摘要:ObjectiveTo investigate the mechanism of Huangqi Gegentang (HGT) in the treatment of type 2 diabetes mellitus (T2DM) through the application of proteomic techniques.MethodsThe rat model of T2DM was established by streptozotocin combined with a high-fat, high-sugar diet. Thirty-two male SD rats were randomized into four groups: blank, model, HGT (8.10 g·kg-1·d-1), and positive control (metformin hydrochloride, 76.5 mg·kg-1·d-1). After 6 weeks of drug intervention, the fasting blood glucose level was measured, and an oral glucose tolerance test (OGTT) was performed. The area under the curve (AUC) was calculated. Enzyme-linked immunosorbent assay was performed to assess the level of glycated hemoglobin (GHbA1c) in the serum. The limulus amebocyte lysate assay was employed to measure the serum level of lipopolysaccharide (LPS). Pathological changes in the colon were observed by hematoxylin-eosin staining. The mRNA levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the colon tissue were quantified via Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Additionally, the protein and mRNA levels of zonula occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon tissue were assessed by Western blot and Real-time PCR, respectively. Label-free quantitative proteomics was employed to identify the differentially expressed proteins between the colon tissue samples from the blank, model, and HGT groups. Key proteins identified were subsequently validated by Western blot and Real-time PCR. Finally, bioinformatics analysis was conducted on the differentially expressed proteins.ResultsCompared with the blank group, the model group exhibited increased fasting blood glucose, AUC, and GHbA1c levels (P<0.01), damaged colonic mucosal epithelial structure and inflammatory cell infiltration, up-regulated mRNA levels of TNF-α, IL-6, and IL-1β in the colon and an increase in serum LPS content (P<0.05, P<0.01), and down-regulated protein and mRNA levels of ZO-1, Occludin, and Claudin-1 in the colon (P<0.01). Compared with the model group, the HGT group showed reductions in fasting blood glucose, AUC, and GHbA1c (P<0.01), alleviated damage to the colonic mucosal epithelium, down-regulated mRNA levels of TNF-α, IL-6, and IL-1β in the colon, a reduction in serum LPS content (P<0.05, P<0.01), and up-regulated protein and mRNA levels of ZO-1, Occludin, and Claudin-1 in the colon (P<0.05, P<0.01). Proteomics analysis identified 70 differentially expressed proteins that exhibited a downward trend in the model group relative to the blank group and an upward trend in the HGT group relative to the model group. These findings were corroborated by Western blot and Real-time PCR, which confirmed that the protein and mRNA levels of mucin 2 (Muc2) and transforming growth factor (TGF)-beta receptor 1 (Tgfbr1) in the colon tissue were consistent with the proteomic data. Bioinformatics analysis showed that these 70 differentially expressed proteins identified were significantly enriched in multiple signaling pathways, among which the TGF-β and advanced glycation endproduct (AGE)/receptor for advanced glycation endproduct (RAGE) signaling pathways were closely associated with damage to the intestinal mucosal barrier. This suggests that HGT may ameliorate intestinal mucosal barrier damage by regulating these pathways.ConclusionHGT potentially exerts anti-T2DM effects by influencing AGE/RAGE and TGF-β signaling pathways, thereby contributing to the restoration of the intestinal mucosal barrier.
摘要:ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 (TGR5/GLP-1) signaling pathway and intestinal flora.MethodsA total of 72 male Sprague Dawley (SD) rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin (55 mg·kg-1) and high sugar and high fat diet (20% sucrose solution + high fat diet) in a humid and hot environment (artificial climate box: temperature 30-34 ℃, relative humidity: 85%-95%). After successful modeling, the rats were randomly divided into a model group, a metformin group (200 mg·kg-1), low-dose, medium-dose, and high-dose Huanglian Wendantang groups (7.10, 14.20, 28.39 g·kg-1), with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period, the weight and blood glucose levels of rats were measured and recorded weekly. After the administration, fresh feces were collected from rats, and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum of rats were detected by enzyme-linked immunosorbent assay (ELISA), and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry, and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot.ResultsCompared with the blank group, the model group showed a decrease in body weight, an increase in blood glucose, and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased (P<0.01). The expression of TGR5 and GLP-1 was decreased (P<0.01), and the pathogenic bacteria were increased. Compared with the model group, the treatment groups exhibited improvements in body weight, blood glucose levels, and damp-heat syndrome in rats. Among them, the high-dose group of Huanglian Wendantang displayed the most significant improvement effect, with significantly reduced inflammation levels (P<0.01) and elevated expression of TGR5 and GLP-1 (P<0.01). Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups.ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy, and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.
关键词:diabetes enteropathy;intestinal flora;G protein coupled bile acid receptor 5/glucagon like peptide-1 (TGR5/GLP-1) signaling pathway;Huanglian Wendantang
摘要:ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C (SFTPC) and lung injury induced by chronic intermittent hypoxia (CIH) and the mechanism of action.MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups: a normoxia group, a CIH group, and low-, medium-, and high-dose Buzhong Yiqitang groups, with eight mice in each group. During the modeling, mice in the normoxia group were housed under standard oxygen concentrations, while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session, mice in the low-, medium-, and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses (8.1, 16.2, 32.4 g·kg-1·d-1 of crude drug, respectively), while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung tissue were evaluated using hematoxylin-eosin (HE) staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Protein expression of SFTPC, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), activating transcript factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue.ResultsCompared to those in the normoxia group, mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels increased, while SFTPC expression in lung tissue was reduced (P<0.05, P<0.01). The rate of apoptotic cells in lung tissue increased, and the expression of endoplasmic reticulum stress markers p-PERK, p-eIF2α, ATF4, and CHOP was upregulated (P<0.05, P<0.01). Compared with the CIH group, Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels were decreased, and lung tissue SFTPC expression was recovered (P<0.05, P<0.01). The apoptotic rate of lung tissue cells was significantly reduced, with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression (P<0.05, P<0.01). Activation and expression of p-PERK, p-eIF2α, ATF4, and CHOP were also decreased (P<0.05, P<0.01).ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion, which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.
关键词:Buzhong Yiqitang;intermittent hypoxia;endoplasmic reticulum stress;pulmonary surfactant-associated protein C
摘要:ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress (CUMS) and explore the mechanism from the histomorphology of frontal cortex, expression of key molecules in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway, and changes in monoamine neurotransmitter levels.MethodsSixty adult male SD rats were randomized into six groups (n=10): blank control, depression model, Chaihu Shugansan (3.3 g·kg-1·d-1), ferulic acid (50 mg·kg-1·d-1), Chaihu Shugansan (3.3 g·kg-1·d-1) + ferulic acid (50 mg·kg-1·d-1), and fluoxetine (2.1 mg·kg-1·d-1). Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used, including fasting with free access to water for 24 h, water deprivation with free access to food for 24 h, wetting the bedding with water in the cage, restraint for 3 h, tail clamping for 1 min, swimming in ice water at 4 ℃, and day and night reversal. Each stimulus was used 1 to 3 times, and the modeling lasted for a total of 21 days. At the same time of stimulation, rats in each medication group were treated with corresponding agents by gavage, while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test, sucrose preference test, and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium, and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF, TrkB, and cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex.ResultsCompared with the blank control group, the depression model group showed reduced body mass (P<0.05, P<0.01), decreased number of crossings and rearings in the open field test and sucrose preference (P<0.01), prolonged time of immobility in the forced swimming test (P<0.01), reduced neuronal cells, increased necrotic cells, and darkening cell staining in the frontal cortex, down-regulated mRNA and protein levels of BDNF, TrkB, CREB, and lowered levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Compared with the depression model group, each intervention group showed improved general state, increased body mass (P<0.05), increased number of crossings (P<0.05), shortened immobility time in the forced swimming test (P<0.01), increased neuronal cells, reduced necrotic cells, and lightened cellular staining in the frontal cortex, up-regulated mRNA and protein levels of BDNF, TrkB and CREB, and elevated levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Moreover, the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex (P<0.05). The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex (P<0.05), and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test, up-regulating the mRNA levels of BDNF, TrkB, and CREB and the protein levels of BDNF and CREB in the frontal cortex, and increasing the DA content in the frontal cortex (P<0.05).ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover, the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.
摘要:ObjectiveTo explore the regulatory effect and mechanism of Danggui Shaoyaosan combined with Yinchenhaotang on lipid metabolism in the mouse model of type 2 diabetes mellitus (T2DM) complicated with metabolic dysfunction-associated steatotic liver disease (MASLD) based on network pharmacology and animal experiments.MethodsTwenty-four MKR transgenic diabetic mice were randomly allocated into 4 groups: Model, low-dose (12.6 g·kg-1) Chinese medicine (concentrated decoction of Danggui Shaoyaosan combined with Yinchenhaotang), high-dose (25.2 g·kg-1) Chinese medicine, and Western medicine (metformin, 0.065 g·kg-1). Six FVB mice were used as the normal group. All groups were treated for 6 consecutive weeks. The mice in the drug treatment groups were administrated with corresponding agents by gavage, and those in the normal group and model group received the same volume of distilled water. Fasting blood glucose, body weight, liver weight, glucose tolerance, liver function indicators, blood lipid levels, and pathological changes in the liver were evaluated for each group. Network pharmacology was employed to analyze the targets and pathways of Danggui Shaoyaosan combined with Yinchenhaotang in the treatment of T2DM complicated with MASLD. Molecular biological techniques were used to verify the enriched key targets.ResultsCompared with the model group, each treatment group showed reduced fasting blood glucose, body weight, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and liver weight (P<0.01). The high-dose Chinese medicine group was superior to the low-dose group in reducing low-density lipoprotein (LDL), increasing high-density lipoprotein (HDL), and recovering glucose tolerance (AUC) and ALT (P<0.05), with the effect similar to that of the Western medicine group. Morphologically, Chinese medicine groups showed reduced lipid accumulation and alleviated pathological damage in the liver tissue, with the high-dose group demonstrating more significant changes. Network pharmacology results showed that Danggui Shaoyaosan combined with Yinchenhaotang may exert therapeutic effects through multiple targets such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), B-cell lymphoma-2 (Bcl-2), MYC oncogene (MYC), and interleukin-1β (IL-1β). Western blot showed that compared with the model group, the treatment groups demonstrated down-regulated protein levels of FAS and ACC (P<0.01) and up-regulated protein levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and UCP1 (P<0.01). Compared with the low-dose Chinese medicine group, the high-dose Chinese medicine group exhibited down-regulated protein levels of FAS and ACC and up-regulated protein levels of PGC-1α and UCP1 (P<0.05).ConclusionDanggui Shaoyaosan combined with Yinchenhaotang has the effect of ameliorating T2DM complicated with MASLD and can improve the liver lipid metabolism by up-regulating the protein levels of Fas and ACC and down-regulating the protein levels of PGC-1α and UCP1.
摘要:ObjectiveTo investigate the effect and mechanism of Bukan Yilidan on perimenopausal psycho-cardiac disease by mitochondrial autophagy mediated by dynamin-related protein 1(Drp1)/phosphatase and tensin homolog(PTEN) induced putative kinase 1(PINK1)/Parkin pathway.MethodsSixty rats were randomly divided into the blank group, model group, western medicine group(isosorbide mononitrate 7.2 mg·kg-1+sertraline hydrochloride tablets 18 mg·kg-1), Bukan Yilidan low, medium and high dose groups(2.59, 5.18, 10.35 g·kg-1), with 10 rats in each group. Except for the blank group, the rat model of perimenopausal psycho-cardiac disease was prepared by ovariectomy(OVX) combined with high-fat feeding, chronic unpredictable mild stress(CUMS) and subcutaneous multi-point injection of isoproterenol hydrochloride. After successful modeling, the general state and tongue image of rats were observed. The depression status of rats in vivo was evaluated by open field test, sucrose preference test, forced swimming immobility time and grip strength value, and the cardiac function of rats was evaluated by electrocardiogram and echocardiography. The levels of serum norepinephrine(NE), dopamine(DA) and 5-hydroxytryptamine(5-HT) were detected by enzyme-linked immunosorbent assay(ELISA), and biochemical detection was used to assess myocardial injury by measuring serum levels of high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglyceride(TG), total cholesterol(TC), aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH) and creatine kinase isoenzyme(CK-MB). Hematoxylin-eosin(HE) and Nissl staining were used to observe the pathological status of hippocampus and myocardial tissue in rats, the status of mitophagosomes in hippocampus and myocardium was observed by transmission electron microscope(TEM), and Western blot was used to detect the contents of Drp1, mitochondrial fusion protein 2(Mfn2), optic atrophy protein 1(OPA1), PINK1, Parkin, p62 and microtubule-associated protein light chain 3B(LC3B) in hippocampus and myocardium.ResultsCompared with the blank group, the food intake and water intake of rats in the model group decreased, the hair was dark yellow, the gloss and smoothness decreased, the spirit was depressed, the tongue was light purple or dark purple, accompanied by petechiae or ecchymosis, the sublingual collaterals were purple and black, and the tongue coating was white and smooth. The indexes of open field test, grip strength and sucrose preference of rats decreased significantly, and the immobility time of forced swimming increased significantly(P<0.01). Electrocardiogram and echocardiography showed that ST segment was significantly depressed, and left ventricular fractional shortening(LVFS) and left ventricular ejection fraction(LVEF) were significantly decreased(P<0.05, P<0.01). Pathological observation showed that the number of hippocampal neurons and myocardial cells decreased, and the structural damage was obvious. The levels of serum TC, TG, LDL-C, CK-MB, LDH, AST and ALT increased, while the levels of HDL-C, 5-HT, DA and NE decreased(P<0.05, P<0.01). TEM showed obvious mitochondrial damage in hippocampus and myocardial tissue. The protein expressions of Drp1, PINK1, Parkin and p62 in hippocampus and myocardium were increased, while the protein expressions of OPA1, Mfn2 and LC3BⅡ/Ⅰ were decreased(P<0.05, P<0.01). Compared with the model group, the mental state, body curling up, fear of cold and other symptoms of rats in each administration group were improved, and the degree of pale purple or dark purple tongue was reduced. The scores of open field test, grip strength, sucrose preference, LVFS and LVEF were increased, and the immobility time of forced swimming was shortened(P<0.05, P<0.01). The ST segment of electrocardiogram had a significant recovery(P<0.01), pathological observation showed that the damage of nerve cells and myocardial tissue was improved. The levels of serum TC, TG, LDL-C, CK-MB, LDH, AST and ALT decreased, while the levels of HDL-C, 5-HT, DA and NE increased(P<0.05, P<0.01). TEM showed that mitochondrial damage was reduced in hippocampal neurons and cardiomyocytes with visible mitochondrial autophagosomes. The protein expressions of Drp1, PINK1, Parkin and p62 in hippocampus and myocardium were decreased, while the protein expressions of OPA1, Mfn2 and LC3BⅡ/Ⅰ were increased(P<0.05, P<0.01).ConclusionBukan Yilidan can alleviate depression, lipid metabolism disorder and myocardial ischemia injury in rats with perimenopausal psycho-cardiac disease, and its mechanism may be related to inhibiting Drp1/PINK1/Parkin signaling pathway and enhancing mitochondrial autophagy.
关键词:perimenopausal psycho-cardiac disease;Yang deficiency of heart and kidneys;Bukan Yilidan;mitochondrial autophagy;mitochondrial dynamics;dynamin-related protein 1(Drp1)/phosphatase and tensin homolog(PTEN) induced putative kinase 1(PINK1)/Parkin pathway
摘要:ObjectiveTo explore the effect and mechanism of modified Dingjingtang in regulating the Toll-like receptor 2 (TLR2)/nuclear factor (NF)-κB/NOD-like receptor protein 3 (NLRP3) signaling pathway to inhibit inflammatory skin lesions in the rat model of acne.MethodsForty-eight rats were randomized into the normal, model, low-, medium-, and high-dose (8.1, 16.2, and 32.4 g·kg-1) modified Dingjingtang, and doxycycline hydrochloride (0.27 g·kg-1) groups, with 8 rats in each group. Rats in other groups except the normal group were modeled by intradermal injection and intraperitoneal injection of Propionibacterium acnes. After successful modeling, rats in the intervention groups were treated with corresponding agents by gavage, and those in the normal and model groups with an equal volume of normal saline, once a day for 14 consecutive days. Then, the samples were collected. The general conditions, ear thickness, and body weight changes of rats were observed. Biochemical methods were used to determine superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the ear tissue. Hematoxylin-eosin staining and Masson's staining were used to observe the pathological changes and collagen deposition, respectively, in the ear tissue. Immunohistochemistry was employed to determine the interleukin (IL)-1β level in the ear tissue. Enzyme-linked immunosorbent assay was adopted to measure the levels of IL-1β, tumor necrosis factor (TNF)-α, and IL-6 in the serum. The total antioxidant capacity method was adopted to assess the reactive oxygen species (ROS) content in the ear tissue. Western blot and real-time fluorescence quantitative polymerase chain reaction were employed to determine the protein and mRNA levels, respectively, of TLR2, myeloid differentiation factor 88 (MyD88), NF-κB, NLRP3, and cysteinyl aspartate-specific proteinase-1 (Caspase-1) in the ear tissue.ResultsCompared with the normal group, the model group had increased ear skin thickness (P<0.01), elevated ROS and MDA levels (P<0.01), reduced SOD content (P<0.05), and increased collagen deposition (P<0.01) in the ear tissue. In addition, the model group showed raised IL-1β, IL-6, and TNF-α levels in the serum (P<0.01) and up-regulated mRNA and protein levels of TLR2, MyD88, NF-κB, NLRP3, and Caspase-1 (P<0.01). Compared with the model group, the high- and medium-dose modified Dingjingtang groups showed significant improving effects regarding the above indicators (P<0.05, P<0.01).ConclusionModified Dingjingtang can ameliorate the inflammatory skin lesions in the rat model of acne by regulating the TLR2/NF-κB/NLRP3 signaling pathway.
关键词:modified Dingjingtang;Toll-like receptor 2 (TLR2)/nuclear factor (NF)-κB/NOD-like receptor protein 3 (NLRP3) signaling pathway;rat model of acne;inflammatory skin lesions;antioxidant capacity
摘要:ObjectiveTo investigate how Xiaoyao Shukun decoction (XYSKD) regulates the formation and release of neutrophil extracellular traps (NETs) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, thereby reducing inflammation, inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue, decreasing adhesion and fibrosis, and repairing the tissue damage in sequelae of pelvic inflammatory disease (SPID).MethodsA total of 84 Wistar rats were randomly allocated into seven groups: blank, model, XYSKD (8 mg·kg-1), mTOR agonist (10 mg·kg-1), mTOR agonist + XYSKD (10 mg·kg-1+8 mg·kg-1), mTOR inhibitor (2 mg·kg-1), and mTOR inhibitor + XYSKD (2 mg·kg-1+8 mg·kg-1). The rat model of SPID was constructed by starvation, fatigue, and ascending Escherichia coli infection. After 14 days of drug intervention, the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus, fallopian tube, and ovary was observed by laparotomy. The levels of interleukin-1β (IL-1β), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay (ELISA). The expression of myeloperoxidase (MPO) and citrullinated histone 3 (H3) in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR) were employed to determine the relative protein and mRNA levels, respectively, of neutrophil elastase (NE), intercellular adhesion molecule-1 (CD54), α-smooth muscle actin (α-SMA), H3, PI3K, and Akt.ResultsCompared with the blank group, the model group presented a large number of collagen fibers in bundles, numerous cytoplasmic folds of fibroblasts, reduced or absent mitochondrial cristae, and disordered and expanded endoplasmic reticulum. By laparotomy, extensive pelvic congestion, connective tissue hyperplasia, thickening and hardening of the tubal end near the uterus, and tubal and ovarian adhesion or cyst were observed in the model group. In addition, the model group showed raised levels of IL-1β, IL-17, and TNF-α in the peritoneal flushing fluid (P<0.01), increased average fluorescence intensities of MPO and H3 (P<0.01), and up-regulated protein and mRNA levels of NE, H3, CD54, PI3K, and Akt (P<0.01). Compared with the model group, the mTOR agonist group showed increased fibroblasts and cytoplasmic folds, absence of mitochondrial cristae, endoplasmic reticulum dilation, and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine, fallopian tube, and ovarian tissues. The levels of IL-1β, IL-17, and TNF-α in the peritoneal lavage fluid elevated (P<0.01) and the average fluorescence intensities of MPO and H3 enhanced (P<0.01) in the mTOR agonist group. In contrast, the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers, alleviated mitochondrial crista loss and endoplasmic reticulum dilation, improved morphology and appearance of the uterine, fallopian tube, and ovarian tissues, lowered levels of IL-1β, IL-17, and TNF-α in the peritoneal lavage fluid (P<0.01), decreased average fluorescence intensities of MPO and H3 (P<0.01), and down-regulated protein and mRNA levels of NE, H3, CD54, PI3K, and Akt (P<0.05). Compared with the mTOR agonist group, the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue, declined levels of IL-1β, IL-17, and TNF-α (P<0.01), decreased average fluorescence intensities of MPO and H3 (P<0.01), and down-regulated protein levels of NE, H3, CD54, α-SMA, p-PI3K/PI3K, and p-Akt/Akt (P<0.01) and mRNA levels of NE, H3, CD54, α-SMA, PI3K, and Akt (P<0.01). Compared with the mTOR inhibitor group, the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue, reduced levels of IL-1β, IL-17, and TNF-α (P<0.01), decreased average fluorescence intensities of MPO and H3 (P<0.01), and down-regulated protein and mRNA levels of NE and CD54 (P<0.05).ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue, thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β, IL-17, and TNF-α and down-regulating the expression of NE, H3, CD54, α-SMA, PI3K, and Akt in the pelvic adhesion tissue.
关键词:Xiaoyao Shukun decoction;sequelae of pelvic inflammatory disease;neutrophil extracellular traps;phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway;fibrosis
摘要:ObjectiveTo observe the effect of Shenshu Fujian decoction on platelet-derived growth factor (PDGF)/naked cuticle homolog 2 (NKD2) /Wnt signaling pathway in rats with chronic renal failure (CRF).MethodsSixty male SD rats were randomly divided into normal group, model group, Niaoduqing group (5 g·kg-1), low-dose Shenshu Fujian decoction group (5.5 g·kg-1), medium-dose Shenshu Fujian decoction group (11 g·kg-1), and high-dose Shenshu Fujian decoction group (22 g·kg-1), with 10 rats in each group. A CRF rat model was established by feeding a 0.5% adenine diet for 21 days. After successful modeling, intragastric administration was given once daily for 28 consecutive days. After treatment, the renal morphology of rats was observed. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected. Hematoxylin-eosin (HE) staining and Masson staining were used to detect renal histopathological changes, and collagen volume fraction (CVF) was calculated. Serum levels of inflammatory markers interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The expressions of fibronectin 1 (FN1), type Ⅰ collagen (ColⅠ), α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-β (PDGFR-β), NKD2, dishevelled protein 2 (DVL2) and β-catenin in renal tissue were detected by immunohistochemistry and Western blot.ResultsCompared with the normal group, the model group showed significant renal pathological changes, a markedly increased kidney weight/body weight ratio (P<0.01), significantly elevated CVF (P<0.01), and notably increased serum levels of SCr, BUN, IL-1β, and IL-6 (P<0.01). Expression levels of FN1, ColⅠ, α-SMA, PDGFR-β, NKD2, DVL2, and β-catenin in renal tissue were also significantly increased (P<0.01). Compared with the model group, all treatment groups showed significantly decreased kidney weight/body weight ratios and CVF (P<0.01), as well as markedly decreased serum SCr, BUN, IL-1β, and IL-6 levels. Protein expression levels of FN1, ColⅠ, α-SMA, PDGFR-β, NKD2, DVL2, and β-catenin in renal tissue were decreased, with more pronounced effects observed in the Niaoduqing, medium-dose, and high-dose Shenshu Fujian decoction groups (P<0.05, P<0.01).ConclusionShenshu Fujian decoction improves renal function, reduces inflammation, and reverses renal fibrosis in CRF rats, possibly by downregulating the expression of PDGF/NKD2/Wnt signaling pathway-related proteins.
摘要:ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B (NF-κB) in co-cultured peripheral blood mononuclear cells (PBMCs) and human fibroblast-like synoviocytes (FLSs) from patients with ankylosing spondylitis (AS).MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs, and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs, while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells(6.48 g·kg-1). To investigate the effect of HQC-containing serum on the viability of co-cultured cells, and the experiment was divided into the following groups based on the dilution concentration: blank group, 10% HQC group, 20% HQC group, and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group, the experiment was divided into three groups: normal group, model group, and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid, the experiment was divided into the following groups: blank group, si-NC group (with transfection reagent), si-circ_0001543-1 group (with transfection reagent and interference plasmid No. 1 targeting circ_0001543), si-circ_0001543-2 group (with transfection reagent and interference plasmid No. 2 targeting circ_0001543), and si-circ_0001543-3 group (with transfection reagent and interference plasmid No. 3 targeting circ_0001543).For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid, the experiment was divided into the following groups: blank group, OE-NC group (with transfection reagent), and OE-circ_0001543 group (with transfection reagent and overexpression plasmid targeting circ_0001543).To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group, the experiment was divided into the following groups: si-NC group, si-CircRNA_0001543 group, OE-NC group, and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin-1β (IL-1β), IL-10, IL-37, and tumor necrosis factor-α (TNF-α). Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to measure the expression of CircRNA_0001543, IκBα, and NF-κB p65.ResultsAfter 48 hours, 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs, which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the model group were significantly increased (P<0.01), while the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly decreased (P<0.01). Compared with those in the model group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased (P<0.05), and the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly increased (P<0.05), with the most prominent changes in the 30% drug-containing serum group (P<0.01). Compared with that in the si-NC group, the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group (P<0.01). Compared with that in the OE-NC group, the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group (P<0.01), indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules, si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α and decreased the expressions of IL-10 and IL-37 (P<0.01). In contrast, OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α (P<0.01) and increased the expressions of IL-10 and IL-37 (P<0.01).ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543, regulating the NF-κB pathway, suppressing pro-inflammatory cytokines, and enhancing anti-inflammatory cytokine expression.
SHI Peizheng, XIAO Shanshan, ZHANG Xinjiang, NIE Yixiang, WANG Xianchao, HUANG Jing, MEI Jie, LAN Huaquan, JI Tuanyun, ZHANG Tianyi, WEI Xiaoyong, YANG Qiaohong
摘要:ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide (APS) on inhibitor of differentiation1 (ID1) and protein kinase B (Akt) in gastric cancer.MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625, 1.25, 2.5, 5, 10, 20 mg·L-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8(CCK-8) method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer, gastric tumor, and stomach cancer were searched against GeneCards, UniProt, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets, and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR, respectively.ResultsCompared with the adjacent normal gastric tissue, the gastric adenocarcinoma tissue showed increased positive expression of ID1 (χ2 =81.00, P<0.01). Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase (PI3K) /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil (0.1 mg·L-1) and APS (10, 20 mg·L-1) groups showed decreased cell proliferation, migration, and colony formation. Compared with the control group, 10, 20 mg·L-1 APS inhibited the proliferation of MGC-803 cells (P<0.01), with 10 mg·L-1 APS demonstrating stronger inhibitory effect. In addition, APS at 10, 20 mg·L-1 inhibited the migration (P<0.01) and colony formation (P<0.05, P<0.01) of MGC-803 cells. Compared with the control group, APS at 10, 20 mg·L-1 down-regulated the protein levels of ID1 (P<0.01) and Akt (P<0.05) and the mRNA levels of ID1 (P<0.05, P<0.01) and Akt (P<0.05, P<0.01) in MGC-803 cells.ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue, which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects, which is expected to provide new therapeutic targets for gastric cancer treatment.
关键词:gastric cancer;Astragali Radix polysaccharide;inhibitor of differentiation1 (ID1);protein kinase B (Akt);proliferation;migration
摘要:ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction (SWD) at different doses on atherosclerosis (AS) in a mouse model induced by a high-fat diet and analyze its potential mechanism of action.MethodsThirty-six male ApoE-/- mice were randomly divided into six groups: blank control group, model group, low-dose, medium-dose, and high-dose SWD groups, and positive control group. Firstly, the AS mouse model was created by feeding mice a high-fat diet. After successful modeling, the low-, medium-, and high-dose SWD groups were intragastrically administered with SWD at 0.65, 1.3, 2.6 g·kg-1, respectively. The positive control group was intragastrically administered with 30 mg·kg-1 of atorvastatin calcium aqueous solution, while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage, all administered for 12 weeks. During the administration period, the general condition of the mice was observed and recorded daily. Before sampling, color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in aortic tissue in mice, and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum lipid indices and the levels of interleukins (IL-1β, IL-4, IL-6, and IL-10) and tumor necrosis factor-α (TNF-α) in mice. Protein expression levels of IKKα, IKKβ, and NF-κB p65 in mouse aortic tissue were detected by Western blot.ResultsCompared with the blank control group, the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo, suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation, fibrous connective tissue proliferation, and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue (P<0.01). ELISA results indicated significantly elevated levels of IL-1β, IL-6, TNF-α, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) in mouse serum (P<0.01), as well as significantly decreased levels of IL-4, IL-10, and high-density lipoprotein (HDL) (P<0.01). Western blot results showed that the expression of IKKα, IKKβ, and NF-κB p65 in mouse aortic tissue increased significantly (P<0.01). Compared with those in the model group, mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group, the aortic vascular wall echoes were weakened, and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD (P<0.05). In the medium-dose SWD group, serum levels of IL-1β, IL-6, TNF-α, TC, TG, and LDL were significantly decreased (P<0.05, P<0.01), while those of IL-4 and IL-10 were significantly increased (P<0.01). In the high-dose SWD group, levels of IL-1β, IL-6, TNF-α, TC, TG, and LDL were significantly decreased (P<0.01), while IL-4, IL-10, and HDL were significantly increased (P<0.01). The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group (P<0.05), and IKKα, IKKβ, and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups (P<0.05, P<0.01).ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway, thereby reducing inflammation, plaque area, and lipid content in the body.
摘要:ObjectiveThis study aims to observe the effect of sinomenine (SIN) on fatty acid binding protein 4 (FABP4) in synovial tissue of rats with osteoarthritis (OA) and investigate the therapeutic mechanism of SIN on OA, further providing new ideas for the management of osteoarthritis by traditional Chinese medicine (TCM).MethodsAn OA rat model was constructed and randomly divided into a control group, an OA group, an OA + SIN-L group (50 mg·kg-1), an OA + SIN-M (100 mg·kg-1), an OA + SIN-H (200 mg·kg-1), and an OA + prednisone (PDN) group (5 mg·kg-1). Following surgical modeling for three weeks, an appropriate medication was administered for four weeks. During modeling and administration, a hot plate test was performed to detect the pain and swelling of the knee joints of the rats. The periarticular tissue was collected for arthropathological observation at the end of drug administration. The expression of cleaved Caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and FABP4 in the synovial tissue of rats was detected by Western blot and real-time quantitative polymerase chain reaction (Real-time PCR), and the expression and distribution of FABP4 protein in the synovial membrane were detected by immunofluorescence.ResultsCompared with those in the control group, the levels of inflammatory factors and FABP4 in the serum of rats in the OA group were significantly increased (P<0.05, P<0.01), and joint swelling was significantly elevated (P<0.01). The thermal pain threshold was significantly reduced (P<0.01), and the expression of FABP4 protein and the fluorescence intensity were significantly increased (P<0.01). The synovial tissue exhibited significantly increased inflammatory infiltration, proliferated fibroblasts, and an elevated apoptotic index (P<0.05, P<0.01). Compared with those in the OA group, the serum lipid metabolism indexes of rats in the SIN administration group gradually returned to normal (P<0.05, P<0.01), while the levels of inflammatory factors and FABP4 in the serum of rats in the SIN-administered group were significantly reduced (P<0.05, P<0.01), and joint swelling was significantly decreased (P<0.05, P<0.01). The thermal pain threshold was significantly elevated (P<0.05, P<0.01), and the expression of FABP4 protein and fluorescence intensity in the synovial tissue were significantly decreased (P<0.05, P<0.01). The synovial tissue displayed significantly reduced inflammatory infiltration and a decreased apoptotic index (P<0.05, P<0.01).ConclusionThe therapeutic effect of SIN on OA may be related to the down-regulation of FABP4 expression, reduction of apoptosis, and inhibition of inflammatory factor expression.
关键词:sinomenine;osteoarthritis;obesity;synovial tissue;fatty acid binding protein 4 (FABP4)
摘要:ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease (WD) through bioinformatics analysis and clinical validation,providing implications and directions for the diagnosis and treatment of WD.Methods(1) Screening of target genes: The differentially expressed genes (DEGs) between WD and healthy control were obtained from GeneCards,and the cuproptosis-related genes were obtained from Gene Expression Omnibus (GEO) and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses,the specific biological process,functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.(2)Validation of target genes: The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR.Results(1) A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO,and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection,including three up-related genes(SQSTM1,MIF1,and TAX1BP1) and nine down-regulated genes(CP,SERPINE1,AOC3,GPX4,SLC27A5,VEGF-A,PDHB,PDK1,and ATP7B).The common target genes were mainly enriched in monocarboxylic acid metabolism,oxidoreductase activity,negative regulation of molecular functions,which mainly involved HIF-1,ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1,SERPINE1,VEGFA,and AOC3 in WD.(2)A total of 30 blood samples were collected,including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers,WD patients had down-regulated mRNA levels of SERPINE1,GPX4,SLC27A5,and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1(P<0.05).ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD,which can provide a new target for the diagnosis and treatment of WD.
摘要:Hepatolenticular degeneration, also known as Wilson disease (WD), is a hereditary disease caused by mutations in the ATP7B gene, leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein, and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs, ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin, this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease, and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis, this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.
关键词:renal injury in Wilson Disease;kidney collaterals;latent toxin;etiology;pathogenesis;treatment
摘要:ObjectiveTo study the correlations between traditional Chinese medicine (TCM) syndromes and lipid metabolism in children with Wilson disease (WD).MethodsClinical data and lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein a (Lpa)] were retrospectively collected from 341 children with WD. The clinical data were compared among WD children with different syndromes, and the correlations between TCM syndromes and lipid metabolism in children with WD were analyzed. Least absolute shrinkage and selection operator (LASSO) regression was used for variable screening, and unordered multinomial Logistic regression was employed to analyze the effects of lipid metabolism indicators on TCM syndromes.ResultsThe 341 children with WD included 121 (35.5%) children with the dampness-heat accumulation syndrome, 103 (30.2%) children with the liver-kidney Yin deficiency syndrome, 68 children with the combined phlegm and stasis syndrome, 29 children with the spleen-kidney Yang deficiency syndrome, and 20 children with the liver qi stagnation syndrome. The liver-kidney Yin deficiency syndrome, combined phlegm and stasis syndrome, and spleen-kidney Yang deficiency syndrome had correlations with the levels of lipid metabolism indicators (P<0.05). Lipid metabolism abnormalities occurred in 232 (68.0%) children, including hypertriglyceridemia (108), hypercholesterolemia (23), mixed hyperlipidemia (67), lipoprotein a-hyperlipoproteinemia (12), and hypo-HDL-cholesterolemia (22). The percentages of hypertriglyceridemia and hypo-HDL-cholesterolemia varied among children with different TCM syndromes (P<0.05). Correlations existed for the liver-kidney Yin deficiency syndrome with TG, TC, and HDL-C, the combined phlegm and stasis syndrome with TG, the spleen-kidney Yang deficiency syndrome with TG, TC, and LDL-C, and the liver Qi stagnation syndrome with TC and LDL-C (P<0.05, P<0.01).ConclusionThe TCM syndromes of children with WD are dominated by the dampness-heat accumulation syndrome and the liver-kidney Yin deficiency syndrome, and dyslipidemia in the children with WD is dominated by hypertriglyceridemia and mixed hyperlipidemia. There are different correlations between TCM syndromes and lipid metabolism indicators, among which TG, TC, LDL-C, and HDL-C could assist in identifying TCM syndromes in children with WD.
关键词:Wilson disease;children;traditional Chinese medicine (TCM) syndrome;lipid metabolism;correlation
摘要:ObjectiveThis paper aims to use the digital muscle function assessment system Myoton PRO to assess the correlation between muscle tension,clinical characteristics, and traditional Chinese medicine(TCM) syndromes in patients with hepatolenticular degeneration [also known as Wilson disease(WD)].MethodsA total of 104 patients with WD accompanied by abnormal muscle tension(increased or decreased,hereinafter the same) who were hospitalized in the Brain Disease Centre of the First Affiliated Hospital of Anhui University of Chinese Medicine from April 2021 to November 2023 were selected,all of whom were subjected to TCM syndrome diagnosis and Myoton PRO for the measurement of F value of muscle tension,Goldstein, and UWDRS-N scales. The age of onset of the disease and disease duration were analyzed,and the differences and correlations of the above indexes in different TCM syndromes of WD were analyzedResultsAmong the 104 patients with WD ,the phlegm and stasis syndrome was the most common(60 patients),followed by the damp-heat syndrome(33 patients),and the least common was the liver-kidney Yin deficiency syndrome(11 patients). The F value of the phlegm and stasis syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group(P<0.01). The F value of the damp-heat syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group(P<0.05),and the F value of the lower limbs of each group was higher than that of the upper limbs(P<0.01). Goldstein and UWDRS-N scores of the patients in the phlegm and stasis syndrome group were higher than those in the damp-heat syndrome group and the liver-kidney Yin deficiency syndrome group(P<0.05). There was no significant difference between the Goldstein and UWDRS-N scores of patients in the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group. Correlation analysis revealed that the age of onset and duration of the disease were positively correlated with the F values of the lower limbs(r=0.20,P<0.05,r=0.38,P<0.01)and had no significant correlation with those of the upper limbs. The F value levels of muscle tension of all limbs in the three groups of patients were positively correlated with the Goldstein and UWDRS-N scores(muscle tension of the upper limbs in the phlegm and stasis syndrome group,r=0.36,P<0.01,r=0.42,P<0.01. muscle tension of the lower limbs in the phlegm and stasis syndrome group,r=0.70,P<0.01,r=0.60,P<0.01. muscle tension of the upper limbs in the damp-heat syndrome group,r=0.64,P<0.01,r=0.53,P<0.01. muscle tension of the lower limbs in the damp-heat syndrome group,r=0.59,P<0.01,r=0.70,P<0.01. muscle tension of the upper limbs in the liver-kidney Yin deficiency syndrome group,r=0.70,P<0.01,r=0.74,P<0.01. muscle tension of the lower limbs in the liver-kidney Yin deficiency syndrome group,r=0.85,P<0.01,r=0.62,P<0.01). Conlusion: The digital muscle function assessment system Myoton PRO can objectively evaluate the muscle tension level of patients with WD accompanied by abnormal muscle tension. This level has significant differences among different TCM syndromes and can evaluate the patient's condition to some extent.
关键词:Wilson disease;muscle tension;traditional Chinese medicine(TCM)syndrome;Myoton PRO;correlation
摘要:ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation (NMES) in the treatment of dysphagia in Wilson disease (WD) with combined phlegm and stasis.MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy, the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group, with 40 patients in each group. In addition, 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days, and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study (VFSS) before and after treatment. During the examination, contrast agents with 4 different characters were used for the swallowing action, and the passing time was recorded. The TCM syndrome score, water swallow test score, standard swallowing assessment (SSA) score, and 24-h urinary copper level before and after treatment were analyzed.ResultsWhen performing VFSS, the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group (P<0.01), while it had no significant difference in the pharyngeal stage. After treatment, the passing time in the oral stage shortened in the control and observation groups (P<0.01), and the observation group outperformed the control group (P<0.01). After treatment, both the control and observation groups showed declines in TCM syndrome score and SSA score (P<0.01) and an increase in water swallow test score (P<0.01), and the changes were more obvious in the observation group than in the control group (P<0.01). In addition, the treatment in the control and observation groups elevated the 24-h urinary copper level (P<0.01), and the elevation in the observation group was more obvious than that in the control group (P<0.01). Neither group showed obvious adverse reaction.ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score, water swallow test score, and SSA score, demonstrating definite clinical efficacy and high safety.
关键词:Wilson disease;syndrome of combined phlegm and stasis;dysphagia;neuromuscular electrical stimulation;Gandouling decoction
摘要:ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang (DGLHT) on patients with type 2 diabetes mellitus (T2DM) complicated by atherosclerotic cardiovascular disease (ASCVD) at high risk, focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation (FMD), atherogenic index of plasma (AIP), and triglyceride-glucose index (TyG), and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B (MyD88/NF-κB) signaling pathway.MethodsThe clinical study was a single-center, double-blind, and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT, while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks, with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD, AIP, TyG, and small dense low-density lipoprotein cholesterol (sdLDL-C) index were compared. Human umbilical vein endothelial cells (HUVECs) were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction (Real-time PCR) and Western blot .ResultsAfter 12 weeks of treatment, the AIP in the treatment group significantly decreased compared with that before the treatment (P<0.05). Compared with the control group, the treatment group showed significant improvements in FMD and TyG (P<0.05). Additionally, the treatment group demonstrated significant reductions in two-hour postprandial glucose (2 hPG), glycated albumin (GA), triglycerides (TG), apolipoprotein E (Apo E), and sdLDL-C (P<0.05). Analysis of traditional Chinese medicine (TCM) syndrome efficacy indicated that in the treatment group, Yin deficiency and fire excess syndromes, including dry throat and mouth (P<0.05), excessive thirst (P<0.01), tidal fever and night sweats (P<0.05), and dry stools (P<0.05), improved. Compared with the control group, the treatment group showed significant improvements in symptoms of dry throat and mouth (P<0.05) and excessive thirst (P<0.01). TCM syndrome scores significantly decreased (P<0.01), and the overall efficacy rate was 56.67%, significantly higher than the 10.34% observed in the control group (P<0.01). At the cellular level, increasing concentrations of DGLHT led to decreased messenger ribonucleic acid (mRNA) levels of pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1β) in lipopolysaccharide (LPS)-stimulated HUVECs (P<0.01), with significant reductions in the high-concentration group (P<0.01). DGLHT may inhibit the expressions of MyD88 and phosphorylated (p)-NF-κB p65 proteins in a concentration-dependent manner.ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.
摘要:ObjectiveTo investigate the characteristics and distribution of traditional Chinese medicine (TCM) syndromes in the patients with esophageal squamous cell carcinoma (ESCC).MethodsAn electronic questionnaire was developed to collect the general data and four examination information of ESCC patients treated in 10 areas with high incidence of esophageal cancer in China from June 2020 to March 2021. Multiple analyses including frequency analysis, factor analysis, and hierarchical cluster analysis were performed to analyze the potential syndrome elements, disease location, and common syndromes of ESCC.ResultsA total of 2 027 patients with ESCC were included. Statistical analysis was performed on 113 symptoms, physical signs, 33 tongue manifestation variables, and 23 pulse manifestation variables of the patients’ four examination information. Factor analysis was performed on 55 variables with frequency>10%, extracting 19 common factors. According to clinical experience and expert opinions, the main lesions of patients with ESCC were in the spleen and stomach, and the main syndrome elements were Qi stagnation, blood stasis, phlegm, dampness, and Qi deficiency, with the syndrome element combination of phlegm obstruction + Qi stagnation + blood stasis being the most common. The syndromes can be classified into four categories of liver-stomach disharmony + combined phlegm and Qi obstruction, kidney-spleen dysfunction + combined phlegm and stasis, spleen-kidney Yang deficiency + obstinate phlegm and blood stasis, and liver-kidney Yin deficiency + obstinate phlegm and blood stasis. The main syndrome of ESCC was liver-stomach disharmony + combined phlegm and Qi obstruction in the early stage, liver-spleen dysfunction + combined phlegm and stasis in the middle stage, and spleen-kidney Yang deficiency + obstinate phlegm and blood stasis in the late stage.ConclusionESCC mainly has main pathological features of internal deficiency and external excess and combined deficiency and excess, with the key syndrome elements being phlegm obstruction, Qi stagnation, and blood stasis. The main disease locations are in the spleen and stomach, involving the liver, kidney, chest and diaphragm, heart, and lung. The main syndrome is liver-stomach disharmony + combined phlegm and Qi obstruction. In clinical practice, it is necessary to grasp the pathogenesis dynamics of the disease and use prescriptions according to patients’ syndromes.
关键词:esophageal squamous cell carcinoma;syndrome elements;etiology and pathogenesis;syndrome differentiation and classification;traditional Chinese medicine syndrome
摘要:ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules(Zhuye Shigaotang) based on fingerprint and determination of index components, and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome.MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography(HPLC), and the methods for determination of total calcium, orientin, isoorientin, ginsenosides Rg1, Re and Rb1 and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group, model group, Zhuye Shigao granules low, medium and high dose groups(9.3, 18.6, 37.2 g·kg-1·d-1), with 10 mice in each group. In addition to the blank group, the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose, while the blank group and model group were given the same volume of normal saline by gavage. Then, the body temperature and organ index of mice in each group were measured, hematoxylin-eosin(HE) staining was used to investigate the lung tissue injury of mice in each group, and enzyme-linked immunosorbent assay(ELISA) was used to detect the changes of tumor necrosis factor-α(TNF-α), interleukin(IL)-lβ, IL-6, IL-10 levels in serum and lung tissue, as well as immunoglobulin(Ig)A and IgM levels in serum.ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950, and 20 common peaks were calibrated. Seven of them were identified, including peak 11(isoorientin), peak 12(orientin), peak 14(apioside liquiritin), peak 15(liquiritin), peak 17(apioside isoliquiritin), peak 19(isoliquiritin) and peak 20(liquiritigenin). The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows:Total calcium of 9.978-11.294 mg·g-1, isoorientin of 0.033-0.041 mg·g-1, orientin of 0.046-0.055 mg·g-1, ginsenoside Rg1+ginsenoside Re of 0.748-0.762 mg·g-1, ginsenoside Rb1 of 0.151-0.197 mg·g-1, liquiritin of 1.106-1.366 mg·g-1, glycyrrhizic acid of 0.904-1.182 mg·g-1. Compared with the blank group, the body temperature of mice in the model group was significantly increased, the organ indexes of liver, lung and spleen were significantly decreased, the organ index of thymus was significantly increased, HE staining of lung tissue showed infiltration of inflammatory cells, a small amount of serous exudation was observed in the alveoli, and lung tissue was damaged. After the intervention of Zhuye Shigao granules, the pathological changes were improved compared with the model group. The expression levels of IL-1β, IL-6 and TNF-α were significantly increased, the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased(P<0.01). Compared with the model group, the body temperature, the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced(P<0.05, P<0.01).ConclusionIn this study, the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components, and the fingerprint of four herbs(Lophatheri Herba, Ophiopogonis Radix, Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma) in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.
摘要:ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma, and to reveal the change law of its material basis.MethodsHigh performance liquid chromatography(HPLC) was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces, and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside, chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics, the contents and quantity ratio relationships of the glycosides, aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed, and the partial least squares-discriminant analysis(PLS-DA) and cluster analysis of the main components in different steaming times were conducted, the statistically significant differential markers were selected with the variable importance in the projection(VIP) value>1.ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma, there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times, the anthraquinone glycosides and aglycones could be roughly divided into three stages, including rapid change stage, fluctuation change stage and stable stage, and the total amount of tannins showed a decreasing trend. However, the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes, while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening, it was found that chrysophanol, emodin, chrysophanol-8-O-β-D-glucoside, rhein, physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times.ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb, which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.
关键词:Rhei Radix et Rhizoma;nine-time repeating steaming and sun-drying;material basis;processing methods;processing principle;characteristic chromatogram;chemometrics
摘要:ObjectiveTo investigate the bacterial diversity in the rhizosphere soil and phyllosphere of Angelica sinensis and examine the effects of foliar applications of a composite bacterial agent,salicylic acid,and coronatine on the bacterial diversity,disease incidence,and plant yield,thus providing a theoretical basis and guidance for the artificial construction of functional minimal communities and the regulation of rhizosphere through foliar treatments.MethodsUnder continuous cropping conditions in the field,foliar applications of a composite bacterial agent,salicylic acid,coronatine,and sterile water were conducted. The 100-plant weight was measured via the conventional method,and the incidence of diseases was recorded. The microbial community composition,diversity,and inter-group differences in the phyllosphere and rhizosphere soil of A. sinensis were analyzed by 16S high-throughput sequencing,and the potential microbial functions were predicted.ResultsCompared with the blank control,foliar applications of salicylic acid and coronatine both significantly reduced the yield and root rot incidence of A. sinensis. The foliar application of salicylic acid decreased the content of ferulic acid and increased that of ligustilide. The foliar application of coronatine increased the content of both ferulic acid and ligustilide. The microbial communities and functions in the phyllosphere and rhizosphere soil were significantly different. The phyllosphere had lower microbial diversity,with all bacteria being Gram-negative,mainly Cyanobacteria and Proteobacteria with limited functions. The rhizosphere soil had higher microbial diversity,harboring dominant phyla including Proteobacteria,Actinobacteria,Acidobacteria,and Bacteroidetes with rich functions. All foliar treatments regulated the microbial community in the rhizosphere soil,with a more significant effect on the microbial community in the rhizosphere soil than that in the phyllosphere. The coronatine treatment significantly reduced the abundance of Proteobacteria and nitrate-reducing and aromatic compound-degrading microorganisms in the rhizosphere soil,thus affecting nutrient cycling and autotoxic substance degradation and leading to a yield reduction. Compared with the salicylic acid treatment,the coronatine treatment significantly increased the abundance of Bacillus and Streptomyces in the rhizosphere soil,demonstrating enhanced disease control efficacy.ConclusionFoliar application of coronatine and salicylic acid can significantly regulate the composition and function of bacterial communities in the rhizosphere soil,thereby reducing the disease incidence and the plant yield.
关键词:Angelica sinensis;16S high-throughput sequencing;phyllosphere and rhizosphere;Paenibacillus polymyxa;Bacillus subtilis
摘要:ObjectiveTo investigate the effects of foliar fertilizer of nano-calcium carbonate and calcium nitrate tetrahydrate on the agronomic traits, carbohydrate and endogenous hormone contents of Dendrobium officinale planted for 1 year under greenhouse cultivation, in order to provide scientific basis for fertilization to improve the yield and quality of D. officinale.MethodsSingle-factor experimental design was adopted. Starting from early spring, D. officinale was treated with foliar spraying according to corresponding fertilizers. Three treatment groups were established based on different fertilizers, namely, a blank group(clear water), a nano-calcium carbonate group(0.727 g·L-1 nano-calcium carbonate water-soluble fertilizer), and a calcium nitrate tetrahydrate group(1.091 g·L-1 calcium nitrate tetrahydrate water-soluble fertilizer). The frequency of spraying was three times per month, and the entire treatment process lasted for nine months. The effects of various treatments on the traits and relative chlorophyll content of D. officinale were dynamically monitored. Sampling was conducted at three specific time points:August 2, 2023, September 8, 2023, and November 1, 2023, respectively. The contents of glucose and mannose in D. officinale stems were determined by high performance liquid chromatography(HPLC), the content of soluble sugars in D. officinale stems and leaves was determined by phenol method, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of cytokinin and auxin.ResultsCompared with the blank group, the treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could significantly increase stem length, stem node number, leaf number, and tiller number. Among them, during the harvesting period in November, the stem length and tiller number, which are indicators related to the yield of D. officinale, increased by 60.85% and 19.23% after treatment with calcium nitrate tetrahydrate, and by 32.54% and 28.85% after treatment with nano-calcium carbonate, respectively. Compared with the blank group, treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could promote the accumulation of sucrose in the stems and leaves of D. officinale to varying degrees, as well as the accumulation of polysaccharides, mannose, and glucose in the stems. In addition, nano-calcium carbonate treatment also facilitated the accumulation of fructose in the stems and leaves of D. officinale. Specifically, during the harvesting period in November, polysaccharides and mannose, which were the main active ingredients in D. officinale stems, increased by 28.48% and 29.36% after treatment with calcium nitrate tetrahydrate, and by 39.91% and 82.62% after treatment with nano-calcium carbonate, respectively. In addition, compared with the blank group, the concentrations of auxin in the stems and leaves of D. officinale were significantly increased after treatment with calcium nitrate tetrahydrate(P<0.05). Similarly, the concentrations of cytokinin and auxin in the stems of D. officinale were also elevated after treatment with nano-calcium carbonate. Correlation analysis further indicated that elongation growth and tillering of D. officinale stems after foliar spraying of nano-calcium carbonate and calcium nitrate tetrahydrate might be related to the accumulation of carbohydrates in the stems and leaves and the synergistic effect of auxin and cytokinin.ConclusionIn production practice, spraying nano-calcium carbonate and calcium nitrate tetrahydrate can promote the accumulation of cytokinin, auxin, and carbohydrate contents in the stems and leaves of D. officinale, and promote tillering and elongation growth of the stems.
摘要:ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components.MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A,epimedin B,epimedin C,icariin,and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China,as well as the effects of 28 environmental factors on the accumulation of each component.ResultsThe average content of flavonoid glycosides 64 (69.56%) producing areas and 30 (83.33%) cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A,epimedin B,epimedin C,icariin,and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other,mainly located in western Hunan,eastern Hubei,eastern Guizhou,and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan,southern Henan,northern Anhui,eastern Guizhou,and southern Chongqing.The hot spots areas of icariin were in southern Chongqing,western Hunan,and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter (q=0.16) and its interaction with temperature seasonality (q=0.35),respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter (q equals 0.15 and 0.22,respectively).The strongest interactions were observed between precipitation of coldest quarter and gravel content (q=0.34),as well as between precipitation of coldest quarter and aspect (q=0.35).ConclusionThirteen cities,including Zhumadian and Nanyang in Henan,Huaihua,Shaoyang,and Zhangjiajie in Hunan,and Zunyi,Qiandongnan,and Tongren in Guizhou,were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation,gravel content,temperature seasonality,and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.
摘要:First recorded in an official medical book from the Northern Song Dynasty called Taiping Huimin Heji Ju Fang (Prescriptions of the Bureau of Taiping People's Welfare Pharmacy), Xiaoyaosan has been developed and refined over generations and is preserved to this day. It specializes in soothing the liver,resolving stagnation,fortifying the spleen,and nourishing blood. In this study,ancient traditional Chinese medicine (TCM) books and contemporary studies were reviewed to obtain information on Xiaoyaosan using bibliometrics,including its historical development,dosage,origin,processing methods,decoction dosage,and ancient and modern indications. Furthermore,a question regarding the presence of Zingiberis Rhizoma Recens and Menthae Haplocalycis Herba in Xiaoyaosan was investigated,and a table of key information on Xiaoyaosan was compiled,providing references for developing Xiaoyaosan preparations. According to the weight and measurement system of the Song dynasty,the contemporary equivalent formulation of the decocted Xiaoyaosan consists of 20.65 g of Glycyrrhizae Radix et Rhizoma and 41.3 g of Angelica Sinensis Radix,Poria,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,and Bupleuri Radix. The formulation is processed to obtain a mixed powder with a particle size of 10 mesh. For each dose,8.25 g of the mixed powder is combined with 1 g of unprocessed Zingiberis Rhizoma Recens and 0.62 g of Menthae Haplocalycis Herba in 300 mL of water. The mixture is decocted until the volume reaches 210 mL,and the residue is then removed,with no specific timing required for administration. After the processing,each dose consists of approximately 0.75 g of Glycyrrhizae Radix et Rhizoma and 1.50 g of Radix Angelica Sinensis,Poria,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,and Bupleuri Radix. Ancient medical literature shows that Xiaoyaosan primarily treats blood deficiency and overstrain,specifically for symptoms including heat caused by blood deficiency and fatigue,irregular menstruation,headache,eye soreness,pain in the ribs and limbs,and emaciation and bone steaming. In the Qing Dynasty,ZHANG Lu clearly proposed the pathogenesis of liver depression,and since then,the use of Xiaoyaosan in treating various syndromes associated with liver depression has been highly praised by physicians in the Qing dynasty and modern times. Xiaoyaosan has a wide application in modern clinical practices,involving digestive diseases,gynecological diseases,psychological diseases,nervous system diseases,and otorhinolaryngologic diseases. Moreover,it is most commonly used to treat depression and other diseases complicated with depression,hyperplasia of the mammary gland,etc. The key information on Xiaoyaosan and its clinical applications in ancient and modern times investigated in the study could serve as a scientific reference for in-depth research and extended clinical applications of the prescription.
关键词:Xiaoyaosan;drug processing;ancient literature;modern clinical application;key information
NIU Weilu, YANG Mengjie, LYU Chengqi, WANG Shunxi, WANG Ziwen, JIA Huangchao, WANG Liyun, LIU Xuewei, MIAO Mingsan, WANG Xiaomeng, YAN Yawei, LIU Chunyong
摘要:Through data collection and collation combined with bibliometrics, this study conducted a series of textual research on Yanghetang, such as the name and origin, the evolution of prescription composition and modern clinical application. Yanghetang was first recorded in Bencao Yidu of WANG Ang in the Qing dynasty. In addition to Yanghetang, there were 3 bynames of Jiawei Yanghetang, Quanshengji Yanghetang and Zhenjun Yanghetang. Regarding the composition of the formula, a total of 4 versions of Yanghetang were collected. The first version is the 5 medicines version of Cervi Cornus Colla, Rehmanniae Radix Praeparata, Cinnamomi Cortex, Zingiberis Rhizoma and Ephedrae Herba in Bencao Yidu. The second version is the 7 medicines version of Waike Zhengzhi Quanshengji, changing Zingiberis Rhizoma to Zingiberis Rhizoma Praeparatum Carbonisata(ZRPC) and adding Sinapis Semen and Glycyrrhizae Radix et Rhizoma(GRR) on the basis of Bencao Yidu, and most of the Yanghetang is of this version. The third version is the 6 medicines version of Wushi Yifang Huibian, that is, on the basis of Bencao Yidu, Zingiberis Rhizoma is changed into ZRPC, and Sinapis Semen is added. The fourth version is the 6 medicines version in Yifang Jiedu, that is, on the basis of Bencao Yidu, Zingiberis Rhizoma is changed into Zingiberis Rhizoma Praeparatum, and GRR Praeparata cum Melle is added. Regarding the dose of Yanghetang, the doses of the medicines in Waike Zhengzhi Quanshengji was converted into the modern doses as follows:37.3 g of Rehmanniae Radix Praeparata, 1.87 g of Ephedrae Herba, 11.19 g of Cervi Cornus Colla, 7.46 g of Sinapis Semen, 3.73 g of Cinnamomi Cortex, 3.73 g of GRR, and 1.87 g of ZRPC. The origins of the above medicines are consistent with the 2020 edition of Chinese Pharmacopoeia. The processing specification of Rehmanniae Radix Praeparata is steaming method, ZRPC is ginger charcoal, Sinapis Semen is the fried products, and the rest of the medicines are raw products. The decoction method was verified by the decoction method in Chonglou Yuyao, which is similar in the time, and it is recommended that the above medicines should be added with 600 mL of water, decocted to 100 mL, and taken warmly 30 min after meal. For each dose, it is recommended to use 1-3 doses per day according to the doctor's advice in combination with clinical practice. The diseases involved in the ancient applications involved 42 diseases in 11 departments, including orthopedics, dermatology and gynecology, which were dominated by Yin-cold syndrome. However, the diseases involved in modern research also include 148 related diseases in 10 departments, such as orthopedics, obstetrics and gynecology, which is consistent with the ancient books. In recent years, the research hotspots of Yanghetang have focused on more than 10 fields, including osteoblasts, malignant tumors, wound healing, traditional Chinese medicine fumigation and so on, which are widely used. It is suitable for comprehensive research and development because of its rational formula composition, clear origin, processing and decoction method, and wide clinical application.
关键词:Yanghetang;Yin-cold syndrome;famous classical formulas;textual research;modern applications;critical information
摘要:In this paper, by referring to ancient and modern literature, the textual research of Kochiae Fructus has been conducted to clarify the name, origin, distribution of production areas, quality specification, taste and efficacy, harvesting time, processing and compatibility taboo, so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation, it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic, and has been used as the official name throughout history. It is also known by other names such as Dimai, Dikui, and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia, which is consistent throughout history. In the Han dynasty, it was recorded that Kochiae Fructus was produced in Jingzhou(Hubei province), while modern literature records its distribution throughout the country, so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn, and the quality is best when it is full, gray green in color, and no impurities. There are two processing methods for its origin:from the Southern and Northern dynasties to the Ming dynasty, it was dried in the shade, and after the founding of the People's Republic of China, it was dried in the sun. There are few records about the processing of Kochiae Fructus, and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar, and the leaves are taken in April and May, processing in the place of origin is shade drying, the processing methods include burning ash and frying frost, pounding juice and wine soaking. For internal use, it is mostly decocted or mashed, while for external use, it is mostly washed with decoction or taken in a soup bath. Throughout history, it has been recorded that Kochiae Fructus is bitter and cold, and is mainly used for treating bladder fever. After the founding of the People's Republic of China, most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia, it has been recorded that Kochiae Fructus has a pungent and bitter taste, and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness, dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history, it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times, it has been used to regulate the liver, spleen and large intestine meridians, with functions such as clearing heat and detoxifying, and diuresis. Based on the textual research, it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus, and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements, the raw products is taken into medicine.
摘要:In the strategic context of "healthy China", the concept of "medicine and food homology", rooted in the culture of traditional Chinese medicine (TCM), has received unprecedented attention. In response to population aging in China, the health of the elderly has become the focus of public health attention, and proactive health is the key to healthy aging. From the perspective of the application of medicinal and edible materials in proactive health and technological responses to population aging for the first time, this paper firstly provided a systematic overview of medicinal and edible materials and the policies related to proactive health. Second, it summarized the situation of modern technology that accelerates the research and development of medicinal and edible products, as well as the current situation of various modern biotechnologies that reveal the mechanism of action of medicinal and edible materials. Third, it discussed the application scenarios of medicinal and edible materials in proactive health and technological responses to population aging, as well as the future research and development of medicinal and edible materials. By exploring in depth the unique value and importance of medicinal and edible materials, the paper lays a theoretical foundation for improving the health care capabilities of TCM and contributes new strategies derived from TCM to healthy aging.
关键词:medicine and food homology;proactive health;traditional Chinese medicine culture;healthy aging
摘要:With the increasing incidence and mortality of malignant tumors year by year, the prevention and treatment of malignant tumors has become a hot field of research. Although the existing anti-tumor treatment methods such as surgery, radiotherapy, chemotherapy, immunity and targeting have achieved some results, there are also obvious shortcomings, which are not conducive to the improvement of patients' quality of life and long-term treatment. Therefore, seeking a new efficient and safe treatment has become a hot topic of concern for many oncologists. adenosine monophosphate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway can participate in intracellular energy metabolism and affect the pathogenesis and outcome of tumors through multiple mechanisms. It is widely mentioned in the occurrence and development of many tumors. The activity level of this pathway is closely related to the abnormal proliferation and invasion of tumor cells, and is considered as an important pathway for anti-tumor therapy research. The anti-tumor treatment of traditional Chinese medicine(TCM) has significant advantages such as syndrome differentiation and treatment and sample consideration. The study found that flavonoids, alkaloids, polyphenols, saponins and other active components of traditional Chinese medicine, as well as the traditional Chinese medicine compound Xiangbei San, Yiqi Fuzheng Jiedu decoction, Yiqi Fuzheng prescription, etc can activate the AMPK/ mTOR signaling pathway by regulating the expression of AMPK/mTOR signaling pathway and upstream and downstream proteins, thereby inducing tumor cell autophagy and apoptosis, inhibiting tumor angiogenesis and epithelial mesenchymal transformation, regulating aerobic glycolysis and energy metabolism, and reversing drug resistance to exert anti-tumor effects. In this paper, by summarizing the research achievements of TCM anti-tumor in recent years, the specific mechanism of action of TCM regulating AMPK/ mTOR signaling pathway against tumor was discussed, aiming to provide ideas and references for the research and development of anti-tumor new drugs.
关键词:Adenosine monophosphate activated protein kinase(AMPK);mammalian target of rapamycin(mTOR);traditional Chinese medicine;anti-tumor;mechanistic studies
摘要:Osteoporosis is a common bone metabolic disease, which is mainly characterized by the decrease in the number of bone trabeculae and the destruction of bone tissue microstructure, leading to increased bone fragility and fracture risks. This disease is common in postmenopausal women, elderly men, diabetes patients, and obese people. Due to the lack of awareness to prevent bone losses and the limitations of bone mass measurement methods, osteoporosis is only concerned when there are serious complications, which imposes a heavy burden on both patients and medical resources. Oxidative stress refers to the excessive production of highly active molecules such as reactive oxygen species and reactive nitrogen in the body subjected to harmful stimuli, leading to the imbalance between the oxidative and antioxidant systems and causing oxidative damage. Studies have shown that oxidative stress can increase the generation and activity of osteoclasts and inhibit the differentiation of osteoblasts, thus playing a role in the occurrence and development of osteoporosis. Traditional Chinese medicine (TCM) is considered an effective antioxidant that can alleviate oxidative stress-induced osteoporosis by regulating a variety of signaling pathways. Studies have shown that TCM can alleviate oxidative stress and promote bone angiogenesis and osteogenesis by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), nuclear factor-kappa B, and nuclear factor erythroid 2-related factor (Nrf2) signaling pathways. TCM alleviates oxidative stress and promotes osteogenesis by regulating the Nrf2, PI3K/Akt/mammalian target of rapamycin, and secreted glycoprotein Wnt/β-catenin signaling pathways. In addition, TCM regulates NF-κB, mitogen-activated protein kinase, and receptor activator of nuclear factor kappa B (RANK)/RANK ligand/osteoprotegerin signaling pathway to alleviate excessive bone resorption induced by oxidative stress. This paper systematically summarizes the literature on the prevention and treatment of osteoporosis by TCM or its active ingredients via the above-mentioned signaling pathways to reduce oxidative stress in recent years. It briefs the possible molecular mechanisms of oxidative stress regulation-related signaling pathways to cause osteoporosis. In addition, this paper discusses the effects and mechanisms of TCM on bone angiogenesis, osteogenesis, and bone resorption by reducing oxidative stress through the regulation of related signaling pathways, aiming to provide a theoretical basis for the research and clinical treatment of osteoporosis.
关键词:osteoporosis;oxidative stress;bone angiogenesis;osteogenesis;bone resorption;traditional Chinese medicine;research progress
摘要:Chronic heart failure (CHF) is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body, or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health, necessitating attention and active intervention. At present, western medicine treatment of CHF is mainly based on diuretics, intravenous vasodilators, intravenous positive inotropic drugs, etc., which, however, have problems such as long medication cycles, serious side effects, and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway, multi-component, and multi-target manner, showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi, activating blood, and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients, which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients, which helps to improve the accuracy of efficacy evaluation. However, there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition, the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment, Buyang Huanwutang can be used alone, or modified, or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance, protecting the mitochondrial structure and function, and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.
摘要:Huaihuasan, first recorded in Experiential Prescriptions for Universal Relief (Pu Ji Ben Shi Fang), is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018, it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients, i.e., Sophorae Flos, Platycladi Cacumen, Schizonepetae Spica, and Aurantii Fructus. It is known for its ability to clear the intestines, dispel wind, cool the blood, and stop bleeding. In modern clinical practice, Huaihuasan, often with modifications, is widely used to treat various digestive tract diseases, including ulcerative colitis (UC), with significant long-term effects. UC is a chronic, non-specific inflammatory bowel disease. Currently, Western medicine primarily treats UC with glucocorticoids, aminosalicylates, and immunosuppressants, which have good short-term efficacy but numerous adverse reactions, high recurrence rates, and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC, such as abdominal pain and diarrhea, reduce disease activity scores (Sutherland), promote intestinal mucosal healing, alleviate anxiety and depression, and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin, rutin, kaempferol, naringenin, and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), nuclear factor-κB (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and the KRAS-regulated mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. These multi-target pathways improve UC symptoms, inhibit inflammation-cancer transition, and help maintain intestinal homeostasis. However, the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs, focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement, aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.
关键词:classic famous prescription;Huaihuasan;ulcerative colitis;active ingredient;pharmacological mechanism
摘要:Renal fibrosis (RF) is the primary pathological feature of chronic kidney disease (CKD) progression to end-stage renal disease (ESRD), with glomerulosclerosis and tubulointerstitial fibrosis as core pathological manifestations. It involves abnormal accumulation of extracellular matrix (ECM) components such as collagen and fibronectin, ultimately leading to structural destruction and functional losses of the kidneys. Sirtuins (SIRTs), a class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, play crucial roles in cellular metabolism, oxidative stress responses, inflammation regulation, and cell survival. In mammals, there are seven distinct SIRT members (SIRT1 to SIRT7), which collectively ameliorate RF progression through multiple pathways. These include regulating the transforming growth factor (TGF)-β/Smad signaling pathway, suppressing inflammatory responses, reducing oxidative stress, modulating mitochondrial and autophagy functions, and promoting fatty acid oxidation. In recent years, traditional Chinese medicine (TCM) and its active components have demonstrated significant potential in activating or modulating the SIRT protease family and its regulatory networks to ameliorate RF in a multi-target and holistic manner. However, systematic reviews in this area remain lacking. This article elucidates the mechanisms by which the SIRT protease family regulates RF and reviews the latest research advances in TCM modulation of SIRTs for the prevention and treatment of RF, aiming to provide new insights and approaches for the TCM treatment of RF.
关键词:traditional Chinese medicine;renal fibrosis;sirtuin family;oxidative stress;fatty acid oxidation;mitochondrial function