摘要:ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3(Sirt3)/adenosine monophosphate dependent protein kinase (AMPK) signaling pathway in chronic heart failure (CHF) rats after myocardial infarction (MI).MethodSD rats randomly divide into sham operation group (normal saline ,thread only without ligature), model group (normal saline, ligation of the left anterior descending coronary artery proximal to the heart), Linggui Zhugantang group (4.8 g·kg-1) and Captopril group (0.002 57 g·kg-1), with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin (HE) staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species (ROS). JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate (ATP), superoxide dismutase (SOD), malondialdehyde (MDA), mitochondrial respiratory chain complex activity (Ⅰ-Ⅳ). TdT-mediated dUTP nick end labeling (TUNEL) staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3, phosphorylated AMPK (p-AMPK), phosphorylated dynamic-related protein 1(p-Drp1), mitochondrial fission protein 1(Fis1), mitochondrial fission factor (MFF), optic atrophy protein 1(OPA1).ResultCompared to the sham group, the left ventricular end diastolic diameter (LVIDd) and left ventricular end systolic diameter (LVIDs) were significantly increased in model group (P<0.01), while the left ventricular short axis shortening rate (LVFS) and left ventricular ejection fraction (LVEF) were significantly decreased (P<0.01). There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS, MDA levels and myocardial cell apoptosis rate were significantly increased (P<0.01), SOD level, ATP content, and membrane potential were significantly decreased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) was significantly decreased (P<0.01). Levels of p-Drp1, Fis1, MFF proteins were significantly up-regulated (P<0.01), while Sirt3, p-AMPK, OPA1 proteins level were significantly down-regulated (P<0.01). Compared with model group, LVIDd and LVIDs were significantly decreased (P<0.01), LVEF and LVFS were significantly increased (P<0.01). Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS, MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group (P<0.01), SOD level, ATP content, and membrane potential significantly increased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) increased significantly (P<0.01),and p-Drp1, Fis1, MFF protein levels were significantly down-regulated (P<0.01), Sirt3, p-AMPK, OPA1 protein were significantly up-regulated (P<0.01).ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells, maintain mitochondrial function stability, and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
关键词:Linggui Zhugantang;chronic heart failure;oxidative stress;apoptosis;mitochondrial fission-fusion;silencing information regulator 3(Sirt3)/adenosine monophosphate dependent protein kinase (AMPK) signaling pathway
摘要:ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan(QWBZS) on diabetic encephalopathy(DE) rat model, and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β) signaling pathway.MethodForty-eight SPF male Wistar rats were randomly divided into blank group(8 rats) and high-fat diet group(40 rats). After 12 weeks of feeding, rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin(STZ) for 2 consecutive days to construct a DE model, and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling, according to blood glucose and body weight, model rats were randomly divided into model group, low, medium and high dose groups of QWBZS(3.15, 6.3, 12.6 g·kg-1), combined western medicine group(metformin+rosiglitazone, 0.21 g·kg-1), with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage, and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage, 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin (FINS) level was detected by enzyme-linked immunosorbent assay(ELISA) and insulin resistance index(HOMA-IR) was calculated. Hematoxylin-eosin(HE) staining was used to observe the morphological changes of hippocampus in rats, ELISA was used to detect the indexes of oxidative stress in hippocampal tissues, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to detect mRNA expression levels of PI3K, Akt, nuclear transcription factor-κB(NF-κB), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in hippocampus, and Western blot was used to detect the protein expression of PI3K, Akt, phosphorylated(p)-Akt, GSK-3β and p-GSK-3β in hippocampus of rats.ResultCompared with the blank group, FINS and HOMA-IR values of the model group were significantly increased(P<0.01), the path of finding the original position of the platform was significantly increased, and the escape latency was significantly prolonged(P<0.01), the morphology of neuronal cells in hippocampal tissues was disrupted, the levels of reactive oxygen species(ROS) and malondialdehyde(MDA) in hippocampus of rats were increased, and the activity of superoxide dismutase(SOD) was decreased(P<0.05, P<0.01), mRNA expression levels of PI3K and Akt were decreased(P<0.01), mRNA expression levels of NF-κB, TNF-α and IL-1β were increased(P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly decreased, and the protein expression of GSK-3β was significantly increased(P<0.01). Compared with the model group, the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased(P<0.01), the path of finding the original position of the platform and the escape latency were significantly shortened(P<0.01), the hippocampal tissue structure of rats was gradually recovered, and the morphological damage of nerve cells was significantly improved, the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased(P<0.01), the mRNA expression levels of PI3K and Akt were increased(P<0.01), and the mRNA expression levels of NF-κB, TNF-α and IL-1β were decreased (P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly increased(P<0.01), and the expression of GSK-3β was significantly decreased(P<0.01).ConclusionQWBZS can alleviate insulin resistance in DE rats, it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.
摘要:ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan (LW) on mitochondrial damage in the Alzheimer's disease (AD) model of Caenorhabditis elegans (C. elegans).MethodC. elegans transfected with human β-amyloid protein (Aβ) 1-42 gene was used as an AD model. The rats were divided into blank group, model group, metformin group (50 mmol·L-1), and low, medium, and high dose (1.04, 2.08, 4.16 g·kg-1) LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine (5-HT) in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate (ATP) kit, and mitochondrial membrane potential was detected by the JC-1 method. In addition, the mRNA expression of Aβ expression gene (Amy-1), superoxide dismutase-1 (SOD-1), mitochondrial transcription factor A homologous gene-5 (HMG-5), mitochondrial power-associated protein 1 (DRP1), and mitochondrial mitoprotein 1 (FIS1) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR).ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT (P<0.05) and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group, in the model group, the mRNA expression of Aβ protein and Amy-1 increased (P<0.01), and the mRNA expression of SOD-1 and HMG-5 decreased (P<0.01). The mRNA expression of DRP1 and FIS1 increased (P<0.01), and the level of mitochondrial membrane potential decreased (P<0.05). The content of ATP decreased (P<0.01). Compared with the model group, in the positive medicine group and medium and high dose LW groups, the mRNA expression of Aβ protein and Amy-1 decreased (P<0.05,P<0.01), and the mRNA expression of SOD-1 and HMG-5 increased (P<0.01). The mRNA expression of DRP1 decreased (P<0.05,P<0.01), and that of FIS1 decreased (P<0.01). The level of mitochondrial membrane potential increased (P<0.01), and the content of ATP increased (P<0.05,P<0.01).ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria, protect mitochondrial DNA, reduce the fragmentation of mitochondrial division, repair the damaged mitochondria, adjust the mitochondrial membrane potential, restore the level of neuronal ATP, and reduce the neuronal damage caused by Aβ deposition.
摘要:ObjectiveTo study the effect of Qizhu Kang'ai prescription (QZAP) on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver of mouse model of liver cancer induced by diethylnitrosamine (DEN) combined with carbon tetrachloride (CCl4) and Huh7 cells of human liver cancer, so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells.MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group, a model group, and a QZAP group were set up, in which QZAP (3.51 g·kg-1) or an equal volume of normal saline was administered daily by gavage, respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and alpha-fetoprotein (AFP) in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin (HE) staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment, Huh7 cells were divided into blank group, QZAP low, medium, and high dose groups and/or PCK1 inhibitor (SKF-34288 hydrochloride) group, and Sorafenib group. The corresponding drug-containing serum and drug treatment were given, respectively. Cell counting kit-8 (CCK-8) method, colony formation experiment, Edu fluorescent labeling detection, intracellular adenosine triphosphate (ATP) content detection, and cell cycle flow cytometry detection were used to evaluate the proliferation ability, energy metabolism changes, and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1, serine/threonine kinase (Akt), phosphorylated Akt (p-Akt), and cell cycle-dependent protein kinase inhibitor 1A (p21).ResultCompared with the model group, the pathological changes such as cell atypia, necrosis, and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated, and the number of liver tumors was reduced (P<0.01). The serum ALT, AST, γ-GT, and AFP levels were reduced (P<0.01). At the cell level, compared with the blank group, low, medium, and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells (P<0.01) and the number of positive cells with Edu labeling (P<0.01) and inhibit clonal proliferation ability (P<0.01). The QZAP groups could also reduce the intracellular ATP content (P<0.05) and increase the distribution ratio of the G0/G1 phase of the cell cycle (P<0.05) in a dose-dependent manner. Compared with the model group and blank group, PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced (P<0.05,P<0.01), and the p-Akt protein level was significantly increased (P<0.01). Compared with the blank group, the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased (P<0.05), but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group, the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content, cell survival rate, and Edu-positive cell ratio of Huh7 cells (P<0.05) and significantly increased the G0/G1 phase distribution proportion (P<0.05).ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression, thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.
摘要:ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism.MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model, dydrogesterone, and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice, and the drug administration lasted for 14 days. After the treatment, the embryo absorption rate of each group was recorded. Hematoxylin-eosin (HE) staining was employed to observe the pathological morphology of the uterine decidua, and the physiological transformation rate of spiral arteries (SPA) was evaluated. Real-time polymerase chain reaction (Real-time PCR) and Western blot were performed to determine the mRNA and protein levels, respectively, of matrix metalloproteinases (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), and Wnt/β-catenin signaling pathway.ResultCompared with the control group, the model group presented increased embryo absorption rate (P<0.05), decreased physiological transformation rate of uterine SPA (P<0.05), cellular swelling, degeneration, and disordered arrangement in the uterine decidua tissue, and down-regulated mRNA and protein levels of key factors involved in SPA remodeling (MMP-2, MMP-9, VEGF) and the Wnt/β-catenin signaling pathway (Wnt2, β-catenin, Cyclin D1, c-Myc) (P<0.05). Compared with the model group, both the low- and high-dose Chinese medicine reduced embryo absorption rate (P<0.05), increased SPA physiological transformation rate (P<0.05), improved uterine decidua tissue morphology, and increased decidua vessel count. Furthermore, they up-regulated the mRNA and protein levels of MMP-2, MMP-9, VEGF, and proteins in the Wnt/β-catenin signaling pathway (P<0.05).ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF, MMP-2, and MMP-9, thus treating recurrent miscarriage.
摘要:ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis (UC) through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) autophagy pathway.MethodUC mouse model was established by allowing mice freely drink 4% DSS, and 56 BALB/c male mice were randomly divided into model group, AMPK inhibitor group (20 mg·kg-1), paeoniflorin (50 mg·kg-1) + inhibitor (20 mg·kg-1) group, and high dose (50 mg·kg-1), medium dose (25 mg·kg-1), and low dose (12.5 mg·kg-1) paeoniflorin groups. After seven days of drug intervention, the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight, disease activity index (DAI) changes, and Hematoxylin-eosin (HE) staining results. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum of mice in each group, and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 (LC3) content in the colon, AMPK, mTOR proteins, and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot, and the mRNA expression levels of AMPK, mTOR, Beclin1, LC3, and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR).ResultCompared with the blank group, the model group showed a decrease in body mass, an increase in DAI score, and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum (P<0.01), while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue, and those of p-mTOR/mTOR were up-regulated (P<0.01). The mRNA expression levels of AMPK and LC3 were down-regulated, while the mRNA expression levels of mTOR and p62 were up-regulated (P<0.01). Compared with the model group and the paeoniflorin + inhibitor group, the mice treated with paeoniflorin showed an increase in body mass, a decrease in DAI score, a reduction in pathological damage to colon tissue, and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum (P<0.05). The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated, while the protein levels of p-mTOR/mTOR were down-regulated (P<0.01). The mRNA expression levels of AMPK, Beclin1, and LC3 were up-regulated, while the mRNA expression of mTOR and p62 were down-regulated (P<0.01). The colon tissue of the inhibitor group was severely damaged, and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group.ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.
关键词:adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway;autophagy;inflammatory response;paeoniflorin;ulcerative colitis
摘要:ObjectiveTo investigate the effect and mechanism of salvianolic acid B combined with puerarin in protecting the SH-SY5Y cells from the damage by oxygen-glucose deprivation/reoxygenation (OGD/R) based on pyroptosis.MethodSH-SY5Y cells were used to establish the model of OGD/R, and cells were classified into the control, OGD/R, 10 μmol·L-1 salvianolic acid B, 100 μmol·L-1 puerarin, 10 μmol·L-1 salvianolic acid B + 100 μmol·L-1 puerarin, and 10 μmol·L-1 NOD-like receptor protein 3 (NLRP3) inhibitor MCC950 groups. Except the control group, other groups were rapidly reoxygenated for 12 h after 6 h OGD for modeling. The cell survival rate was determined by the methyl thiazolyl tetrazolium (MTT) assay. An optical microscope was used to observe the cell morphology. A spectrophotometer was used to determine the content of lactic dehydrogenase (LDH) in culture supernatant. Cell damage was measured by Hoechst/PI staining. The mRNA levels of NLRP3, cysteinyl aspartate specific proteinase-1 (Caspase-1), gasdermin D (GSDMD), apoptosis-associated speck-like protein (ASC), and interleukin-1β (IL-1β) were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The protein activation of Caspase-1 and NLRP3 was detected by immunofluorescence. Western blot was employed to determine the protein levels of IL-1β, ASC, NLRP3, Caspase-1, and cleaved Caspase-1.ResultCompared with the control group, the OGD/R group showed decreased cell survival rate (P<0.01), damaged cell morphology, increased leakage rate of LDH (P<0.01), up-regulated mRNA levels of NLRP3, Caspase-1, GSDMD, ASC, and IL-1β (P<0.01), and up-regulated protein levels of IL-1β, ASC, NLRP3, Caspase-1, and cleaved Caspase-1 (P<0.01). Compared with the OGD/R group, salvianolic acid B, puerarin, and salvianolic acid B combined with puerarin improved cell survival rate (P<0.01), and the combined treatment group outperformed salvianolic acid B and puerarin used alone (P<0.01). Salvianolic acid B combined with puerarin and MCC950 both improved cell morphology, reduced the leakage of LDH (P<0.01), alleviated cell damage, and down-regulated the mRNA levels of NLRP3, Caspase-1, GSDMD, ASC, and IL-1β (P<0.05, P<0.01) and also the protein levels of IL-1β, ASC, NLRP3, Caspase-1, and cleaved Caspase-1 (P<0.05, P<0.01).ConclusionThe results indicated that salvianolic acid B combined with puerarin can alleviate the OGD/R-induced damage of SH-SY5Y cells by inhibiting pyroptosis.
关键词:ischemic stroke;model of oxygen-glucose deprivation/reoxygenation;salvianolic acid B;puerarin;pyroptosis
摘要:ObjectiveTo investigate the effects and mechanism of Zuogui Jiangtang Tongmai prescription (ZJTP) on human umbilical vein endothelial cells (HUVECs) damaged by high glucose combined with lipopolysaccharide (LPS).MethodThe survival rate of cells was determined by cell counting kit-8 (CCK-8), and the level of tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay (ELISA) to determine the optimal injury concentration and action time of LPS, as well as the optimal action concentration of ZJTP drug-containing serum. HUVECs were divided into a blank control group, a model group, a ZJTP drug-containing serum group, and an SCFA mixed liquid group. ELISA was used to detect the level of endothelin-1 (ET-1), nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α. Western blot was performed to detect the protein expression of G protein-coupled receptor43 (GPR43), β-suppressor protein-2 (β-arrestin-2), nuclear factor-κB suppressor α (IκBα), and nuclear factor κB p65 (NF-κB p65). The nucleation of NF-κB p65 was observed by immunofluorescence staining (IF). The role of GPR43 in the regulation of inflammatory injury was observed by means of small interfering ribonucleic acid (siRNA). The cells after intervention were divided into an empty carrier group, a ZJTP drug-containing serum group, a Si-GPR43 group, and a Si-GPR43 + ZJTP drug-containing serum group. The content of IL-1β, IL-6, and TNF-α was detected by ELISA. The protein expression of pathways was detected by Western blot. IF was used to observe the nucleation of NF-κB p65.ResultThe optimal molding condition was 1 mg·L-1 LPS for 24 h. The optimal drug intervention condition was 5% ZJTP drug-containing serum for 24 h. Compared with the blank control group, the content of ET-1 in the model group was significantly increased, and the content of NO was significantly decreased (P<0.01). The levels of inflammatory factors were significantly increased (P<0.01). The expressions of GPR43 and IκBα were significantly decreased, while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly increased (P<0.01). NF-κB p65 protein was transferred from the extranuclear to the intranuclear (P<0.01). Compared with the model group, the content of ET-1 in the ZJTP drug-containing serum group was decreased, and the content of NO was increased (P<0.05). The levels of inflammatory factors decreased (P<0.05). The protein expressions of GPR43 and IκBα were increased, while the expressions of β-arrestin-2 and NF-κB p65 were decreased (P<0.05). The amount of NF-κB p65 transferred from the intranuclear to the extranuclear decreased (P<0.01). The mechanism study showed that compared with the Si-GPR43 group, the content of IL-1β, IL-6, and TNF-α were significantly decreased after treatment with ZJTP drug-containing serum (P<0.01). The protein expressions of GPR43 and IκBα were significantly increased (P<0.01), while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly decreased (P<0.01). The amount of NF-κB p65 transferred from the extranuclear to the intranuclear decreased (P<0.01).ConclusionZJTP has a protective effect on HUVECs with high glucose and LPS-induced inflammatory injury, which may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB pathway.
摘要:The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years, randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine (TCM), but the quality of the implementation of blind methods is uneven, and the evaluation criteria have not yet been formed. In this paper, the data collection methods, calculation principles, advantages, and disadvantages of two quantitative quality evaluation methods of blind methods, namely James Blinding Index (JBI) and Bang Blinding Index (BBI), were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time, a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally, the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.
关键词:blind method;quality evaluation;clinical trials;traditional Chinese medicine;methodology
摘要:ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis (ONFH, syndrome of liver and kidney deficiency) and its influences on bone metabolism indexes: N-terminal propeptide (PINP) and β-collagen degradation product (β-CTX).MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method, with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally, while the control group received Xianlinggubao Capsules orally, with a treatment cycle of 6 months. The visual analogue scale (VAS) score, Harris score, Association Research Circulation Osseous (ARCO) staging, imaging changes, quantitative scores of TCM symptoms, and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded.ResultThe total response rate in the experimental group was 83.87% (26/31), which was higher than that (68.75%, 22/32) in the control group (Z=-2.096, P<0.05). After treatment, the single and total scores of TCM symptoms, VAS score, and β-CTX level decreased in the two groups (P<0.05). Moreover, the decreases in the scores of hip pain, lower limb mobility, soreness of waist and knees, and lower limb flaccidity, total score of TCM symptoms, VAS score, and β-CTX level in the experimental were larger than those in the control group (P<0.05). After treatment, the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment (P<0.05), and the increases were more obvious in the experimental group than in the control group (P<0.05). No serious adverse event or adverse reaction appeared during the observation period.ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH, increase PINP, and decrease β-CTX. No obvious side effect appears during the clinical observation period, which shows that Bushen Huoxue prescription has good safety.
关键词:Bushen Huoxue prescription;osteonecrosis of femoral head;syndrome of liver and kidney deficiency;bone metabolism;Youguiwan
摘要:ObjectiveTo observe and compare the intervention effect of modified Cangfu Daotantang on glucose and lipid metabolism in simple obese children with phlegm dampness and stagnation.MethodA total of 60 children with simple obesity were randomly divided into two groups according to the simple randomization method of the random number table. The odd number was included in the test group, and the even number was included in the basic treatment group, with 30 cases in each group. On the basis of signing the informed consent notice, the treatment group was given modified Cangfu Daotantang combined with basic treatment, while the control group was only given basic treatment. After three months of treatment, the body mass index (BMI), glucose and lipid metabolism level [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), fasting insulin (FINS), and homeostasis model assessment-insulin resistance (HOMA-IR)], the change in the total score of traditional Chinese medicine (TCM) syndromes, and the effective rate of treatment were observed and compared.ResultAfter treatment, the BMI of the observation group and the control group decreased significantly (P<0.01). Compared with the control group, the BMI level in the observation group decreased significantly (P<0.05). After treatment, the levels of TC, TG, and LDL-C in the observation group and the control group decreased significantly (P<0.01). Compared with the control group, the levels of TC, TG, and LDL-C in the observation group decreased significantly (P<0.05). In addition, the level of TC in the observation group improved significantly compared with that in the control group (P<0.01). The levels of FPG, FINS, and HOMA-IR in the observation group and the control group were significantly lower than those before treatment (P<0.05). After treatment, compared with the control group, the levels of FPG, FINS, and HOMA-IR in the observation group were significantly reduced (P<0.05). The level of FPG in the observation group was significantly improved compared with that in the control group (P<0.01). After treatment, the total score of TCM syndromes in the two groups decreased significantly (P<0.01). Compared with the control group, the total score of TCM syndromes in the observation group was lower (P<0.01). After treatment, the total effective rate of treatment was 86.67% (26/30) in the observation group and 73.33% (22/30) in the control group. By rank sum test, the total effective rate of the observation group was better than that of the control group (Z=-2.100, P<0.05).ConclusionModified Cangfu Daotantang combined with basic treatment can effectively reduce the BMI of obese children and improve their glucose and lipid metabolism. It has good clinical effects and high clinical application value, which is worth further in-depth research and promotion.
关键词:modified Cangfu Daotantang;simple obesity;child;glucose and lipid metabolism;phlegm dampness and stagnation
摘要:The clinical value of Chinese patent medicine is the core direction of the development of the traditional Chinese medicine industry. The precise clinical positioning determines the way to prove the value of the drug, and is a key link to highlight the clinical value. This paper presented a case study of clinical positioning for Chinese patent medicine, namely Qizhi Tongluo capsules, and the key technical framework of precise clinical positioning of Chinese patent medicine, which was manifested as a comparison of prescription target spectral effect, discovery of core value of prescription, and confirmation of clinical positioning trial. The technical framework was designed to address a range of issues in the realm of precise clinical positioning. Before the clinical positioning trial, based on the multi-component, multi-target, and multi-phenotype data of prescription and clinical indication, the multi-omics network analysis technology was used to identify the core value of the traditional Chinese medicine varieties and predict the potential clinical advantages. Then, based on the predicted clinical advantages, reasonable efficacy indicators were selected, and the clinical efficacy was judged and verified by dynamic and flexible innovative clinical trials to improve the success rate of clinical positioning. This research paradigm integrates "omics technology" with "evidence-based" principles and follows the "precise evidence-based" concept. This research aims to provide a new strategy and method for the precise medication and positioning of Chinese patent medicine with traditional Chinese medicine characteristics after being put into the market and provide more technical thinking for traditional Chinese medicine to move towards precise medicine.
摘要: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.
关键词:Wujiwan;compatibility of formulas;pharmacokinetics;tissue distribution;Coptidis Rhizoma;Euodiae Fructus;Paeoniae Radix Alba
摘要:ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus(SCF) based on sequential metabolism combined with liquid chromatography-mass spectrometry.MethodBlood and cerebrospinal fluid samples of integrated metabolism, intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration, and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC Q-Exactive Orbitrap MS) was used to analyze and compare the differences in the spectra of SCF extract, blank plasma, administered plasma, blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column(2.1 mm×100 mm, 1.7 µm), the mobile phase was acetonitrile(A)-0.1% formic acid aqueous solution(B) for gradient elution(0-7 min, 95%B; 7-12 min, 95%-35%B; 12-17 min, 35%-15%B; 17-20 min, 15%-12%B; 20-22 min, 12%-5%B; 22-23 min, 5%B; 23-25 min, 5%-95%B; 25-28 min, 95%B). And heated electrospray ionization(HESI) was used with positive and negative ion modes, the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time, characteristic fragments, molecular formulae and the information of reference substances.ResultA total of 42 chemical components were identified in the extract of SCF, including lignans, flavonoids, amino acids, tannins, and others, of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation, methylation, demethoxylation and hydroxylation.ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats, it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.
关键词:Schisandrae Chinensis Fructus;sequential metabolism;in vivo metabolism;Cerebrospinal fluid;central nervous system;ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC Q-Exactive Orbitrap MS);plasma
摘要:ObjectiveTo analyze the antidepressant quality markers(Q-Marker) of Bupleuri Radix(BP) before and after vinegar-processing by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), multivariate statistical analysis and network pharmacology.MethodUPLC-Q-TOF-MS was used to analyze the chemical basis of raw and vinegar-processed products of BP, and principal component analysis(PCA) orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to identify the differential components in BP that changed significantly before and after vinegar-processing, which were regarded as candidate quality markers(Q-Marker). Then the disease-drug-component-target network related to antidepressant effect of BP was constructed by network pharmacology, and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined. Rats were randomly divided into blank group, model group, fluoxetine group(2.67 mg·kg-1) and total saponin group(0.72 mg·kg-1), except the blank group, rats in the other groups were subjected to chronic unpredictable mild stress(CUMS). Three weeks after the start of modeling, rats in each administration group were given the corresponding dose of drugs once a day for 4 weeks, and rats in the blank and model groups were given normal saline with dose of 10 mL·kg-1. At 1 day before modeling, 21 days and 28 days after administration, body mass weighing, sucrose preference test and open field test were performed on each group . After 28 days of administration, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to detect the mRNA expression levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), glycogen synthase kinase-3β(GSK-3β), forkhead box transcription factor O3a(FoxO3a) and β-catenin in hippocampal tissues of rats in each group, while protein expression levels of PI3K, Akt, mTOR and FoxO3a in hippocampal tissues of rats in each group were detected by Western blot.ResultThere were 19 components in BP showed significant changes before and after vinegar-processing, and 9 components such as saikosaponin A, saikosaponin B1, saikosaponin B2, saikosaponin C and saikosaponin D were identified as potential Q-Marker through S-plot differential marker screening. Combined with the disease-drug-component-target network, saikosaponin A, saikosaponin B1, saikosaponin B2 and saikosaponin D were identified as antidepressant Q-Marker of raw and vinegar-processed products of BP. According to the results of pharmacodynamic tests, after 28 d of administration, compared with the blank group, the body mass, sucrose preference index and open field total score of rats in model group, fluoxetine group and total saponin group decreased significantly(P<0.01). Compared with the model group, the body mass, sucrose preference index and open field total score in total saponin group increased significantly(P<0.01). Compared with the blank group, mRNA expression levels of PI3K, Akt, mTOR and β-catenin in hippocampus of rats in the model group decreased significantly(P<0.05), while mRNA expression levels of GSK-3β and FoxO3a increased significantly(P<0.05). Compared with the model group, mRNA expression levels of PI3K, Akt, mTOR and β-catenin in hippocampus of rats in the total saponin group were increased significantly(P<0.05), while mRNA expression levels of GSK-3β and FoxO3a decreased significantly(P<0.05). Compared with the blank group, the protein expression levels of Akt and mTOR in hippocampus of the model group decreased significantly(P<0.01), while the protein expression levels of PI3K and FoxO3a increased significantly(P<0.01). Compared with the model group, the expression level of Akt in hippocampus of the total saponin group increased significantly(P<0.01), the mTOR expression level was increased but not statistically significant, while the protein expression levels of PI3K and FoxO3a decreased significantly(P<0.01).ConclusionThe chemical constituents of BP changed greatly after vinegar-processing, and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined by chemical basis, pharmacodynamics, network pharmacology and signaling pathway, which provided a reference for further research on quality control, pharmacodynamic substance basis and processing mechanism of BP.
关键词:Bupleuri Radix;antidepressant;quality markers(Q-Marker);ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS);network pharmacology;Chinese medicine decoction pieces;phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway
摘要:ObjectiveTo study the correlation between the content of active ingredients of Aurantii Fructus in different main production areas and soil factors, so as to provide a theoretical basis for implementing ecological regulation of soil, improving the quality of Aurantii Fructus, and revealing the origin of genuine medicinal materials.MethodThe content of naringin, neohesperidin, total flavonoids, volatile oil, total nitrogen, total phosphorus, total potassium, and 17 soil factor-related indicators in 25 batches of Aurantii Fructus from different production areas were determined. The main soil factors affecting the content of active ingredients of Aurantii Fructus were analyzed by Pearson correlation analysis, principal component analysis, and grey correlation analysis.ResultThe pH value of the soil is between 4.83 and 8.21, and the soil is weakly acidic and neutral in general. Soil fertility exceeds the average. Pearson correlation analysis shows that the soil factors most related to the four active ingredients of Aurantii Fructus are total phosphorus, available copper, available zinc, exchangeable magnesium, available sulfur, available phosphorus, and available molybdenum. Principal component analysis shows that total nitrogen, alkali-hydrolyzable nitrogen, organic matter, available phosphorus, and available zinc are the main characteristic factors in soil. Grey correlation analysis shows that the main soil factors affecting the active ingredients of Aurantii Fructus are total phosphorus, total nitrogen, available zinc, available copper, exchangeable magnesium, and pH.ConclusionIn the cultivation of Aurantii Fructus, the medicinal material quality of Aurantii Fructus could be improved by adjusting the level of beneficial factors in the soil and improving the soil texture.
摘要:ObjectiveBioinformatics methods were used to systematically identify the Salvia miltiorrhiza terpenoid synthase (SmTPS) gene family members and predict their functions from the perspective of the genome.MethodThe genome and transcriptome data of S. miltiorrhiza, Arabidopsis thaliana, and tomato were obtained from the national genomics data center (NGDC), national center for biotechnology information (NCBI), the Arabidopsis information resource (TAIR), and tomato functional genomics database (TFGD), and the whole genome identification and bioinformatics analysis of the SmTPS gene family member were carried out with the help of Perl language programming, Tbtools, and other bioinformatics tools.ResultA total of 52 TPS gene family members were identified, and they were distributed on eight chromosomes of S. miltiorrhiza. Their coding amino acid number was 207-822 aa. The isoelectric points were 4.76-9.16. The molecular mass was 24.11-94.81 kDa, and all members are hydrophilic proteins. Gene structure analysis showed that there were significant differences in the number of introns among different subfamilies. The number of introns in 72.6% of TPS-a, b, and g subfamilies was 6, and that in 88.9% of TPS-c and e/f subfamilies was more than 10. Protein motifs were conserved among TPS subfamilies. The analysis of promoter cis-acting elements showed that all promoters of the SmTPSs contained a large number of light-responsive elements, and most of them had hormone-responsive elements. Gene expression analysis showed that SmTPS gene family members exhibited tissue-specific expression, and 24 of them responded to exogenous methyl jasmonate.ConclusionBased on the published S. miltiorrhiza genome, 52 SmTPS gene family members were identified, and their functions were predicted based on the phylogenetic analysis and expression patterns. This paper provides reference information for the further biosynthesis pathway and regulatory mechanism analysis of terpenoids in S. miltiorrhiza.
关键词:Salvia miltiorrhiza;terpenoid synthase (TPS);bioinformatics;function analysis;gene family
摘要:ObjectiveThe biosynthetic pathways of benzylisoquinoline alkaloids(BIAs) in Nelumbo nucifera are of great theoretical and economic value. In this paper, N. nucifera O-methyltransferase(NnOMT) and N. nucifera N-methyltransferase(NnNMT) gene families were identified and analyzed by bioinformatics in order to facilitate the biosynthetic pathway of BIAs in N. nucifera.MethodBased on the whole genome of N. nucifera, UniPort and National Center for Biotechnology Information(NCBI) databases were used to identify the NnOMT and NnNMT gene families of N. nucifera, and analyze their physicochemical properties and subcellular localization, then TBtools, MEME, MEGA 11.0, FigTree 1.4.4 and other tools were used to analyze the phylogeny, sequence characteristics, gene structure, functional annotation and cis-acting elements of NnOMT and NnNMT genes identified in the previous stage.ResultA total of 61 NnOMT and NnNMT genes were identified in this paper, the number of amino acids encoded by these genes ranged from 168 aa to 580 aa, the isoelectric point ranged from 4.76 to 9.16, and the relative molecular weight ranged from 18 699.52 Da to 64 934.53 Da, most of which showed acidic and mostly hydrophilic proteins. There were 10 conserved motifs, Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis enriched a total of 12 pathways, including metabolism, biosynthesis of phenylpropane and isoquinoline alkaloids, etc. And Visualization of Gene Ontology(GO) enrichment results showed that 61 NnOMT and NnNMT genes were annotated to 32 items, which included 16 molecular functions[such as reduced nicotinamide adenine dinucleotide(NADH) activity and exopeptidase activity] and 16 biological processes(such as metabolic process of carbon tetrachloride, anaerobic carbon tetrachloride metabolic process and responses to exogenous biological stimuli). There were a variety of cis-acting elements in the promoter regions of NnOMT and NnNMT genes, mainly promoter and enhancer regions element, light responsive element and methyl jasmonate responsive element.ConclusionIn this study, a comprehensive bioinformatics analysis of 61 NnOMT and NnNMT genes is carried out based on the genome data of N. nucifera, which lays a foundation for research on the gene structure and function of NnOMT and NnNMT gene families, and provides a reference for biosynthetic pathway elucidation of BIAs in N. nucifera.
摘要:ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus(AFI) and Aurantii Fructus(AF) based on the total statistical moment analysis and molecular connectivity index(MCI).MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) were consulted to establish the chemical composition database of AFI and AF, and set up their fingerprints by ultra-high performance liquid chromatography(UPLC), and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI, all components of AFI and AF were divided into different component groups, the average values of 0-8th order(0χ-8χ) MCI of the common component groups of AFI and AF were calculated.ResultThe values of total zero-order moment(AUCT) of AFI and AF were (10.57±2.45)×106, (5.09±0.89)×106 μV·s, the values of total first-order moment(MCRTT) were (11.57±1.58), (12.10±1.29) min, the values of total second-order moments(VCRTT) were(24.49±2.30), (26.49±2.54) min2, respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin, hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI, such as alysifolinone and imperatorin, and the non-common components of AF, such as neoeriocitrin and isosakuranin, with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories, and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997, the average values of 0χ-8χ MCI of alkaloids in AFI and AF were 3.65 and 3.14, the average values of 0χ-8χ MCI of flavonoids were 8.47 and 8.47, the average values of 0χ-8χ MCI of volatile oils were 2.71 and 3.48, respectively. It showed that there were some differences in MCI of chemical constituents(groups) between AFI and AF.ConclusionThe chemical constituents(groups) of AFI and AF not only differ in content and species, but also in structural characteristics and structure-activity relationship, which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.
摘要:Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by persistent and often progressive airflow obstruction, including airway abnormalities (e.g., bronchitis and bronchiolitis) and chronic respiratory symptoms (e.g., dyspnea, cough, and expectoration). It is one of the leading causes of death worldwide. According to the theory of traditional Chinese medicine (TCM), the lung and large intestine are interior-exterior related. Therefore, COPD can be treated from both the lung and intestine by the methods of tonifying and invigorating lung, spleen, and kidney, dispelling phlegm, and expelling stasis. Gut microbiota plays a key role in human immunity, nerve, and metabolism and may act on COPD by affecting the structures and functions of lung and intestine tissue and regulating lung inflammation and immunity. TCM can restore the balance of gut microbiota, which is conducive to the recovery from COPD. For example, the treatment method of tonifying lung and invigorating kidney can regulate gut microbiota, alleviate pulmonary and intestinal injuries, and improve lung immunity. The treatment methods of dispelling phlegm and expelling stasis can regulate gut microbiota and reduce pulmonary inflammation. According to the TCM theory of lung and large intestine being interior-exterior related, this review elaborates on the connotation of TCM in the treatment of COPD by regulating gut microbiota, aiming to provide new ideas for the clinical treatment of COPD via gut microbiota.
关键词:chronic obstructive pulmonary disease;gut microbiota;traditional Chinese medicine;lung and large intestine being exterior-interior related
摘要:Diabetic kidney disease (DKD) is the main cause of end-stage renal disease. Its high prevalence, mortality rate, and medical cost bring a heavy economic burden to society and families, and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body, which is involved in important life activities such as material and energy metabolism, immune system regulation, and signal transduction, thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken, intestinal microbiota imbalance, intestinal mucosal barrier damage, immune dysfunction, and reduction of metabolite short-chain fatty acids (SCFAs) will occur, which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine (TCM), the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang, or Yin deficiency affecting Yang, or Yang deficiency affecting Yin, or waning and waxing of Yin and Yang. For different pathogenesis changes, "Yin disease treated through Yang", "treating Yin for Yang", or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota, inhibit immune inflammation, protect intestinal mucosal barrier, and increase SCFAs through TCM, thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory, this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.
关键词:diabetic kidney disease;intestinal microecology;Yin-Yang theory;traditional Chinese medicine
摘要:The syndrome differentiation of Yin and Yang has the function of controlling the other six principles in the eight principles syndrome differentiation,which is a higher level or general induction of the disease. In the clinical process of traditional Chinese medicine,syndrome differentiation of Yin and Yang runs through the whole process of disease diagnosis and treatment. For Parkinson's disease,syndrome differentiation of Yin and Yang is particularly important. Different symptoms,the transformation of pathogenesis during the development of the disease and the treatment of traditional Chinese and western medicine all reflect the characteristics of Yin and Yang opposition restriction,mutual root and mutual use,and the transformation of ebb and flow. This article discusses the background,application and value of Yin-Yang syndrome differentiation from three aspects:the origin and application of yin-yang syndrome differentiation,the basis of Parkinson's disease syndrome differentiation,and the status and role of Yin-Yang syndrome differentiation in Parkinson's disease. It is of great significance to guide the diagnosis and treatment of Parkinson's disease with "Yin-Yang as the key point".
关键词:Parkinson's disease;syndrome differentiation of Yin and Yang;clinical application;traditional Chinese medicine
摘要:Ginseng Radix et Rhizoma(GRR) has the function of replenishing vital energy and can lighten the body and prolong the life when taken for a long time, which is suitable for the development of anti-aging products, so this paper intends to sort out the progress of anti-aging research on GRR. After combing, the results of modern studies have shown that a variety of components in GRR have anti-aging effect, which can prolong the lifespan of aging animal models, as well as delay the aging of various systems. The anti-aging mechanisms mainly include anti-cellular senescence, anti-oxidative stress, inhibiting telomere shortening, maintaining mitochondrial homeostasis and so on. The anti-aging ingredients of GRR involved in the researches mainly include ginsenoside Rg1 and ginsenoside Rb1, in addition, ginsenoside Rg3, ginsenoside Rd, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb2, oligosaccharides of GRR, polysaccharides of GRR, water extract of GRR, total saponins of Panax ginseng stems and leaves are also included. Therefore, under current background of population aging, the in-depth development of GRR and its transformation into anti-aging products are of great significance for delaying senility and improving the health conditions of aging population.
关键词:population aging;Ginseng Radix et Rhizoma;anti-aging;saponins;polysaccharides;oxidative stress;mitochondrial homeostasis
摘要:Heart failure is one of the main cardiovascular system diseases at present, and it is a clinical syndrome caused by changes in cardiac structure and function, resulting in impaired ejection function or ventricular filling. Therefore, heart failure has become the most important cardiovascular disease in the 21st century. In recent years, the incidence of heart failure is increasing, and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine, more and more attention has been paid to the research, development, and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus, a traditional Chinese medicine, is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics, protecting myocardial muscle, and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure, yielding remarkable results. In recent years, it has been found that astragaloside, Astragalus polysaccharide, quercetin, calyx isoflavones, and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response, myocardial apoptosis, and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature, with a view to providing a reference for its further research, development, and application in the prevention and treatment of heart failure.
摘要:Chronic obstructive pulmonary disease (COPD) is a common disease in clinical practice. It is associated with obvious exposure to toxic particles or gases and has become the leading cause of death and disability worldwide. The pathogenesis of COPD is complex, and the oxidative stress involved in COPD plays a crucial role in the pathological process of the disease. Patients with COPD usually have high levels of oxidative stress in the lungs, which will affect the whole body for a long time, causing a variety of complications and accelerating the development of the disease. On the one hand, oxidative stress can directly damage the airway and lung tissue. On the other hand, it also drives other pathological mechanisms to jointly promote the development of disease, such as participating in inflammatory reactions and protease/anti-protease imbalance, promoting mucus secretion, accelerating cellular senescence, causing autoimmunity, and involving in genetic regulatory pathways. At present, western medicine treatment is mostly based on conventional drug treatment, and antioxidant-targeted oxidative stress is adopted, but there are still some challenges in efficacy and safety. Traditional Chinese medicine has a long history of preventing and treating COPD. In particular, Chinese herbal medicine formulas have great potential to interfere with the oxidative stress of COPD. Whether it is the modified classical traditional Chinese medicine or the new formulation developed by modern doctors, the research results reflect the multi-target and multi-channel advantages of traditional Chinese medicine treatment, and their efficacy and safety are gradually verified. This paper reviewed the literature in recent years, starting with the basic and clinical research on the intervention of traditional Chinese herbal medicine formulas on oxidative stress of COPD, so as to provide further ideas for related research on the prevention and treatment of oxidative stress of COPD by traditional Chinese medicine.
关键词:Chinese herbal medicine formulas;chronic obstructive pulmonary disease;oxidative stress;basic research;clinical research
摘要:Esophageal cancer is a common malignant tumor of the digestive tract. At present, the pathogenesis of esophageal cancer has not been fully clarified. Although surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy have achieved good clinical results in the treatment of esophageal cancer, there are still many complications and severe adverse reactions. As an important part of traditional Chinese medicine (TCM), in recent years, many basic experiments and clinical studies have proved that Chinese medicine has a good effect in treating esophageal cancer. At the same time, the multi-component and multi-target characteristics of Chinese medicine and unclear pathogenesis of esophageal cancer determine that there are some problems such as unclear mechanisms of Chinese medicine in preventing and treating esophageal cancer. It is necessary to start with modern medicine and reveal the mechanism of Chinese medicine in preventing and treating diseases from the aspects of molecular biology and network pharmacology. It is believed in TCM that the occurrence of esophageal cancer is mostly attributed to stagnation of liver Qi, phlegm stasis and Qi stagnation, fluid consumption and heat accumulation, the decline of healthy Qi, and the cementation of cancer toxicity. According to the literature review, Chinese medicinal compounds mainly include tonic formulae (such as Liu Junzitang), drying and moistening formulas (such as Qigesan), and heat-clearing formulas (such as Fufang Kushen injection). Chinese medicinal monomers mainly include drugs potent in attacking poison and killing insects, clearing heat, activating blood and resolving stasis, and regulating Qi, which is consistent with the etiology and pathogenesis of esophageal cancer in TCM. It is also found that Chinese medicine can promote cell apoptosis and autophagy, block cell cycle, and reverse cell resistance by regulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), neurogenic locus notch homolog protein (Notch), Wnt/β-catenin, mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and other related signaling pathways, but there is no systematic summary. This study systematically summarized the relevant signaling pathways of Chinese medicine in regulating esophageal cancer, which is helpful to clarify the relevant mechanisms of Chinese medicine in the process of esophageal cancer occurrence, development, invasion, and metastasis, so as to provide new targets and new perspectives for the treatment of esophageal cancer and promote the modernization of TCM.
摘要:Parkinson's disease (PD) is a kind of chronic progressive neurodegenerative disease that has a high prevalence rate in recent years, especially in the elderly. PD belongs to the category of "tremor disease" and "tremor" in traditional Chinese medicine, and Tianma Goutengyin is a classic prescription contained in the Synopsis of The New Significance of Patterns and Treatment in Miscellaneous Diseases(《中医内科杂病证治新义》). This article explored the theory of Tianma Goutengyin in the treatment of PD, and based on network pharmacological research, the article summarized relevant research on Tianma Goutengyin and its single herb in the treatment of PD. Moreover, it discussed the clinical applications and mechanisms of Tianma Goutengyin and its single herb in the treatment of PD. It is found that the mechanisms of Tianma Goutengyin in treating PD may be related to resisting oxidative stress, inhibiting inflammatory response, regulating neurotransmitters, and protecting dopamine (DA) neurons. Besides, the main components of the single herb in Tianma Goutengyin for treating PD are gastrodin, rhynchophylline, geniposide, gardenial alcohol, eucommitol glycoside, motherwort alkaloid, baicalin, pachyman, and achyranthes bidentata sterol. They can improve the related symptoms of PD patients by inhibiting inflammatory response, resisting oxidative stress, affecting calcium ion concentration, restoring mitochondrial function, and and protecting DA neurons. This article summarized the research progress of Tianma Goutengyin and its single herb in treating PD, so as to provide a reference for the prescription and medication of Tianma Goutengyin in the treatment of PD and subsequent research on the mechanisms of Tianma Goutengyin and its single herb in the treatment of PD and give play to the advantages of traditional Chinese medicine in the treatment of PD.
关键词:Tianma Goutengyin;Parkinson's disease;traditional Chinese medicine;research progress
摘要:Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss, which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway, and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP, which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts, which is beneficial to maintain bone homeostasis, slow down the development process of OP, improve the clinical symptoms of patients, reduce the risk of disability, and improve their quality of life. However, there are few studies on ferroptosis in OP. Traditional Chinese medicine (TCM) is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP, with high safety, few toxic and side effects, and low treatment cost, and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis, discussed the role of ferroptosis in bone homeostasis, and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis, so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.
关键词:ferroptosis;iron accumulation;lipid peroxides;bone homeostasis;traditional Chinese medicine
摘要:Qinghao Biejiatang, first recorded in the Detailed Analysis of Warm Diseases (《温病条辨》) written by WU Jutong in the Qing Dynasty, is composed of Artemisiae Annuae Herba, Trionycis Carapax, Rehmanniae Radix, Anemarrhenae Rhizoma, and Moutan Cortex. With the effects of nourishing Yin and relieving heat, this prescription is often used to treat the syndrome of Yin deficiency and internal heat. The deficiency of healthy Qi, invasion of pathogenic toxins, loss of lung Yin, and generation of deficiency-heat are pathogenesis of lung cancer, pneumonia and other lung diseases, the treatment of which usually follows the principles of nourishing Yin, reinforcing healthy Qi, clearing lung, and eliminating heat. With the effects basically in accordance with the treatment principles of lung diseases, Qinghao Biejiatang is widely used in the treatment of lung diseases such as lung cancer-associated fever, hemoptysis or combined with bone metastasis, tuberculosis, community-acquired pneumonia, and pneumonia caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Basic experiments have shown that Qinghao Biejiatang may exert the therapeutic effects by reducing inflammation, maintaining immune balance, regulating intestinal flora, hormone secretion, lipid metabolism, and inhibiting tumor and oxidative damage. In addition, the main active ingredients of this prescription include artemisinin, luteolin, sitosterol, stigmasterol, polysaccharides, catalpol, paeoniflorin, quercetin, paeonol, gallic acid, timosaponin, and mangiferin, which have anti-tumor, anti-oxidant, anti-virus, inflammation-regulating, and immunomodulatory activities. The paper reviewed the clinical and basic studies of Qinghao Biejiatang in the treatment of lung diseases, aming to provide a theoretical basis for the clinical application.
摘要:Fibrosis can occur in diverse tissue and organs and is the common outcome as multiple chronic diseases progress. It is characterized by over-activation of fibroblasts and excessive deposition of extracellular matrix. Targeting transforming growth factor-β (TGF-β), a classical signaling molecule in fibrosis, is currently a routine strategy for drug therapy of this disease. The use of traditional Chinese medicine (TCM) in the treatment of fibrotic diseases has been supported by mature theories. The theories emphasize that the internally-accumulated pathogens and mixed deficiency-excess underlie the shared pathology of fibrotic diseases. Qi stagnation, blood stasis, phlegm turbidity, and mass accumulation are key pathological factors. "Yin suppression by Yang" is the core thought for treatment with TCM of the disease. Pharmacological investigations reveal the scientific nature of TCM in treating fibrotic diseases, namely multilevelled and multitargeted. In other words, it refers to networked regulation of signaling activities of fibrosis-related molecules such as TGF-β/Drosophila protein homolog (Smad), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), Hedgehog, Wnt/β-catenin, and inflammatory cytokines, so as to inhibit fibroblast function and provide a promising insight into novel anti-fibrotic drug. This paper summarized the conventional understanding of fibrotic disease treatment with TCM and its mechanism of action by reviewing ancient literature and modern research reports, which offers an idea for follow-up research in this field.
关键词:traditional Chinese medicine;fibrosis;conventional theory;molecular mechanism
摘要:By consulting ancient herbal books and modern literature, this paper systematically sorted out and researched the processing history, relevant processing norms in recent years, modern processing technology, chemical composition changes of processed products and their pharmacological mechanism of Scutellariae Radix, in order to provide a basis for the further development of Scutellariae Radix decoction pieces. According to the textual research of ancient books, there were many kinds of processing auxiliary materials of Scutellariae Radix, such as wine, vinegar, salt, honey, pig bile and so on, among which the wine processing was the most diverse and detailed, and the processed products such as raw products, stir-fried products, wine-processed products, fried charcoal products were still in use. The modern processing techniques of Scutellariae Radix mainly focus on the processing aspects of softening and slicing, wine processing and charcoal frying, and the research methods are relatively unified. At present, it is found that the changed chemical constituents of Scutellariae Radix after processing are flavonoids, polysaccharides, volatile oils and trace elements, etc. Pharmacological effects of processed products are hemostasis, antibacterial, anti-inflammatory, antioxidant, analgesic and antipyretic, treatment of lung diseases, treatment of colitis, etc. However, in the studies of Scutellariae Radix processing, there is a lack of research on the structural changes of chemical components caused by processing and a comprehensive comparative study on the pharmacological effects of various processed products. Based on this, it is suggested to carry out systematic research on the processing technology to processing mechanism, further explore the relationship between the change rule of material basis and pharmacological action before and after processing of Scutellariae Radix, and deepen the exploration of molecular mechanism and clinical application of processed products of Scutellariae Radix, in order to clarify the scientific connotation of the processing mechanism of Scutellariae Radix, and lay a foundation for the subsequent expansion of the application of Scutellariae Radix decoction pieces and the formulation of processing standards.
关键词:Scutellariae Radix;processing specification;historical evolution;chemical composition;pharmacological effect;traditional Chinese medicine decoction pieces;material basis
摘要:A sesquiterpene natural substance called artemisinin was discovered in Artemisia annua. One of its derivatives, artesunate (ART), has the properties of economy, immediate effect, low toxicity, and good tolerance. Since it has a quick and powerful killing effect on plasmodium in the erythrocyte phase and can quickly handle clinical seizure and symptoms, it is currently mostly utilized to treat cerebral malaria and other severe instances of malaria. In addition, it has antitumor, antivirus, anti-hepatic fibrosis, anti-inflammatory, antibacterial, hepatocyte protection, immunological modulation, and other pharmacological properties and can inhibit cell proliferation, induce cell apoptosis, and reduce the incidence of sepsis. In many countries, artemisinin-based combination therapies (ACTs), such as artemether-benflumetol, artesunate-amodiaquine, and artemether-lumefantrine, are the first-line treatments for malaria. Recent research on artesunate by Chinese and international scholars has revealed that compared with monotherapy, artesunate combination therapy offers more benefits in terms of improving pharmacological effects, shortening the duration of medicine, and minimizing adverse effects. Through systematic retrieval of Web of Science Core Collection and integration through CiteSpace (6.2.1) software, this article reviewed the mechanism of artesunate combined with other medications with regard to antimalarial, antitumor, antibacterial, and antiviral features in the previous five years, so as to provide some theoretical basis for rational development and utilization of ART and new drug research and development.