject(s)
Animals , Male , Rats , Cytochrome P-450 CYP1A2 Inhibitors , Drugs, Chinese Herbal , Pharmacology , Medicine, Chinese Traditional , Microsomes, Liver , Powders , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To in vitro compare the induction of extracts of Stellera chamaejasme ESC, ESC-1 and ESC-2 on NCI-H157 cell apoptotic.</p><p><b>METHOD</b>The apoptosis rate was inspected by flow cytometry; caspase-3, 8, 9 activities was measured by spectrophotometry. Fas, Fas-L, TNF-alpha, Trail-R, Cyto-C, Smac/diablo protein expressions of apoptosis pathway was observed by Elisa method.</p><p><b>RESULT</b>Compared with the control group, ESC, ESC-1, ESC-2 can significantly improve the apoptosis rate of NCI-H157 cell. ESC significantly improved cells caspase-3, 8 activity, ESC-2 can significantly improve the activity of caspase-3, 8, 9. ESC, ESC-1, ESC-2 significantly increased Fas expression and ESC significantly increased Fas/Fas-L ratio. ESC, ESC-1, ESC-2 significantly increased TNF-alpha protein expression. ESC-1 significantly lowered TRAIL-R expression. ESC, ESC-1, ESC-2 had no significant effect on Cyto-C. ESC-1, ESC-2 significantly reduced Smac protein expression.</p><p><b>CONCLUSION</b>The apoptotic effect induced by ESCs may be related to the regulation of death receptor pathway proteins. Induction mechanisms of ESCs were so complicated that it may have a two-way regulatory effect. Its induction in apoptosis is a result from comprehensive regulation and control.</p>
Subject(s)
Humans , Apoptosis , Caspases , Metabolism , Cell Line, Tumor , Neoplasms , Chemistry , Drug Therapy , Pathology , Plant Extracts , Pharmacology , Receptors, TNF-Related Apoptosis-Inducing Ligand , Thymelaeaceae , Chemistry , Tumor Necrosis Factor-alpha , fas ReceptorABSTRACT
<p><b>OBJECTIVE</b>To study the scientific theory on detoxification (attenuation) of Stellera chamaejasme (ScL) by processing and the impact on drug effect of ScL before and after being processed with vinegar.</p><p><b>METHOD</b>The difference in ingredients of ScL before and after being processed vinegar was compared by using PHLC-MS technique. A subcutaneously transplanted tumor model of H22 hepatoma was established to compare the lethal effect and weight change between tumor-loaded mice and normal mice. After consecutive oral administration in tumor-loaded mice, the impacts on tumors and immune organs were compared before and after being processed with vinegar. Luciferase Report Gene was employed to investigate the target genes TGF-beta, AP1 and NF-kappaB.</p><p><b>RESULT</b>The LD50 (median fatal dose) of extract Zp1102 exhibited higher than that of the processed one Zp1103, that is 9. 89 g x kg(-1) vs. 16.85 g x kg(-1). According to the test, Zp1102 showed more effective anti-tumor activities in vivo than that of Zp1103 in a same dosage, with the tumor inhibitory rate 36.24% (P < 0.01) at the dosage of2 g x kg(-1) and 34.40% (P < 0.05) at the dosage of 1 g x kg(-1). At the dosage of 1 g x kg(-1), Zp1102 showed a tumor inhibitory rate of 34.52% (P < 0.05), much higher from 21.55% in Zp1103. Both Zp1102 and Zp1103 had basically no impact on the report gene NF-kappaB, besides that Zp1102 up-regulated the report gene after increase in NF-kappaB concentration and down-regulated TGF-beta, but Zp1103 can only up-regulate NF-kappaB expression without any impact on TGF-beta.</p><p><b>CONCLUSION</b>Processed ScL extracts show less toxic than unprocessed extracts and slight reduction in anti-tumor activity, which may be related to the regulation of transforming growth factor TGF-beta.</p>
Subject(s)
Animals , Male , Mice , Acetic Acid , Chemistry , Chromatography, High Pressure Liquid , Lethal Dose 50 , NF-kappa B , Physiology , Neoplasms, Experimental , Drug Therapy , Phytotherapy , Thymelaeaceae , Chemistry , Toxicity , Transforming Growth Factor beta , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of Tiangou Jiangya capsule on blood pressure and hemodynamics in anesthetized Beagle dogs.</p><p><b>METHOD</b>Anesthetized 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.</p><p><b>RESULT</b>The 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.</p><p><b>CONCLUSION</b>Tiangou 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.</p>
Subject(s)
Animals , Dogs , Female , Male , Antihypertensive Agents , Pharmacology , Therapeutic Uses , Benzyl Alcohols , Pharmacology , Therapeutic Uses , Blood Pressure , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Therapeutic Uses , Furans , Pharmacology , Therapeutic Uses , Glucosides , Pharmacology , Therapeutic Uses , Heart Rate , Hemodynamics , Hypertension , Drug Therapy , Lignans , Pharmacology , Therapeutic Uses , Oxygen Consumption , Vascular ResistanceABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Tiangou Jiangya capsule (TJC) on blood pressure in renovascular hypertension rats and explore its possible mechanism.</p><p><b>METHOD</b>Seventy-two Wistar rats were randomly divided into normal control group, model group, captopril group, TJC small, medium and high dose groups. Non-invasive blood pressure measurement was used to detect the arterial blood pressure of rat tails. PRA, Ang II , ALD, 6-Keto-PGF1alpha, ET and TXB2 content in blood was measured by radioimmunoassay. NO content in blood was determined by method of nitrate reductase.</p><p><b>RESULT</b>The systolic, diastolic and mean pressure significantly increased, serum PRA, Ang II , ALD decreased, ET levels significantly increased in model group rats. TJC significantly reduced blood pressure, improved the plasma renin activity, decreased ET levels and increased NO content of model rats.</p><p><b>CONCLUSION</b>TJC can reduce blood pressure of renovascular hypertention rats, and the mechanism may be related to its regulating lower blood pressure regulation of the secretion of RAAS system and improving vascular endothelial function.</p>
Subject(s)
Animals , Rats , Angiotensin II , Blood , Antihypertensive Agents , Pharmacology , Therapeutic Uses , Benzyl Alcohols , Pharmacology , Therapeutic Uses , Blood Pressure , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Therapeutic Uses , Furans , Pharmacology , Therapeutic Uses , Glucosides , Pharmacology , Therapeutic Uses , Hypertension, Renovascular , Blood , Drug Therapy , Lignans , Pharmacology , Therapeutic Uses , Rats, Wistar , Renin , Blood , Renin-Angiotensin SystemABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of Tiangou Jiangya capsule on isolated rabbit aortic strips, and to discuss its antihypertensive mechanism.</p><p><b>METHOD</b>The isolated rabbit aortic strips were placed in perfusion baths, and induced to contract by norepinephrine (NE), KCl and CaCl2 respectively, then Tiangou Jiangya capsule extraction was added to observe its effect on the contraction. The effect on intracellular Ca2+ dependent contraction and extracellular Ca2+ dependent contraction induced by NE were also studied.</p><p><b>RESULT</b>The Tiangou Jiangya capsule (1, 3, 5 g x L(-1)) can reduce the largest contract reaction of aortic strips induced by NE or CaCl2 (P < 0.01). It can reduce both intracellular Ca2+ dependent contraction and extracellular Ca2+ dependent contraction induced by NE (P < 0.01), and the effect on extracellular Ca2+ dependent contraction is more significant. But the Tiangou Jiangya capsule has no significant effect on KCl induced contraction.</p><p><b>CONCLUSION</b>Tiangou Jiangya capsule can regulate intracellular Ca2+ concentration and help to relax the vascular smooth muscle. The mechanism could be regulating the receptor-operated Ca2+ channel. The effect on extracellular Ca2+ dependent contraction is more obvious than on intracellular Ca2+ dependent contraction induced by NE.</p>
Subject(s)
Animals , Male , Rabbits , Antihypertensive Agents , Pharmacology , Aorta , Benzyl Alcohols , Pharmacology , Blood Pressure , Calcium Chloride , Pharmacology , Diuresis , Drugs, Chinese Herbal , Pharmacology , Flavonoids , Pharmacology , Furans , Pharmacology , Glucosides , Pharmacology , In Vitro Techniques , Lignans , Pharmacology , Muscle Contraction , Muscle, Smooth, Vascular , Norepinephrine , Pharmacology , Potassium Chloride , Pharmacology , Renin-Angiotensin System , Ventricular Function, LeftABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Tiangou Jiangya capsule on blood pressure of spontaneous hypertensive rats.</p><p><b>METHOD</b>The 13-14 week SPF rats were selected and randomly divided into model groups, the low, middle, high dose of Tiangou Jiangya capsule groups, positive control group administrated with captopril. Drugs were intragastric administrated once per day, lasting four weeks. The blood pressure, heart rate, heart ventricle indexes, urinary volume and the level of PRA,angiotensing II (Ang II), aldosterone (ALD) of rats were observed.</p><p><b>RESULT</b>The low, middle, high dose of Tiangou Jiangya capsule can remarkably reduce the systolic pressure, diastolic pressure and mean arterial pressure of spontaneous hypertensive rats (P < 0.05 or P < 0.01). The low, middle dose can reduce the heart rate of rats (P < 0.01). The low dose can effectively inhibit the left ventricle indexes (P < 0.05). The Tiangou Jiangya capsule has no markedly effects on the renin-angiotensin-aldosterone system (RAAS) activity and urinary output of rats.</p><p><b>CONCLUSION</b>The results indicate that the Tiangou Jiangya capsule has evident effect of lowering blood pressure of rats, which is related to reducing heart rate, heart ventricle indexes, and has no effect on the RAAS and diuresis.</p>
Subject(s)
Animals , Male , Rats , Antihypertensive Agents , Pharmacology , Therapeutic Uses , Benzyl Alcohols , Pharmacology , Therapeutic Uses , Blood Pressure , Disease Models, Animal , Diuresis , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Therapeutic Uses , Furans , Pharmacology , Therapeutic Uses , Glucosides , Pharmacology , Therapeutic Uses , Heart Rate , Hypertension , Drug Therapy , Lignans , Pharmacology , Therapeutic Uses , Rats, Inbred SHR , Renin-Angiotensin System , Ventricular Function, LeftABSTRACT
<p><b>OBJECTIVE</b>To establish the atherosclerosis models (AS) in rats and observe the change process of AS and Shenlian decoction's pharmacological effect.</p><p><b>METHOD</b>Two hundreds and forty rats were randomly divided into blank control group, model group, positive medicine group, the high-dose, middle dose and low-dose Shenlian decoction groups. Vascular pathological changes were observed by the methods of HE stain. The levels of TC, TG, LDL-C, HDL-C, NO in serum were determined respectively by enzyme colorimetric, clear and nitrate reductase methods. ET, TXB2, 6-keto-PGF1 alpha, TNF-alpha, IL-6 and IL-8 levels in serum were detected by radioimminoassay.</p><p><b>RESULT</b>Compared with the model group, vascular lesion of different doses of Shenlian decoction groups were significantly improved, the TG, NO, TXB2 levels in serum were significantly lower (P < 0.05), while high-dose Shenlian decoction can significantly reduce TNF-alpha, IL-6, IL-8 levels in serum (P < 0.05).</p><p><b>CONCLUSION</b>Shenlian decoction can inhibit the formation and development of AS by regulating blood lipids, improving endothelial function and reducing inflammatory factors release.</p>
Subject(s)
Animals , Humans , Male , Rats , Atherosclerosis , Blood , Drug Therapy , Pathology , Disease Models, Animal , Drugs, Chinese Herbal , Interleukin-6 , Blood , Protective Agents , Random Allocation , Rats, Wistar , Tumor Necrosis Factor-alpha , BloodABSTRACT
Cathepisn D plays a key role in early process of apoptosis before mitochondrion damage and caspases activations, and also involves in Alzheimer's disease (AD). Glycosaminoglycans (GAGs) have been suggested to inhibit the progress of apoptosis. Fucoidan, a nature GAGs mimetic, is shown as a potential candidate for neuroregressive disease. Here we reported PC12 cells response to oxidative stress with clear cathepsin D release, followed by caspase-3 activation. We found that fucoidan treatment can alleviate cathepsin D and caspase-3 activation, and improve cell survival. Furthermore, for the first time, fucoidan was shown to directly inhibit human liver cathepsin D by a dose-dependent way. These results support that cathepsin D involves in early apoptosis, suggest that fucoidan can decrease apoptosis at lysosome-cathepsin D level, which opens a new therapeutic approach to AD.
Subject(s)
Animals , Humans , Rats , Alzheimer Disease , Drug Therapy , Metabolism , Apoptosis , Caspase 3 , Metabolism , Caspase Inhibitors , Cathepsin D , Metabolism , Cell Line, Tumor , Cell Survival , Hydrogen Peroxide , Metabolism , Oxidative Stress , PC12 Cells , Polysaccharides , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>Develop an LC-MS method to determine evodiamine and rutaecarpine in rats plasma simultaneously. The method was employed to investigate pharmacokinetics of evodiamine and rutaecarpine.</p><p><b>METHOD</b>Blood samples were collected in different time after oral administrated with the extracts of Euodiae Fructus, the plasma concentration of evodiamine and rutaecarpine was determined by LC-MS, pharmacokinetic parameters were calculated by WinNonlin 5.1 software.</p><p><b>RESULT</b>The linear ranges of evodiamine and rutaecarpine were 0.5-100 microg x L(-1) (r = 0.995 9), 1-200 microg x L(-1) (r = 0.999 3) respectively. The average recovery were exceeded 76% (n = 5), the precision of inner-day and inter-day were less than 15%. The pharmacokinetics parameters AUC, t1/2, CL _F of evodiamine were: (2 215.24 +/- 414.49), (4 230.62 +/- 753.77), (13 219.21 +/- 3 740.95) min x ng(-1) x mL(-1); (146.57 +/- 38.38), (114.38 +/- 14.65), (163.37 +/- 8.83) min; (184 607.29 +/- 32 502.21), (192 878.22 +/- 31 897.37), (19 3224.63 +/- 62 278.74) mL x min(-1). The pharmacokinetics parameters AUC, t1/2, CL_F of rutaecarpine were (2 283.53 +/- 298.51), (4 424.84 +/- 276.95), (14 239.93 +/- 3648.27) min x ng(-1) x mL(-1); (167.10 +/- 15.82), (131.58 +/- 20.07), (144.41 +/- 13.65) min; (1 177 340.54 +/- 2 4942.21), (181 262.92 +/- 11 162.22), (177 508.10 +/- 52 611.80) mL x min(-1).</p><p><b>CONCLUSION</b>The method described in this report has high sensitivity and selectivity, and was suitable for pharmacokinetic studies of evodiamine and rutaecarpine. The kinetic process of evodiamine and rutaecarpine in rats in vivo were all yielded to be one-compartment model.</p>