摘要:ObjectiveTo observe the regulatory effect of Buyang Huanwutang on mitochondrial homeostasis in renal tubular epithelial cells of spontaneous diabetic db/db mice through modulation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.MethodsThirty db/db mice were randomly divided into three groups (n=10 each): model group, Buyang Huanwutang group (21.47 g·kg-1), and Empagliflozin group (10 mg·kg-1). Additionally, 10 db/m mice were used as the normal group. After 12 weeks of corresponding treatment, the kidney weight-to-body weight ratio (KW/BW), 24-hour urinary protein quantification (24 h UTP), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), N-acetyl-β-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin C (Cys C), and kidney injury molecule-1 (KIM-1) were measured. Renal histopathological and morphological changes were observed by hematoxylin and eosin (HE) staining. The expression of KIM-1, apoptosis-related proteins, inflammatory cytokines, mitochondrial dynamics-related proteins, and JAK2/STAT3 pathway-related proteins was detected by Western blot and immunofluorescence (IF). Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the expression of JAK2 and STAT3 mRNA in renal tissues was analyzed by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR).ResultsCompared with the normal group, KW/BW was significantly increased in the model group (P<0.05), and 24 h UTP and UACR were also significantly increased (P<0.05, P<0.01). Urinary KIM-1, NAG, NGAL, and Cys C levels were significantly increased (P<0.01). HE staining revealed enlarged glomeruli, dilated renal tubules, and vacuolar degeneration in the model group. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were significantly elevated (P<0.01). The expression of B-cell lymphoma 2-associated X protein (Bax) and cleaved Caspase-3 was significantly upregulated (P<0.01), while B-cell lymphoma 2 (Bcl-2) expression was significantly downregulated (P<0.01). Serum MDA levels were markedly increased (P<0.05), and SOD levels were significantly decreased (P<0.05). The expression of mitochondrial dynamics-related proteins dynamin-related protein 1 (DRP1) and fission protein 1 (FIS1) was significantly upregulated (P<0.01), while the fusion proteins optic atrophy 1 (OPA1) and mitofusin 2 (MFN2) were significantly downregulated (P<0.01). Moreover, the expression of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) was significantly increased (P<0.01). Compared with the model group, there was no statistically significant difference in KW/BW between the Buyang Huanwutang and Empagliflozin groups, but 24 h UTP, UACR, urinary KIM-1, NAG, NGAL, and Cys C levels showed varying degrees of decrease (P<0.05, P<0.01). IL-6 and TNF-α expression decreased, Bax and cleaved Caspase-3 expression was significantly reduced (P<0.01), while Bcl-2 expression was significantly elevated (P<0.01). MDA levels were markedly decreased (P<0.05, P<0.01), SOD levels were significantly increased (P<0.01), DRP1 and FIS1 expression was significantly downregulated (P<0.01), and OPA1 and MFN2 expression was significantly upregulated (P<0.05, P<0.01). The expression of p-JAK2 and p-STAT3 was significantly decreased (P<0.01). Real-time PCR showed consistent trends, and renal pathological damage was alleviated.ConclusionBuyang Huanwutang can alleviate renal injury and apoptosis in db/db mice, improve renal inflammation and oxidative stress, and its mechanism may be related to the inhibition of excessive activation of the JAK2/STAT3 signaling pathway, thereby maintaining mitochondrial dynamics homeostasis.
关键词:Buyang Huanwutang;renal tubular epithelial cells;mitochondria;modulating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway
摘要:ObjectiveTo study the improvement effect and mechanism of Huanglian Jiedutang on acute lung injury (ALI) in sepsis.MethodsExploring the pharmacological substance basis and potential mechanisms of Huanglian Jiedutang in improving ALI in sepsis through online pharmacology platforms; sixty SD rats were randomly divided into 6 groups: sham group, model group, positive group (10 mL·kg-1), Huanglian Jiedutang low-dose group, Huanglian Jiedutang high-dose group(3.6、14.4 g·kg-1), and Huanglian Jiedutang high-dose+nuclear factor-erythroid 2-related factor 2(Nrf2)inhibitor group (Huanglian Jiedutang+ML385)(14.4 g·kg-1+30 mg·kg-1). A sepsis induced ALI model was created by cecal ligation and perforation surgery for 12 hours, followed by gavage administration. After 7 days of modeling, lung tissue was euthanized and isolated, and histopathological changes and expression of related key targets were observed.ResultsThe results showed that the high-frequency active ingredients of Huanglian Jiedutang in treating ALI were β- sitosterol, quercetin, stigmasterol, berberine, and berberine; By acting on 9 core targets including (GPX4), Nrf2, Heme Oxygenase-1(HO-1), TP53, mitogen-activated protein kinase 3(MAPK3), tumor necrosis factor(TNF), signal transducer and activator of transcription(STAT3), interleukin(IL)-1β, MYC, and regulating signaling pathways such as ferroptosis, the effect of sepsis induced ALI is regulated. Huanglian Jiedutang can improve pathological damage such as alveolar interstitial edema and alveolar wall thickening in ALI rats with sepsis. The levels of malondialdehyde (MDA), Fe2+, and reactive oxygen species (ROS) were significantly reduced(P<0.05), while the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH) were significantly increased(P<0.05). Electron microscopy and Prussian blue staining showed significant improvement in mitochondrial microstructure and iron deposition. Significantly increase the expression of Nrf2, solute carrier family 7 member 11(SLC7A11), GPX4, and HO-1 proteins(P<0.05). ML385 can significantly reverse the protective effect of Huanglian Jiedutang on sepsis induced ALI lung tissue.ConclusionHuanglian Jiedutang can improve ALI in sepsis through multiple pathways and targets, and its representative mechanism may be the activation of the Nrf2/SLC7A11/GPX4 signaling pathway.
关键词:Huanglian Jiedutang;sepsis;acute lung injury;nuclear factor-erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4(Nrf2/SLC7A11/GPX4)signal pathway;network pharmacology
摘要:ObjectiveTo investigate the therapeutic effects of Erdong Tang on hepatic glycolipid metabolism disorders in type 2 diabetes mellitus (T2DM) mice and explore the mechanism on the basis of the insulin receptor substrate 1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway.MethodsA T2DM mouse model was established by high-fat and high-sugar feed combined with intraperitoneal injection of streptozotocin (STZ). Mice successfully modeled were divided into a model group, a metformin group, and high-dose, medium-dose, and low-dose groups of Erdong Tang. The gavage doses for the metformin group and the high-dose, medium-dose, and low-dose groups of Erdong Tang were 0.15, 22.64, 11.32, 5.66 g·kg-1, respectively. At the same time, a blank group was set up, and the model and blank groups were administered with equal amounts of saline by gavage. After eight weeks of gavage administration, mice were measured for fasting blood glucose (FBG), body mass, liver weight, liver coefficient, and an oral glucose tolerance test (OGTT) was conducted. Serum insulin (FINS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay (ELISA), and insulin resistance index (HOMA-IR) was calculated. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were detected. Hematoxylin-eosin (HE) staining was used to observe the histopathological damage of the liver. Western blot was used to detect the protein expression of IRS-1, PI3K, Akt, and p-Akt in liver tissue.ResultsCompared with those in the blank group, FBG, FINS, HOMA-IR, IL-6, TNF-α, ROS, TC, TG, LDL-C, liver weight, and liver coefficient were significantly increased in the model group (P<0.01), and HDL-C, IRS-1, PI3K, Akt, p-Akt/Akt protein, and body mass were significantly reduced (P<0.01). The pathological tissue in the liver showed unclear morphology of hepatic lobules, disordered arrangement of hepatocytes, enlarged nuclei of hepatocytes, unclear nuclear membrane, obvious fatty degeneration, and infiltration of inflammatory cells. Compared with that in the model group, the FBG, FINS, HOMA-IR, IL-6, TNF-α, ROS, TG, TC, and LDL-C content of mice was significantly reduced in the metformin group and the high-dose, medium-dose, and low-dose groups of Erdong Tang (P<0.05, P<0.01). The expression of HDL-C, IRS-1, PI3K, and Akt protein was significantly increased in the metformin group and the high-dose and medium-dose groups of Erdong Tang (P<0.05, P<0.01). The expression of p-Akt/Akt in mice was significantly increased in the metformin group and the high-dose, medium-dose, and low-dose groups of Erdong Tang (P<0.01), and fatty degeneration and inflammatory cell infiltration were significantly improved in the pathological tissues of the mouse liver in each dosing group.ConclusionErdong Tang ameliorates glycolipid metabolism, inflammatory responses, and oxidative stress in T2DM mice, potentially by activating the IRS-1/PI3K/Akt signaling pathway.
摘要:ObjectiveTo investigate the protective effects and mechanisms of the optimized Tanyu Tongzhi decoction (TYTZ) on myocardial ischemia reperfusion rats with no-reflow (NR).MethodsForty-eight male Sprague Dawley (SD) rats were randomly divided into a sham group, a model group, a DNase Ⅰ group (5 mg·kg-1), a low-dose TYTZ group (3.6 g·kg-1), a medium-dose TYTZ group (7.2 g·kg-1), and a high-dose TYTZ group (14.4 g·kg-1), with eight rats in each group. The TYTZ groups received pre-treatment for seven days, while the DNase Ⅰ group was administered intraperitoneally one hour before modeling. The NR model was established by in situ ligation of the left anterior descending coronary artery. Myocardial NR area was assessed by Thioflavin S staining, and infarct size was measured via TTC staining. Cardiac function was detected by echocardiography, and microcirculation function changes were assessed via myocardial contrast echocardiography. Hematoxylin-eosin (HE) staining evaluated myocardial pathological changes and microthrombosis. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the myocardium. Blood chemistry assay was used to detect the level of creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in serum. Enzyme-linked immunosorbent assay (ELISA) quantified neutrophil extracellular traps (NETs) markers myeloperoxidase (MPO) and citrullinated histone H3 (CitH3), and inflammatory cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α). Immunofluorescence detected the myocardial CitH3 and cluster of differentiation 34 (CD34) expressions, and Western blot analyzed the myocardial CD34 protein expression.ResultsCompared to the sham group, the model group exhibited significant increases in NR area, infarct size, myocardial enzymes (CK, CK-MB, LDH, and AST) in serum (P<0.01). The HE staining results showed disrupted myocardial fibers, inflammatory cell infiltration, and microvascular thrombosis. TEM results showed myocardial filament rupture and mitochondrial structure destruction. The echocardiogram showed significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01), and the myocardial contrast echocardiogram showed significantly prolonged perfusion peak time (P<0.01). ELISA results showed significantly elevated NETs markers MPO and CitH3, and inflammatory cytokines IL-6, IL-1β, and TNF-α (P<0.01). Western blot and immunofluorescence results showed upregulated myocardial CitH3 expression (P<0.01). Compared to the model group, the DNase Ⅰ group and the TYTZ groups reduced NR area, infarct size, and myocardial enzyme levels, protected myocardial tissue, improved microcirculation and heart function, suppressed NETs generation, and attenuated inflammation. The DNase Ⅰ group showed the most significant improvement in rat myocardium, serum NETs, and inflammatory markers, while the high-dose TYTZ group showed the most significant effect among the groups at each dose.ConclusionThe optimized TYTZ demonstrates protective effects against NR, which is potentially mediated by inhibiting NETs expression, mitigating inflammation, and ameliorating myocardial microcirculatory dysfunction.
摘要:ObjectiveTo investigate the mechanism of Nuanxinkang in ameliorating doxorubicin-induced cardiomyopathy (DOXIC) in mice by regulating the NOD-like receptor protein 3 (NLRP3)/damage-associated molecular patterns (DAMPs) signaling pathway and inhibiting the formation of neutrophil extracellular traps (NETs).MethodsDOXIC was modeled in mice by tail vein injection of doxorubicin. Mice were randomly allocated into control, model, low-dose, medium-dose, and high-dose Nuanxinkang, and pravastatin groups, with 10 mice in each group. After 4 weeks of treatment, echocardiography was employed to assess the cardiac function. Histopathological changes in the heart tissue were observed by hematoxylin-eosin (HE) staining, and myocardial collagen deposition was analyzed by Masson staining. Oxidative stress levels in the myocardial tissue were evaluated via dihydroethidium (DHE) staining. Immunofluorescence and Western blotting were used to detect the expression of NETs markers, such as myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (CitH3). Immunohistochemistry, Western blot, and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were performed to determine the mRNA and protein levels of NLRP3, interleukin-1β (IL-1β), and high mobility group box 1 (HMGB1). Transcriptomic analysis combined with experimental validation was conducted to explore the role and mechanism of Nuanxinkang in ameliorating DOXIC.ResultsCompared with the control group, the model group showed decreases in body weight, heart weight/body weight ratio, and cardiac function (P<0.01), along with myocardial fiber disarrangement, increased collagen fiber deposition, and elevated oxidative stress levels (P<0.01). Compared with the model group, medium-dose and high-dose Nuanxinkang delayed the body weight loss, improved the cardiac function, reduced myocardial fibrosis, and alleviated oxidative stress (P<0.05, P<0.01). Gene set enrichment analysis and heatmap results revealed that Nuanxinkang inhibited the formation of NETs and downregulated the expression of the NOD-like receptor signaling pathway. Compared with the control group, the model group exhibited up-regulated expression levels of NETs markers (MPO, NE, and CitH3) and mRNA and protein levels of NLRP3, IL-1β, and HMGB1 (P<0.05, P<0.01). Compared with the model group, Nuanxinkang down-regulated the expression of NETs markers, NLRP3, IL-1β, and HMGB1 (P<0.05, P<0.01).ConclusionNuanxinkang effectively ameliorates DOXIC in mice by inhibiting the expression of NLRP3/DAMPs signaling pathway and the formation of NETs.
关键词:doxorubicin-induced cardiomyopathy;neutrophil extracellular traps;Nuanxinkang;NOD-like receptor protein 3 (NLRP3);damage-associated molecular patterns
摘要:ObjectiveTo observe the effect of Niupo Zhibao Pellet (NPZB) on collagen deposition in a mouse model of rapid pulmonary fibrosis (RPF) and explore the underlying cellular mechanisms involved.MethodsThe 40 C57BL/6 mice were randomly divided into a control group, a model group, a dexamethasone group (1.0 mg·kg-1), a low-dose NPZB group (0.75 g·kg-1), and a high-dose NPZB group (1.5 g·kg-1). Based on the previous studies and results, the "lipopolysaccharide (LPS) three-hit" protocol was employed to establish a mouse model of RPF. Following model establishment, NPZB was administered via gavage, and dexamethasone was delivered through intraperitoneal injection once a day. On the 5th day, the lung tissue was collected. Hematoxylin-eosin (HE) staining was employed to observe pathological alterations in the lung tissue, while Masson's trichrome staining was used to assess collagen deposition. Western blot was employed to detect the expression level of Col Ⅰ, osteopontin (OPN), and transforming growth factor (TGF)-β1 in the lung tissue. Immunohistochemical (IHC) staining was conducted to localize CD163-positive macrophages (CD163+ Mφ), and immunofluorescence (IF) staining was performed to detect the colocalization of CD163+ Mφ and OPN. Flow cytometry was utilized to quantify the number of CD163+ Mφ in the lung tissue. The mouse model of RPF was prepared, and CD163+ Mφ were isolated from the lung tissue by magnetic-activated cell separation. The non-toxic dosages of NPZB for these cells were determined by the cell counting kit-8 (CCK-8). Subsequently, an enzyme-linked immunosorbent assay (ELISA) was used to detect the effect of NPZB on the OPN secretion level of CD163+ Mφ. The 24 CD163 knockout (CD163-/-) mice were randomly assigned to a control group, a model group, and a high-dose NPZB group (1.5 g·kg-1), with wild-type mice serving as controls. Flow cytometry was utilized to confirm the knockout of CD163, and Western blot was conducted to assess the expression level of OPN and Col Ⅰ in the lung tissue of CD163-/- mice. HE staining was used to observe pathological changes, and Masson staining was employed to assess collagen deposition.ResultsIn comparison to the control group, the model group exhibited a significant increase in collagen deposition (P<0.01), the expression level of Col Ⅰ, OPN (P<0.01), and TGF-β1 (P<0.01), as well as the number of CD163+ Mφ (P<0.01) in the lung tissue. Compared to the model group, both the low-dose and high-dose groups of NPZB demonstrated a reduction in collagen deposition (P<0.05, P<0.01), the expression of Col Ⅰ (P<0.05, P<0.01), OPN (P<0.01), and TGF-β1 (P<0.05, P<0.01) in lung tissue, and the number of CD163+ Mφ (P<0.01). Furthermore, compared with the control group, NPZB significantly decreased the OPN level in the supernatant of CD163+ Mφ (P<0.01). Compared to the model group in wild-type mice, CD163-/- mice exhibited a significant reduction in collagen deposition (P<0.01) and a decrease in the expression level of Col Ⅰ and OPN (P<0.01).ConclusionNPZB inhibits collagen deposition in mice with RPF by reducing the number of CD163+ Mφ and their OPN secretion levels.
摘要:ObjectiveTo investigate the inhibitory effect of Bupleuri Radix processed with Trionyx sinensis blood on the depletion of liver Yin and its protective effect in a rat model of liver injury with liver Yin deficiency syndrome.MethodsSPF male Sprague-Dawley (SD) rats were randomly divided into blank, 40%, 30%, and 20% CCl4 groups. Liver injury with liver Yin deficiency syndrome were induced by intraperitoneal injection of CCl4 combined with intragastric administration of warming Chinese medicines (Aconiti Radix Lateralis Praeparata, Cinnamomi Cortex, and Zingiberis Rhizoma). SPF SD rats were then randomly assigned to blank group, model group, Yiguanjian group (0.7 g·kg-1), high-, medium-, and low-dose raw Bupleuri Radix groups, and high-, medium-, and low-dose Bupleuri Radix processed with T. sinensis blood groups (1.0, 2.0, 4.0 g·kg-1). From the third week, treatments were administered. Rat activity, anal temperature, body weight, and water intake were monitored. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), total bilirubin (TBiL), direct bilirubin (DBiL), and γ-glutamyltransferase (γ-GT) were measured using an automatic biochemical analyzer. Thyroxine (T4), aldosterone (ALD), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Liver homogenates were assayed for malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Liver pathology was assessed by hematoxylin-eosin (HE) staining, and phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) protein expression in liver tissue was determined by Western blot.ResultsCompared with the blank group, the 30% CCl4 group showed significantly increased anal temperature (P<0.05) and decreased body weight (P<0.01). The 20% CCl4 group exhibited significantly increased water intake and anal temperature (P<0.01) and decreased body weight (P<0.05). All CCl4 groups had significantly elevated serum ALT, AST, γ-GT, DBil, TBil, T3, T4, ALD, cAMP, and cGMP levels (P<0.05, P<0.01), with T3, T4, and ALD increasing most prominently in the 20% CCl4 group. Liver injury in the 20% CCl4 group was milder, with limited hepatic lobule adhesion. HE staining revealed fewer necrotic cells, milder fatty degeneration, fewer neutrophils, and fibrosis without pseudolobule formation. Compared with the blank group, the Yiguanjian group, high- and medium-dose raw Bupleuri Radix groups, and high- and medium-dose Bupleuri Radix processed with T. sinensis blood groups showed no significant increase in body weight or anal temperature, and there was no difference between groups receiving equivalent doses of Raw Bupleuri Radix and Bupleuri Radix processed with T. sinensis blood. Compared with the model group, the Yiguanjian group, raw Bupleuri Radix groups, and Bupleuri Radix processed with T. sinensis blood groups showed significant reductions in ALT, AST, AKP, TBil, T4, ALD, cAMP, and cGMP (P<0.05, P<0.01). The Bupleuri Radix processed with T. sinensis blood groups had significantly increased SOD and MDA levels (P<0.05, P<0.01). All treatment groups exhibited decreased IL-6 and TNF-α (P<0.01) and increased IL-10 (P<0.01). PI3K and Akt protein expression in liver tissues was significantly downregulated in the high-, medium-, and low-dose raw Bupleuri Radix groups, and Bupleuri Radix processed with T. sinensis blood groups (P<0.01). Compared with the equivalent raw Bupleuri Radix group, the low-dose Bupleuri Radix processed with T. sinensis blood group showed lower IL-6 and TNF-α (P<0.01) and higher IL-10 (P<0.01). All doses of Bupleuri Radix processed with T. sinensis blood significantly decreased cAMP and cGMP (P<0.01), and T4 and ALD levels were closer to those of the blank group. PI3K protein expression was significantly reduced in all doses of Bupleuri Radix processed with T. sinensis blood groups (P<0.05, P<0.01).ConclusionRats in the 20% CCl₄ combined with warming Chinese medicine model exhibited irritability and mania in the late stage, with significant Yin deficiency-heat indicators and mild liver injury, reflecting clinical liver Yin deficiency syndrome. Bupleuri Radix processed with T. sinensis blood effectively protected against liver injury with liver Yin deficiency syndrome, with superior overall efficacy compared to raw Bupleuri Radix. These findings suggest that Bupleuri Radix processed with T. sinensis blood can mitigate its tendency to impair liver Yin, effectively alleviate symptoms of Yin deficiency and internal heat, and enhance its protective effect on the liver. Its mechanism is associated with inhibition of PI3K and Akt protein expression.
摘要:ObjectiveTo investigate the mechanism by which Shugan Bushen Yulin decoction improves oligoasthenozoospermia in rats with liver qi stagnation by regulating the glucose transporter 4 (GLUT4)/insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and modulating glucose uptake in the hypothalamus.MethodsMale Sprague-Dawley rats were randomly divided into a blank control group, a liver Qi stagnation model group, high- and low-dose Shugan Bushen Yulin decoction groups, and a fluoxetine group, with eight rats in each group. A liver Qi stagnation model was established by chronic restraint combined with tail-pinching for 14 days. After modeling, the low- (9.75 g·kg-1) and high-dose (39 g·kg-1) decoction groups received the decoction by gavage, while the fluoxetine group (0.021 g·kg-1) received fluoxetine solution by gavage for 14 consecutive days. Emotional stress was evaluated using the open-field test and the sucrose preference test. According to the theory of traditional Chinese medicine (TCM), the modeling of liver Qi stagnation was assessed by observing tongue color and tongue edge color under good lighting. Body weight was measured using a precision scale. The testes and epididymis were removed and weighed to calculate organ indices. Changes in the hypothalamic-pituitary-adrenal (HPA) axis were determined by enzyme-linked immunosorbent assay (ELISA) to measure the levels of β-endorphin (β-EP), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotropin-releasing hormone (CRH) in the blood. Testicular morphology and spermatogenic function were assessed by hematoxylin-eosin (HE) staining. Sperm from the epididymis was analyzed for density and motility using a computer-assisted sperm analysis system, and sperm maturity was evaluated by aniline blue staining. Western blot was used to detect the expression of GLUT4, IRS-1, PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt) in hypothalamic tissue, and follicle-stimulating hormone receptor (FSHR) and μ-opioid receptor (MOR) in testicular tissue.ResultsCompared with the blank group, rats in the model group showed significantly reduced total movement distance and duration, and increased resting time in the open-field test (P<0.05, P<0.01). Sucrose consumption significantly decreased (P<0.01), indicating anhedonia induced by emotional stress. The tongues of model rats appeared dark red or purplish. Testicular sections showed atrophy, reduced spermatogenic cell number, and disordered cell arrangement. The testicular and epididymal indices, sperm density, and motility were significantly reduced (P<0.01), and aniline blue staining revealed decreased sperm maturity. Serum levels of ACTH, CORT, CRH, and β-EP were significantly increased (P<0.01), while the expression of GLUT4, IRS-1, PI3K, p-PI3K, Akt, p-Akt, and FSHR proteins was significantly decreased (P<0.01). Compared with the model group, rats in the treatment groups showed lighter tongue color, significantly increased testicular and epididymal indices (P<0.05, P<0.01), improved testicular morphology and spermatogenic function, and significantly increased sperm maturity, density, and motility (P<0.01). Serum ACTH, CORT, CRH, and β-EP levels were significantly increased (P<0.05, P<0.01), while the expression of GLUT4, IRS-1, PI3K, Akt, and FSHR proteins was significantly upregulated (P<0.05, P<0.01), and MOR protein expression was significantly downregulated (P<0.05, P<0.01).ConclusionNegative emotions induce a stress response that causes abnormal glucose metabolism in the hypothalamus, leading to HPA axis dysfunction and impaired sperm quality. Shugan Bushen Yulin decoction can improve oligoasthenozoospermia in rats with liver Qi stagnation by regulating the GLUT4/IRS-1/PI3K/Akt signaling pathway to enhance hypothalamic glucose uptake and modulate the HPA axis.
摘要:ObjectiveTo investigate the potential molecular mechanism by which betulinic acid (BA) exerts a protective effect on non-alcoholic fatty liver disease (NAFLD).MethodsA mouse model of NAFLD was established via induction with a high-fat and high-cholesterol (HFD + HCD) diet. Fifty male C57BL/6J mice were divided into a normal group, a model group, a silybin group (100 mg·kg-1), and low-dose and high-dose (10, 30 mg·kg-1) BA groups, with 10 mice in each group. A cellular model of NAFLD was constructed by stimulating human hepatocellular carcinoma cells (HepG2) with oleic acid/palmitic acid (OA/PA 500/250 μmol·L-1), and cellular experimental groups comprised a normal group, a model group (OA/PA), low-dose, medium-dose, and high-dose BA groups (20, 40, 80 μmol·L-1), an OA/PA + BA group, a p53-targeting small interfering (si) RNA (sip53) + OA/PA group, and a sip53 + OA/PA + BA group. This study investigated whether BA can ameliorate NAFLD in vivo and in vitro. Biochemical assays were performed to evaluate markers of liver function injury, including serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Body weight and liver index of mice in each group were measured following sample collection. Hematoxylin-eosin (HE) staining, oil red O staining, and Nile red fluorescent staining were utilized to observe pathological changes and lipid accumulation in liver tissue and HepG2 cells. Intracellular reactive oxygen species (ROS) levels were detected via fluorescence microscopy. Molecular docking technology was employed to analyze the targeting interaction between BA and the p53 gene, and Western blot and real-time polymerase chain reaction (Real-time PCR) were used to determine the mRNA and protein expression levels of ferroptosis markers, including glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11), and tumor protein p53 (p53).ResultsThe experimental results indicated that BA intervention significantly alleviated liver damage induced by the HFD + HCD diet in mice. Compared with those in the model group, ALT and AST in the serum of mice in the low-dose and high-dose BA groups were significantly decreased (P<0.01). The liver index improved, and lipid droplet deposition in liver tissue was markedly reduced. In cell experiments, BA treatment significantly alleviated OA/PA-induced oxidative stress, intracellular lipid droplet deposition, and ferroptosis in HepG2 cells. Specifically, ROS generation within the cells was reduced (P<0.01), and intracellular lipid droplets decreased. The mRNA/protein expression of GPX4 and SLC7A11 was significantly upregulated (P<0.01), while ACSL4 mRNA/protein expression was significantly downregulated (P<0.01). Mechanistic studies showed that BA inhibited its phosphorylation level by targeting the p53 gene (P<0.01). Notably, after sip53 was used, the regulatory effect of BA on ferroptosis was diminished, as there were no significant differences between the sip53 group and the BA + sip53 group in terms of lipid droplet deposition and the protein expression level of GPX4/SLC7A11/ACSL4. This result confirmed that p53 knockdown could eliminate the regulatory effect of BA on ferroptosis in HepG2 cells and block the effect of BA on the p53/GPX4 signaling axis.ConclusionBA alleviates ferroptosis by inhibiting the p53 signaling pathway, likely by suppressing p53 phosphorylation levels, which in turn inhibits ferroptosis and exerts a protective effect against NAFLD. This provides important theoretical evidence and potential therapeutic targets for the development of new NAFLD treatments.
摘要:The literature research on key information in the Catalogue of Ancient Classic Prescriptions is a crucial and fundamental issue for the research, development, and registration of compound preparations derived from ancient classic prescriptions. Currently, the process of literature research on ancient classic prescriptions has matured. However, due to the unique characteristics of each prescription and the different tendencies of researchers in their research principles, the results often vary significantly. There are also controversies regarding key issues such as the source and origin of the prescriptions, composition, medicinal material origin, processing methods, and dosages. Based on the latest articles on literature research of ancient classic prescriptions published in the past two years, this paper summarized the main points of the literature research and compared the different situations and points, aiming to explore how to arrive at better research conclusions and provide assistance for future literature research on ancient classic prescriptions and the publication of their key information tables. It is recommended that, while adhering to the research principles issued by the state and fully referencing the already published key information tables, the research results should be comprehensively judged according to differences in specific issues and based on the original meaning of the prescription, historical evolution, and current usage. Overall, the adherence to tradition and compliance with contemporary standards should be combined.
摘要:ObjectiveTo observe the effects of Zhengan Xifengtang on the blood pressure, bile acid spectrum in plasma, and the expression of farnesoid X receptor (FXR) and fibroblast growth factor 21 (FGF21) in spontaneously hypertensive rats (SHR).MethodsSixty 9-week-old males of SHR were randomized into SHR, benazepril (1.0 mg·kg-1·d-1), high-, medium-, and low-dose (34.5, 17.25, 8.625 g·kg-1·d-1) Zhengan Xifengtang, and agonist (10 mg·kg-1·d-1) groups, and 10 male Wistar-Kyoto (WKY) rats of 9 weeks old were selected as the WKY group. The WKY and SHR groups were administrated with an equal volume of distilled water for 8 consecutive weeks. The liver and plasma samples were collected from the rats. The blood pressure of rats in each group was measured by a tail-cuff method with an animal non-invasive sphygmomanometer. The bile acid spectrum in the plasma of rats in each group was determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The expression of FGF21 in the plasma was measured by enzyme-linked immunosorbent assay. The mRNA and protein levels of FXR and FGF21 in the liver tissue were determined by real-time PCR and Western blot, respectively.ResultsZhengan Xifengtang reduced the systolic and diastolic blood pressure of SHR. Compared with the WKY group, the SHR group presented declined levels of ursodeoxycholic acid, hyodeoxycholic acid, deoxycholic acid, lithocholic acid, glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycohyodeoxycholic acid in the plasma (P<0.05, P<0.01), reduced expression of FGF21 in the plasma (P<0.01), and down-regulated mRNA levels of FXR and FGF21 in the liver (P<0.01). Compared with those in the SHR group, the levels of ursodeoxycholic acid, hyodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycohyodeoxycholic acid became lowered in the high-dose Zhengan Xifengtang group (P<0.05, P<0.01). The level of deoxycholic acid declined in the low- and medium-dose Zhengan Xifengtang groups (P<0.05). The level of glycocholic acid reduced in the low-dose Zhengan Xifengtang group (P<0.05) and the agonist group (P<0.05). The expression of FGF21 in the plasma and the mRNA levels of FXR and FGF21 in the liver increased in the high-, medium-, and low-dose Zhengan Xifengtang groups and the agonist group (P<0.05, P<0.01). The protein level of FXR in the liver of the medium-dose group and the agonist group was up-regulated (P<0.05, P<0.01). The expression of FGF21 in the liver of the high-dose group increased (P<0.01).ConclusionZhengan Xifengtang may exert the antihypertensive effect by regulating the bile acid spectrum in the plasma and up-regulating the expression of FXR-FGF21 in the liver of SHR.
关键词:Zhengan Xifengtang;hypertension;bile acid spectrum in the plasma;farnesoid X receptor (FXR);fibroblast growth factor 21 (FGF21)
摘要:Chronic heart failure is a severe and terminal stage of various heart diseases. Studies have confirmed that ferroptosis is involved in the development and progression of chronic heart failure as a key causative factor. Inhibiting iron overload and lipid peroxidation can alleviate ferroptosis, thus improving the cardiac function and preventing heart failure. This theoretically suggests that heart failure can be treated by regulating ferroptosis. This paper reviews the research advances in the mechanism of ferroptosis in chronic heart failure at home and abroad in recent years and the traditional Chinese medicine interventions in ferroptosis in the treatment of chronic heart failure. The review aims to provide new research perspectives on the pathogenesis and prevention of chronic heart failure from ferroptosis and promote the modern development and clinical application of traditional Chinese medicine.
关键词:chronic heart failure;ferroptosis;traditional Chinese medicine;treatment
摘要:ObjectiveTo investigate the effect and mechanism of Wenxin decoction on cardiac function in patients with acute myocardial infarction-induced heart failure (AMI-HF) of Qi deficiency and blood stasis syndrome.MethodsA total of 60 patients with AMI-HF of Qi deficiency and blood stasis syndrome were randomly divided into a treatment group and a control group. Both groups received standard Western medical therapy, while the treatment group additionally received Wenxin Decoction orally for 4 weeks. The levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and traditional Chinese medicine (TCM) syndrome scores before and after treatment were observed in both groups. Peripheral blood mononuclear cells from seven randomly selected patients in each group were subjected to transcriptome sequencing. Differentially expressed genes (DEGs) were screened using DESeq2 software with | log2 (fold change) | ≥ 2 and P<0.01. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. The STRING database and Cytoscape software were used to construct a protein - protein interaction (PPI) network and identify key targets.ResultsCompared with the control group, the treatment group showed significantly decreased NT-proBNP, LVEDD, and TCM syndrome scores, and significantly increased LVEF after treatment (P<0.05). A total of 270 DEGs were identified, including 89 upregulated genes and 181 downregulated genes. GO enrichment analysis showed that the DEGs were mainly involved in functions such as cellular processes, metabolic processes, biological regulation, cellular structure, protein activity, and regulator activity. KEGG pathway analysis indicated that the DEGs primarily exerted biological effects through participation in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, pyruvate metabolism, mitophagy, the Apelin signaling pathway, and the FoxO signaling pathway. PPI network analysis identified 136 node proteins and 425 interaction edges. The top 10 key targets were mitogen-activated protein kinase 13 (MAPK13), non-receptor tyrosine-protein kinase (LYN), C-X-C motif chemokine receptor 4 (CXCR4), Ras homolog family member F (RHOF), Janus kinase 3 (JAK3), syndecan-1 (SDC1), C-X-C motif chemokine ligand 11 (CXCL11), dopamine receptor D2 (DRD2), protein kinase C beta (PRKCB), and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta (PIK3C2B).ConclusionWenxin decoction can effectively improve cardiac function in AMI-HF patients with Qi deficiency and blood stasis syndrome. Its mechanism may be related to the regulation of cell signal transduction, functional modulation, energy metabolism, cellular immunity, and inflammatory response, providing new insights and supporting evidence for the clinical application of Wenxin Decoction.
摘要:ObjectiveTo observe the effects of modified Huanglian Wendantang on chronic inflammation and vascular endothelial function in metabolic syndrome (MS).MethodsA total of 182 patients with MS in the outpatient and ward of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from June 2022 to June 2024 were enrolled and assigned into two groups (91 cases) according to the random number table method. The basic treatment of the two groups was the same, and the observation group was additionally treated with modified Huanglian Wendantang for 3 months. The traditional Chinese medicine (TCM) efficacy was observed in the two groups of patients. Before and after treatment, the following indicators were determined, including the degree of obesity [waist circumference (WC), body weight, body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)], blood pressure indicators [systolic blood pressure (SBP) and diastolic blood pressure (DBP)], blood lipid- and glucose-related indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2 h PG), and glycosylated hemoglobin (HbA1c)], insulin resistance-related indicators [homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-glucose index (TYG index), and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL) ratio], inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin (ADP), C-reactive protein (CRP)], and vascular endothelial function indicators [nitric oxide (NO), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1)]. In addition, the safety of treatment was assessed.ResultsIn terms of TCM efficacy, the observation group was significantly effective in 26 cases, effective in 47 cases, and ineffective in 17 cases, with the total effective rate of 81.1%. The control group was significantly effective in 15 cases, effective in 38 cases, and ineffective in 35 cases, with the total effective rate of 60.2%. The observation group had higher total effective rate than the control group (χ2=10.114, P<0.05). After treatment, both groups showed decreases in body weight, WC, BMI, WHR, WHtR, SBP, DBP, TC, TG, LDL-C, FPG, FINS, 2 h PG, HbA1c, HOMA-IR, TG/HDL ratio, TYG index, CRP, TNF-α, IL-6, ET-1, and iNOS (P<0.05) and increase in the levels of HDL-C, ADP, NO, and eNOS (P<0.05). Compared with the control group, the observation group showed declines in body weight, WC, BMI, WHR, WHtR, TC, TG, LDL-C, FPG, FINS, 2 h PG, HbA1c, HOMA-IR, TG/HDL ratio, TYG index, CRP, TNF-α, IL-6, ET-1, and iNOS (P<0.05) and elevations in HDL-C, ADP, NO, and eNOS (P<0.05). However, after treatment, there was no significant difference in SBP or DBP between the observation group and the control group. Adverse reactions were observed in neither group.ConclusionModified Huanglian Wendantang can significantly ameliorate the symptoms, reduce inflammation, and improve the vascular endothelial function of MS patients, with no adverse reactions and high safety.
关键词:metabolic syndrome;modified Huanglian Wendantang;cardiovascular risk factors;inflammatory factors;vascular endothelial function
摘要:ObjectiveTo explore the typical traditional Chinese medicine (TCM) syndrome patterns and their highly diagnostic symptoms and signs in patients with chronic kidney disease stage 5 (CKD G5) undergoing hemodialysis.MethodsTCM four-diagnostic data were collected from 100 CKD G5 hemodialysis patients. Latent class analysis (LCA) was employed to identify the major TCM syndrome patterns. Based on these patterns, relevant symptoms and signs were analyzed, and binary logistic regression models were constructed to determine those with high diagnostic value.ResultsAmong the 100 CKD G5 hemodialysis patients, a total of 338 symptoms and signs were recorded, with 2 790 occurrences. Thirty-five syndrome elements were extracted, with a cumulative frequency of 728. Among them, 11 elements appeared ≥30 times (totaling 536 occurrences), including pathological nature elements such as Qi deficiency (n=63), Yin deficiency (n=58), Yang deficiency (n=55), dampness (n=53), heat (n=46), phlegm (n=44), blood deficiency (n=44), and Qi stagnation (n=31), and pathological location elements including the kidney (n=57), liver (n=44), and spleen (n=41). LCA classified 84 CKD G5 hemodialysis patients with identifiable syndrome elements into two groups, with Qi deficiency and Yin deficiency as the distinguishing features, forming the predominant syndrome pattern of Qi-Yin deficiency. Based on the Qi-Yin deficiency syndrome, nine high-frequency symptoms and signs were identified, including greasy tongue coating (n=42), deep pulse (n=41), yellow-white mixed tongue coating (n=39), thready pulse (n=38), thirst (n=34), insomnia (n=34), weak Chi pulse (n=30), wiry pulse (n=30), and poor sleep quality (n=30). Further binary logistic regression analysis combining these nine features with the LCA classification results showed that greasy tongue coating, thirst, insomnia, and poor sleep quality were statistically significant (P<0.05).ConclusionThe predominant TCM syndrome among CKD G5 hemodialysis patients is Qi-Yin deficiency. Greasy tongue coating, thirst, insomnia, and poor sleep quality are typical symptoms and signs strongly associated with the diagnosis of Qi-Yin deficiency in this population.
摘要:ObjectiveTo observe the efficacy of Erhuang suppository in treating high-risk human papillomavirus (HR-HPV) infection and investigate its effects on vaginal microecology and related factor expression.MethodsNinety-two patients were randomly assigned into an observation group and a control group, with 46 patients in each group. The control group was treated with recombinant human interferon α-2b gel, while the observation group was treated with Erhuang suppository. The two groups were compared in terms of their changes in traditional Chinese medicine (TCM) symptom scores, efficacy for HR-HPV, average HR-HPV DNA load, thinprep cytologic test (TCT) results, improvement of vaginal microecology, and expression of related factors.ResultsAfter treatment, the observation group showed decreases in the average DNA load of 2 HR-HPV types, abnormalities in microbial diversity, dominant bacteria, hydrogen peroxide, leukocyte esterase, pH value, vaginal microenvironment, and levels of tumor necrosis factor-α (TNF-α) and nuclear factor kappa-B (NF-κB), and an increase in the interleukin-12 (IL-12) level (P<0.05). The control group showed a decrease in the incidence β-glucuronylase abnormalities after treatment (P<0.05). Compared with the baseline before treatment, the observation group and the control group showed decreases in the total score of TCM symptoms, the average DNA load of 12 HR-HPV types, average DNA load of 2+12 HR-HPV types, interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), and myeloid differentiation factor 88 (MyD88) after treatment (P<0.05). After treatment, the observation group had lower total TCM symptom score, average DNA load of two HR-HPV types, and levels of TNF-α, IL-6, TLR4, MyD88, and NF-κB, and higher IL-12 level than the control group (P<0.05). Moroever, the observation group outperformed the control group in reducing the abnormalities in dominant bacteria, hydrogen peroxide, leukocyte esterase, pH value, and vaginal microenvironment (P<0.05). The total response rate of HR-HPV infection was 83.3%(35/42) in observation group and 74.4%(32/43) in control group. The total response rate of TCT was 88.1%(37/42) in observation group and 88.3%(38/43) in control group, with no statistical significance.ConclusionIn the treatment of HR-HPV infection and TCT, Erhuang Suppository has comparable efficacy with recombinant human interferon α-2b gel and is superior to recombinant human interferon α-2b gel in improving multiple indicators of vaginal microecology, alleviating clinical symptoms of HR-HPV patients, and reducing the average DNA load of two HR-HPV types. The mechanism may be related to the decreases in TNF-α, IL-6, TLR4, MyD88, and NF-κB levels and the increase in the IL-12 level.
关键词:high-risk human papillomavirus;Erhuang Suppository;vaginal microecology;therapeutic effect;viral load
摘要:ObjectiveTo conduct a comprehensive review and synthesis of research pertaining to the treatment of diarrhea using Changyanning granules, showcasing their effectiveness and unique attributes, and thereby offering guidance for clinical rational drug utilization, hospital procurement strategies, and drug supply management.MethodsIncorporating evidence-based medicine, epidemiology, pharmacoeconomics, and health technology assessment(HTA), along with other relevant methodologies, this study employed a combined qualitative and quantitative evaluation approach. Through questionnaires, official website data information, published literature and secondary evaluation of real-world data, a total of "6+1" dimensions were used to build an evaluation system for the safety, effectiveness, economy, innovation, suitability, accessibility and characteristics of traditional Chinese patent medicines and simple preparations.Results①Safety:The comprehensive safety evaluation of Changyanning granules was A, indicating sufficient safety evidence, clear results, and good safety. ②Effectiveness:Compared with the treatment plan of using probiotics alone, the combination of Changyanning granules and probiotics demonstrated superior efficacy in treating pediatric diarrhea, and was evaluated as Grade B, indicating good effectiveness. ③Economy:Compared to probiotic monotherapy, the use of Changyanning granules combined with probiotics to treat pediatric diarrhea could shorten the duration of diarrhea by an average of 1 day, this additional day of treatment incurred an extra cost of 29.7 Yuan. The economic evaluation was B-level, which meant that the economic evidence was relatively sufficient, the results were clear, and the economy was good. ④Innovation:Changyanning granules not only had a protective inhibitory effect on excessive intestinal peristalsis, but also could relieve smooth muscle spasm, restore intestinal motility, regulate bidirectionally, and stop diarrhea without constipation. The innovation evaluation was B-level, with good innovation. ⑤Suitability:Changyanning granules was easy to use, no special administration time was required, and it was evaluated as grade B, indicating sufficient evidence of suitability and good suitability. ⑥Accessibility:The winning bid price for Changyanning granules was 9.16 Yuan/pack or 9.67 Yuan/pack. The limited daily expenses accounted for 0.08%-0.09% of the median disposable income of urban residents and 0.31%-0.32% of the median disposable income of rural residents, indicating good affordability. The sales scope covered 31 provinces, municipalities, and autonomous regions, with good accessibility and a comprehensive evaluation level of A. ⑦Traditional Chinese medicine(TCM) characteristics:Changyanning granules was derived from a traditional folk formula, which had the functions of clearing heat and removing dampness with promoting Qi. Post-marketing clinical studies evaluating TCM characteristics of this drug yielded 3+ ratings, placing it in grade B. The evidence of TCM characteristic dimension was relatively sufficient, and the results were clear, indicating that Changyanning granules exhibited particularly prominent TCM characteristics. ⑧Comprehensive evaluation of clinical value:Based on the "6+1" dimensions mentioned above, combined with multi-criteria decision analysis(MCDA) model and calculations using CSC v2.0 software, the results showed that there was sufficient evidence for the clinical value of Changyanning granules, and the results were clear.ConclusionAfter comprehensive evaluation, Changyanning granules demonstrates sufficient evidences of safety, effectiveness, economy, innovation, suitability, accessibility and TCM characteristics and clinical value, with clear results and definitive conclusions. It is recommended that, under specific conditions, relevant policy achievements be translated into practical guidance for basic clinical medication management to better serve clinical treatment.
摘要:ObjectiveTo analyze the alcohol oxidase gene AlAOX1 in Arctium lappa and lay a theoretical foundation for the subsequent study of the role of the alcohol oxidase gene.MethodsThe AlAOX1 gene was screened based on the pre-transcriptomic data of our group. In this paper, gene cloning, bioinformatics analysis, phylogenetic analysis, and subcellular localization analysis were performed to clarify the gene characteristics and physicochemical properties of AlAOX1, and the gene expression of A. lappa in the germination process and different tissues was analyzed by Real-time polymerase chain reaction (Real-time PCR), and the gene expression of A. lappa was analyzed under different abiotic stresses.ResultsThe AlAOX1 gene was successfully cloned and uploaded to the National Center of Biotechnology Information (NCBI) database. The sequence length of the AlAOX1 gene was 2 214 bp, encoding 737 amino acids. The AlAOX1 protein is hydrophilic and belongs to the category of stabilized proteins, non-transmembrane structure, and signal peptide, and it contains 75 phosphorylation sites. Phylogenetic tree analysis showed that this protein clustered into a clade with Asteraceae, with the highest similarity to homologous proteins in Cynara cardunculus. Subcellular localization analysis showed that AlAOX1 was localized in chloroplasts. The Real-time PCR analysis showed that the expression of the AlAOX1 gene varied with different tissues during seed germination, and the highest expression was found in seedlings and roots at day 9, reaching (25.62±3.24) (P<0.01) and (1.70±0.11) (P<0.01), respectively, which were significantly higher than the control group. The results of abiotic stress experiments showed that A. lappa roots were treated with high salt stress (200 mmol·L-1), drought stress (25% PEG), and low-temperature stress (4 ℃) at 24, 24, 12 h, respectively, at (2.63±0.93) (P<0.01), (1.58±0.21) (P<0.05), and (2.51±0.44) (P<0.01), all significantly higher than the control group, which possessed the effect of resistance to abiotic stresses.ConclusionIn this study, the AlAOX1 gene was successfully cloned, and the molecular characterization and expression properties of the AlAOX1 gene were determined. It was hypothesized that it plays a regulatory role in the growth and development of A. lappa, as well as in abiotic stress, which lays a theoretical foundation for further research on the specific roles of alcohol oxidase genes in A. lappa.
摘要:ObjectiveTo compare the differences in volatile components among raw products and ginger-processed products of Coptidis Rhizoma, and the processing auxiliary material of ginger juice, and screen the characteristic volatile markers of ginger-processed products, in order to reveal the material basis changes before and after ginger processing of Coptidis Rhizoma.MethodsHeadspace solid-phase microextraction-gas chromatography-quadrupole-time-of-flight mass spectrometry(HS-SPME-GC-Q-TOF-MS) was used to analyze the volatile compositions of raw products, ginger-processed products and ginger juice, and chemometric analysis of the peak area data was performed using SIMCA 14.1, and the components with variable importance in the projection(VIP) value>1.0, P<0.05 and |log2fold change(FC)|>20 were selected as the characteristic volatile markers of ginger-processed Coptidis Rhizoma, and the differential components before and after processing were visualized by log2 values of peak area response values.ResultsA total of 105 volatile components were identified, among which olefins, terpenes, alcohols, esters, aromatics, heterocycles, ketones and aldehydes were the main volatile components of raw products, ginger-processed products and ginger juice. Among them, six components in the ginger-processed products were derived from ginger juice, and another 13 components might be newly generated components after ginger processing. Chemometric analysis showed that there were significant differences among the three samples and they could be clearly distinguished and clustered. The content differences of 26 volatile components such as 4,5-dimethyl-2,6-octadiene, 4-methyl-3-penten-1-ol and 2-methylpentanoic acid were particularly obvious, which could be used as the characteristic components to distinguish raw products from ginger-processed products of Coptidis Rhizoma.ConclusionThe volatile component profile of Coptidis Rhizoma before and after ginger processing changed significantly, and the mechanism may involve the introduction of active ingredients in excipients and the transformation of chemical components. This study can provide a basis for research on the processing theory, quality control and pharmacodynamic mechanism of ginger-processed Coptidis Rhizoma.
摘要:Shengmaisan is known as "the holy medicine for nourishing Qi", and there are other alternative names, such as Shengmaitang, Qianjin Shengmaisan, Yilu Shengmaisan, Renshen Shengmaisan, Shengmaiyin, Shenmai Wuweiyin, Shenmaisan, etc. It was first recorded in Yixue Qiyuan written by ZHANG Yuansu, a doctor in the Jin dynasty. It is composed of Ginseng Radix et Rhizoma, Ophiopogonis Radix and Schisandrae Chinensis Fructus with the effect of benefiting Qi and generating fluid, moistening lung and stopping thirst, effectively treating both Qi and Yin deficiency. In this study, the method of bibliometrics was used to systematically examine Shengmaisan from the aspects of formula name and origin, formula composition evolution and meaning, dose evolution, drug origin and processing, decoction method and clinical application. Regarding the origin, the origins of the three constituent drugs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The dose and decoction method of the formula were not recorded in Yixue Qiyuan, and were all from Danxi Xinfa Fuyu, which was the closest to Yixue Qiyuan. After the conversion of ancient and modern doses, the dose of each drug was determined as follows:3.73 g of Ginseng Radix et Rhizoma, 7.46 g of Ophiopogonis Radix, 2.98 g of Schisandrae Chinensis Fructus. The decoction method involves grinding the herbs into granules with a particle size of 2-4.75 mm, adding 200 mL of water, boiling down to 140 mL, and taking it on an empty stomach before meals or at any convenient time, twice a day. Modern research has identified over 200 kinds of diseases primarily involving the cardiovascular, respiratory, and endocrine systems, with patterns such as Qi and Yin deficiency serving as key diagnostic criteria. In summary, through the textual research on the ancient literature of Shengmaisan, a philological basis is established for its further research and development.
摘要:Foshousan is included in the Catalogue of Ancient Classic Formula (Second Batch) and is recorded in An Complete Collection of Effective Prescription for Women (hereinafter referred to Liangfang). The formula in Liangfang contains five herbs: Angelicae Sinensis Radix, Chuanxiong Rhizoma, Astragali Radix, Bupleurum Radix, and Peucedani Radix. Research shows that a two-herb version composed only of Angelicae Sinensis Radix and Chuanxiong Rhizoma, also called "Xionggui Tang", was more widely transmitted in the past dynasties. Xionggui Tang was first recorded in Experimental Formulas for Universal Relief written by XU Shuwei in the Song Dynasty and has since served as a paradigm for later applications. Through the systematic collation of ancient and modern literature, the historical origin, composition, botanical origins, processing, dosage, decoction methods and indications of the five-herb Foshousan in Liangfang and of Xionggui Tang were investigated and analyzed by bibliometric methods. The results showed that the five-herb Foshousan in Liangfang was composed of Angelicae Sinensis Radix, Chuanxiong Rhizoma, Astragali Radix, Bupleuri Radix, and Peucedani Radix. Their botanical origins were the dried rhizome of Angelica sinensis, the dried rhizome of Ligusticum chuanxiong, the dried root of Astragalus membranaceus var. mongholicus or A. membranaceus, the dried root of Bupleurum chinense, and the dried root of Peucedanum praeruptorum. All herbs were used raw. The dosage was 4.10 g of each of Angelicae Sinensis Radix, Chuanxiong Rhizoma, and Astragali Radix, and 0.04 g each of Bupleuri Radix and Peucedani Radix. The decoction method was to crush the five herbs into coarse powder with a particle size of 2-4 mm, 12.39 g per dose, decocted with 600 mL of water together with 9.42 cm of peach branch and willow branch respectively, 0.5 g of black plum, 3 g of Jujubae Fructus and 3 g of Zingiberis Rhizoma Recens, until 360 mL remained, remove the residue and take the decoction warm. If there was phlegm, black plum was omitted. The formula could tonify Qi and nourish blood, promote Qi movement and disperse evil, and was indicated for postpartum blood deficiency with fatigue, night sweating, somnolence with debility, and cough with phlegm. Xionggui Tang consisted of Chuanxiong Rhizoma and Astragali Sinensis Radix. Their botanical origins were the dried rhizomes of Angelica sinensis and Ligusticum chuanxiong. The recommended processing was Angelica sinensis Radix with wine and Chuanxiong Rhizoma raw. The dosage was 4.95 g of Angelicae Sinensis Radix and 3.30 g of Chuanxiong Rhizoma. The decoction method was to crush the two herbs into coarse powder with a particle size of 2-4 mm, 8.26 g per dose, decoct with 180 mL of water until nearly dry, then add 600 mL of wine, bring to a boil once, remove the residue, and take warm. This formula nourishes and activates blood, moves Qi and resolves stasis, and can be used for all prenatal and postpartum symptoms and all blood loss symptoms.
关键词:Foshousan;historical origin;dosage;decoction method;classic formula
摘要:This article systematically analyzed the historical evolution of the name, origin, Latin name, medicinal parts, production area, harvesting, processing and clinical efficacy of Tougucao by referring to ancient and modern research materials, so as to provide a basis for the development and utilization of famous classical formulas containing Tougucao. Tougucao was first recorded in Jiuhuang Bencao, its original plant was Leonurus japonicus. Throughout history, the main botanical sources have been Speranskia tuberculate and Impatiens balsamina. Since modern times, the medicinal use of Tougucao across different regions has become increasingly complex and confusing due to variations in resource distribution and traditional usage habits, involving a total of 49 plant species across 28 genera and 20 families. The medicinal parts of Tougucao typically consist of the dried aerial parts or complete stems and leaves of the plant. These are usually harvested during the summer and autumn when the plants are at their most vigorous. After harvesting, the parts are cleaned of impurities and non-medicinal parts and then dried. Generally, the best quality is achieved with branches and leaves that are dry, green in color, root-free, free from mold and insect damage, and freshly collected in the same year. The processing methods for the botanical sources of Tougucao have remained largely unchanged over time, they typically involve removing impurities and residual roots, washing thoroughly with water, slightly moistening, cutting into segments, and drying. The properties of the main botanical sources of Tougucao are primarily characterized as pungent and warm, which can help to dispel cold and promote the circulation of Qi and blood. Based on the research results, it is recommended to use Speranskia tuberculate and Impatiens balsamina, which are widely used and have a long history of application in various regions, as the main botanical sources of Tougucao. To address the issue of difficulty in standardizing the quality of medicinal herbs due to multiple botanical sources, it is recommended to standardize the plant sources and names of Tougucao.
关键词:Tougucao;herbal textual research;origin;quality evaluation;processing;producing area;nature, flavor and efficacy
摘要:Chronic obstructive pulmonary disease (COPD) is a progressive, incurable respiratory disease and the third leading cause of death worldwide. The primary pathological manifestation of COPD is a pulmonary inflammatory response, in which macrophages play a key role. M1 macrophages secrete pro-inflammatory mediators, clearing invading pathogens in the early stages of inflammation. M2 macrophages have anti-inflammatory and tissue-repairing effects. This study explored the mechanism of macrophage polarization in the immunoinflammatory process of COPD based on the traditional Chinese medicine (TCM) theory of "Yin-Yang balance", aiming to provide new insights for COPD treatment. During the pathological process of COPD, an imbalance in macrophage polarization leads to persistent inflammatory responses, further exacerbating the condition. Given the characteristics of macrophage polarization in COPD pathogenesis, this study explored the potential mechanisms by which TCM modulates macrophage polarization to intervene in COPD, focusing on aspects such as inflammatory imbalance, oxidative stress, dysregulation of the protease-antiprotease balance, and metabolic disorders. Research indicated that various TCM components can influence macrophage polarization by regulating signaling pathways such as Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) and mitogen-activated protein kinase (MAPK), thereby restoring the dynamic balance between M1 and M2 macrophages and alleviating inflammatory responses. The article further proposed a COPD treatment strategy based on the "Yin-Yang balance" theory and emphasized TCM intervention in macrophage polarization and regulation of immunoinflammatory responses. The study provides a new theoretical basis and treatment strategies for the comprehensive prevention and treatment of COPD.
摘要:In vitro fertilization and embryo transfer (IVF-ET) is a key technology for addressing infertility. However, clinical bottlenecks remain, resulting in generally low pregnancy and live birth rates, and reproductive problems are not yet effectively resolved. Traditional Chinese medicine (TCM) has unique characteristics and advantages in assisted reproduction, but standardized protocols are lacking. This article summarizes innovations in the theories of nationally renowned TCM practitioners in assisted reproduction and their experience in integrating TCM with IVF-ET, aiming to incorporate TCM's distinctive advantages into assisted reproductive technologies and to provide strategies and approaches for improving IVF-ET success rates.
关键词:integration of traditional Chinese and Western medicine;reproduction;assisted reproduction technology;in vitro fertilization and embryo transfer;infertility
摘要:Hashimoto's thyroiditis (HT) is an autoimmune disease mediated by cells and antibodies. The pathogenesis of this disease is not clear, and it is mainly closely related to genetic and environmental factors. It is characterized by B-cell dysfunction and disruption of immune homeostasis by abnormal T-cell subsets, which result in damage to thyroid autoantibodies and thyroid tissue. The mainstream of Western clinical treatment is thyroid hormone replacement therapy. This method is effective to a certain extent, but the efficacy is unstable, with more adverse reactions and a high recurrence rate, which aggravates the burden on patients. In recent years, traditional Chinese medicine (TCM) has made some progress in the treatment of HT. The intervention of TCM in HT has the advantages of a broad pathway, many targets, a simple and inexpensive effect, and small side effects. Several studies have shown that TCM monomers and compounds can inhibit pathological processes such as inflammatory response, oxidative stress, cellular autophagy, apoptosis, ferroptosis, and endoplasmic reticulum stress by acting on multiple targets in thyroid cells and modulating disease-related signaling pathways, thereby attenuating autoimmune responses and slowing down the progression of the disease. Therefore, this paper summarized the main signaling pathways of TCM intervention in HT [phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, nuclear transcription factor-κB (NF-κB) signaling pathway, Notch signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, NOD-like receptor protein 3 (NLRP3)/cysteine-containing aspartic protein Caspase-1 signaling pathway, protein kinase R-like endoplasmic reticulum kinase (PERK)/activating factor for transcription 4 (ATF4)/endoplasmic reticulum stress (CHOP) signaling pathway, and chemokine ligand 2 (CCL2)/chemokine receptor 2 (CCR2) signaling pathway], aiming to provide a certain reference for the development of new drugs.
关键词:traditional Chinese medicine;hashimoto's thyroiditis;signaling pathway;mechanism of action;research progress
摘要:Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder characterized by infiltrative lesions in the periocular and orbital tissues. Currently, the pathogenesis of TAO has not been fully elucidated. Modern medicine often employs treatments such as glucocorticoids and immunosuppressants, which, although effective to some extent, are associated with significant adverse effects and high rates of drug resistance. Traditional Chinese medicine (TCM), with its long history of development, plays an important role in the prevention and treatment of TAO. Although numerous studies have investigated the use of TCM in the treatment of TAO, systematic summaries remain limited. Based on a systematic review of relevant literature, this paper finds that, in basic research, many studies have focused on the active components of Chinese herbal medicines for the treatment of TAO, mainly including alkaloids, terpenes, quinones, flavonoids, and saponins. Their mechanisms of action involve reducing autophagy, inducing cell cycle arrest, inhibiting orbital oxidative stress and inflammatory responses, and possibly regulating signaling pathways such as peroxisome proliferator-activated receptor γ (PPARγ), adenosine monophosphate-activated protein kinase (AMPK), β-catenin, nuclear factor-κB (NF-κB), and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE). Chinese herbal formulae are mainly derived from the Pingmu decoction and Pingtu Powder series, with mechanisms related to inhibiting immune-inflammatory responses and reducing the accumulation of orbital adipocytes. In clinical research, TCM practitioners throughout history have primarily used treatments aimed at resolving phlegm and dispersing blood stasis, soothing the liver and strengthening the spleen, and tonifying Qi and Yin, all of which have shown favorable clinical efficacy. At the same time, external TCM therapies for TAO mainly include acupuncture, bloodletting, massage, and herbal atomization. Furthermore, it has been found that combining internal herbal medication with external therapies can further enhance clinical outcomes in patients. In summary, through literature retrieval and systematic review, this paper comprehensively analyzes and summarizes the current status of TCM research on TAO, aiming to provide new perspectives and ideas for the prevention and treatment of TAO with TCM.
关键词:traditional Chinese medicine;thyroid-associated ophthalmopathy;clinical application;mechanism of action
摘要:Traumatic optic neuropathy (TON) refers to the irreversible loss of vision caused by optic nerve damage due to eye or head trauma. At present, the treatment of TON faces multiple challenges, including the inconsistency of intervention methods, the delayed treatment, and the limited effect of visual recovery. These challenges make the prognosis of TON patients complicated, which necessitate new treatment options. In this context, traditional Chinese medicine (TCM) has gradually attracted the attention of researchers due to its unique theoretical framework and definite clinical efficacy in the cognition and treatment of TON, as well as the multi-target and multi-channel regulation characteristics. With the deepening of basic research on TON, more and more studies have revealed the potential mechanism of TCM in the treatment of TON, mainly involving alleviating oxidative stress, reducing inflammation, inhibiting apoptosis, and regulating neurotrophic factors and their receptors. Related signaling pathways include nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), mitogen-activated protein kinase (MAPK), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt). Although TCM has shown potential value in the treatment of TON, systematic literature review on its mechanisms and signaling pathways is still scarce. Through the review, collation, and induction of relevant literature at home and abroad, the mechanisms and signaling pathways of TCM in the treatment of TON are systematically summarized, which provides reference for subsequent research, clinical application, and further development of TCM in the treatment of TON.
摘要:Diminished ovarian reserve (DOR) has become one of the major challenges in women's reproductive health, with a continuously increasing prevalence that significantly affects female fertility and quality of life. The pathogenesis of DOR is complex, involving aging, autoimmunity, genetic factors, environmental influences, and other aspects, and its specific pathological mechanisms have not yet been fully elucidated. Hormone replacement therapy is the main treatment for DOR, but long-term use of hormonal drugs carries certain side effects. Chinese medicine has the therapeutic advantages of multi-target, multi-pathway, and multi-component actions. It emphasizes holistic treatment and individualized therapy, and its mild pharmacological effects can help reduce the side effects of Western medicines. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a crucial role in regulating ovarian function by controlling follicular activation and dormancy, inhibiting granulosa cell autophagy, reducing ovarian oxidative stress and apoptosis, promoting oocyte maturation, stimulating granulosa cell proliferation, and facilitating ovarian angiogenesis, thereby intervening in DOR. Chinese medicine monomers and compound formulas can modulate the ovarian microenvironment, enhance follicular activity, and inhibit apoptosis by regulating the PI3K/Akt signaling pathway, effectively protecting ovarian cells in DOR patients and restoring ovarian function and fertility. This review aims to systematically summarize the pathological association between the PI3K/Akt signaling pathway and DOR, and to highlight the latest research progress on Chinese medicine monomers and compound formulas that intervene in DOR by modulating this pathway, providing a theoretical basis for the development of novel Chinese medicine-based therapeutic strategies.
关键词:diminished ovarian reserve;phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway;traditional Chinese medicine;mechanism of action;research progress
摘要:As precision and individualization become an inevitable trend in the future development of medicine, the sex differences in drug efficacy and toxicity have once again received global attention. The potential sex differences in the efficacy and toxicity of Chinese materia medica are objectively existent. In the theoretical model of traditional Chinese medicine (TCM), sex differences are deconstructed as specific manifestations of the exuberance and decline of Yin and Yang and the imbalance of Qi and blood. This cognitive approach naturally integrates sex factors into the syndrome differentiation system rather than treating them as independent variables. However, it already implies a unique understanding of sex differences and is reflected in the clinical application of TCM prescriptions. Modern medicine has a scientific and systematic understanding of the biological basis of sex differences, and it has partially revealed the sex differences in the pathological mechanisms of common diseases, providing a theoretical framework for analyzing the sex-specific effects of TCM. By reviewing traditional theories and modern literature, this article elaborates on the sex differences in the efficacy, toxicity, and pharmacokinetics of prescriptions, Chinese medicinal materials, and their components. However, the studies on sex differences in Chinese materia medica are still scarce. In the future, new technologies and methods can be combined to gradually solve the limitations of existing methods and promote the traceability of sex differences from clinical research to basic research. Revealing the sex differences in Chinese materia medica helps to explain the scientific connotation of traditional medication experience, guide the precise development and application of TCM health products with both edible and medicinal values, clarify their target audience and product positioning, and provide a scientific basis for optimizing clinical medication strategies. This review aims to provide a reference for similar studies.
摘要:Over the past half century, a large number of bamboo slips and silk books have been unearthed across the country, which is one of the most important achievements of Chinese archaeology. Among them, the discovery of a large number of documents on Shushu and Fangji has a significant and profound impact on the research on the origin and formation of traditional Chinese medicine. Up to now, the number of unearthed bamboo and silk medical texts has exceeded 10 000, of which medical formulae account for more than 60%. These are important historical materials that cannot be ignored for the current research on the origin of classical formulae, the historical evolution of classic formulae, formulae composition theory and the elementary morphism source of Chinese medicines. This article systematically reviews the progress in the discovery, compilation and research of medical formulae since the 1970s, highlighting that there has been a significant amount of research related to ancient literature surrounding unearthed medical formulae materials, as well as exploratory clinical application results. Moreover, it showcases the innovative application of research methods such as data mining and knowledge graph. Overall, the research on unearthed Qin and Han medical formulae has the most abundant results in textual interpretation, academic origin research, and medical history. Although the compatibility rules and diagnostic modes are involved, it is mostly based on the traditional literature study, and no breakthrough results have been achieved. It is necessary to introduce the perspective of historical restoration and use interdisciplinary research to conduct in-depth exploration. At the same time, combining modern scientific and technological methods to carry out herbal archaeology and clinical application of prescriptions and medicines is a direction that can be further explored in the future.
关键词:Qin and Han dynasties;formulae;unearthed literature;review;famous classical formulas;Compatibility Law