摘要:ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology.MethodWistar rats were randomized into blank, model, and Danshenyin groups (n=10) according to the blood lipid level. The rats in the blank group were fed with a basic diet, and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week, the tissue samples were collected for the measurement of related indicators, and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 (CD36), focal adhesion kinase (FAK), phosphatidylinositol 4-phosphate 5-kinase (PIP5K), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (Akt), and phosphorylated protein kinase B (p-Akt).ResultCompared with the model group, Danshenyin lowered the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in the plasma (P<0.05), elevated the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05), and reduced the platelet aggregation rate (P<0.05). Compared with the blank group, the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group, Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group, Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology (GO) functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux, production of cytokines, dyslipidemia, and platelet activation. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction, peroxisome proliferators-activated receptors (PPAR), focal adhesion, and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36, FAK, PIP5K, PI3K, p-Akt (Ser473), and p-Akt1/2/3 (Thr308).ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.
关键词:hyperlipemia;Danshenyin;activating blood and resolving stasis;platelet membrane glycoprotein 4 (CD36)
摘要:ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase (AMPK)/UNC-51-like kinase 1 (ULK1)/key molecule of autophagy, benzyl chloride 1 (Beclin1) pathway and elucidate the underlying mechanism.MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group, metformin group (0.26 g·kg-1), and low-, middle-, and high-dose groups (2.25, 4.5, 9 g·kg-1) of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set, with 12 mice in each group. After eight weeks of continuous intragastric administration, the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed, and fasting blood glucose (FBG) was measured using a Roche blood glucose device. Fasting serum insulin (FINS) was measured using an enzyme-linked immunosorbent assay, and the insulin resistance index (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK, Beclin1, autophagy associated protein 5 (Atg5), and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B (LC3B) and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR (Real-time PCR) was used to measure mRNA expression levels of AMPK, Beclin1, Atg5, ULK1, and p62.ResultCompared with the blank group, the model group exhibited a significant increase in body mass (P<0.01). Additionally, the levels of FBG, FINS, and HOMA-IR significantly changed (P<0.01). The structure of liver cells was disordered. The protein expression levels of AMPK, Beclin1, and Atg5 in liver tissue were significantly decreased (P<0.01), while the expression level of p62 protein was significantly increased (P<0.01). The expression levels of mRNA and proteins were consistent. Compared with the model group, the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased (P<0.05). FBG, FINS, and HOMA-IR were significantly decreased (P<0.05,P<0.01). After treatment, the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK, Beclin1, Atg5, LC3B, and ULK1 were increased (P<0.05,P<0.01), while the protein expression of p62 was decreased (P<0.01). The expression levels of mRNA and proteins were generally consistent.ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance, regulate the AMPK autophagy signaling pathway, alleviate insulin resistance in db/db mice, and effectively prevent the occurrence and development of type 2 diabetes.
关键词:Rhei Radix et Rhizoma-Coptidis Rhizoma;liver damage;insulin resistance;obese type 2 diabetes;adenylate activated protein kinase (AMPK)/UNC-51-like kinase 1 (ULK1)/key molecule of autophagy, benzyl chloride 1 (Beclin1)
摘要:ObjectiveTo preliminarily confirm the effective anti-lung cancer sites of Momordicae Semen and Epimedii Folium and study their mechanism of action.MethodOn the basis of preliminary research, the extraction method of Momordicae Semen and Epimedii Folium was optimized and the effective parts were screened under the guidance of pharmacological effects. Different ethanol elution and water elution sites of Momordicae Semen and Epimedii Folium were obtained through adsorption and elution with D101 macroporous resin. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay was used to detect the effects of total drug extracts and different elution sites on the proliferation of various tumor cell lines, and to screen for the optimal elution site and tumor sensitive strains. Flow cytometry was used to detect the effect of the elution sites of Momordicae Semen and Epimedii Folium on intracellular reactive oxygen species (ROS) and apoptosis in A549 cells. Western blot was used to compare the expressions of tumor protein 53 (p53), Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-3 and 9 (Caspase-3 and Caspase-9) proteins in A549 cells.ResultThe inhibitory effect of Momordicae Semen on the proliferation of A549 cells was better than the kernel of Momordicae Semen, with 50% inhibitory concentration (IC50) being (86.83±2.88) mg·L-1 and (95.10±18.13) mg·L-1, respectively. The effect of total extracts of Epimedii Folium on A549 anti proliferation IC50 value was (4.71±0.81) mg·L-1. The IC50 values of the 40%, 60%, and 80% ethanol and anhydrous ethanol eluted macroporous resins of the total extracts of Momordicae Semen and Epimedii Folium inhibiting A549 proliferation were (45.32±4.38)、 (14.95±0.73)、 (17.07±1.76)、 (14.46±2.35)、 (51.7±2.26)、 (12.37±0.67)、 (20.29±0.93)、 and (3.43±0.91) mg·L-1, respectively. Compared with the normal group, the 1∶1 combination of Momordicae Semen and Epimedii Folium inhibited A549 cell proliferation in a time-dependent and concentration-dependent manner. Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased intracellular ROS expression (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of A549 cell apoptosis (P<0.01). Compared with the normal group, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of p53 in A549 cells (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of Bax (P<0.01). Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly reduced the expressions of Caspase-3 and Caspase-9 (P<0.01).ConclusionThe anti-tumor effect of Momordicae Semen is better than that of the kernel of Momordicae Semen. The anti-tumor substances of Momordicae Semen and Epimedii Folium mainly concentrate in the 60% ethanol to anhydrous ethanol elution site. A549 cells are sensitive to the 1∶1 combination of Momordicae Semen and Epimedii Folium, which can effectively inhibit the cell proliferation. The mechanism may be related to increasing the generation of ROS in A549 cells, promoting their apoptosis, increasing the expressions of apoptotic proteins such as p53 and Bax, and reducing the expressions of Caspase-3 and Caspase-9.
关键词:Momordicae Semen;Epimedii Folium;anti tumor;screening;lung cancer
摘要:ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism.MethodMale SD rats were randomized into sham operation, model, low- and high -dose (3.5 g·kg-1 and 7 g·kg-1) Rehmannia Radix Praeparata, and nimodipine (0.01 g·kg-1) groups. The rat model of middle cerebral artery occlusion (MCAO) was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile, the serum levels of lactate dehydrogenase (LDH), oxidative stress-related indicators superoxide dismutase (SOD), glutathione peroxidase 4 (GPX4), and malondialdehyde (MDA), and the iron (Fe) content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats, Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector (beclin-1), microtubule-associated protein light chain 3 (LC3B), and ubiquitin-binding protein p62 (p62). The ferroptosis-associated proteins included transferrin (TF), transferrin receptor 1 (TFR1), ferritin heavy chain 1 (FTH1), and ferropotin (FPN1). The neurological function injury-associated proteins included brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB).ResultCompared with the sham operation group, the model group showed increased neurological function score, cerebral infarction volume, and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition, the model group presented elevated levels of LDH, MDA, and Fe (P<0.01) and lowered levels of SOD and GPX4 (P<0.01). Compared with the model group, Rehmanniae Radix Praeparata decreased the content of LDH, MDA, and Fe (P<0.05, P<0.01) and elevated the levels of SOD and GPX4 (P<0.05, P<0.01). Compared with the sham operation group, the modeling promoted the expression of beclin-1,LC3B Ⅱ/Ⅰ, TF, and TFR1 and inhibited the expression of p62, FTH1, FPN1, BDNF, and TrkB (P<0.01). The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata.ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.
摘要:ObjectiveTo investigate the effects of epigallocatechin-3-gallate (EGCG) on learning and memory abilities of amygdala electrical kindling-induced epilepsy in rats and its mechanism.MethodMale SD rats were randomly divided into the normal group, model group, intervention group (model+25 mg·kg-1 EGCG), and EGCG group (25 mg·kg-1 EGCG). Rats in the EGCG group were only given EGCG intraperitoneal injection, those in the normal group were only given electrode implantation, and those in the other experimental groups were given amygdala electrical kindling stimulation to establish a chronic kindling epilepsy model. EGCG was injected intraperitoneally daily before electrical stimulation. Twenty-four hours after the last electrical stimulation, the escape latency and percentage of target quadrant were recorded by the Morris water maze. Twenty-four hours after the behavioral test, rats in each group were sacrificed by decapitation. The number of hippocampal neurons was observed by Nissl staining. The thickness of postsynaptic density in the hippocampus, synaptic cleft, length of active zone and the curvature of synaptic interface were observed by transmission electron microscopy (TEM). The expressions of synapse-related proteins synaptotagmin (Syt), postsynaptic density-95 (PSD-95) and Kalirin-7 in the hippocampus were examined by Western blot.ResultCompared with those in the normal group, the escape latency was significantly prolonged (P<0.05, P<0.01) and the target quadrant ratio was significantly decreased in the model group (P<0.05). The number of hippocampus neurons decreased significantly (P<0.01). The synaptic cleft of the hippocampus was widened significantly, and the length of active zone and the thickness of postsynaptic density were significantly decreased (P<0.05, P<0.01). The expressions of synapse-related proteins Syt, PSD-95 and Kalirin-7 in the hippocampus were significantly decreased (P<0.05,P<0.01). Compared with those in the model group, the escape latency was significantly shortened and the percentage of target quadrant was significantly increased in the intervention group (P<0.05, P<0,01). The number of hippocampal neurons significantly increased (P<0.01). The synaptic cleft of the hippocampus was significantly shortened, and the length of active zone and postsynaptic density were significantly increased (P<0.05, P<0.01). The expressions of synaptic related proteins Syt, PSD-95 and Kalirin-7 were significantly increased (P<0.05, P<0.01).ConclusionEGCG can effectively improve cognitive dysfunction after epilepsy. Its protective effect may be achieved by protecting the ultrastructure of hippocampal synapses and regulating the expressions of synapse-related proteins Syt, PSD-95 and Kalirin-7.
关键词:amygdala electrical kindling;epilepsy;epigallocatechin-3-gallate;cognition;ultrastructure of hippocampus
摘要:ObjectiveTo investigate the role and mechanism of total saponins of Dioscorea (TSD) in mitigating nonalcoholic steatohepatitis (NASH) in mice.MethodForty-eight C57BL/6J mice were randomized into a normal group and a modeling group. The mice for modeling were fed with a high-fat and high-cholesterol diet + 20% fructose solution for 16 weeks and randomized into model, atorvastatin (4 mg·kg-1·d-1), and high-, medium-, and low-dose (200, 60, and 20 mg·kg-1·d-1) TSD groups. The mice were administrated with corresponding doses of drugs by gavage for 8 weeks. The mouse activity, liver index, levels of total cholesterol (TC), triglycerides (TG), and free fatty acids (FFAs) in the liver, and levels of TC, TG, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the serum were measured. Hematoxylin-eosin staining, Masson staining, oil red O staining, and transmission electron microscopy were employed to observe the pathological changes, lipid accumulation, and morphological changes of liver ultrastructure. Western blot was employed to determine the protein levels of AMP-activated protein kinase (AMPK), sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and phosphorylated ACC (p-ACC) in the liver tissue.ResultCompared with the normal group, the activity of mice in the model group decreased(P<0.05, P<0.01), the levels of TC, TG, FFA and serum TC, TG, ALT, AST, GGT, IL-1β and TNF-α, liver coefficient and liver pathology scores were significantly increased, the expression of p-AMPK/AMPK and p-ACC proteins in liver tissues was significantly reduced, and the expressions of SREBP-1c and ACC proteins were significantly increased (P<0.01). Compared with the model group, atorvastatin increased the mouse activity (P<0.05), while each dose of TSD caused no significant changed in the mouse activity. The levels of TC, TG, FFA in liver and serum TC, TG, ALT, AST, GGT, IL-1β, TNF-α, liver coefficient and liver pathological score in TSD and atorvastatin groups were significantly decreased, and the expressions of p-AMPK/AMPK and p-ACC in liver tissue were significantly increased. The expressions of SREBP-1c and ACC were significantly decreased (P<0.05,P<0.01).ConclusionTSD may alleviate NASH in mice by regulating the AMPK/SREBP-1c/ACC signaling pathway to reduce lipid synthesis.
关键词:nonalcoholic steatohepatitis;total saponins of Dioscorea;AMPK/SREBP-1c/ACC signaling pathway;lipid synthesis;experimental research
摘要:ObjectiveTo explore the effect and mechanism of Qizhu prescription on liver lipid anabolism and oxidative stress in mice with non-alcoholic steatohepatitis (NASH) based on adenylate activated protein kinase (AMPK) signaling pathway.MethodA total of 60 male C57BL/6J mice were randomly divided into a normal group (n = 10) and a modeling group (n = 50). The modeling group was fed by high-fat and high-cholesterol diet for 16 weeks to establish the NASH mice model and was randomly divided into model group, low-, medium, and high-dose groups of Qizhu prescription, and Yishanfu group, with 10 mice in each group. Qizhu prescription was administered intragastrically once a day at a dose of 4.75, 9.50, and 19.00 g·kg-1 in each group and 228 mg·kg-1 in Yishanfu group. The normal group and model group were given equal volumes of pure water for eight weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), and glucose (GLU) levels were detected. The pathological changes of liver tissue were observed by hematoxylin-eosin (HE) and oil red O staining. Serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), free fatty acids (FFA), reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of acetyl-CoA carboxylase (ACC), carnitine palmitoyl transferase 1A(CPT1A), and mitochondrial uncoupling protein 2 (UCP2) were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Protein expression levels of AMPK, p-AMPK, ACC, CPT1A, and UCP2 in liver tissue were detected by Western blot.ResultCompared with the normal group, the liver steatosis of the model group was obvious, with multiple inflammatory clusters and large amounts of intracellular lipid deposition. The activity of serum AST, ALT, as well as levels of IL-6, IL-1β, TNF-α, FFA, and MDA were significantly increased, the activity of CAT and SOD was significantly decreased, and the mRNA and protein expressions of ACC were significantly increased. The mRNA and protein expressions of CPT1 and UCP2 were significantly decreased, and the protein expression of p-AMPK was significantly decreased (P<0.01). Compared with the model group, the degree of liver steatosis in the Qizhu prescription and Yishanfu groups was reduced, the activity of AST and ALT, as well as the levels of IL-6, IL-1β, TNF-α, FFA, and MDA was significantly decreased, and the activity of CAT and SOD was significantly increased (P<0.01). The mRNA and protein expressions of ACC in liver tissue of mice in medium- and high-dose groups of Qizhu prescription were significantly decreased, while the mRNA and protein expressions of CPT1A and UCP2, as well as p-AMPK protein were significantly increased (P<0.01).ConclusionQizhu prescription can improve liver lipid metabolism, reduce oxidative stress, and promote liver cell repair in NASH mice by activating the AMPK signaling pathway.
关键词:Qizhu prescription;non-alcoholic steatohepatitis;adenylate activated protein kinase (AMPK) pathway;lipid metabolism;oxidative stress
摘要:ObjectiveTo observe the therapeutic effect of Shugan Huazheng prescription on hepatic fibrosis model rats induced by carbon tetrachloride (CCl4) and explore whether it plays its role through hypoxia-induced factor-1α/vascular endothelial growth factor/transforming growth factor-β1 (HIF-1α/VEGF/TGF-β1) pathway.MethodA total of 54 male SPF SD rats were randomly divided into six groups: blank group, model group, colchicine group (0.2 mg·kg-1), and high-, medium-, and low-dose groups (29.52, 14.76, and 7.38 g·kg-1) of Shugan Huazheng prescription, with nine rats in each group. The molding was conducted three times a week for eight weeks. Administration began the day after the first injection, and the drug intervention was once a day for eight weeks. On the day after the last administration, the rats were deprived of food and water, and they were killed the next day, during which the physiological status of each group of rats was dynamically monitored. The pathological changes in the liver were observed by hematoxylin-eosin (HE) staining, and the content of hydroxyproline (HYP) and angiotensin Ⅱ (AngⅡ) in liver tissue were detected by enzyme-related immunosorbent assay (ELISA). Real-time fluorescent quantitative PCR (Real-time PCR) was used to determine the mRNA expression levels of HIF-1α, VEGF, and TGF-β1 in liver tissue, and immunohistochemical method (IHC) and Western blot were used to detect the protein expression levels of HIF-1α, VEGF, and TGF-β1 in liver tissue.ResultCompared with the blank group, the overall condition of rats in the model group decreased significantly. The proliferation of connective tissue and the increase in adipose cells between hepatocytes were obvious. The content of HYP and Ang was increased. The mRNA and protein expressions of HIF-1α, VEGF, and TGF-β1 were increased to varying degrees (P<0.05). Compared with the model group, the proliferation of connective tissue and inflammatory cell infiltration in the liver tissue of colchicine and Shugan Huazheng prescription groups were reduced. The content of HYP and Ang was decreased. The mRNA and protein expression levels of HIF-1α, VEGF, and TGF-β1 were decreased, and the colchicine group and high-dose group of Shugan Huazheng prescription were the most significant (P<0.05).ConclusionShugan Huazheng prescription has an obvious therapeutic effect on CCl4-induced hepatic fibrosis model rats. Its therapeutic mechanism may be related to the regulation of the HIF-1α/VEGF/TGF-β1 signaling pathway and the improvement of hepatic hypoxia, vascular remodeling, and the syndrome of Qi deficiency and blood stasis in hepatic fibrosis.
摘要:ObjectiveTo explore the therapeutic mechanism of Faeces Bombycis on diabetic gastroparesis (DGP) rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/Akt/mTOR) signaling pathway.MethodDGP rat model was prepared by random selection of 15 out of 105 rats as blank group. The rats successfully constructed were randomly divided into model group, high-,medium- and low- dose groups (3.2, 1.6, 0.8 g·kg-1) and moxapride group (1.5 mg·kg-1), with 12 rats in each group, and were given gavage for 4 weeks. The gastric emptying rate and random blood glucose were measured. The morphological changes of gastric antrum were observed by hematoxylin-eosin (HE) staining, and the expression of the c-Kit gene was analyzed by immunohistochemistry. The apoptosis of Cajal interstitial cells was observed by in situ end labeling (TUNEL) staining, and the protein expressions of PI3K, phosphorylation(p)-PI3K, Akt, p-Akt, mTOR, and p-mTOR were detected by Western blot.ResultCompared with the blank group, the gastric emptying rate of the model group decreased significantly (P<0.01), and the glandular structure of the gastric antrum was destroyed. The expression of c-Kit decreased (P<0.01), and the apoptosis of Cajal interstitial cells (ICC) increased. Compared with the model group, the gastric emptying rate in the high, middle, and low-dose groups of Faeces Bombycis extract and mosapride group increased significantly (P<0.01). The glandular structure of the gastric antrum became closer, and the apoptosis of ICC decreased. The expression of c-Kit in the high dose group of Faeces Bombycis extract increased significantly. After Western blot testing, compared with the blank group, the protein expression of p-Akt/Akt, p-PI3K/PI3K, and p-mTOR/mTOR in the model group increased. Compared with the model group, the protein expression of p-Akt/Akt in the high dose group of Faeces Bombycis extract decreased (P<0.01), and the protein expression of p-PI3K/PI3K decreased in the middle and low dose groups of Faeces Bombycis extract and mosapride group decreased (P<0.05, P<0.01). The protein expression of p-mTOR/mTOR decreased in the low dose group of Faeces Bombycis extract (P<0.05). In terms of random blood glucose, compared with the blank group, the random blood glucose in the model group increased significantly (P<0.01), and compared with the model group, the random blood glucose in the high and middle dose groups of Faeces Bombycis extract decreased significantly (P<0.05). Compared with mosapride group, the protein expression of p-Akt/Akt decreased in the high dose group of Faeces Bombycis extract (P<0.05), and the protein expression of p-PI3K/PI3K increased in the high, middle, and low dose groups of Faeces Bombycis extract (P<0.05, P<0.01).ConclusionFaeces Bombycis extract can increase gastric emptying rate, reduce ICC apoptosis, and lower random blood glucose in DGP rats. The high dose group of Faeces Bombycis extract has a significant effect on inhibiting ICC apoptosis, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.
摘要:ObjectiveTo investigate the effect of Shugan Quyu Jiedu prescription (SGQYJDF) on inducing ferroptosis in hepatocellular carcinoma cells based on the tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway.MethodMHCC97H cells were divided into the blank serum group (10% blank serum medium), SGQYJDF-containing serum low concentration group (5% SGQYJDF-containing serum and 5% blank serum medium), SGQYJDF-containing serum medium concentration group (7.5% SGQYJDF-containing serum and 2.5% blank serum medium), SGQYJDF-containing serum high concentration group (10% SGQYJDF-containing serum medium) and sorafenib group (sorafenib concentration of 10 μmol·L-1 in 10% blank serum medium). After 24 hours of intervention, the cell survival rate was detected by cell counting kit-8 (CCK-8) assay. The cell proliferation ability was detected by 5-ethynyl-2′-deoxyuridine (EdU) staining. The intracellular ferrous ion (Fe2+) level was detected by ferrous ion fluorescent probe (FerroOrange) staining. The intracellular malondialdehyde (MDA) and glutathione (GSH) levels were detected by colorimetric assays. The ultrastructure of mitochondria was observed by transmission electron microscopy. The expression levels of ferroptosis-related proteins p53, SLC7A11 and GPX4 were detected by Western blot.ResultIn terms of cell viability, compared with the blank serum group, the SGQYJDF group showed a dose-dependent decrease in the survival rate of MHCC97H cells. Effect of the medium and high concentrations of SGQYJDF on the survival rate of MHCC97H cells were significantly decreased (P<0.01). Additionally, the results of the EdU assay showed that both the medium and high concentrations of SGQYJDF were able to inhibit the proliferation ability of MHCC97H cells (P<0.05, P<0.01). Regarding the biochemical indicators of ferroptosis, compared to the blank serum group, the medium and high concentrations of SGQYJDF were able to dose-dependently increase the intracellular Fe2+ level (P<0.01). The low, medium, and high concentrations of SGQYJDF were able to dose-dependently decrease the level of GSH in MHCC97H cells (P<0.01) and increase the level of MDA in the cells (P<0.05, P<0.01). In terms of pathway-related protein expression, compared to the blank serum group, the medium and high concentrations of SGQYJDF could significantly increase the expression of p53 (P<0.01). The low, medium, and high concentrations of SGQYJDF could significantly decrease the expression of GPX4 (P<0.01). The high concentration of SGQYJDF could decrease the expression of SLC7A11 (P<0.01). In terms of the cell morphology of ferroptosis, compared with the blank serum group, transmission electron microscopy revealed that the low concentration of SGQYJDF caused mitochondrial deformation, while the medium and high concentrations of SGQYJDF resulted in reduced mitochondrial volume, increased double-layer membrane density, and decreased mitochondrial cristae. These features were similar to those of sorafenib-induced ferroptosis. Furthermore, compared with the sorafenib group, the high concentration of SGQYJDF showed no statistically significant differences in cell survival rate, proliferation ability, Fe2+ level, MDA level, and GSH level.ConclusionThe results suggest that SGQYJDF may induce ferroptosis and inhibit proliferation in hepatocellular carcinoma MHCC97H cells by upregulating the expression of p53, suppressing the expressions of GPX4 and SLC7A11, downregulating the level of GSH, and leading to the accumulation of intracellular Fe2+ and MDA.
摘要:ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription (QHJ) on colitis-associated colorectal cancer (CAC) in mice, and its related mechanism.MethodC57BL/6 mice were randomly divided into four groups including the normal, model, QHJ low-dose (QHJ-L, 10 g·kg-1), and QHJ high-dose (QHJ-H, 40 g·kg-1) groups. Azoxymethane (AOM) and dextran sodium sulfate (DSS) were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5th week to the 14th week, once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate, colon length, weight, and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling (Wnt3a), β-catenin, Non-phosphor-β-catenin (Non-p-β-catenin), and cholesterol-binding glycoproteins 133 (CD133) were detected by Western blot. The localization and expression of the cluster of differentiation (CD) 80 and CD11 antigen-like family member B (CD11b) were detected by immunohistochemistry (IHC). The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins.ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group, the expression levels of Wnt3a, β-catenin, Non-p-β-catenin, and CD133 in colon tissues in the model group were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased (P<0.01), and the protein levels of Wnt3a, β-catenin, Non-p-β-catenin, and CD133 in the QHJ-H group were significantly decreased (P<0.05, P<0.01). Meanwhile, the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased (P<0.05, P<0.01). Compared with those in the model group, CD11b in QHJ-L and QHJ-H groups was significantly decreased, and CD80 was significantly increased(P<0.05, P<0.01). The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased, while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids (P<0.01).ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice, the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.
摘要:ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription (YHP) on the learning and memory of accelerated aging model mice, as well as its underlying mechanism.MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups, including the model group, low-dose YHP group, high-dose YHP group, and donepezil group. Additionally, 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group, each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg-1 and 12.48 g·kg-1, while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial (MG) polarization marker inducible nitric oxide synthase (iNOS) and M2 MG polarization marker arginase-1 (Arg-1) in the hippocampus region. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of pro-inflammatory factor interleukin 1β (IL-1β) and anti-inflammatory factor transforming growth factor-β1 (TGF-β1). Furthermore, Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 (Aβ1-42) along with triggering receptor expressed on myeloid cells 2 (TREM2)/nuclear factor kappa B (NF-κB) signaling pathway-related proteins TREM2, phospho (p)-NF-κB p65, and phospho-inhibitory kappa B kinase β (IKKβ) in the hippocampus.ResultCompared with the control group, the model group exhibited a significantly prolonged escape latency (P<0.01), a significant reduction in neuron-specific nuclear protein (NeuN) expression in the hippocampus, a significant increase in iNOS expression in MG, and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased, while the TGF-β1 content was significantly decreased. Additionally, there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions (P<0.05, P<0.01). However, no significant changes were observed in escape latency, times of crossing the platform, and hippocampal NeuN expression in the YHP treatment control group. Conversely, iNOS expression in MG as well as the hippocampal p-NF-κB p65, p-IKKβ, and Aβ1-42 expressions were significantly decreased. Furthermore, TREM2 expression was significantly increased (P<0.05, P<0.01). In comparison to the model group, the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform (P<0.05, P<0.01). In the high-dose YHP group, the escape latency was significantly shortened (P<0.05). In the low-dose YHP group, high-dose YHP group, the expression of NeuN in the hippocampus was significantly increased, the expression of iNOS in MG was significantly decreased, and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased, while the TGF-β1 content was significantly increased. Furthermore, the expression of TREM2 in the hippocampus was significantly increased, and the expressions of p-NF-κB p65, p-IKKβ, and Aβ1-42 were significantly decreased (P<0.01).ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway, reduce the release of neuroinflammatory factors, protect hippocampal neurons, and reduce the deposition of Aβ1-42, and finally delay the occurrence of learning and memory decline in SAMP8 mice.
摘要:ObjectiveTo decipher the mechanism of Wenxiao powder in alleviating corticosterone-induced depression-like behaviors in mice.MethodMale ICR mice were randomized into normal, model, paroxetine (20 mg·kg-1), and low- and high-dose (3.27, 6.54 g·kg-1, respectively) Wenxiao powder groups. The mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with corticosterone subcutaneously 0.5 h after gavage to induce depression. Mice were tested for depression-like behaviors after drug administration. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the corticosterone content in the serum. Nissl staining was performed to observe the damage of hippocampal neurons. Immunofluorescence staining was employed to observe the expression of double cortin (DCX) in the dentate gyrus (DG) of the hippocampus. Western blot was employed to determine the expression of proteins in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB)/extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB) pathway in the hippocampus.ResultCompared with the normal group, the model group showed decreased sucrose preference rate, increased immobility time in the tail suspension test (P<0.01), and reduced residence time in the central area of the open field and the total movement distance (P<0.05, P<0.01). In addition, the modeling elevated the corticosterone level in the serum (P<0.01), decreased the volume and intensified the nuclear staining of hippocampal neurons in the DG area, reduced the expression of DCX in the DG area, and down-regulated the protein levels of BDNF, phosphorylated (p)-TrkB, p-ERK, and p-CREB in the hippocampus (P<0.05, P<0.01). Compared with the model group, low-dose Wenxiao powder improved the mouse behavivors in the sucrose preference, open field, and tail suspension tests (P<0.05, P<0.01), and high-dose Wenxiao powder improved the behaviors in the sucrose preference and open field tests (P<0.05, P<0.01). In addition, Wenxiao powder lowered the serum corticosterone level (P<0.01) and recovered the structure and morphology of neurons with obvious nuclei and presence of Nissl bodies in the DG area of the hippocampus. Moreover, Wenxiao powder at both doses promoted the expression of DCX in the DG area, and high-dose Wenxiao powder up-regulated the protein levels of BDNF, p-TrkB, p-ERK, and p-CREB in the hippocampus (P<0.05, P<0.01).ConclusionWenxiao powder can alleviate corticosterone-induced depression-like behaviors and promote neurogenesis in mice possibly by activating the BDNF/TrkB/ERK/CREB signaling pathway.
关键词:Wenxiao powder;depression;brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB)/extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB);neurogenesis
摘要:ObjectiveBased on network pharmacology and transcriptomics, the mechanism of Zishen Qinggan prescription (ZSQGF) in improving glucose and lipid metabolism in type 2 diabetes (T2DM) model rats was explored.MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM, gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG) analysis were conducted, and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin (STZ). The rats were randomly divided into the control group, model group, metformin (Met, 72 mg·kg-1) group, and ZSQGF high-, medium-, and low-dose groups (ZSQGF-H, ZSQGF-M, and ZSQGF-L, with 4.8, 2.4, and 1.2 g·kg-1 raw drug in the solution). The living status of rats was monitored and the levels of total cholesterol (TC), total triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin(HE) staining and oil red O staining. The differential genes were analyzed through transcriptomics, GO and KEGG analysis, and the protein-protein interaction(PPI) network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results, the protein pathways were identified. The expression levels of nuclear factor-κB (NF-κB), matrix metalloproteinase(MMP)-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2(Bcl-2) modifying factor(BMF), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), and fatty acid synthase(FASN) was detected by real-time polymerase chain reaction(Real-time PCR). The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining.ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration, the body weight, blood sugar, serum indicators, and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB, MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF, NOX4, and FASN in the ZSQGF-H group, while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups.ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN, reducing lipid synthesis, and regulating the NF-κB signaling pathway.
关键词:Zishen Qinggan prescription;type 2 diabetes;glucose and lipid metabolism;network pharmacology;transcriptomics
摘要:ObjectiveTo investigate the clinical efficacy of Qihuang Jianpi Zishen Granules in the treatment of systemic lupus erythematosus (SLE) and its effect on the signal transducer and activator of tranSCription 3/mammalian target of rapamycin (STAT3/mTOR) signaling pathway, and to decipher the possible mechanism.MethodSixty female SLE patients who met the criteria in the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2022 to May 2023 were selected and randomized into a control group and an observation group (30 cases in each group). The control group was treated with prednisone acetate + hydroxychloroquine sulfate orally, and the observation group was additionally treated with Qihuang Jianpi Zishen granules. The treatment lasted for 8 weeks. The SLE disease activity (SLEDAI), TCM syndrome score, erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP), immune indexes [immunoglobulin G (IgG), C3, C4, CD4+, and CD8+], interleukin (IL)-17, IL-23, interferon (IFN)-γ, 24 h urinary protein (24 h PRO), serum creatinine (SCr), and expression of proteins [STAT3, phosphorylated (p)-STAT3, mTOR protein and STAT3,mTOR mRNA] in the STAT3/mTOR signaling pathway were determined before and after treatment. In addition, the adverse reactions were recorded.ResultAfter 8 weeks of treatment, the total response rate in the observation group was 93.33% (28/30), which was higher than that (70.00%, 21/30) in the control group (χ2=4.007, P<0.05). After treatment, both groups showed declined SLEDAI, TCM syndrome score, ESR, hs-CRP, IgG, CD8+, IL-17, IL-23, IFN-γ, 24 h PRO, SCr, and expression of proteins in the STAT3/mTOR pathway (P<0.01) and elevated levels of C3, C4, and CD4+ (P<0.01). Moreover, the observation group had lower SLEDAI, TCM syndrome score, ESR, hs-CRP, IgG, CD8+, IL-17, IL-23, IFN-γ, 24 h PRO, SCr, and expression of proteins in the STAT3/mTOR pathway (P<0.05, P<0.01) and higher levels of C3, C4, and CD4+ (P<0.05, P<0.01) than the control group after treatment. Neither group showed serious adverse reactions during the treatment period.ConclusionQihuang Jianpi Zishen Granules can ameliorate the inflammatory response, reduce the disease activity, and mitigate the kidney injury in SLE by inhibiting the STAT3/mTOR signaling pathway to regulate the immune function.
关键词:systemic lupus erythematosus;Qihuang Jianpi Zishen granules;signal transducer and activator of transcription 3/mammalian target of rapamycin (STAT3/mTOR) signaling pathway;immunoinflammation;Liuwei Dihuangtang;Si Junzitang
摘要:ObjectiveTo explore the clinical efficacy of Gandou decoction in treating Wilson's disease (WD) with dampness heat accumulation accompanied by rapid eye movement (REM) sleep behavior disorder (RBD).MethodFrom April 2019 to August 2023,62 patients with dampness heat accumulation type WD accompanied by RBD who met the inclusion criteria were selected from the Department of Encephalopathy at the First Affiliated Hospital of Anhui University of Chinese Medicine. They were randomly divided into a control group and an observation group with 31 cases each using a computer distributor. The control group received routine copper removal treatment,while the observation group received additional treatment with Gandou decoction on the basis of the control group. Eight days was one course of treatment,totaling three courses. The scores of traditional Chinese medicine syndromes,RBD screening questionnaire (RBDSQ) scores,RBD questionnaire-Hong Kong (RBDQ-HK) scores,polysomnography (PSG) parameters,24-hour urine copper (24 h U-Cu) levels,and non-ceruloplasmin-bound copper (NCC) levels between the two groups before and after treatment were compared,and adverse reactions were observed.ResultSixty trial cases were ultimately completed,with 30 cases in each group. Before treatment,there was no statistically significant difference in various indicators between the two groups, and thus they were comparable. Compared with those before treatment,the traditional Chinese medicine syndrome scores,RBDSQ scores and RBDQ-HK scores of the two groups were significantly reduced,the 24 h U-Cu levels were significantly increased,and the NCC levels were significantly reduced (P<0.05,P<0.01). Compared with the control group, the observation group showed better improvement in traditional Chinese medicine syndrome scores, RBDSQ scores, RBDQ-HK scores, and NCC levels (P<0.05,P<0.01). Compared with those before treatment,the total sleep time (TST),sleep efficiency (SE),sleep/REM latency,the proportion of N1/N2/REM stages,arousal index (ARI),and proportion of phasic electromyographic activity (P-EMG-A) were significantly improved in both groups (P<0.05). Compared with the control group after treatment,the observation group showed more significant improvements in the proportion of TST,SE,REM stages,ARI,and P-EMG-A proportion (P<0.05).ConclusionGandou decoction can not only improve the traditional Chinese medicine syndrome of WD patients with dampness heat accumulation accompanied by RBD but also alleviate their RBD symptoms.
摘要:ObjectiveTo evaluate the efficacy and safety of Rongjin Tongbi decoction on sciatica caused by lumbar intervertebral disc herniation with liver and kidney deficiency type based on a randomized controlled study.MethodFrom January 2019 to July 2022, 90 patients in the department of Traditional Chinese medicine(TCM) of Beijing Jishuitan Hospital who met the inclusion criteria were selected and divided into two groups according to the random number table, with 45 patients in each group. During the study, 19 cases dropped out, with 41 cases included in the final observation group and 30 cases in the control group. The observation group was given Rongjin Tongbi decoction orally, and the control group was given Loxoprofen Sodium Tablets orally for 28 days. The differences in the visual analog scale (VAS) scores, the Japanese Orthopaedic Association (JOA) scores, activities of daily living (ADL) assessments, TCM clinical symptoms, subjective symptoms, and clinical signs scores between two groups before and after treatment were observed. Liver and kidney functions and gastrointestinal adverse reactions were detected for safety evaluation.ResultBefore treatment, there was no statistically significant difference in scores between the observation group and the control group. After treatment, the absolute values of the differences in VAS and ADL scores in the observation group were higher than those in the control group (P<0.05). There was no statistically significant difference in the absolute value of the difference in JOA scores between two groups. The absolute value of the difference in TCM clinical symptom scores in the observation group was higher than that in the control group (P<0.01). There was no statistically significant difference in the absolute values of the differences in subjective symptom and clinical sign scores between two groups. The levels of liver and kidney function indicators in both groups before and after the experiment were normal, and there was no significant difference in gastrointestinal reactions.ConclusionRongjin Tongbi decoction can significantly improve the symptoms of sciatica patients caused by lumbar intervertebral disc herniation with liver and kidney deficiency type. After treatment, the patients exhibited significant improvements in pain, activity and other aspects, and it is proven to be safe and reliable, which is conducive to the recovery of physical function.
关键词:sciatica;Rongjin Tongbi decoction;liver and kidney deficiency type;therapeutic applications
摘要:ObjectiveTo explore the common syndrome elements of cerebral ischemic stroke (CIS) complicated with obstructive sleep apnea-hypopnea syndrome (OSAHS), reveal the characteristics of traditional Chinese medicine (TCM) syndromes of the disease, clarify the syndrome differentiation and syndrome types, provide evidence for clinical syndrome differentiation, and provide reference for establishing the TCM syndrome type standards of CIS complicated with OSAHS.MethodThe clinical information form of CIS complicated with OSAHS formulated by the research group was used for syndrome survey, and the four-examination information of 300 patients with CIS complicated with OSAHS was collected. The four-examination information of patients was analyzed by latent structure method and comprehensive cluster analysis, and the common syndrome elements of CIS complicated with OSAHS were extracted by combining the TCM basic theory and clinical experience. On this basis, the characteristics of TCM syndromes and the syndrome types in line with reality were summarized.ResultThe top five syndrome elements in patients with CIS and OSAHS are sleep snoring, open mouth breathing, physical obesity, night awakening and dizziness. The top five tongue and pulse manifestations are enlarged tongue, slippery pulse, slippery coating, thick and white coating and purple tongue. The disease locations are the lung, spleen, stomach, kidney, liver and brain. The nature of disease includes deficiency, depression, blood stasis, phlegm, dampness and fire. The clinical syndrome types include the syndrome of stagnation of phlegm and dampness, syndrome of phlegm-dampness blocking the mind, syndrome of spleen deficiency with dampness, syndrome of Yin deficiency leading to fire hyperactivity, syndrome of Qi depression blocking collaterals, syndrome of liver depression and blood stasis, syndrome of Qi deficiency with dampness, and syndrome of Yang deficiency induced water retention.ConclusionIn addition to the common phlegm-, dampness- and blood stasis-related syndromes in patients with CIS and OSAHS, there are also depression- and deficiency-related syndromes. The main etiology and pathogenesis is the disturbance of Qi movement. In clinical practice, attention should be paid to the specific situation of individual patients to differentiate between deficiency and excess, and the treatment should be performed by the method of soothing and reinforcing, or unblocking and clearing, or both.
关键词:latent structure;ischemic stroke;obstructive sleep apnea-hypopnea syndrome;syndrome elements;syndrome type
摘要:ObjectiveTo qualitatively analyze the chemical constituents and their tissue distribution in Lujiao formula based on ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS).MethodThe separation was performed on an ACQUITY UPLC® BEH C18 column(2.1 mm×100 mm, 1.7 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-methanol(B) in a gradient elution(0-2 min, 4%B; 2-6 min 4%-12%B; 6-38 min, 12%-70%B; 38-38.5 min, 70%B; 38.5-39 min, 70%-95%B; 39-43 min, 95%B; 43-43.1 min, 95%-4%B; 43.1-45 min, 4%B), the flow rate was 0.3 mL·min-1 with the column temperature of 40 ℃ and the injection volume of 5 µL. The data were acquired by an electrospray ionization(ESI) in the full scanning mode of positive and negative ions, the scanning rang was set at m/z 100-1 500, the collision energies were 10, 20, 40 eV. Retention time, precise relative molecular mass and secondary mass spectrometry fragment ions were used to identify the compounds in Lujiao formula and analyze their tissue distribution, combing with self-established database and comparing with standard substances and published literature data.ResultA total of 260 compounds, including 156 flavonoids, 43 terpenoids, 18 coumarins, 13 organic acids, 7 phenylethanoids, 7 alkaloids and 16 others, were identified or hypothesized from Lujiao formula, 68 of which were identified by comparison with standard substances. And the results of tissue distribution showed that 100, 143, 129 and 126 prototype components were detected in blood, heart, liver and kidney, respectively.ConclusionThe chemical composition of Lujiao formula and their tissue distribution were systematic analyzed, which can provide reference for the quality control, clinical application, pharmacokinetics and pharmacodynamic material basis of Lujiao formula and its medicinal materials.
关键词:Lujiao formula;Epimedii Folium;Ligustri Lucidi Fructus;Psoraleae Fructus;Corni Fructus;Citri Reticulatae Pericarpium;chemical composition;tissue distribution;ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS)
摘要:ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique, and then to clarify the mechanism of the two, as well as their similarities and differences.MethodTwenty-four gerbils were randomly divided into control group(CG), model group(MG), Aconiti Coreani Radix group(RA) and Typhonii Rhizoma group(RT). Except for the CG, ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG, rats in the other groups received whole powder suspension(0.586 mg·g-1) was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0, 3, 7 and 14. After the end of administration, the serum, brain tissue and urine of gerbils in each group were collected, and the rate of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC), and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and nitric oxide(NO) in serum and brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), and the data were processed by multivariate statistical analysis, and differential metabolites were screened based on value of variable importance in the projection(VIP) of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG) database and Metaboanalyst 5.0.ResultCompared with the CG, the neurological deficit score was significantly increased in the MG(P<0.05), compared with the MG, the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d(P<0.05). Compared with the CG, the rate of cerebral infarction was significantly increased in the MG(P<0.05), compared with the MG, the rates of cerebral infarction in the RA and RT were significantly reduced(P<0.05). Compared with the CG, the levels of IL-6, TNF-α, and MDA in the serum and brain tissue of gerbils from the MG were significantly increased(P<0.05), and the levels of SOD, GSH and NO were significantly reduced(P<0.05). Compared with the MG, Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6, TNF-α and MDA, and up-regulated the levels of SOD, GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics, of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma, and could be used as potential biomarkers for both treatments in stroke gerbils, respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism, pyrimidine metabolism, and aminoacyl-tRNA biosynthesis. In addition, Aconiti Coreani Radix could also regulate riboflavin metabolism, Typhonii Rhizoma could also regulate purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of pantothenate and coenzyme A, and β-alanine metabolism.ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke, with Aconiti Coreani Radix having stronger effects. From the metabolomics results, the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism, oxidative stress and so on, while Typhonii Rhizoma mainly involve amino acid metabolism, lipid metabolism, energy metabolism, etc.
关键词:Aconiti Coreani Radix;Typhonii Rhizoma;metabolomics;ischemic stroke;multivariate statistical analysis;biomarkers;ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS)
摘要:ObjectiveTo analyze the effects of new integration processing method in producing area and traditional method on the composition and pharmacological action of Polygoni Multiflori Radix Praeparata(PMRP), and to illustrate the advantages of toxicity reducing and efficacy enhancing of the decoction pieces prepared by the new method.MethodFresh Polygoni Multiflori Radix(PMR) was taken from Dao-di producing area, and was processed by new integration processing method in producing area(steaming with black bean juice under pressure of 0.1 MPa and temperature at 120 ℃ for 10.5 h) and traditional method(steaming with black bean juice under water for 36 h), respectively. Samples were collected during the processing process of the two methods, For new method, the samples were collected at 0.5, 3, 5.5, 8, 10.5 h, separately. For traditional method, the samples were collected every 4 h. High performance liquid chromatography(HPLC) was used to establish fingerprint and identify common peaks, the content of polysaccharides was determined by anthrone-sulfuric acid colorimetry at 627 nm, and the contents of anthraquinones and stilbene glycosides in different processed products were determined according to the methods under the item of determination of PMR and PMRP in the 2020 edition of Chinese Pharmacopoeia. In pharmacological experiments, 90 SD rats were randomly divided into 9 groups with 10 in each group(half of male and half of female), including the blank group, and raw products, 24 h processed products under atmospheric pressure, 30 h processed products under atmospheric pressure, 8 h processed products under high pressure groups with low and high dosages(4.125, 16.5 g·kg-1). Rats were given the drug by gavage for 29 d with once a day, blood was collected from the abdominal aorta after the last administration, and the serum was isolated, the body mass and liver mass of rats were weighed and the organ index was calculated. The pathological change of liver tissue was observed by hematoxylin-eosin(HE) staining, and biochemical methods were used to detect the contents of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), γ-glutamyltransferase(GGT), lactic dehydrogenase(LDH) in serum which used as liver function indicators and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px) in brain tissues which used as oxidation indicators.ResultA total of 14 common peaks were identified in the fingerprint of PMR, PMRP prepared by new method and traditional method, and three of the peaks were designated as stilbene glycoside, emodin and emodin methyl ether, respectively. The characteristic peak areas of each processed products changed significantly from 0 min to 25 min, indicating that different processing methods had an effect on the contents of components with high polarity in PMRP, and the trend of the changes of the two methods was similar, with the higher degree of change in the new method. The determination results showed that compared with the traditional method, the content of polysaccharide(a kind of beneficial component in PMRP obtained by the new method) significantly increased, while the contents of stilbene glycoside and bound anthraquinone(liver-damaging ingredients) significantly decreased. The pharmacological results showed that compared with the blank group, AST and LDH levels of male rats in the low and high dose groups of 24 h processed products under atmospheric pressure and AST level of male rats in the low and high dose groups of 8 h processed products under high pressure were significantly reduced(P<0.05, P<0.01), while compared with the raw product groups with the same dose, AST and LDH levels of male rats in the low dose group of 30 h processed products under atmospheric pressure were significantly reduced(P<0.05, P<0.01), the AST levels of male rats in the low and high dose groups of 8 h processed products under high pressure were significantly decreased(P<0.01), and there was no statistical significance in the differences of biochemical indexes of female rats in each administration group as compared with those of the blank group.ConclusionThe new integration processing method in producing area of PMRP can reach the quality of relevant regulations in 8 h. The processed products obtained by this method have more advantages than the traditional method in terms of toxicity reducing and efficacy enhancing, and energy saving to avoid the loss of ingredients, which can provide ideas for the production of high-quality decoction pieces of PMRP, and the integration processing method in producing area of other roots and rhizomes of traditional Chinese medicines.
关键词:Polygoni Multiflori Radix;integration processing in producing area;contents of main components;fingerprints;toxicity reducing and efficacy enhancing;anthraquinones;stilbene glycoside;antioxidant;liver injury
摘要:Tuoli Xiaodusan is the 65th formula in the Catalogue of Ancient Famous Classical Formulas(First Batch). In this study, the bibliometric method was used to summarize and verify the ancient books about Tuoli Xiaodusan in terms of its historical origin, composition and dosage of the formula, indications, decoction and administration method, and processing, etc. According to the research, there is no definite date of the formation of Tuoli Xiaodusan, the earliest can be traced back to Lizhai Waike Fahui in Ming dynasty, which has been widely circulated, with many versions of prescription composition, and the modern influential version is from Waike Zhengzong in Ming dynasty, which is made up of 12 Chinese herbs including Ginseng Radix et Rhizoma(3.73 g), Chuanxiong Rhizoma(3.73 g), Paeoniae Radix Alba(3.73 g), Astragali Radix(3.73 g), Angelicae Sinensis Radix(3.73 g), Atractylodis Macrocephalae Rhizoma(3.73 g), Poria(3.73 g), Lonicerae Japonicae Flos(3.73 g), Angelicae Dahuricae Radix(1.87 g), Glycyrrhizae Radix et Rhizoma(1.87 g), Gleditsiae Spina(1.87 g), Platycodonis Radix(1.87 g). The herb origins almost follow the 2020 edition of Chinese Pharmacopoeia, except that Angelica dahurica var. formosana is only recommended as the origin of Angelicae Dahuricae Radix, and Glycryyhiza uralensis is only recommended as the origin of Glycyrrhizae Radix et Rhizoma. All the herbs are recommended to be used in the raw products. As for the preparation method, it is recommended to decoct with water, add 400 mL of water, boil until 160 mL, and take 2-3 times a day. The formula has the functions of nourishing Qi and nourishing blood, detoxifying and draining pus, and was mainly used to treat ulcerative diseases with the syndrome of syndrome of healthy Qi deficiency and pathogenic factors excess in ancient times, and in modern times, it is used for a wide range of treatment, involving the skin and soft tissues, bones, digestion and many other systemic diseases, and is also mainly used for syndrome of healthy Qi deficiency and pathogenic factors excess. In this study, the ancient and modern applications of Tuoli Xiaodusan were summarized, and its key information was identified, providing a basis for its wider clinical application, in-depth research and formulation development.
关键词:famous classical formulas;Tuoli Xiaodusan;ancient literature of traditional Chinese medicine;historical evolution;modern clinical application;literature research;key information
摘要:Huangqitang comes from the Taiping Huimin Hejiju Fang of the Song dynasty. It consists of four medicinal materials: Astragalus membranaceus var. mongholicus, Citrμs reticμlata, Cannabis sativa, and Apis cerana. It is a classic prescription for treating constipation in the elderly. This study systematically collated the literature records about Huangqitang in ancient Chinese medicine books and combined it with the current status of modern clinical applications to conduct in-depth analysis and research on the origin,composition, dosage, processing, preparation and administration, drug base, main symptoms, and other key information of the formula, so as to provide a strong reference for the development and clinical application of the classic Huangqitang compound preparation. Through systematic combing and textual research on the previous literature of Huangqitang, it can be seen that the formula of Huangqitang was first recorded in the Taiping Huimin Hejiju Fang, and the medical books of the past dynasties mostly adopted this formula. In terms of drug base, the dried roots of the leguminous plant Astragalus membranaceus var. mongholicus are used, and for tangerine, the dried outer peel of the Rutaceae plant Citrus reticμlata and its cultivated varieties are used. The Moraceae plant Cannabis sativa with the peel removed is selected, and the Apis cerana is selected from the honey brewed by Apis cerana, an insect of the Apidae family. In terms of dosage, although the dosage of some drugs changed during the Ming and Qing dynasties, the dosage records basically followed the original prescriptions from the Song dynasty. In terms of processing, preparation, and usage, although the drug processing, preparation, and usage of Huangqitang in the medical books of the past dynasties have changed slightly, they are basically the same as the original prescription of the Song dynasty. In terms of main symptoms, Huangqitang is designed to treat constipation in the elderly. From the Song dynasty to the Qing dynasty, it was mostly used to treat constipation, secret congestion, asthenia, etc. in the elderly. In modern times, it is clinically used to treat constipation due to Qi deficiency, functional constipation, irritable bowel syndrome, and other diseases in the elderly. No adverse reactions have been found yet. In the subsequent research and development, it is necessary to carry out mass spectrometry analysis of Huangqitang, in-depth exploration of its prescription efficacy and mechanism of action, and other multi-omics scientific research. At the same time, it is important to establish quality control standards to provide a reliable scientific basis for the research and development, clinical treatment, and drug supervision of Huangqitang compound preparations.
关键词:classic famous prescription;Huangqitang;Taiping Huimin Hejiju Fang;clinical application;literature research
摘要:With the increasing incidence of diabetes mellitus in recent years, cardiomyopathy caused by diabetes mellitus has aroused wide concern and this disease is characterized by high insidiousness and high mortality. The early pathological changes of diabetic cardiomyopathy (DCM) are mitochondrial structural disorders and loss of myocardial metabolic flexibility. The turbulence of mitochondrial quality control (MQC) is a key mechanism leading to the accumulation of damaged mitochondria and loss of myocardial metabolic flexibility, which, together with elevated levels of oxidative stress and inflammation, trigger changes in myocardial structure and function. Qi deficiency and stagnation is caused by the loss of healthy Qi, and the dysfunction of Qi transformation results in the accumulation of pathogenic Qi, which further triggers injuries. According to the theory of traditional Chinese medicine (TCM), DCM is rooted in Qi deficiency of the heart, spleen, and kidney. The dysfunction of Qi transformation leads to the generation and lingering of turbidity, stasis, and toxin in the nutrient-blood and vessels, ultimately damaging the heart. Therefore, Qi deficiency and stagnation is the basic pathologic mechanism of DCM. Mitochondria, similar to Qi in substance and function, are one of the microscopic manifestations of Qi. The role of MQC is consistent with the defense function of Qi. In the case of MQC turbulence, mitochondrial structure and function are impaired. As a result, Qi deficiency gradually emerges and triggers pathological changes, which make it difficult to remove the stagnant pathogenic factor and aggravates the MQC turbulence. Ultimately, DCM occurs. Targeting MQC to treat DCM has become the focus of current research, and TCM has the advantages of acting on multiple targets and pathways. According to the pathogenesis of Qi deficiency and stagnation in DCM and the modern medical understanding of MQC, the treatment should follow the principles of invigorating healthy Qi, tonifying deficiency, and regulating Qi movement. This paper aims to provide ideas for formulating prescriptions and clinical references for the TCM treatment of DCM by targeting MQC.
关键词:diabetic cardiomyopathy;mitochondrial quality control;mitochondria;Qi deficiency and stagnation;traditional Chinese medicine
摘要:ObjectiveOvarian cancer is the third most common gynecologic cancer worldwide, with the second highest mortality rate among gynecologic cancers, and age-standardized rates are gradually increasing in many low- and middle-income countries. At present, its etiology and pathogenesis are not clear. There are no obvious symptoms in the early stage, and when the symptoms become obvious, it often indicates the advanced stage. The 5-year survival rate of the advanced stage is only 17%, which poses a great threat to women's health. Therefore, an in-depth study of the etiology and pathogenesis of ovarian cancer is very important to the exploration of prevention and treatment methods for ovarian cancer. Based on the clinical characteristics of ovarian cancer in traditional Chinese and Western medicine, and combined with the existing evaluation methods of animal models, this study evaluated the animal model of ovarian cancer, and provided analysis and suggestions.MethodThis study searched China National Knowledge Infrastructure (CNKI), Wanfang data, VIP information database, and PubMed database using the keywords "ovarian cancer" and "animal model", excluded the articles that did not meet the criteria, and then classified the remaining studies. Combined with the clinical diagnostic criteria of Western medicine and traditional Chinese medicine syndrome differentiation, the related indicators of ovarian cancer animal models were assigned and the degree of agreement was evaluated.ResultThe use of the transplanted animal model exhibited the highest frequency, followed by that of the induced model. The degree of agreement of traditional Chinese medicine for each model was lower than that of Western medicine. The induced ovarian cancer model had a high degree of clinical agreement and was similar to human ovarian cancer in terms of tumor growth pattern, disease progression and complications, which is an ideal animal model of ovarian cancer. Although this animal model can simulate the etiology and pathogenesis of ovarian cancer to a certain extent and reflect some indicators of traditional Chinese and Western medicine, it lacks differentiation of traditional Chinese medicine syndromes.ConclusionOn the basis of the original model, the animal model of ovarian cancer was added with Qi deficiency syndrome, blood deficiency syndrome, Qi stagnation syndrome, blood stasis syndrome, heat-toxin syndrome, and Yang deficiency syndrome to establish an animal model combining traditional Chinese medicine disease and syndrome of ovarian cancer, which could better simulate the clinical actual situation of traditional Chinese and Western medicine and lay a solid foundation for the study of integrated traditional Chinese and Western medicine for the treatment of ovarian cancer.
关键词:ovarian cancer;traditional Chinese and Western medicine;disease characteristics;animal model;analysis of degree of agreement
摘要:Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine (TCM) mainly involves peripheral vestibular diseases of Western medicine, such as Meniere's disease, benign paroxysmal positional vertigo, vestibular neuritis, and vestibular migraine, being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo, aural vertigo affecting the quality of life, aural vertigo not relieved after surgery, aural vertigo with complex causes, and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM: Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo, the control and mitigation of the symptoms, and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.
关键词:aural vertigo;peripheral vestibular diseases;diseases responding specifically to traditional Chinese medicine (TCM);combination of TCM and western medicine
摘要:ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome, and to provide guidance for national medical decision-making, clinical drug promotion, and pharmaceutical services.MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version, 2021) using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software, this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions, including safety pre- and post-market launch, effectiveness in treating migraine, economy (cost-effectiveness), and innovation, suitability, accessibility, and traditional Chinese medicine (TCM) characteristics in both its technology and clinical applications.ResultSafety: Duliang soft capsules were found to have good safety based on evidence from known adverse reactions (spontaneous reporting system (SRS) data, literature data, etc.), pre-marketing toxicological research, and post-marketing drug monitoring. Effectiveness: A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy: Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation: Duliang soft capsules, with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components, hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction (CO2 supercritical extraction technology) and formulation (soft capsule) processes. The product's innovation was rated as "Better". Suitability: A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility: Duliang soft capsules are moderately priced, making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics: The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio (Shi Zhai Bai Yi Xuan Fang) from the Song Dynasty, and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue (Jing Yue Quan Shu) as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch, and its TCM characteristics were rated as outstanding with sufficient evidence.ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness, suitability, and accessibility, and outstanding TCM characteristics. The product's safety, economy, and innovation received good ratings. In summary, Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics, the evidence was sufficient, and the result was confirmed, providing crucial references for clinical decision-making and pharmaceutical management.
关键词:Duliang soft capsules;comprehensive clinical evaluation of drugs;migraine;effectiveness;safety;economy
摘要:Ulcerative colitis (UC) is a chronic inflammatory bowel disease primarily affecting the colon and rectum, with the typical symptoms such as abdominal pain, bloody diarrhea, and tenesmus. The pathogenesis of UC remains to be fully elucidated. The disease is prone to recurrence, seriously affecting the patients' quality of life. Conventional therapies for UC have limitations, including unsatisfactory clinical efficacy, lengthy courses, and adverse reactions. Therefore, there is an urgent need to explore new therapeutic agents. Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-dependent nuclear receptor protein that plays a crucial role in maintaining intestinal homeostasis, is closely associated with the onset and development of UC. Traditional Chinese medicine (TCM) has advantages such as multi-targeting and mild side effects in the treatment of UC. Recent studies have shown that TCM can exert the therapeutic effects on UC by modulating PPARγ. The TCM methods for regulating PPARγ include clearing heat, drying dampness, moving Qi, activating blood, resolving stasis, invigorating the spleen, warming the kidney, and treating with both tonification and elimination. On one hand, TCM directly activates PPARγ or mediates signaling pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), and regulates helper T cell 17 (Th17)/regulatory T cell (Treg) balance to promote macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby inhibiting intestinal inflammation. On the other hand, TCM regulates the intestinal metabolism to activate PPARγ, lower the nitrate level, and maintain local hypoxia. In this way, it can restore the balance between specialized anaerobes and facultative anaerobes, thereby improving the gut microbiota and treating UC. This article summarizes the role of PPARγ in UC and reviews the research progress of TCM in treating UC by intervening in PPARγ in the last five years, aiming to give insights into the treatment and new drug development for UC.
关键词:peroxisome proliferator-activated receptor γ (PPARγ);ulcerative colitis;nuclear factor-κB (NF-κB);mitogen-activated protein kinase (MAPK);Toll-like receptor 4 (TLR4);traditional Chinese medicine
摘要:A chronic refractory wound is caused by continuous skin damage. At the same time, it may be formed due to repeated infection, vascular insufficiency, diabetes, tumors, chronic osteomyelitis, and other reasons, resulting in wound repair interruption and recovery delay. Chronic refractory wound seriously affects the quality of life of patients and consumes a lot of medical resources. Polysaccharides in traditional Chinese medicine (TCM) are the effective components of most TCM. Modern pharmacological studies have found that polysaccharides contained in TCM have anti-inflammatory, antioxidant, anti-radiation, hypoglycemic, antiviral, anti-tumor, hypolipidemic, and immunomodulatory effects. Through the summary and analysis of the literature, it was found that the mechanism of polysaccharides in TCM to promote chonic refractory wound repair was mainly realized from the following aspects: firstly, regulating inflammatory cytokines like interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) or regulating macrophage-related inflammatory proteins and chemotactic proteins like MIP-2, MCP-1, to shorten the inflammatory period. Secondly, activating growth factors like platelet-derived growth fator (PDGF), basic fibroblast growth factor (bFGF), TGF-α, and vascular endothelial growth factor (VEGF) to recruit endothelial cells and fibroblasts into tissue proliferation. Thirdly, activationg VEGF and its downstream receptor vascular endothelial growth factor receptor-1 (VEGFR-1) and vascular endothelial growth factor receptor-2 (VEGFR-2)-mediatated protein kinase C/extracellular regulated kinases (PKC/ERK) signaling pathway or promoting angiogenesie and improving wound blood flow through angiotensin (ANG). Fourthly, promoting the ablility of collagen synthesis by enhancing the secretion of hydroxyproline and hyaluronic acid (HA) from fibroblasts (FB) and regulating relevant matrix metalloenzymes and their enzyme inhibitor to regulate the extracellular matrix. Fifthly, eliminating free radiccals to reduce the damage caused by oxidative stress to tissue. Sixthly, enhancing the phagocytic ability of macrophages, the activity of natural killer cells, and the proliferation of T cells to improve the defense ability of tissue. Polysaccharides in TCM can repair wounds in many ways at the same time. Its advantage lies in the multiple targets and multiple pathways. It is expected that the research will pay more attention to the mechanism of wound repair by polysaccharide components in TCM when improving the treatment of chronic refractory wounds.
关键词:polysaccharides in traditional Chinese medicine (TCM);chronic refractory wound;repair;mechanism
摘要:Lung cancer is the fastest-growing cancer type in terms of incidence and mortality worldwide, posing a huge threat to the health and life of the population. Radiation therapy is one of the main methods for treating lung cancer, and there is a clear dose-effect relationship between the radiation dose and local control rate of lung cancer. However, the lung is a radiation dose-limiting organ, and the radiation resistance of lung cancer tissues and the radiation damage to normal tissues limit the radiation efficacy for lung cancer. The pathogenesis of lung cancer in traditional Chinese medicine (TCM) is characterized by an initial deficiency in vital Qi, followed by the internal invasion and gradual accumulation of pathogenic Qi. After radiation therapy for lung cancer, the body's vital Qi becomes weaker, and syndromes of phlegm coagulation, Qi stagnation, and static blood blocking collaterals become more severe, leading to radiation resistance of lung cancer tissues. Therefore, the key issue to better clinical efficacy of radiation therapy for lung cancer patients is to use drugs to enhance the radiation sensitivity of lung cancer cells and improve the radiation tolerance of normal lung tissues. TCM can be used as a radiation sensitizer by regulating the cell cycle to increase the proportion of cells in the radiation-sensitive phase, promoting upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes to induce cell apoptosis, enhancing DNA damage caused by radiation and inhibiting damage repair, improving blood circulation and tissue oxygen supply, and so on, to enhance the sensitivity of tumor cells to radiation and amplify the toxicity of radiation to tumor tissues. TCM can also be used as a radiation protector by inhibiting cell damage, regulating cytokines and immune balance, reducing the release of inflammatory and fibrotic factors, and inhibiting the activation of related signaling pathways to prevent and treat radiation-induced lung injury. This article systematically reviewed the research results of TCM on radiation sensitization and radiation protection in lung cancer in recent years, aiming to elucidate the mechanism of TCM in regulating the effect of radiation therapy for lung cancer and provide more theoretical and practical basis for TCM to participate in improving the prognosis of lung cancer patients undergoing radiation therapy.
关键词:traditional Chinese medicine;lung cancer;radiation sensitization;radiation protection;radiation-induced lung injury
摘要:Lung cancer is one of the most common malignant tumors in the world, with its morbidity and mortality ranking at the top. The early symptoms are not obvious, and the biological structure is complex, so many patients have missed the optimal treatment time. At present, the treatment of lung cancer in modern medicine is dominated by first-line chemotherapy and surgical treatment with platinum-containing regimen, which has relatively large side effects, poor prognosis, and a high risk of metastasis and recurrence. With the gradual rise of targeted therapy and immunotherapy for lung cancer, the overall recovery of patients with lung cancer is still poor and the survival rate is low, despite more abundant treatment methods. From the perspective of holistic concept and syndrome differentiation, traditional Chinese medicine (TCM) plays an important role in the prognosis of tumor patients, with many targets, a wide range and light toxic and side effect. Modern studies have shown that the occurrence and development of lung cancer are closely related to the abnormality of multiple signaling pathways, and the Wnt/β-catenin signaling pathway, as one of the most important pathways in cancer, is involved in the whole process of lung cancer development by regulating the expression of related signaling proteins and genes. In recent years, many studies have confirmed that TCM monomers and TCM compounds can inhibit the epithelial-mesenchymal transition (EMT) process of lung cancer and the activity of lung cancer stem cells (LCSCs) by regulating the Wnt/β-catenin signaling pathway, induce lung cancer cell apoptosis, inhibit the proliferation, invasion and migration of lung cancer cells, and thus play an anti-lung cancer role. In recent years, research in this field has made breakthroughs, but there is a lack of systematic reviews and summaries. Thus, this paper reviewed relevant literature worldwide to analyze and interpret the mechanism of TCM intervention in the Wnt/β-catenin signaling pathway against lung cancer. The TCM monomers targeted to regulate this signaling pathway were summarized in four categories: promoting blood circulation for removing blood stasis, clearing heat and removing dampness, clearing heat and removing toxicity, and awakening the spirit. TCM compounds included Buzhong Yiqitang, Xuefu Zhuyutang, et al. This study aims to provide new ideas for clinical research and drug development for lung cancer.
关键词:lung cancer;Wnt/β-catenin signaling pathway;traditional Chinese medicine;research progress
摘要:Chronic constipation (CC) is one of the most common functional gastrointestinal diseases. At present, the overall therapeutic effect of CC is still not satisfactory worldwide, which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity, social psychology, diet, intestinal flora imbalance, intestinal motility disorder, visceral sensitivity change, pelvic floor muscle group dysfunction and enteric nervous system (ENS) disorder. Among them, the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain, integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it, and can communicate with the intestinal tract and the central nervous system through nerve, endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis, 5-hydroxytryptamine (5-HT) is involved in the regulation of gastrointestinal motility, sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine(TCM) is a unique precious resource in China, which has good curative effects and safety. In recent years, it has received extensive attention in the treatment of constipation. TCM and active ingredients, acupuncture and massage specifically regulate 5-HT signal transmission, so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms, with unique advantages. Therefore, this study used ''constipation'', ''intestinal flora'', ''5-HT'', and ''traditional Chinese medicine'' as the keywords to search PubMed, China National Knowledge Infrastructure (CNKI) and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.
关键词:Chronic constipation;5-hydroxytryptamine;intestinal flora;brain-gut-microbiome axis;traditional Chinese medicine;traditional Chinese drugs;research progress
摘要:As one of the most difficult-to-cure neuropsychiatric disorders in clinical practice, schizophrenia is mainly manifested by behavioral abnormalities and multidimensional cognitive dysfunction, and the recurrence rate and disability rate of the disease are increasing year by year, which seriously affects patients' social functioning and quality of life, and even threatens the physical and mental health of the surrounding population. At present, the treatment of schizophrenia is mainly based on antipsychotic drugs combined with psychotherapeutic techniques, which have limited long-term therapeutic effects and a high relapse rate. Traditional Chinese medicine (TCM) boasts the advantages of multi-targets, multi-pathways, multi-links, and multi-levels, and plays a crucial role in the prevention and treatment of schizophrenia and its prognosis. Phosphatidylinositol 3-kinase (PI3K) is widely present in cells and is involved in the regulation of protein synthesis and apoptosis, and the different isoforms of protein kinase B (Akt) are of great significance in cell growth, oxidative stress, neuronal development and other processes. In recent years, a large number of studies have found that the PI3K/Akt signaling pathway is closely related to schizophrenia. Through regulating the PI3K/Akt signaling pathway, TCM monomers and TCM compounds mainly affect key signaling molecules such as mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK), glucose transporter (GLUT) for glucose uptake and transport, and nuclear factor E2-associated factor 2 (Nrf2), which organize the intracellular network of centers and regulate the formation and plasticity of neuronal synapse, and they play an important role in mitigating schizophrenia by regulating the processes of cell proliferation, migration and apoptosis of neurons, and has the advantages of multi-targets, all-encompassing and low toxicity. This article analyzes and explains the mechanism of TCM intervention in the PI3K/Akt signaling pathway against schizophrenia, in order to provide a theoretical basis and reference for the prevention and treatment of schizophrenia by TCM.
关键词:schizophrenia;traditional Chinese medicine;phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt);signaling pathway;research progress
摘要:Alzheimer's disease (AD) is a neurodegenerative disease often characterized by cognitive impairment in clinical practice. The main pathogenesis includes β amyloid protein (Aβ) excessive deposition, neuroinflammatory response, Tau protein hyperphosphorylation, and other factors, and currently only a few chemical drugs have been approved for clinical treatment of AD. The mechanism of action is relatively single, so it is imperative to find new treatment strategies. Traditional Chinese medicine theory believes that the loss of nourishment in the brain and marrow, as well as the loss of vital energy, is the internal mechanisms underlying the occurrence and development of AD, which runs through the entire treatment process. The pathogenesis of AD is closely related to the inflammasome signaling pathway of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3). Activating the NLRP3 signaling pathway increases neuroinflammatory response, intervenes in microglial polarization, and regulates Aβ sedimentation, cellular autophagy, brain homeostasis, etc. This article takes the NLRP3 signaling pathway as the starting point to sort out and summarize the upstream and downstream targets under the AD mechanism in the past five years, as well as the research on the NLRP3 signal pathway targets with the participation of the relevant traditional Chinese medicine compounds, such as Danggui Shaoyaosan, modified Shuyu Wan, Qingxin Kaiqiao prescription, Kaixin San, Jiedu Yizhi prescription, and modified Buwang San, traditional Chinese medicine monomer extracts, such as silibinin, Lycium barbarum polysaccharides, liquiritigenin, salidroside, baicalin, cinnamaldehyde, betaine, acacetin, and Hericium erinaceus, and acupuncture and moxibustion. It also reviews the latest achievements in the prevention and treatment of AD. This study provides ideas and directions for in-depth research on the prevention and treatment of cognitive dysfunction related diseases with traditional Chinese medicine.
关键词:nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway;Alzheimer's disease;traditional Chinese medicine monomers;traditional Chinese medicine compounds;inflammation