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1.
Article in Chinese | WPRIM | ID: wpr-906045

ABSTRACT

Objective:To explore the protective effect and the mechanism of Danggui Shaoyaosan(DSS) on angiotensin Ⅱ (AngⅡ)/transient receptor potential cation channel 6 (TRPC6) pathway in nephrotic syndrome (NS) rats. Method:In animal experiments, doxorubicin (4 mg·kg<sup>-1</sup> for the 1<sup>st</sup> week and 2 mg·kg<sup>-1</sup> for the 2<sup>nd</sup> week) was injected twice to the tail vein of rats to induce NS model in 160 rats, which were then randomly divided into model group (normal saline), losartan group (30 mg·kg<sup>-1</sup>·d<sup>-1</sup>), and low-(4.3 g·kg<sup>-1</sup>·d<sup>-1</sup>), medium-(8.6 g·kg<sup>-1</sup>·d<sup>-1</sup>), and high-dose (17.2 g·kg<sup>-1</sup>·d<sup>-1</sup>) DSS groups. Besides, a normal group was also set. After intervention for four weeks, ultrastructure changes of the kidney were identified by transmission electron microscopy (TEM). The 24-hour urine protein was detected by kits. Radioimmunoassay was used to detect the content of AngⅡ and Calcineurin (CaN) in plasma. Western blot was used to detect the protein expression of TRPC6, angiotensin Ⅱ type 1 receptor (AT1R), podocyte slit diaphragm-specific protein (Nephrin), and cysteine-aspartic acid protease-3 (Caspase-3) in the renal cortex. Immunohistochemistry was used to detect the expression of TRPC6 and AT1R in the slit diaphragm. In cell experiments, AngⅡ stimulated MPC5 podocytes. The cells were randomly divided into a normal group, an AngⅡ group, an AngⅡ+SAR7334 (TRPC6-specific inhibitor) group, an AngⅡ+5%DSS group, an AngⅡ+10%DSS group, and an AngⅡ+15%DSS group. Western blot was used to detect the protein expression of TRPC6, AT1R, Nephrin, and Caspase-3 in podocytes. Result:Compared with the normal group, the model group showed increased 24-hour urine protein content (<italic>P</italic><0.01) and AngⅡ and CaN in plasma (<italic>P</italic><0.01), incomplete glomerular structure, the extensive fusion of podocyte process with elevated fusion rate (<italic>P</italic><0.01), increased expression distribution of AT1R and TRPC6 in the renal cortex, and up-regulated protein expression of AT1R, TRPC6, and Caspase-3 in renal tissues (<italic>P</italic><0.01), and reduced Nephrin protein expression (<italic>P</italic><0.01). Compared with model group, the losartan group and the high-dose DSS group exhibited decreased 24-hour urine protein content (<italic>P</italic><0.01) and the content of AngⅡ and CaN in plasma (<italic>P</italic><0.01), improved glomerular structure, reduced fusion rate of podocyte process (<italic>P</italic><0.01), diminished expression distribution of TRPC6 and AT1R in the renal cortex, declining protein expression of AT1R, TRPC6 and Caspase-3 in renal tissues (<italic>P</italic><0.01), and elevated Nephrin protein expression (<italic>P</italic><0.01). Additionally, compared with the normal podocytes, AngⅡ-stimulated podocytes showed increased protein expression of AT1R, TRPC6 and Caspase-3 (<italic>P</italic><0.01), and decreased expression of Nephrin (<italic>P</italic><0.01). Compared with the AngⅡ group, the AngⅡ+SAR7334 group displayed reduced protein expression of AT1R, TRPC6, and Caspase-3 (<italic>P</italic><0.01) and increased protein expression of Nephrin (<italic>P</italic><0.01). Conclusion:DSS can improve the pathological characteristics of NS presumedly by inhibiting the interaction between AngⅡ and TRPC6 in podocytes and improving the structural integrity of podocytes to repair the damage of glomerular molecular barrier and slow down the progression of NS-induced proteinuria.

2.
Article in Chinese | WPRIM | ID: wpr-906044

ABSTRACT

Objective:To investigate the neuroprotective effect of Danggui Shaoyaosan (DSS) in a rat model of amyloid-<italic>β</italic>-peptide<sub>1-42</sub> (A<italic>β</italic><sub>1-42</sub>)-induced Alzheimer's disease (AD) as well as its regulatory effect on NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase-1) signaling pathway. Method:The AD animal model was established via intracerebral injection of A<italic>β</italic><sub>1-42</sub> and treated with different concentrations of DSS after the division of rats into the sham operation group, model group, as well as the high-, medium-, and low-dose DSS groups. Morris water maze test was conducted to determine the learning and memory abilities of rats. The morphology and function of neurons were detected by hematoxylin-eosin (HE) staining and Golgi staining, followed by immunofluorescence co-localization of NLRP3 inflammasome activation. The mRNA expression levels of interleukin (IL)-1<italic>β</italic> and IL-18 were measured by Real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β </italic>were assayed by Western blot. Result:Compared with the sham operation group, the model group exhibited significantly decreased learning and memory abilities (<italic>P</italic><0.01), impaired neuronal morphology and function, up-regulated IL-1<italic>β</italic> and IL-18 mRNA expression, enhanced NLRP3 inflammasome activation, and elevated NLRP3, Caspase-1, and IL-1<italic>β</italic> protein expression (<italic>P</italic><0.01). Compared with the model group, DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats (<italic>P</italic><0.05, <italic>P</italic><0.01), restored neuronal morphology and function, down-regulated the mRNA expression levels of inflammatory factors IL-1<italic>β</italic> and IL-18, reduced the activation of NLRP3 inflammasomes, and lowered the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β</italic> (<italic>P</italic><0.01). Conclusion:DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway, thus exerting the neuroprotective effect.

3.
Article in Chinese | WPRIM | ID: wpr-905984

ABSTRACT

Objective:To explore<italic> </italic>the efficacy and mechanism of Danggui Shaoyaosan on rats of nonalcoholic fatty liver disease (NAFLD). Method:Sixrty SPF SD male rats were randomly divided into normal group, model group,essentiale (0.144 g·kg<sup>-1</sup>) and low, middle and high-dose of Danggui Shaoyaosan groups (2.44, 4.88, 9.76 g·kg<sup>-1</sup>). High fat diet were fed to bulid the NAFLD model, and each treatment group was given corresponding drugs at the same time. After 8 weeks, the serum and liver tissue were collected to detect the contents or activities of total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartic acid aminotransferase (AST), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) and interleukin-10 (IL-10) in serum, the contents of TC, TG and free fatty acid (FFA) in liver tissue, Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to observe the gene and protein expressions of Toll-like receptor 4 (TLR4), myeloid different factory 88 (MyD88) and c-Jun n-terminal kinase (JNK) and the protein expression of phosphorylation JNK(p-JNK) in liver tissue. Hematoxylin-eosin (HE) staining and Oil red staining to observe the pathological morphological changes of liver. Result:Compared with control group, the contents or activities of TC, TG, ALT, AST and TNF-<italic>α</italic> in serum, the contents of TC, TG and FFA in liver and the gene and protein expressions of TLR4, MyD88, JNK, and the protein expression of p-JNK in liver tissue of model group were distinctly increased (<italic>P</italic><0.01), the content of IL-10 was significantly decreased (<italic>P</italic><0.01). Compared with model group, the contents or activities of TC, TG, ALT, AST and TNF-<italic>α</italic> in serum, the contents of TC, TG and FFA in liver and the mRNA and protein expressions of TLR4, MyD88 and JNK, and the protein expression of p-JNK in liver tissue of Danggui Shaoyaosan groups were significantly reduced (<italic>P</italic><0.05,<italic>P</italic><0.01), the content of IL-10 in serum of Danggui Shaoyaosan groups was distinctly increased(<italic>P</italic><0.05,<italic>P</italic><0.01), HE staining and Oil red staining show that the degree of liver steatosis was alleviated obviously by Danggui Shaoyaosan. Conclusion:Danggui Shaoyaosan has a better treatment on NAFLD by inhibiting TLR4/MyD88/JNK pathway and alleviating the inflammation response.

4.
Article in Chinese | WPRIM | ID: wpr-905956

ABSTRACT

Objective:To observe the improving effect of Danggui Shaoyaosan on diminished ovarian reserve (DOR) in rats triggered by Tripterygia wilfordii polyglycoside tablet combined with stress, and to explore the role of transforming growth factor-<italic>β</italic><sub>1 </sub>(TGF-<italic>β</italic><sub>1</sub>)/Smads signaling pathway in such improvement. Method:Forty-eight female SD rats with normal sexual cycle were selected and randomly divided into a normal group (<italic>n</italic>=8) and a modeling group (<italic>n</italic>=40), and the ones in the modeling group were given Tripterygium wilfordii polyglycoside tablets (50 mg·kg<sup>-1</sup>) combined with random stress for 15 d. After successful modeling, the rats were randomized into the model group, low-, medium-, and high-dose (3.96, 7.92, 15.84 g·kg<sup>-1</sup>) Danggui Shaoyaosan groups, and estradiol valerate group (0.09 mg·kg<sup>-1</sup>), with eight in each group. Under the premise of stress exposure, they were separately gavaged with the normal saline, low-, medium- and high-dose Danggui Shaoyaosan, and estradiol valerate for 15 successive days. The estrous cycle of rats in each group was observed daily. After intervention, the rats were sacrificed and the ovarian visceral index was calculated. The pathological changes in ovarian tissues were observed by hematoxylin eosin (HE) staining. The protein expression levels of TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1 </sub>receptor (TGF-<italic>β</italic><sub>1</sub>R) in the ovarian tissues of rats were measured by immunohistochemistry (IHC), and the mRNA expression levels of Smad2, Smad3, and Smad7 in the ovarian tissues by real-time polymerase chain reaction (Real-time PCR). Result:Compared with the normal group, the model group exhibited disordered estrus cycle (<italic>P</italic><0.05), reduced visceral index (<italic>P</italic><0.01), and down-regulated TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1</sub>R protein and Smad2 and Smad3 mRNA expression in the ovarian tissues (<italic>P</italic><0.01), and up-regulated Smad7 mRNA expression (<italic>P</italic><0.01). Compared with the model group, Danggui Shaoyaosan at the low, medium, and high doses and estradiol valerate improved the estrus cycle of rats to varying degrees (<italic>P</italic><0.05) and increased the visceral index, with better effects observed in the medium-group and high-dose Danggui Shaoyaosan groups (<italic>P</italic><0.05,<italic>P</italic><0.01). Besides, the protein expression levels of TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1</sub>R and the mRNA expression levels of Smad2 and Smad3 in the ovarian tissues were elevated to varying degrees (<italic>P</italic><0.01), and the Smad7 mRNA expression declined (<italic>P</italic><0.01). The improvements in TGF-<italic>β</italic><sub>1</sub> and TGF-<italic>β</italic><sub>1</sub>R protein expression of the medium-dose Danggui Shaoyaosan group and estradiol valerate group were more obvious. Conclusion:Danggui Shaoyaosan significantly improves ovarian reserve in DOR rats, which is closely related to the regulation of TGF-<italic>β</italic><sub>1</sub>/Smads signaling pathway.

5.
Article in Chinese | WPRIM | ID: wpr-905825

ABSTRACT

Objective:To observe the effect of Danggui Niantongtang on the protein and mRNA expression of key regulatory factors of the extrinsic and intrinsic apoptotic pathway in synovial tissue of adjuvant arthritis (AA) rats, and to further explore the mechanism of Danggui Niantongtang in the prevention and treatment of rheumatoid arthritis. Method:The general condition of AA rats, including its body weight, were observed. The changes of toe volume were detected by toe volume meter. Histopathological changes of synovium of knee joint were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expression levels of tumor necrosis factor receptor super family 6 (Fas), Fas-associating protein with a novel death domain(FADD), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase Caspase-3 (Caspase-3) were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. Result:Compared with the normal group, the toe volume of the model group increased significantly (<italic>P</italic><0.01), with significantly proliferated synovial cells, significantly reduced mRNA and protein expression levels of Fas, FADD, Bax and Caspase-3 in synovial tissues(<italic>P</italic><0.05,<italic> P</italic><0.01), and significantly increased Bcl-2 level (<italic>P</italic><0.01). Compared with the model group, the swelling degree of toes in Danggui Niantongtang group and Tripterygium group was significantly alleviated (<italic>P</italic><0.01), with significantly improved synovial hyperplasia, significantly increased mRNA and protein expression levels of Fas, FADD, Bax and Caspase-3 (<italic>P</italic><0.05, <italic>P</italic><0.01), and significantly decreased expression levels of bcl-2 mRNA and protein (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:Danggui Niantongtang can effectively reduce joint swelling and abnormal proliferation of synovial tissue in AA rats. Its mechanism may be related to regulating the expression of Fas, FADD, Bax, Bcl-2 and Caspase-3, and promoting the apoptosis of synovial cells.

6.
Article in Chinese | WPRIM | ID: wpr-905057

ABSTRACT

Objective:Powders and decocted powders account for about 1/3 in the Catalogue of Ancient Famous Classical Formulas (the First Batch), and have a very important position. Determination of preparation technology and particle size in the pulverization process is the key step in the research and development of powders and decocted powders following the original methods. However, there are many terms describing the preparation technology and particle size of powders and decocted powders in ancient Chinese medical books, and the parameters are not clear. Due to the lack of unified basis of particle size, the existing research results have not formed a uniform consensus. Based on ancient textual researches and experimental results, this article discusses the particle size of decocted powders and powders. Method:Through textual researches of the preparation technology and particle size of powders and decocted powders and powder classification in the 2020 edition of Chinese Pharmacopoeia, the specifications of pulverized particle size were suggested. In addition, Xiebaisan and Danggui Buxuetang were taken as examples to investigate the influence of different particle sizes (4, 10, 24 mesh) on the preparation process of decocted powders and the obtained decoction. Result:The particle size of 4 mesh was equivalent to that of ancient as big as hemp bean. The contents of index components in Xiebaisan and Danggui Buxuetang with particle size of 4 mesh were higher than that of 10 mesh and 24 mesh, but the particle size of 50 mesh was too fine to be filtered. Conclusion:The suggested particle sizes of powders and decocted powders are recommended as Cumo is the power through 10-mesh sieve, Mo is the power through 24-mesh sieve, Ximo is the power through 80-mesh sieve, as big as hemp bean is the power through 4-mesh sieve and not through 10-mesh sieve.

7.
Article in Chinese | WPRIM | ID: wpr-906534

ABSTRACT

Astragali Radix-Angelicae Sinensis Radix (AA) is a basic pair of drugs mainly targeting the syndrome characteristics of Qi and blood diseases. LI Dong-yuan's Danggui Buxuetang (DBT) is composed of AA, which is mainly used to tonify Qi and generate blood, with main indications of Qi deficiency and blood deficiency, blood heat and so on. It is favored by doctors because of its refined prescription and remarkable curative effect. However, there are many compatibility ratios of AA in different prescriptions in ancient books, and their efficacy and indications are also slightly different. This research showed that DBT also had the effect of invigorating Qi and activating blood, and the previous study of the group showed that 3∶1 compatibility ratio of the two herbs in the total amount of 36 g had more obvious effect of invigorating Qi and activating blood. By consulting the relevant literature, it was found that the drug pair had a certain effect of invigorating Qi and activating blood in various compatibility ratios such as 1∶1, 3∶1, 1∶5, 3∶2, 2∶1, 5∶1. The corresponding pharmacological effect mainly included regulating the energy metabolism of substances, regulating immune function, reducing blood viscosity, anti-oxidation stress, anti-inflammation, lowering blood lipids, lowering blood sugar, protecting heart function, protecting blood vessel wall, intervening angiogenesis, fighting against organ tissue fibrosis and so on. Regardless of the AA single-medicine's activating blood effect and the theory that "Qi circulation leads to blood circulation" or the drug pair's manifestation in modern pharmacological effects, all of these have confirmed that AA's effect of invigorating Qi and activating blood does exist, and the difference of action performance caused by different ratios of AA is closely related to dosage and proportion, which needs further study. Based on the study focusing on the effect of tonifying Qi and generating blood, it is easy to ignore the effect of invigorating Qi and activating blood, which limits the clinical application of the latter. Therefore, the tonifying Qi and activating blood circulation effect of the drug pair is reviewed in this paper, so as to provide a theoretical basis for its clinical rational drug use and related research.

8.
Article in Chinese | WPRIM | ID: wpr-906265

ABSTRACT

Objective:To investigate the neuroprotective effects of Danggui Shaoyaosan (DSS) on APP<sub>swe</sub>/PS1<sub>ΔE9 </sub>transgenic (APP/PS1) mice and its mechanism related to circular RNA (circRNA). Method:Totally twenty 6-month-old APP/PS1 mice were divided into model group and DSS group, and 10 C57BL/6 wild-type mice were set as the normal control group. The normal group and model group received the same volume of normal saline, and DSS group received drug by gavage administration, all for 8 weeks. The differentially expressed circRNA of APP/PS1 mice before and after DSS intervention was analyzed by circRNA sequencing to construct circRNA-miRNA mRNA interaction network. The results of cricRNA sequencing were then verified by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of phosphoinositide 3-kinase (PI3K), p-PI3K, protein kinase B1 (Akt1), p-Akt1, B lymphocytoma-2 (Bcl-2), and Bcl-2-Associated X protein (Bax) in the hippocampus were detected by immunoblotting (Western blot). The protein expression of Caspase-3 in the hippocampus was detected by immunohistochemistry and the level of apoptosis in the hippocampus was detected by the TUNEL method. Result:Compared with the model group, there were 90 differentially expressed circRNA after intervention with DSS, of which 46 were up-regulated and 44 down-regulated. Compared with the normal group, the expression levels of circRNA1398 and circRNA1399 in the model group decreased, and the expression levels of miR-103-3p, miR-153-3p, miR-143-3p, and miR-143-5p increased. Compared with the model group, the expression levels of circRNA1398 and circRNA1399 in the DSS group were up-regulated, while the expression levels of miR-103-3p, miR-153-3p, miR-143-3p, and miR-143-5p were down-regulated. Compared with the normal group, the expression of p-PI3K, Akt1, p-Akt1, and Bcl-2 in the model group decreased (<italic>P</italic><0.05,<italic> P</italic><0.01), and the expression of Bax and Caspase in the model group increased (<italic>P</italic><0.01). Compared with the model group, the expression of p-PI3K, Akt1, p-Akt1, and Bcl-2 in the hippocampus of the DSS group increased (<italic>P</italic><0.01), and the protein expression of Bax and Caspase decreased (<italic>P</italic><0.01). Compared with the normal group, the apoptosis level in the hippocampus of the model group increased, with an apoptosis rate of (43.76±2.92)%. Compared with the model group, the apoptosis rate of DSS group was (24.64±3.39)%. Conclusion:DSS can activate PI3K/Akt pathway and inhibit apoptosis in hippocampal neurons of APP / PS1 mice, and play a neuroprotective role. The specific mechanism may be related to the regulation of circRNA1398 and circRNA1399 expression and the corresponding miRNA expression.

9.
Article in Chinese | WPRIM | ID: wpr-906228

ABSTRACT

Danggui Liuhuang Tang, as one of classical traditional Chinese medicine prescriptions, has been used by major medical experts in clinic since Jin and Yuan dynasties. After review and summarization of relevant literatures on the pharmacological effects and clinical application of Danggui Liuhuang Tang, it was found that Danggui Liuhuang Tang has a wide range of pharmacological activities, and exerts its anti-inflammatory and anti-insulin resistance effects mainly by inhibiting the production of inflammatory factors, such as tumor necrosis factor and interleukin and activating related pathways. In addition, Danggui Liuhuang Tang inhibits the occurrence and development of hepatic fibrosis by attenuating proinflammatory signaling and extracellular matrix accumulation with multiple components, multiple targets, and multiple pathways. Danggui Liuhuang Tang has been widely used in sweat syndromes, with an obvious effect in the treatment of thyroid diseases, diabetes, respiratory tract and other diseases. This paper reviews and summarizes the pharmacological effects and clinical application of Danggui Liuhuang Tang,in an attempt to provide some valuable clues for the subsequent development of Danggui Liuhuang Tang.

10.
Article in Chinese | WPRIM | ID: wpr-906198

ABSTRACT

Objective:To investigate the effect of Danggui Buxuetang(DGBX)on the functional activity of rat endothelial progenitor cells(EPCs)exposed to different luminar shear stress (SS). Method:EPCs isolated from rat bone marrow were incubated on a parallel plate flow chamber at a steady SS of 0, 0.12, 1.2, 2.4 Pa for 6 h,then the cells exposed to different SS were randomly divided into 8 groups: control group (perfused with serum free medium),simvastatin group(0.1 μmol·L<sup>-1 </sup>simvastatin),3 DGBX groups(low,medium,high-dose DGBX)and 3 inhibitor groups(3 DGBX groups with LY294002). After 12 h,the samples were collected for the detection of cell proliferation ,migration,tubule formation ,the secretion of nitric oxide (NO) ,and the expressions of endothelial nitric oxide synthase(eNOS) mRNA and protein kinase B(Akt),respectively. Result:Compared with the control group,simvastatin and DGBX(high-dose)could both promote the functional activities and NO secretion,and up-regulate the expressions of eNOS mRNA and Akt protein in EPCs exposed to different SS(<italic>P</italic><0.05),while DGBX(mid-dose)could do these only at 0 Pa. However,LY294002 could inhibit all effects of DGBX on EPCs. Conclusion:SS seems to play an important role in the effect of DGBX on EPCs,and DGBX could promote the functional activity of EPCs exposed to SS by up-regulating the expressions of NO/eNOS/Akt.

11.
Article in Chinese | WPRIM | ID: wpr-887937

ABSTRACT

Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-β-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.


Subject(s)
Astragalus Plant , Drugs, Chinese Herbal/pharmacology , Plant Roots
12.
Article in Chinese | WPRIM | ID: wpr-878949

ABSTRACT

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.


Subject(s)
Animals , Drugs, Chinese Herbal , Dysmenorrhea/drug therapy , Female , Humans , Molecular Docking Simulation , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A
13.
Article in English | WPRIM | ID: wpr-881083

ABSTRACT

Colon cancer-related anemia (CCRA) is mainly caused by systemic inflammation, intestinal bleeding, iron deficiency and chemotherapy-induced myelosuppression in colon cancer. However, the best therapeutic schedule and related mechanism on CCRA were still uncertain. Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction (DBD), Fe and rhEPO based on CCRA and gut microbiota modulation were conducted in this paper. Here, CCRA model was successfully induced by subcutaneous inoculation of CT-26 and i.p. oxaliplatin, rhEPO + DBD high dosage + Fe (EDF) and rhEPO + DBD high dosage (ED) groups had the best blood enrichment effect. Attractively, EDF group also showed antitumor activity. The sequencing results of gut microbiota showed that compared to P group, the relative abundances of Lachnospiraceae and opportunistic pathogen (Odoribacter) in ED and EDF groups were decreased. Interestingly, EDF also decreased the relative abundances of cancer-related bacteria (Helicobacter, Lactococcus, Alloprevotella) and imbalance-inducing bacteria (Escherichia-Shigella and Parabacteroides) and increased the relative abundances of butyrate-producing bacteria (Ruminococcaceae_UCG-014), however, ED showed the opposite effects to EDF, this might be the reason of the smaller tumor volume in EDF group. Our findings proposed the best treatment combination of DBD, rhEPO and Fe in CCRA and provided theoretical basis and literature reference for CCRA-induced intestinal flora disorder and the regulatory mechanism of EDF.

14.
Article in Chinese | WPRIM | ID: wpr-873274

ABSTRACT

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Its main complications of diabetes, such as diabetic angiopathy, have seriously affected the quality of life for patients, and have become an important cause of death and disability. The underlying pathological changes include macrovascular lesions and microvascular lesions. Diabetic macrovascular lesions mainly involve thoracic aorta, coronary artery, carotid artery, cerebral artery and peripheral blood vessels, etc., and the common clinical diseases include coronary heart disease, stroke, peripheral neuropathy, lower extremity arteriosclerosis, etc. Diabetic microvascular lesions mainly involve the heart, brain, kidney and other microvessels. Nowadays, various new oral hypoglycemic agents and insulin have emerged in the society and are widely used in clinical practice. However, traditional Chinese medicines(TCMs) have stable curative effect, less side effect, and can improve glucose metabolism, lipid metabolism, insulin resistance, oxidative stress, expression of inflammatory cytokines, vascular endothelial injury, microcirculation disorders, balance of fibrinolysis system and blood coagulation system, and improve the syndromes of TCMs, etc. They have been widely recognized and applied in the prevention and treatment of diabetic angiopathy. A profound understanding on the etiology, pathogenesis and treatment of diabetic angiopathy has been formed in Chinese medicine. Therefore, in this paper, we would summarizes the understanding on Chinese medicine for diabetic angiopathy and the mechanism of Yiqi Huoxue prescription in the treatment of diabetic angiopathy in the past three years.

15.
Article in Chinese | WPRIM | ID: wpr-873241

ABSTRACT

Objective::To investigate the regulatory effect of Danggui Shaoyaosan (DSS)-containing serum on oxidative stress and inflammation in H2O2-induced SH-SY5Y cells. Method::Methyl thiazolyl tetrazolium(MTT) assay was used to determine the cell activity and construct the H2O2-induced cell damage model with the optimal time and dose. Normal group, model group and high, medium and low-dose DSS groups(2.5%, 5%, 10%) were set up. MTT method was used to detect cell activity, spectrophotometry anti-oxidation indexes of malonaldehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) and glutathione (GSH). Real-time quantitative PCR (Real-time PCR) was used to detect tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) mRNA expressions. And immunofluorescence test was adopted to detect nuclear transcription factor-κB(NF-κB) p65 nuclear translocation of the DSS after the intervention. Result::After 24 h intervention with 250 μmol·L-1 H2O2, SH-SY5Y cell viability was about 55%, which was the best modeling condition. After high, medium and low-dose DSS intervention on H2O2-damaged cell model, compared with the model group, the cell activity showed a dose-dependent increase (P<0.05), MDA was significantly reduced (P<0.05), and antioxidant indexes CAT, SOD and GSH were significantly increased (P<0.05). H2O2 could significantly increase SH-SY5Y cell inflammatory factor TNF-α, IL-6 and IL-1β mRNA expressions, and promote activation of cytoplasmic NF-κB and nuclear translocation. DSS-containing serum showed a dose-dependent inhibition of NF-κB p65 from nuclear, and reduced inflammatory factor levels, such as TNF-α, IL-6 and IL-1β. Conclusion::DSS-containing serum can significantly reduce the oxidative damage in H2O2-induced SH-SY5Y cells by improving their antioxidant status, and reduce the inflammatory response by inhibiting NF-κB signaling pathway.

16.
Article in Chinese | WPRIM | ID: wpr-873227

ABSTRACT

Objective:To observe the clinical efficacy of modified Danggui Niantongtang combined with Xuanbitang in treating damp-heat type acute gouty arthritis, and investigate its effect on levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). Method:Totally 126 patients were randomly divided into control group and observation group, with 63 cases in each group. In addition to non-medication treatment, patients in control group were given conventional western medicine treatment for 1 week, while patients in observation group were given modified Danggui Niantongtang combined with Xuanbitang for 1 week. The levels of IL-1β,IL-6,IL-8,TNF-α before and after treatment were observed. Result:The total effective rate was 79.37% in control group and 95.24% in observation group, with significant differences (P<0.05). After treatment, the scores of arthralgia, tenderness, swelling, activity restriction in both groups were significantly decreased (P<0.01), and those in observation group were lower than those in control group (P<0.05). The levels of uric acid (UA), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) were significantly decreased (P<0.01) after treatment, and those in observation group were lower than those in the control group (P<0.05). The levels of IL-1β,IL-6,IL-8,TNF-α were significantly decreased (P<0.01) after treatment, and those in the observation group were lower than those in the control group (P<0.05). Conclusion:Compared with conventional western medicine treatment, modified Danggui Niantongtang combined with Xuanbitang has a better efficacy in treating damp-heat type acute gouty arthritis and reducing levels of IL-1β,IL-6,IL-8,TNF-α.

17.
Article in Chinese | WPRIM | ID: wpr-873186

ABSTRACT

Objective:To observe the effect of Danggui Buxuetang on lung histopathology and protein kinase D1 (PKD1), nuclear transcription factor-κB (NF-κB) and manganese superoxide dismutase (MnSOD)-mediated oxidative stress pathway in rats with pulmonary fibrosis induced by bleomycin, so as to explore the mechanism of intervention of pulmonary fibrosis.Method:Thirty-two male SPF SD rats were randomly divided into sham operation group, model group, Danggui Buxuetang group and prednisone group, with 8 rats in each group. Except the sham operation group, the other groups were prepared through the intratracheal instillation with bleomycin. After modeling for 24 h, the rats of Danggui Buxuetang group were administered with Danggui Buxuetang (0.81 g·kg-1). The rats of prednisone group were given aqueous solution of prednisone (0.005 g·kg-1). The rats of sham operation group and model group were given the same volume of saline. After 14 days of administration, blood was collected from the femoral artery, serum was separated, and the lungs were taken by thoracotomy. The pathological changes of rat lung tissues were observed by hematoxylin-eosin staining (HE) and Masson trichrome staining, and graded by Szapiel score and Ashcroft score at the same time. The content of serum malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were determined. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to measure mRNA and protein expressions of PKD1, NF-κB, MnSOD.Result:Compared with the rats in sham operation group, the rats in model group had higher Szapiel scores and Ashcroft scores (P<0.05), higher serum MDA content , but lower SOD, CAT and GSH-Px activities(P<0.01), moreover, the rat lung tissues in model group had higher mRNA and protein expressions of PKD1, NF-κB and MnSOD (P<0.01) than those in sham operation group. Compared with the rats in model group, the Szapiel scores and Ashcroft scores of the rats in Danggui Buxuetang group were decreased significantly(P<0.05). The serum MDA content was decreased significantly, and SOD, CAT, GSH-Px activities were increased, whereas mRNA and protein expressions of PKD1, NF-κB, MnSOD in the rat lung tissues were decreased(P<0.05,P<0.01).Conclusion:Danggui Buxuetang can reduce the degree of pulmonary fibrosis by regulating the anti-oxidation pathway of PKD1/NF-κB/MnSOD mitochondrial nucleus and improving the body's antioxidant capacity.

18.
Article in Chinese | WPRIM | ID: wpr-873153

ABSTRACT

Objective:To investigate the effect of Danggui Yinzi on allergic reaction in chronic urticaria (CU) mice model and the mechanism of autophagy intervention. Method:The SPF BALB/c mice were used to replicate the CU mice model by intraperitoneal injection of ovalbumin and aluminum hydroxide suspension. The animals were randomly allocated into six groups: a normal group (normal saline 20 mL·kg-1·d-1), a model group (normal saline 20 mL·kg-1·d-1), a loratadine group(0.001 3 g·kg-1·d-1), a Danggui Yinzi high,medium and low-dose group(39.3,19.6,9.8 g·kg-1·d-1). The pathological changes of skin tissues were observed by hematoxylin-eosin (HE) staining. Morphological changes of autophagy in skin tissues epithelial cells were observed by transmission electron microscope. The mRNA levels of microtubule-associated protein 1 light chain 3B(LC3B) and ubiquitin-binding protein p62 mRNA in skin tissues were detected by real-time quantitative polymerase chain reaction (Real-time PCR). The expressions of LC3B and p62 in skin tissues were detected by immunohistochemistry (IHC). Result:Danggui Yinzi can significantly improve the pathological manifestations of dermal edema, collagen bundles separation, telangiectasia in CU mice, it can also improve autophagosomes formation and abnormal cell ultrastructure such as nuclear chromatin condensation, mitochondrial swelling, endoplasmic reticulum expansion, etc. Compared with the normal group, the protein expressions of LC3B in skin tissues of the model group was significantly increased (P<0.01), LC3B mRNA level was increased too, while p62 mRNA levels and its protein expressions were decreased-regulated (P<0.01). Compared with the model group, levels of LC3B mRNA and protein expressions of the Danggui Yinzi groups were significantly increased (P<0.05,P<0.01), while p62 mRNA levels and its protein expressions were significantly decreased-regulated (P<0.05,P<0.01). Conclusion:Danggui Yinzi can regulate the expression of LC3B, p62 mRNA and protein expressions, enhance the level of autophagy, and improve the pathological state of CU mice.

19.
Article in Chinese | WPRIM | ID: wpr-873003

ABSTRACT

Objective::This paper aims to explore the potential anti-neoplasm targets and mechanism of Danggui Sinitang on hepatocellular carcinoma by analyzing the prescription of Danggui Sinitang with the method of network pharmacology, in order to provide targeted guidance for further studies. Method::The Traditional Chinese Medicine System Platform (TCMSP) and SwissTargetPrediction database were adopted to establish the database of Danggui Sinitang' s effective ingredients and targets. The Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and Human Phenotype Ontology (HPO) were used to build the hepatocellular carcinoma target database, which was then matched with Danggui Sinitang' s target database. Based on the matching results, STRING database was applied to analyze the interactions between the targets and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was utilized for the enrichment analysis on gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then Cytoscape 3.6.0 software was used for networks analysis. Result::A total of 56 significant targets of Danggui Sinitang were found for treatment of hepatocellular carcinoma. The 106 cellular biological processes were obtained through GO biological process enrichment analysis and 23 related pathways were obtained by KEGG enrichment analysis, mainly including TNF signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, p53 signaling pathway, phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt) signaling pathway, AMP activated protein kinase(AMPK) signaling pathway, Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling pathway, et al. Conclusion::The therapeutic effect of Danggui Sinitang on hepatocellular carcinoma may be multi-target, multi-channel and multi-level. It can be inferred that quercetin and kaempferol may be two important active components, and PI3K/Akt signaling pathway and MAPK signaling pathway may be two important signaling pathways. This study not only makes a contribution to a better understanding of the anti-hepatocellular carcinoma mechanism of Danggui Sinitang, but also proposes a strategy to develop new TCM candidates at a network pharmacology level.

20.
Article in Chinese | WPRIM | ID: wpr-872822

ABSTRACT

Objective:To observe protective effect of Danggui Buxuetang (DBT) on oxidative stress injury of mouse bone marrow-derived endothelial progenitor cells (EPCs) against induced by hydrogen peroxide (H2O2). Method:Monocytes from bone marrow of mice were obtained by density gradient centrifugation, and EPCs were obtained by specific culture medium. The experiment was divided into blank group,model group,DBT group (100,200,400 mg·L-1). Methyl thiazolyl tetrazolium(MTT) assay was used to determine the survival rate of EPCs and establish the cell injury model induced by H2O2. MTT,transwell chamber,matrigel and superoxide fluorescent anion probe (DHE) were used to detect the proliferation,migration,in vitro angiogenesis and ROS level,detection of autophagy by Western blot. Result:Compared with blank group,the proliferation ability,migration ability,the number of lumens and the length of tubule branches of EPCs in the model group were significantly reduced (P<0.01),the level of intracellular reactive oxygen species (ROS) was significantly increased (P<0.01),the expression of p62,the light chain microtubule associated protein 1 protein light chain 3 Ⅱ type (LC3-Ⅱ) protein of microtubule associated protein 1,was significantly increased (P<0.01). Compared with model group,DBT group increased the ability of cell proliferation and migration (P<0.01). In addition,DBT increased the expression of LC3-Ⅱ protein in a concentration dependent manner (P<0.01),and decreased the expression of p62 protein (P<0.01). Conclusion:DBT can improve the autophagy level of EPCs under oxidative stress, promote the proliferation, migration and angiogenesis of injured EPCs, and protect the biological function of EPCs under oxidative stress.

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