摘要:ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 (TRPV1) and bitter taste receptor 14 (TAS2R14) in the lung tissue of the rat model of cold asthma.MethodSeventy SD rats were randomized into 7 groups: normal, model, Shegan Mahuangtang, pungent Chinese herbs, bitter Chinese herbs (6.43 g·kg-1), dexamethasone (0.5 g·kg-1), and Guilong Kechuanning (10 g·kg-1). The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin (OVA) and aluminium hydroxide in the limbs, combined with 2% OVA atomization and cold (2-4 ℃) stimulation. The rats were treated with corresponding drugs by gavage and atomization, and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation, airway inflammation and cell proliferation were observed by hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining of the lung tissue. The levels of interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin (TSLP), and transforming growth factor-β1 (TGF-β1) in the serum were measured by enzyme-linked immunosorbent assay (ELISA). The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1, TAS2R14, phospholipase Cβ2 (PLCβ2), B-cell lymphoma-2 (Bcl-2), and α-smooth muscle actin (α-SMA) in the lung tissue was determined by Western blot.ResultCompared with the normal group, the model group showed decreased water intake, food intake, and body weight, increased airway inflammatory cell infiltration, goblet cell proliferation, tissue fibrosis and collagen deposition, elevated levels of IL-5, TNF-α, TSLP, and TGF-β1 in the serum (P<0.01), upregulated expression of TRPV1, PLCβ2, and α-SMA, and downregulated expression of TAS2R14 and Bcl-2 (P<0.05, P<0.01). Compared with model group, Shecgan Mahuangtang, pungent Chinese herbs, and bitter Chinese herbs increased the water intake, food intake, and body weight, reduced the inflammatory cell infiltration and goblet cell proliferation, alleviated tissue fibrosis and collagen deposition, lowered the levels of IL-5, TNF-α, TSLP, and TGF-β1 in the serum (P<0.01), downregulated the expression of TRPV1, PLCβ2, and α-SMA, and upregulated the expression of TAS2R14 and Bcl-2 (P<0.05, P<0.01).ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation, downregulate the expression of TRPV1, PLCβ2, and α-SMA, and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover, bitter Chinese herbs outperformed pungent Chinese herbs, and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.
关键词:pungent Chinese herbs;bitter Chinese herbs;cold asthma;transient receptor potential vanilloid-1 (TRPV1);bitter taste receptor 14 (TAS2R14)
摘要:ObjectiveTo investigate the effect and possible mechanism of Sishenwan in ameliorating visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome (IBS-D) due to spleen-kidney Yang deficiency.MethodForty male SPF-grade rats were randomly assigned into five groups: blank control, model, low- (3.51 g·kg-1) and high-dose (7.02 g·kg-1) Sishenwan, and Peifikang (0.54 g·kg-1) groups. Except the blank control group, the other groups underwent maternal separation stress and Sennae Folium decoction gavage for the modeling of IBS-D due to spleen-kidney Yang deficiency. After corresponding drug interventions, the general conditions of the rats were observed, and the number of defecation pellets within 6 h and the minimum threshold of abdominal withdrawal reflex (AWR) were measured. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of tumor necrosis factor (TNF)-α, gastrin (GAS), corticosterone (CORT), and adrenocorticotropic hormone (ACTH). Hematoxylin-eosin (HE) staining was employed to observe pathological changes in the colon tissue. Toluidine blue staining was used to assess mast cell degranulation in the colon tissue. Western blot was performed to determine the protein levels of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), transient receptor potential vanilloid 1 (TRPV1), and protease-activated receptor 2 (PAR2) in the colon tissue. Immunohistochemistry was employed to measure the protein level of TRPV1 in the colon tissue, and immunofluorescence was used to detect the positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in the colon tissue.ResultCompared with the blank control group, the model group showed increased number of defecation pellets within 6 h (P<0.01), decreased minimum threshold of AWR (P<0.01), elevated serum TNF-α level (P<0.01), lowered levels of GAS, CORT, and ACTH (P<0.05, P<0.01), increased mast cell degranulation rate (P<0.01), increased positive expression of TRPV1, SP, and CGRP (P<0.05, P<0.01), and upregulated protein levels of p38 MAPK, JNK, TRPV1, and PAR2 (P<0.01). Compared with the model group, the high-dose Sishenwan group showed increased minimum threshold of AWR (P<0.01), reduced defecation frequency in both the high-dose Sishenwan and Peifikang groups (P<0.05, P<0.01), lowered TNF-α level (P<0.05, P<0.01), elevated levels of GAS, CORT, and ACTH (P<0.05, P<0.01), decreased mast cell degranulation rate (P<0.01), reduced positive expression of TRPV1, SP, and CGRP (P<0.05, P<0.01), and downregulated protein levels of p38 MAPK, JNK, TRPV1, and PAR2 (P<0.05, P<0.01).ConclusionSishenwan can ameliorate visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome due to spleen-kidney Yang deficiency by regulating the p38 MAPK/JNK/TRPV1 signaling pathway.
关键词:diarrhea-predominant irritable bowel syndrome;syndrome of spleen-kidney Yang deficiency;Sishenwan;p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK)/transient receptor potential vanilloid 1 (TRPV1) pathway;visceral sensitivity
摘要:ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology and pharmacodynamics, to investigate the pharmacodynamic material basis and mechanism of Hei Xiaoyaosan in improving learning and memory ability of insomnia rats.MethodUPLC-Q-TOF-MS was used to characterize the chemical constituents of Hei Xiaoyaosan. Network pharmacology was applied to construct the network of active ingredients-intersecting targets-pathways, and molecular docking was performed on key ingredients and core targets. Sixty 8-week-old male SD rats were selected and randomly divided into blank group, model group, Hei Xiaoyaosan low, medium, and high dose groups(3.82, 7.65, 15.30 g·kg-1), and zolpidem tartrate group(0.5 mg·kg-1), with 10 rats in each group. Except for the blank group, the insomnia model was induced by intraperitoneal injection of p-chlorophenylalanine(PCPA) for 4 consecutive days. Rats in each dosing group were administered the corresponding dose by gavage, once a day for 14 consecutive days. Morris water maze test was utilized to assess the learning and memory ability of rats, transmission electron microscopy was employed to examine the ultrastructure of hippocampal synapses, enzyme-linked immunosorbent assay(ELISA) was conducted to analyze the levels of 5-hydroxytryptamine(5-HT), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in hippocampal tissues, and Western blot was performed to detect the expression levels of tumor suppressor protein p53(TP53), rat sarcoma virus(RAS), epidermal growth factor receptor(EGFR), cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) binding protein(CREBBP), glycogen synthase kinase-3β(GSK-3β), protein kinase B1(Akt1), nitric oxide synthase 1(NOS1), phosphorylated(p)-Akt1, and p-GSK-3β in hippocampal tissues. Additionally, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to assess the mRNA expression levels of TP53, RAS, EGFR, CREBBP, GSK-3β, Akt1 and NOS1.ResultA total of 176 components were identified in Hei Xiaoyaosan, mainly flavonoids, triterpene saponins, phenylpropanoids and other compounds. Network pharmacological analysis revealed that TP53, V-Ha-Ras Harvey Rat sarcoma viral oncogene homolog(HRAS), neuroblastoma sarcoma viral oncogene homolog(NRAS), EGFR, CREBBP, GSK-3β, Akt1 and NOS1 were the key targets of Hei Xiaoyaosan in treating insomnia. The core targets were predominantly associated with cAMP, RAS, Ras-associated protein 1(Rap1), advanced glycation end products(AGE)/receptor for AGE(RAGE), and EGFR signaling pathways, and the key active ingredients of Hei Xiaoyaosan in treating insomnia were 8-shogaol, ligustilide F, 6-gingerol, levistilide A and senkyunolide E. Animal experiment results demonstrated that Hei Xiaoyaosan medium and high dose groups significantly increased body weight, shortened sleep latency and prolonged sleep duration in insomnia rats(P<0.01), significantly decreased escape latency and increased platform crossing frequency(P<0.01), and improved the pathological changes of hippocampal synaptic ultrastructure. Meanwhile, the two groups could significantly elevate 5-HT level, Akt1 mRNA expression, Akt1 and p-Akt1 protein expression(P<0.01), reduce inflammatory factor levels(P<0.01), and down-regulate protein expression levels of TP53, RAS, NOS1, EGFR, CREBBP, GSK-3β and p-GSK-3β(P<0.01), as well as mRNA expression levels of TP53, RAS, NOS1, EGFR, CREBBP and GSK-3β in hippocampal tissues(P<0.01).ConclusionThis study determined that the five key active ingredients(8-shogaol, ligustilide F, 6-gingerol, levistilide A and senkyunolide E) in Hei Xiaoyaosan may improve the learning and memory ability of insomnia rats by regulating signaling pathways such as cAMP, RAS, and EGFR, providing an important reference for its mechanism research and clinical application.
关键词:Hei Xiaoyaosan;insomnia;learning and memory ability;ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS);network pharmacology;material basis;hippocampal tissues
摘要:ObjectiveTo observe the effects of Xuefu Zhuyu capsules (XFZY) on blood lipid levels and aortic plaques in the mouse model of atherosclerosis (AS) induced by a high-fat diet by regulating the silencing regulatory factor 2-like protein 3 (Sirt3)/exchange protein directly activated by cAMP 1 (EPAC1) signaling pathway and explore the mechanism of XFZY in ameliorating AS.MethodMice were assigned into normal, model, blank, rosuvastatin (0.05 g·kg-1·d-1), and low-, medium-, and high-dose (0.3, 0.6, 1.2 g·kg-1·d-1, respectively) XFZY groups. The normal group consisted of normal C57BL/6J mice, while the other groups consisted of ApoE-/- C57BL/6J mice. The normal group and blank group were fed routinely, and the rest groups were fed with a high-fat diet for 24 consecutive weeks for the modeling of AS. The drug intervention groups were administrated with corresponding drugs by gavage, and model group and blank group with an equal volume of deionized water for 6 consecutive weeks. The small animal B-ultrasound was used to evaluate the mouse heart function and aortic plaque condition. A fully automated biochemical analyzer was used to measure the levels of blood lipids such as total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and extremely low-density lipoprotein (VLDL) in mice. Oil red O staining was employed to observe lipid deposition in the aorta. Hematoxylin-eosin staining and Masson staining were employed to observe the pathological changes and collagen deposition in mouse blood vessels. Transmission electron microscopy was employed to observe the mitochondrial damage in mouse aorta. The levels of adrenocorticotropic hormone (ACTH), adenosine triphosphate (ATP), and nicotinic choline receptor α1 (CHRNα1), and total superoxide dismutase (T-SOD) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were performed to determine the mRNA and protein levels, respectively, of Sirt3, EPAC1, Caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the mouse aorta and heart.ResultMultiple AS plaques were observed in the aortic arch, indicating that the model was successfully established. Compared with the model group, the XFZY groups showed reduced and narrowed plaques. Compared with the normal group, the model group showed elevated CHOL level (P<0.01). Compared with the model group, rosuvastatin and low-dose XFZY lowered the CHOL and TG levels (P<0.01). Compared with the normal group, the model group presented a large number of protruding red lipid plaques on the aortic wall and increased percentage of AS plaque area to total tissue area (P<0.01). Compared with the model group, low-dose XFZY reduced the plaque load (P<0.05). Compared with the model group, XFZY at different doses reduced the lipid plaques and collagen deposition. Compared with the normal group, the model group showed decreased or disappeared mitochondrial cristae and presented severe damage of the membrane structure in endothelial cells. The mitochondria of endothelial cells in each treatment group approached the normal structure, with mitochondrial cristae faintly visible. Compared with the normal group, the model group showcased reduced myocardial mitochondrial ATP activity (P<0.01), which were rescored in the drug intervention groups (P<0.01). Compared with the normal group, the modeling inhibited the expression of Sirt3 (P<0.01) and promoted the expression of EPAC1 (P<0.01). Compared with the model group, low-dose XFZY increased the Sirt3 content (P<0.01) and medium-dose XFZY increased the EPAC1 content (P<0.01), which indicated that XFZY treatment upregulated the mRNA and protein levels of Sirt3 and downregulated the mRNA and protein levels of EPAC1.ConclusionXFZY can alleviate the aortic lipid deposition, reduce the AS plaque area, improve the mitochondrial morphology and functions in endothelial cells, increase the ATP activity, upregulate the expression of Sirt3, and downregulate the expression of EPAC1 in AS mice by regulating mitochondrial energy metabolism via the Sirt3/EPAC1 signaling pathway.
关键词:Xuefu Zhuyu capsules;atherosclerosis;silencing regulatory factor 2-like protein 3 (Sirt3);exchange protein directly activated by cAMP 1 (EPAC1);mitochondria
摘要:ObjectiveTo observe the mechanism of Jiawei Guizhi Fuling decoction (JGFD) in alleviating sciatic nerve injury in painful diabetic peripheral neuropathy (PDPN) rats by regulating mitophagy through the PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway.MethodThe PDPN model was established by intraperitoneal injection of streptozotocin (STZ). After modeling, the rats were randomly divided into JGFD high, medium, and low dose groups (JGFD-H, JGFD-M, JGFD-L; 39.6, 19.8, 9.9 g·kg-1·d-1, respectively), a positive drug group (lipoic acid capsules, LA; 50 mg·kg-1·d-1), and a model group (PDPN). A blank control group (CON) was established. Drug intervention was administered continuously for 8 weeks after modeling. Measurements included body weight and fasting blood glucose of PDPN rats at weeks 0, 2, 4, and 8, mechanical pain threshold and thermal pain threshold at weeks 0 and 8, and motor nerve conduction velocity at week 8. Hematoxylin-eosin (HE) staining was used to observe the morphology of sciatic nerve tissue. The ultrastructure of mitochondria and autophagosomes was observed by transmission electron microscopy. Western blot was performed to detect the protein expression levels of PINK1, Parkin, p62, Beclin-1, and LC3 in sciatic nerve tissue. Additionally, real-time quantitative PCR (Real-time PCR) was performed to detect the mRNA expression levels of PINK1, Parkin, p62, Beclin-1, and LC3 in sciatic nerve tissue.ResultCompared with the CON group, the PDPN group showed a significant decrease in body weight at all time points, a significant increase in fasting blood glucose, significantly shortened mechanical pain and thermal pain thresholds, and significantly reduced motor nerve conduction velocity. The protein and mRNA expression of PINK1, Parkin, Beclin-1, and microtubule-associated protein light chain 3(LC3) in sciatic nerve tissue was significantly reduced, while p62 protein and mRNA expression was significantly increased (P<0.01). Pathological changes included edema of sciatic nerve fibers, segmental demyelination, loose and disordered arrangement of the myelin sheath layers, significant swelling of mitochondria, reduced electron density, disappearance of cristae, and absence of typical autophagosome and autolysosome structures. Compared with the PDPN group, each JGFD dose group showed a significant increase in body weight and a significant reduction in fasting blood glucose (P<0.05, P<0.01). The mechanical pain threshold and thermal pain threshold were significantly prolonged, and motor nerve conduction velocity was significantly increased across all JGFD and LA groups. The expression levels of PINK1, Parkin, Beclin-1, and LC3 proteins and mRNA in sciatic nerve tissue were significantly increased, while p62 protein and mRNA expression levels were significantly decreased (P<0.05, P<0.01). Pathological damage to the sciatic nerve was alleviated to varying degrees, with a relatively intact myelin sheath morphology and intact or slightly edematous outer mitochondrial membrane. Autophagolysosome structures were observed in the JGFD-M and JGFD-H groups. Compared with the LA group, the JGFD-H group showed a significant increase in body weight, a significant reduction in fasting blood glucose, a significant increase in motor nerve conduction velocity, a significant increase in PINK1 protein expression and PINK1, Parkin, and Beclin-1 mRNA expression in sciatic nerve tissue, and a significant decrease in p62 mRNA expression (P<0.05, P<0.01).ConclusionJGFD may alleviate sciatic nerve injury in PDPN rats by activating mitophagy through the regulation of the PINK1/Parkin signaling pathway.
摘要:ObjectiveTo observe the effects of Tongmai Kaiqiao pills on the hypoxia-inducible factor-1α (HIF-1α)/adenovirus E1B 19 kD-interacting protein 3 (BNIP3) signaling pathway and mitochondrial autophagy in the hippocampus of the rat model of vascular dementia (VD).MethodNinety male SD rats underwent adaptive feeding for one week before the study. Ten rats were randomly assigned to the sham group, where the common carotid artery was isolated without ligation. The remaining rats were subjected to sequential ligation of the common carotid artery for the modeling of VD. The successfully modeled rats were randomly assigned into the following groups: model, high-, medium-, and low-dose (27.6, 13.8, 6.9 g·kg-1, respectively) Tongmai Kaiqiao pills, donepezil hydrochloride (0.45 mg·kg-1), and combination (27.6 g·kg-1 Tongmai Kaiqiao pills + 2.5 mg·kg-1 HIF-1α inhibitor YC-1) groups. After 4 weeks of treatment, samples were collected. Nissl staining and hematoxylin-eosin staining were performed to observe the loss of neurons and pathological changes, respectively, in the hippocampal region. Western blot was employed to determine the protein levels of HIF-1α, BNIP3, Beclin-1, and microtubule-associated protein 1 light chain 3B (LC3B) in the hippocampal tissue. Transmission electron microscopy was used to observe the mitochondrial ultrastructure and the number of autophagosomes in the hippocampal tissue. Immunofluorescence was employed to observe the fluorescence intensity of HIF-1α, BNIP3, and LC3B in the hippocampal tissue.ResultCompared with the sham group, the model group showed prolonged escape latency (P<0.01), decreased number of platform crossings (P<0.01), reduced and disarranged neuronal layers in the hippocampal region, decreased number of Nissl bodies, disrupted mitochondrial cristae, damaged mitochondrial double-membrane structures, increased number of autophagosomes, upregulated expression of HIF-1α, BNIP3, beclin1, and LC3B (P<0.05, P<0.01), and enhanced fluorescence intensity of HIF-1α, BNIP3, and LC3B (P<0.05, P<0.01). Compared with the model group, Tongmai Kaiqiao pills and donepezil hydrochloride shortened the searching time for the platform (P<0.01) and increased the number of platform crossings (P<0.01). Moreover, the drugs increased the number of neurons with normal morphology and orderly arrangement and the number of Nissl bodies, alleviated the damage, increased the number of autophagosomes, upregulated the expression of HIF-1α, BNIP3, Beclin1, and LC3B (P<0.05, P<0.01), and enhanced the fluorescence intensity of HIF-1α, BNIP3, and LC3B (P<0.05, P<0.01). Compared with high-dose Tongmai Kaiqiao pills, the combination group prolonged the escape latency (P<0.01), reduced the number of crossing platforms (P<0.01), decreased the number of hippocampal neurons, aggravated the damage, decreased the number of Nissl bodies and autophagosomes, downregulated the expression of HIF-1α, BNIP3, beclin1, and LC3B (P<0.01), and decreased the fluorescence intensity of HIF-1α, BNIP3, and LC3B (P<0.01).ConclusionTongmai Kaiqiao pills may activate the HIF-1α/BNIP3 signaling pathway to promote the occurrence of mitochondrial autophagy, clear damaged mitochondria, provide energy for healthy cells, reduce neuronal cell death, and restore the brain function, thereby reducing ischemic damage to the hippocampal tissue, improving learning and memory abilities, and exerting therapeutic effects on VD in rats.
摘要:ObjectiveTo explore the role and molecular mechanism of Weifuchun (WFC) in inhibiting inflammation and alleviating gastric precancerous lesions (GPL).MethodHuman gastric mucosal epithelial cells (GES-1) were stimulated with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) for the modeling of GPL (MC cells), with Caspase-3 inhibition by Z-DEVD-FMK. MC cells were divided into control (20% blank serum), WFC (15% and 20% WFC-containing serum), and caspase-3 inhibitor groups. The cell counting kit-8 (CCK-8) was used to examine the viability of GES-1 cells or MC cells. The Transwell assay and 5-acetylidene-2′-deoxyuridine (EdU) staining were employed to examine cell invasion and proliferation, respectively. Flow cytometry was employed to determine the level of reactive oxygen species. Real-time PCR was conducted to determine the mRNA levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α. Gene Expression Omnibus (GEO) was used to analyze the role of pyroptosis in gastric cancer progression. Western blotting was employed to determine the protein levels of nuclear factor-κB (NF-κB) p65, gasdermin E (GSDME), and Caspase-3. Immunofluorescence staining was employed to detect the NF-κB p65 protein level and nuclear translocation. Hematoxylin-eosin staining was carried out to observe the pathological changes in the gastric mucosa before and after WFC treatment in the patients.ResultCompared with the control group, MC cells presented enhanced proliferation and invasion energy (P<0.01). Compared with the blank serum group, WFC-containing serum inhibited the proliferation and invasion of MC cells (P<0.01), down-regulated the mRNA levels of IL-1, IL-6, and TNF-α, and lowered the level of reactive oxygen species (P<0.05, P<0.01). The transcriptome data at different stages of gastric cancer showed that pyroptosis was involved in gastric cancer progression, and the GSDME level was significantly higher in GPL patients than in the normal group. Compared with the blank serum, WFC-containing serum lowered the level of NF-κB and inhibited the nuclear translocation of NF-κB (P<0.05), and it inhibited pyroptosis by suppressing the cleavage of Caspase-3 on GSDME (P<0.05, P<0.01). The analysis of patient specimens further demonstrated that WFC treatment down-regulated the NF-κB level and GSDME cleavage (P<0.01), inhibited pyroptosis, and alleviated gastric mucosal inflammation and intestinal epithelial metaplasia.ConclusionPyroptosis is involved in the progression of gastric cancer, and WFC inhibits pyroptosis via the NF-κB/GSDME pathway, thereby alleviating gastric mucosal inflammation in GPL.
关键词:Weifuchun;gastric precancerous lesions;nuclear factor (NF)-κB;gasdermin E (GSDME);pyroptosis
摘要:ObjectiveTo investigate the effect of Dendrobium officinale polysaccharides (DOP) in reversing carbon tetrachloride (CCl4)-induced hepatic fibrosis (HF) in rats via the Notch signaling pathway and evaluate the therapeutic effect of DOP by ultrasound elastography.MethodFifty-six male SD rats were randomized into normal, model, colchicine (1×10-4 g·kg-1), Fuzheng Huayu powder (0.45 g·kg-1), and low-, medium-, and high-dose (0.05, 0.1, 0.2 g·kg-1) DOP groups (n=8). The rats in the model group and each treatment group were injected subcutaneously with a mixture of CCl4-olive oil (2∶3) once every 3 days for 10 weeks. After 6 weeks of modelling, the rats were administrated with corresponding drugs once a day for 4 weeks. Hematoxylin-eosin (HE) staining and Masson staining were employed to observe the pathomorphological changes of the liver tissue. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bile acids (TBA). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the serum levels of hyaluronic acid (HA), laminin (LN), type Ⅲ precollagen (PC-Ⅲ), and type Ⅳ collagen (Col-Ⅳ). The mRNA and protein levels of α-smooth muscle actin (α-SMA), Notch1, Jagged1, and Hes1 in the liver tissue were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The Young's modulus (YM) of the rat liver was measured by acoustic radiation force impulse (ARFI) elastography before and after treatment. Then, the correlations of YM with the serum levels of HA, LN, PC-Ⅲ, and Col-Ⅳ and the protein levels of α-SMA and Notch1 signaling pathway-related factors in the liver tissue were analyzed.ResultCompared with the normal group, the model group showed disordered arrangement of liver cell cords, obvious infiltration of inflammatory cells, appearance of a large number of fat vacuoles, and fibrous proliferation, elevated levels of ALT, AST, TBA, ALP, HA, LN, PC-Ⅲ, and Col-Ⅳ in the serum, and up-regulated mRNA and protein levels of α-SMA, Notch1, Jagged1, and Hes1 in the liver tissue (P<0.01). Compared with the model group, drug interventions alleviated the pseudolobule formation and the collagen deposition in confluent areas. Except that the serum level of ALT in the low-dose DOP group had no significant changes, drug interventions, especially high-dose DOP, lowered the levels of ALT, AST, TBA, ALP, HA, LN, PC-Ⅲ, and Col-Ⅳ in the serum and down-regulated the mRNA and protein levels of α-SMA, Notch1, Jagged1, and Hes1 in the liver tissue (P<0.05, P<0.01). The results of ARFI and correlation analysis showed that the YM of the liver tissue was increased in the model group (P<0.01) compared with that in the normal group, Compared with the model group, drug interventions decreased YM (P<0.01). YM was positively correlated with the expression levels of HA, LN, PC-Ⅲ, α-SMA, Notch1, Jagged1, and Hes1s (r=0.754, 0.734, 0.801, 0.885, 0.896, 0.757, and 0.800, respectively, P<0.01), and it had a moderate correlation with Col-Ⅳ (r=0.688, P<0.01).ConclusionDOP can reverse HF by down-regulating the Notch1/Jagged1/Hes1 signaling pathway. YM can be used as an indicator in the assessment of the efficacy of DOP against HF.
摘要:ObjectiveTo observe the effect and mechanism of curcumin on cognitive function in the mouse model of low oxygen-induced chronic nerve injury.MethodEighty male C57BL/6 mice were randomized into eight groups: control, low-, medium-, and high-dose (100, 200, and 300 mg·kg-1, respectively) curcumin, model, model + low-dose curcumin, model + medium-dose curcumin, and model + high-dose curcumin groups (n=10). The mouse model of low oxygen-induced nerve injury was prepared by continuous stimulation with simulated oxygen concentration at Lhasa altitude (13% O2 at about 3 700 m) for 14 days. After the completion of modeling, mice in the six curcumin groups were administrated with curcumin at corresponding doses by gavage, while those in the control group and the model group were administrated with the same amount of normal saline once a day for one week. After that, open field, novel object recognition, and Morris water maze tests were carried out to reveal the behavioral changes of mice. The morphological changes of the hippocampus were observed by hematoxylin-eosin staining. The mRNA levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the hippocampus and peripheral blood of mice were determined by real-time PCR. The activation of microglia in the hippocampus was observed by Iba-1 staining. The protein levels of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) in the hippocampus were determined by Western blot.ResultCompared with the control group, the model group showed decreased new object recognition rate (P<0.01), extended time to find the platform (P<0.01), and reduced platform crossings (P<0.05), which proved that the cognitive function of mice was impaired. Compared with model group, the model + medium-dose curcumin group showed increased new object recognition rate, shortened time to find the platform, and increased platform crossings (P<0.05,P<0.01). Moreover, the application of curcumin repaired the abnormal morphological and structural changes in the hippocampus, reduced the inflammatory cytokine levels and activation of microglia, and upregulated the expression of CREB and BDNF (P<0.05).ConclusionCurcumin demonstrates a therapeutic effect on low oxygen-induced cognitive decline, which provide a potential cure for treating chronic brain injury induced by high-altitude low oxygen in clinical practice.
摘要:ObjectiveTo investigate the effect and mechanism of ginsenoside Rg1 (G-Rg1) combined with hirudin in treating myocardial fibrosis in the mouse model of acute myocardial infarction (AMI).MethodSeventy-five C57BL/6N mice were randomized into sham, model, G-Rg1 (20 mg·kg-1), hirudin (20 mg·kg-1), and G-Rg1 (20 mg·kg-1) + hirudin (20 mg·kg-1) groups. The mouse model of AMI was established by ligation of the anterior descending branch of the left coronary artery and continued gavage for 4 weeks. The success of the modeling was judged by ECG changes of mice before and after ligation. The heart weight index, echocardiography, myocardial fibrosis, type Ⅰ collagen α1(COL1A1), platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31), α-smooth muscle actin (α-SMA), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were measured before and after treatment.ResultAfter ligation of the anterior descending branch of the left coronary artery, the R wave and T wave merged into a tall tented wave, and the ST segment presented a "damaged" change, indicating that the model was successfully prepared. Compared with the sham group, the model group showed dull and dry hair, slow movement, increased heart weight index (P<0.01), decreased left ventricular ejection fraction (EF) and left ventricular shortening fraction (FS) (P<0.01), increased left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) (P<0.01), disarranged myocardial fibers, collagen fiber hyperplasia (P<0.01), increased expression of COL1A1 (P<0.01), upregulated protein levels of ICAM-1 and VCAM-1 (P<0.01), downregulated CD31 expression, and upregulated α-SMA expression (P<0.01). Compared with the model group, the treatment groups recovered the above indexes in different degrees (P<0.05, P<0.01), and the combined group had better effect (P<0.05).ConclusionG-Rg1 combined with hirudin can ameliorate myocardial fibrosis after AMI by inhibiting the expression of adhesion molecular protein in the heart tissue, reducing the adhesion of inflammatory cells, alleviating cardiac inflammation, and inhibiting cardiac endothelial-to-mesenchymal transition.
摘要:ObjectiveTo explore new targets and herbal medicines of total ginsenosides in ameliorating alcoholic hepatitis (AH) by data mining and experimental validation and to provide new directions for the clinical treatment of AH.MethodGSE28619 was selected as the test set from the GEO database and GSE83148 and GSE103580 were selected as the validation sets. The limma package and weighted gene co-expression network analysis (WGCNA) were employed to identify the AH-related differentially expressed genes and modular genes, and Venny was used to extract the common genes. The protein-protein interaction (PPI) network was constructed and the enrichment analysis was carried out. The hub genes were further screened and evaluated for their diagnostic value. After validation with the datasets, new potential targets of AH and traditional Chinese medicine were predicted. Molecular docking between the targets and active ingredients of traditional Chinese medicine was performed, and the results were validated by experiments. Eight out of 48 SD rats were randomly selected into a blank group and received an equal amount of normal saline. The rest rats were subjected to modeling with ethanol by gavage and then randomized into low- (10 mg·kg-1), medium- (20 mg·kg-1), and high-dose (40 mg·kg-1) total ginsenosides, model, and positive control (metadoxine, 117 mg·kg-1) groups. After 3 weeks of gavage, serum samples were collected for the measurement of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and liver samples were collected for hematoxylin-eosin (HE) staining. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of potential targets in the liver tissue.ResultData mining predicted the potential genes: Proto-oncogene FOS and collagen type Ⅰ alpha 2 (COL1A2). Experimental validation showed that the liver injury was alleviated after drug administration compared with that after modeling. The serum AST and ALT levels were reduced after drug administration. The protein and mRNA levels of FOS were significantly up-regulated, while those of COL1A2 were down-regulated after drug administration.ConclusionTotal ginsenosides ameliorate HA via FOS and COL1A2.
关键词:bioinformatics;alcoholic hepatitis;hub genes;prediction of traditional Chinese medicine;total ginsenosides
摘要:ObjectiveTo explore the effects of different emulsion mixtures and emulsification methods on the inflammation severity in an experimental autoimmune uveitis (EAU) model in rats, and to analyze the characteristics of the current EAU model.MethodEAU was induced in Lewis rats by subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) 1177-1191 emulsified with Freund's complete adjuvant (CFA), with or without intraperitoneal injection of pertussis toxin (PTX). Slit lamp examination, HE staining, and optical coherence tomography were used to evaluate factors affecting EAU modeling, including different doses of the emulsion mixture (IRBP1177-1191, PTX, and inactivated Mycobacterium tuberculosis) and four different emulsification methods. The classification, characteristics, modeling methods, advantages, and disadvantages of EAU animal models were summarized and analyzed based on the clinical diagnostic criteria and syndrome characteristics of chronic uveitis in both traditional Chinese medicine (TCM) and western medicine, to evaluate the consistency between TCM and western medical syndromes.ResultIncreasing the dose of inactivated M. tuberculosis and antigen peptide in the emulsion mixture exacerbated the anterior segment inflammation in EAU rats. Increasing the injection of PTX also exacerbated anterior segment inflammation and increased retinal thickness in EAU rats. The severity of the EAU model was closely related to the emulsification method used. All four emulsification methods successfully induced EAU in rats. Comparatively, the ultrasonic cell disruptor and T10 basic disperser achieved successful emulsification in a short time. The degree of emulsification of the mixture also influenced the severity of the EAU model in rats. The existing EAU animal model shows a high degree of consistency with western medical diagnoses and the main ocular syndromes in TCM.ConclusionIRBP1177-1191, PTX, inactivated M. tuberculosis, and emulsification methods can affect the severity of the EAU model through different pathways. The existing EAU animal models can simulate the clinical characteristics of western medicine well but lack the etiology, pathogenesis, and syndrome characteristics of TCM. Therefore, it is necessary to construct an EAU animal model that combines disease and syndrome characteristics.
关键词:experimental autoimmune uveitis;factors influencing modeling;integration of traditional Chinese and Western medicine;disease and symptom characteristics
摘要:Heart failure (HF) is a group of syndromes caused by cardiac dysfunction with impaired ventricular pumping, seriously affecting patients' health and quality of life. The pathogenesis of HF is complex, including myocardial contractility decline, myocardial fibrosis, and ventricular remodeling, and it is related to neuroendocrine regulation, inflammation, and cardiomyocyte autophagy. Autophagy is a key regulatory mechanism by which cells degrade themselves to maintain body homeostasis. In the process of HF, moderate autophagy can remove aging and damaged cardiomyocytes and maintain the balance of myocardial energy metabolism, while abnormal autophagy may lead to functional decline and pathological changes of cardiomyocytes. The adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway is one of the classical pathways regulating autophagy. This pathway can mediate the autophagy of cardiomyocytes and play a role in protecting the cardiac function and delaying HF progression. Traditional Chinese medicine (TCM) with a long history has a unique theoretical system and shows satisfactory therapeutic effects and wide application prospects amid the integration with modern medicine. The clinical practice of TCM has accumulated rich experience in the treatment of cardiovascular diseases. A large number of studies have shown that the active components and compound prescriptions of TCM and Chinese patent medicines can mediate autophagy by regulating the AMPK/mTOR signaling pathway to treat HF. This article explains the role of AMPK/mTOR signaling pathway-mediated autophagy in the treatment of HF, introduces the understanding of autophagy, AMPK/mTOR signaling pathway, and HF based on TCM theories, and reviews the research progress in the regulation of autophagy by TCM in the treatment of HF via the AMPK/mTOR pathway. This review is expected to tap the potential of TCM in the treatment of cardiovascular diseases, provide theoretical support for subsequent experimental studies, and demonstrate the advantages of TCM in clinical practice to achieve more accurate treatment.
关键词:adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway;autophagy;traditional Chinese medicine;heart failure;research progress
摘要:ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function, inflammation, and quality of life of the patients with chronic heart failure resistant to diuretics.MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups (39 cases). Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition, the observation group received Bushen Huoxue prescription. The cardiac function indicators, total response rate regarding symptom alleviation, exercise endurance, urine volume, body mass, quality of life, and levels of inflammatory cytokines were compared between the two groups before and after treatment.ResultBefore treatment, the two groups of patients showed no significant differences in terms of 24 h urine volume, body mass, 6 minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left ventricular ejection fraction (LVEF), stroke volume (SV), and serum levels of interleukin-6 (IL-6), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α). After treatment, the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association (NYHA) grading of cardiac function (P<0.05). After treatment, the body mass, MLHFQ score, and IL-6, TNF-α, and NT-proBNP levels decreased in both groups (P<0.05, P<0.01), and the observation group showed more significant decreases than the control group (P<0.05, P<0.01). Both groups showed increases in 24-h urine volume, 6MWT, LVEF, SV, and IL-4 after treatment (P<0.05, P<0.01), and the observation group showed more significant increases than the control group (P<0.05, P<0.01).ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover, it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.
摘要:ObjectiveTo explore the effects of Bushen Huoxue prescription on the expression of arginine vasopressin (AVP) and aquaporins (AQP)1 and AQP4 in the brain and AQP1, AQP4, and AQP7 in the myocardial tissue of the rat model of heart failure after myocardial infarction.MethodSixty healthy male SD rats were selected and randomized into sham surgery, model, Bushen Huoxue prescription, and tolvaptan groups. The rats in the sham surgery group only had their coronary arteries exposed without ligation, while those in the other groups were subjected to ligation of the left coronary artery combined with exhaustive swimming and starvation for the modeling of heart failure after myocardial infarction. After the successful modeling, the rats in the tolvaptan (1.35 mg·kg-1) and Bushen Huoxue prescription (15.75 g·kg-1) groups were treated with corresponding drugs, and those in the sham surgery and model groups were treated with an equal volume of normal saline for 4 weeks. Color doppler echocardiography was employed to measure changes of the left ventricular structure and function in rats. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Hematoxylin-eosin (HE) staining was conducted to reveal the pathological changes in the myocardial tissue. Western blotting was employed to measure the protein levels of AVP, AQP1, and AQP4 in the brain tissue and AQP1, AQP4, and AQP7 in the myocardial tissue. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of AVP, AQP1, and AQP4 in the brain tissue and AQP1, AQP4, and AQP7 in the myocardial tissue.ResultCompared with the sham surgery group, the model group showed increased left ventricular internal diameter (LVID) (P<0.01), decreased ejection fraction (EF) and short axis fractional shortening rate (FS) (P<0.01), increased left ventricular septal and posterior wall thicknesses (LVS and LVPW) (P<0.01), elevated serum NT-proBNP level (P<0.01), edema and vacuolar degeneration of nerve cells in the brain tissue, necrosis of myocardial cells and rupture of myocardial fibers in the infarcted area, and upregulated mRNA and protein levels of AVP, AQP1, and AQP4 in the brain tissue (P<0.01) and AQP1, AQP4, and AQP7 in the myocardial tissue (P<0.01). Compared with the model group, tolvaptan and Bushen Huoxue prescription restored LVID, EF, FS, LVS, and LVPW (P<0.05, P<0.01), lowered the serum NT-proBNP level (P<0.05), alleviated the edema of nerve cells in the brain tissue, improved the arrangement of myocardial fibers, mitigated the necrosis of myocardial cells, and downregulated the mRNA and protein levels of AVP, AQP1, and AQP4 in the brain tissue (P<0.01) and AQP1, AQP4, and AQP7 in the myocardial tissue (P<0.05, P<0.01).ConclusionBushen Huoxue prescription can regulate cardiovascular and cerebrovascular fluid metabolism disorders, delay ventricular remodeling, and improve the cardiac function by downregulating the expression of AVP, AQP1, and AQP4 in the brain tissue and AQP1, AQP4, and AQP7 in the myocardial tissue in the rat model of heart failure after myocardial infarction.
摘要:ObjectiveTo explore the clinical efficacy of Huangjin Shuangshen Jiawei (HJSSJW) granules in treating postoperative anxiety and depression after percutaneous coronary intervention (PCI) for coronary heart disease and the effects of this medicine on inflammatory cytokines.MethodNinety-four patients diagnosed with anxiety and depression after PCI were randomized into observation and control groups (47 cases) by the double-blind method. On the basis of conventional Western medical treatment, the observation group was treated with HJSSJW granules for 12 weeks, and the control group with the simulant of HJSSJW granules for 12 weeks. The two groups were compared in terms of Hamilton Anxiety and Depression Scales (HAMA-14, HAMD-24), Pittsburgh Sleep Quality Inventory (PSQI), Seattle Angina Score (SAQ), TCM symptom scores, traditional Chinese medicine (TCM) symptom score and response rate, serum levels of hypersensitive-C reactive protein (hs-CPR), tumor necrosis factor (TNF)-α, and interleukin (IL-6), and incidence of major adverse cardiovascular events (MACEs) and adverse reactions.ResultAfter treatment, both groups showed declined scores of HAMA-14, HAMD-24, and PSQI (P<0.05, P<0.01) and the observation group had lower scores of HAMA-14, HAMD-24, and PSQI than the control group (P<0.01). The scores of SAQ in both groups increased after treatment (P<0.01), and the observation group had higher score of each dimension than the control group (P<0.05). The TCM symptom scores decreased in both groups after treatment (P<0.01), and they were lower in the observation group than in the control group (P<0.05). The total response rate regarding TCM symptoms in the observation group was higher than that in the control group (χ2=9.225, P<0.01). After treatment, the levels of hs-CPR, IL-6, and TNF-α became lowered in both groups (P<0.01), and the observation group had lower levels of hs-CPR, IL-6, and TNF-α than the control group (P<0.05). The incidence of MACEs in the observation group was lower than that in the control group during the 90 d of the follow-up period (χ2=4.242, P<0.05). No adverse reactions associated with the use of HJSSJW granules were observed during the trial period.ConclusionHJSSJW granules can alleviate the bad mood, improve sleep, mitigate somatic symptoms, improve the quality of life, reduce inflammatory damage, and improve prognosis, being safe for clinical use in patients with postoperative anxiety and depression after PCI for coronary heart disease.
关键词:Huangjin Shuangshen Jiawei granules;after percutaneous coronary intervention (PCI) for coronary heart disease;anxiety and depression;inflammatory cytokine;syndrome of stasis and toxin stagnation
摘要:Qizhi Weitong granules composed of Bupleuri Radix, Paeoniae Radix Alba, Aurantii Fructus, Cyperi Rhizoma (processed), Corydalis Rhizoma (processed), and Glycyrrhizae Radix et Rhizoma have the effects of soothing the liver, regulating Qi movement, and harmonizing the stomach to relieve pain. This preparation is thus used for the treatment of liver depression, Qi stagnation, chest distension, and epigastric pain. It has become a first-line medication for the treatment of epigastric pain after years of clinical practice. At present, researchers have carried out extensive studies on Qizhi Weitong granules, including the optimization of the extraction and purification process, identification of chemical components, characterization of absorbed components, establishment of quality control methods, validation of pharmacological effect on digestive system diseases, exploration of the mechanism, and observation of clinical efficacy. The studies have achieved fruitful results. This article summarizes the research achievements related to Qizhi Weitong granules in recent years from pharmacological substances, quality control, pharmacological effect, mechanism of action, and clinical efficacy, aiming to provide ideas for in-depth research and modern development of Qizhi Weitong granules.
摘要:ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics.MethodOn the basis of the previous in vitro efficacy study by our research group, this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Swiss TargetPrediction, and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man (OMIM). The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects, and protein-protein interaction (PPI) network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1, PyMol, and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets.ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out, and the core targets with high activities were protein kinase B1 (Akt1), interleukin-1β (IL-1β), cellular tumor antigen p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), and matrix metalloproteinase-9 (MMP-9). According to the structures, the flavonoids in Cyperi Rhizoma were classified into bioflavonoids, flavonols, flavones, and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets, while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53, while the change of B ring substituents was not the main factor affecting the binding affinity. The 3,4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53, while the two compounds showed similar binding affinity to PTGS2.ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.
关键词:Cyperi Rhizoma;flavonoids;anti-inflammatory and analgesic effects;structure-activity omics;molecular docking
摘要:ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics.MethodOn the basis of the previous study about the screening of active components in vitro, this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Swiss TargetPrediction, DisGeNET, and Online Mendelian Inheritance in Man (OMIM). STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction (PPI) network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma, on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets, the relationships between compound structures and core targets were discussed.ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E2 (PGE2) in the rat model of pain induced by formalin, demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds (flavonoids) with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard, prostaglandin-endoperoxide synthase 2 (PTGS2) and mitogen-activated protein kinase 3 (MAPK3) were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3, the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3, and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge, liposolubility, and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity.ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.
关键词:Glycyrrhizae Radix et Rhizoma;flavonoids;structure-activity omics;molecular docking;anti-inflammatory and analgesic effects
摘要:ObjectiveTo elucidate the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba from structure-activity omics.MethodOn the basis of the previous in vitro efficacy study by our research group, a mouse model of foot swelling was induced by methyl aldehyde and used to study the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba in vivo. The core targets of the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and Search Tool for Recurring Instances of Neighbouring Genes (STRING). Molecular docking was conducted for the total glucosides of Paeoniae Radix Alba with the core targets, and the key core targets with high binding affinity were screened out according to the comprehensive score of each target and active structure. The structure-activity relationship was analyzed with targets as a bridge through the combination of compound structures and pharmacological effects.ResultThe total glucosides of Paeoniae Radix Alba had good anti-inflammatory and analgesic effects in vivo. The core targets of 23 active components of Paeoniae Radix Alba were epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (TP53), and proto-oncogene transcription factor (JUN). According to the structure of the parent nucleus, there were 16 pinane monoterpene glycosides, 4 pinene monoterpene glycosides, 2 monoterpene lactone glycosides, and 1 monoterpene ketone. The key core targets screened out by molecular docking were EGFR and STAT3. The structure-activity analysis of the active compound structures and the key core targets showed that the introduction of ketone group and benzene ring group on the parent nucleus affected the binding activity.ConclusionThis study analyzed the material basis for the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba from structure-activity omics, providing new ideas and methods for revealing the pharmacodynamic substances in traditional Chinese medicine.
关键词:Paeoniae Radix Alba;total glucosides of paeoniae Radix Alba;anti-inflammatory and analgesic effects;structure-activity omics;molecular docking
摘要:In this paper, we systematically sorted out and verified the name, origin, producing area change, quality, efficacy and processing of Halloysitum Rubrum by consulting materia medica, medical books, prescription books from past dynasties, and modern literature, and combined with the comprehensive analysis of trait identification, hygroscopicity measurement and X-ray diffraction(XRD) detection, in order to provide a basis for understanding the original source of the mineral medicine. The results indicated that Halloysitum Rubrum was first contained in the Shennong Bencaojing, it had been consistently named Chishizhi, there were also aliases such as Chifu, Hongxinshi and Chiyouzhi. The description of Halloysitum Rubrum in ancient materia medica aligns with modern findings, categorizing it under the silicate kaolinite family, specifically polyhydrous kaolinite, with associated minerals mainly being dickite, nacrite, hematite, gibbsite, mica, etc. Historically, the production area of Halloysitum Rubrum was mainly located in the Qinling Mountains, Shandong and Henan, and is now primarily distributed in most parts of China, including Henan, Hubei and other provinces. Quality evaluation in ancient times included descriptions like "fresh and greasy color", "delicately sticky tongue and lips" and "smooth as fat". Modern materia medica mostly evaluates its quality based on color, luster, texture and hygroscopicity, noting characteristics such as red color, smoothness, delicacy, softness and strong viscosity. Halloysitum Rubrum is sweet, sour and pungent in flavor, warm in nature, non-toxic, and belongs to the heart and large intestine meridians. It acts as an astringent and solidifying agent, particularly useful in the treatment of long-term dysentery and diarrhea, common processing methods include fire calcination, water flying, and vinegar quenching. Comprehensive analysis of the traits, XRD and humidity absorption of different batches of samples showed that the commercially available Halloysitum Rubrum is mainly bright red or brownish red, with a smooth surface like grease, soft and smooth texture, delicate cross-sectional texture, and some have waxy luster and strong water absorption. It is mainly composed of 10 Å(1 Å=0.1 nm) polyhydric kaolinite, and is often accompanied by 7 Å polyhydric kaolinite, nacrite, etc. Genuine products tend to have higher moisture absorption than counterfeit ones, which can be used as a key indicator to distinguish the authenticity. The quality evaluation of Halloysitum Rubrum aligns with historical materia medica, where "fresh color, delicate and greasy lips" could serve as a key feature for its quality evaluation.
摘要:By reviewing the historical materia medica, medical books and modern literature, this paper has systematically sorted out and verified the name, origin, quality and other aspects of Ophicalcitum. After herbal textual research, it is shown that before the Qing dynasty, the mineral medicine was mostly recorded in the name of Huarushi, but now it is called Huaruishi, and there is another mixed name Baiyunshi. The light white spots described in the historical materia medica are consistent with the characteristics of marble with sparkling star-like luster, combined with the color like sulfur, color are green, black spots and other serpentine features, it is deduced that it is serpentine marble, consistent with the present-day Ophicalcitum, and Ophicalcitum in the Song dynasty has a high content of serpentine. The main producing areas are Henan, Shaanxi, Shanxi and Sichuan, Jiangsu, Zhejiang, Hebei and other places are also available. Successive generations of materia medica on the quality evaluation of Ophicalcitum is less, the modern to neat and firm in the texture, sandwiched with yellow-green mottled for the best. Ophicalcitum is acidic, astringent and neutral in nature, belonging to the liver meridian, with the efficacy of treatment of gold sores and blood flow, internal leakage of cataracts, dropping afterbirth, now describing its efficacy as removing blood stasis and stopping bleeding. In ancient times, the earliest processing method was burning, followed by calcination by sulphur, calcination, quenching with vinegar and other methods. In modern times, it has been simplified to open calcination, processing with vinegar and the addition of water quenching. The gravimetric method and ethylenediaminetetraacetic acid titration were used to detect the contents of CO32- and CaCO3 in Ophicalcitum, respectively, and it was found that the gap in CaCO3 content among commercially available products was wide, and the content of CaCO3 in sample S13 and sample S18 was the same, but their compositions were different, and according to the contents of CO32- and CaCO3, the dolomite and calcite contents could be calculated, of which the higher the calcite content the more obvious the sparkling star-like luster. Raman spectroscopy and X-ray diffraction(XRD) were used to detect the physical phase composition of the powder of the samples, and Raman spectroscopy was used for the rapid non-destructive testing of the striped part, which showed that Ophicalcitum was mainly composed of dolomite, calcite, serpentine, olivine and pyroxene, with serpentine dominanting the striped part. In summary, the 2020 edition of Chinese Pharmacopoeia stipulates that the content of CaCO3 in Ophicalcitum is not less than 40%, which is difficult to control its quality, and it is suggested to increase the detection of CO32- content. This study can provide a scientific basis for the traceability of Ophicalcitum and better guide the clinical medication and rational utilization of resources.
摘要:In this research, a comprehensive examination of historical materia medica, medical literature, medical books and contemporary literature was conducted to systematically compile and verify the naming, origin, geographical variations, quality, medicinal properties and processing of Tremolitum, and combined with the physical analysis of 15 batches of samples, with a view to providing a basis for the quality evaluation. The evidences unequivocally support Yangqishi as the rectification of name, while alternative aliases include Baishi, Shisheng, Yangjushi and Yangshi. The primary source of Tremolitum has been the silicate hornblende mineral tremolite throughout recorded history, and its accompanied minerals are mainly chlorite, talc schist, anthophyllite asbestos, etc. In ancient times, the main production area of Tremolitum was situated in the "Yaoshan Mountain" region of Jinan, Shandong province. Presently, it is primarily produced in Hubei, Henan, Shanxi, Hebei and Shandong provinces. The ancient quality evaluation of Tremolitum includes "white color", "wolf teeth", "cloud head and rain foot", "heron hair", etc. While, modern materia medica mostly evaluates its quality in terms of color, luster and texture, including the characteristics of needle bundle, grayish-white, glossy and easy to be twisted and crushed. Tremolitum is slightly warm, non-toxic, and possesses a salty taste. It is associated with the kidney meridian, known for its benefits in nourishing the fire of the gate of life, warming the kidneys and strengthening the Yang. Common processing methods include fire calcination, elutriation, and processing with wine. Additionally, there is an exclusive processing method known as the "ascending Tremolitum method". Through the X-ray diffraction(XRD) analysis, the commercially available Tremolitum is mainly composed of tremolite[Ca2Mg5(Si4O11)2(OH)2], and the accompanied minerals are calcite and quartz, etc. Its color includes white, light gray, light green and so on, and it is weight and soft texture, irregular cross-section, with obvious fibrous texture and mostly glassy luster. Among the commercially available Tremolitum, samples with high content of tremolite are characterized by high quality features, such as "white color", "heron hair" and "ease of tearing". Also, Tremolitum is the Fe-bearing heterogeneous species of tremolite, and the two are often symbiotic. Therefore, by the herbal textual research and the comparison of the properties and composition of Tremolitum and its similar species, it has been verified that the primary source of Tremolitum is the silicate hornblende minerals tremolite and actinolite.
摘要:Aiming to provide the foundation for the quality evaluation, in this paper, a comprehensive examination of historical materia medica, medical books and modern literature was conducted to systematically compile and verify the naming, origin and quality of Stalactitum, combined with the phase analysis of 20 batches of samples. The investigation indicates that before the Qing dynasty, Stalactitum was often referred to as Shizhongru, and there are other aliases such as Xuzhong, Xiashi and Huangshisha. In addition, there are some homologous mixed names such as Konggongnie, Yinnie, Ruchuang, Ruhua, but Zhongrushi is more commonly used. The descriptions of Stalactitum in ancient materia medica align with modern carbonate mineral calcite, slightly conical or cylindrical in shape, mostly white, grey and yellow in colour, often with a hole in the centre, and has a calcium carbonate content of 95% or more. Historical quality assessments include phrases such as gooseneck tube, cicada wing, bright and white, and brightness, the gloss is the most crucial feature. Modern evaluations encompass features like white color, hollow interior, brightness, multiple layers of patterns, and cross-sectional mask spark-like luminosity. Under the scanning electron microscope, Stalactitum showed obvious layered characteristics and uniform particle size, while the OS Balanophylliae was irregular. By comparing the characteristics and micro-features of Stalactitum from different batches, along with X-ray diffraction(XRD) and determination of calcium carbonate, the phase composition of different batches of Stalactitum was roughly similar, all of them were dominated by calcite, with magnesium calcite as an additional ingredient, the content of CaCO3 was relatively higher for those with brightness and a lot of spark-like luminosity, which were key features of its quality evaluation, the white color could be used as a quality reference, and layered patterns and papillary bulge could be used as a medicinal material identification feature, which were basically consistent with the results of herbal textual research. This study can provide a reference for the quality evaluation of mineral medicines, and can better guide their clinical use and rational utilization of resources.
摘要:ObjectiveTo observe the effect of tendon clearing combined with Zizhu ointment on the serum levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, and IL-18 in the treatment of non-ischemic diabetic foot ulcers.MethodA total of 106 patients with non-defective diabetic foot ulcers who attended the outpatient clinic and wards of the Vascular Surgery Department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2023 to March 2024 were selected. The patients with non-ischemic diabetic foot ulcers who met the inclusion criteria were assigned with the random number table method into an observation group and a control group, with 53 patients in each group. Patients in both groups received basic treatment. The local ulcers in the observation group received tendon clearing combined with Zizhu ointment, while those in the control group received conventional debridement combined with topical solution of bovine basic fibroblast growth factor. The serum NLRP3, IL-1β, and IL-18 levels, ulcer area, traditional Chinese medicine (TCM) symptom scores, visual analogue scale (VAS) score, and DMIST score were measured and recorded in the two groups before and after treatment. The ulcer healing rate and incidence of adverse reactions were compared between the two groups.ResultThe observation group had higher ulcer healing rate than the control group (P<0.01). After treatment, both groups showed lowered serum NLRP3, IL-1β, and IL-18 levels, reduced ulcer area, and declined TCM symptom score, VAS score, and DMIST score (P<0.01). Moreover, these indicators were lower in the observation group than in the control group (P<0.05, P<0.01). Neither group showed significant changes in the liver and kidney function indicators after treatment. Significant adverse reactions occurred in neither group during the treatment course.ConclusionTendon clearance combined with Zizhu ointment was effective and safe in treating non-ischemic diabetic foot ulcers. It may exert the therapeutic effect by reducing the inflammation of the local ulcers.
摘要:ObjectiveTo explore the preventive and therapeutic effects of Jianpi Bushen prescription (JBP) on hematopoiesis and immune system damage in tumor patients after radiotherapy.MethodSixty-four patients diagnosed with tumors of qi and blood deficiency syndrome, who received radiotherapy for the first time at the department of oncology and radiotherapy of Central Theater General Hospital of PLA from January 2023 to December 2023, were enrolled and randomly divided into the JBP combined with radiotherapy group (observation group) and the radiotherapy alone group (control group) at a ratio of 1∶1, with 32 patients in each group. The clinical efficacy of Western medicine, traditional Chinese medicine (TCM) syndrome efficacy, TCM syndrome scores, blood routine tests, immunological indicators, cytokines, and Karnofsky Performance Status (KPS) scores were compared between the two groups before and after treatment. Adverse reactions during the treatment process were observed to assess the safety of the treatment.ResultA total of 61 patients were ultimately included in this study, with 29 patients in the observation group and 32 in the control group. Compared with pre-treatment levels, the observation group showed significant reductions in the primary and secondary symptoms of qi and blood deficiency syndrome, total symptom score, peripheral blood white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), blood platelet (PLT), lymphocyte (LYM), CD3+, CD4+, CD4+/CD8+ ratio, interleukin (IL)-4, and IL-10 levels after treatment (P<0.05,P<0.01).Meanwhile,the levels of peripheral blood CD8+,IL-6,interferon (IFN)-γ,tumor necrosis factor (TNF)-α,IL-17, and KPS scores significantly increased (P<0.05, P<0.01). In the control group, significant reductions were also observed in the primary symptoms of qi and blood deficiency syndrome, total symptom score, peripheral blood WBC, RBC, HGB, PLT, LYM, CD3+, CD4+, CD4+/CD8+ ratio, IL-4, IL-10, and IL-17 levels (P<0.05, P<0.01), along with significant increases in peripheral blood CD8+, IL-6, IFN-γ, TNF-α, and KPS scores (P<0.05, P<0.01). After treatment, the total effective rate of TCM syndrome in the observation group was 86.2% (26/29), , higher than 50.0% (22/32) in the control group (χ2 = 16.543, P<0.01). The total clinical remission rate in the observation group was 51.7% (15/29), higher than 25.0% (8/32) in the control group (χ2 = 9.159, P<0.05). Compared with the control group after treatment, the observation group had higher levels of peripheral blood WBC, RBC, HGB, PLT, LYM, CD3+, CD4+, CD4+/CD8+ ratio, IL-4, IL-10, and KPS scores (P<0.05), and lower levels of peripheral blood CD8+, IL-6, IFN-γ, TNF-α, and IL-17 (P<0.05). The most common adverse events in both groups were bone marrow suppression, radiation dermatitis, radiation esophagitis, nausea, and vomiting. The incidence of bone marrow suppression, nausea, and vomiting in the observation group was significantly lower than that in the control group (P<0.05).ConclusionJBP can effectively improve the clinical efficacy in tumor patients undergoing radiotherapy, alleviate symptoms of qi and blood deficiency, slow down the reduction rate of peripheral blood WBC, RBC, HGB, PLT, and LYM levels, improve hematopoietic function, slow down the reduction rate of peripheral blood CD3+ T cells, CD4+ T cells, CD4+/CD8+ ratio, and cytokines IL-4 and IL-10, enhance the immunity of tumor patients, reduce the expression of cytokines IFN-γ, IL-6, IL-17, and TNF-α, alleviate inflammatory reactions, and reduce the occurrence of post-radiotherapy adverse reactions, thus demonstrating high clinical application value.
关键词:tumor;radiotherapy;radiation injury;Jianpi Bushen prescription;hematopoietic function;immune function
摘要:ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease (CKD) and the effect of the therapy on the neutrophil-to-lymphocyte ratio (NLR) as an inflammation marker.MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories, while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment, the clinical efficacy was assessed based on the changes in traditional Chinese medicine (TCM) symptom scores, renal function indicators, and NLR.Result① Both groups showed decreases in TCM symptom scores after treatment (P<0.01), and the decreases were more significant in the observation group than in the control group (P<0.05). The total response rate of TCM symptoms in the observation group was 79.31% (23/29), which was higher than that (62.96%, 17/27) in the control group (Z=0.604,P<0.05). ② After treatment, the observation group showed declined serum levels of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C (Cys C) and increased glomerular filtration rate (GFR) (P<0.01), and the control group showed lowered SCr level and increased GFR (P<0.05). The observation group had lower SCr level and higher GFR than the control group after treatment (P<0.05). The total response rate of renal function in the observation group was 79.31% (23/29), which was higher than that (55.56%, 15/27) in the control group (Z=1.127,P<0.01). ③ The NLR in the observation group decreased after treatment (P<0.05), and it was lower than that in the control group (P<0.05). ④ There were no significant differences in safety indicators between the two groups before and after treatment.ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.
关键词:chronic kidney disease;Chinese medicine enema;Tongfu Xiezhuo enema;low-grade inflammation;randomized controlled trial
HU Shiwan, LIANG Haiyan, MA Kun, MA Xiaona, FANG Zihan, BAI Wenpei, LIU Xinmin, LI Hongtian, LIAN Fengmei, ZHANG Wei, QIN Lihua, SHANG Min, LAI Ailuan, TENG Xiuxiang, MO Mei, ZHANG Xiaoxiao, ZHAO Linhua
摘要:Perimenopausal syndrome (MPS), a common endocrine system disease, is one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in endocrinology, gynecology, and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine, TCM, and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency, with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause, whereas such a therapy has certain risks, necessitating close monitoring of adverse reactions. Moreover, the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes, sweating, sleep disorders, and emotional abnormalities of MPS without causing obvious adverse reactions. However, its efficacy is slower than the hormone replacement therapy, and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First, an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second, high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third, efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.
关键词:perimenopausal syndrome;disease responding specifically;integrated Chinese and western medicine;expert advice;consensus
摘要:Chronic heart failure (CHF) is a clinical syndrome resulting from damage to the myocardium, leading to changes in the function or structure of the heart and causing reduced pumping and/or filling capacity. Its pathogenesis is complex, potentially involving myocardial fibrosis, apoptosis and autophagy of cardiomyocytes, inflammatory responses, oxidative stress, and myocardial remodeling. Our team believes that the fundamental pathogenesis of CHF is heart-Qi deficiency, with the disease location in the heart, which is closely related to other organs. Due to heart-Qi deficiency, blood circulation weakens, leading to blood stasis, which in turn generates water-dampness and phlegm turbidity that accumulate over time and become toxic. The interaction between water stasis, Qi stagnation, blood stasis, and phlegm toxicity further weakens the body, creating a vicious cycle (deficiency, stasis, water retention, and toxicity) that is difficult to resolve. Under physiological conditions, the nuclear factor-κB (NF-κB) signaling pathway functions normally, maintaining vital activities and immune responses. However, in pathological states, the NF-κB signaling pathway becomes imbalanced, triggering inflammatory responses and other issues. Research has shown that traditional Chinese medicine (TCM) can regulate the NF-κB signaling pathway through multiple pathways, targets, and effects, effectively improving the progression of CHF. As a result, this has become a research hotspot for the prevention and treatment of the disease. Guided by TCM theory, this research group reviewed the literature to summarize the activation pathways of the NF-κB pathway and its interactions with other pathways. Additionally, the group summarized the research progress on the regulation of the NF-κB pathway in the treatment of CHF using Chinese medicines, their active ingredients, Chinese medicine compounds, and Chinese patent medicines. This study is expected to clarify the mechanisms and targets by which TCM treats CHF by regulating the NF-κB pathway, thereby guiding clinical treatment and drug development for CHF.
关键词:chronic heart failure;nuclear factor-κB (NF-κB);traditional Chinese medicine treatment;inflammatory response;myocardial fibrosis
摘要:PPerimenopausal depression (PMD) is a mental disorder that occurs in women before and after menopause. It has become a major public health problem posing a threat to the health of perimenopausal women due to its high incidence, low prevalence, low diagnostic rate, and recurrent episodes. The pathogenesis of PMD is complex and mainly involves the aging of the hypothalamic-pituitary-ovarian (HPO) axis, which leads to abnormal fluctuations in reproductive hormones, inflammation and cascade reactions, and oxidative stress. Currently, there are no specific pharmacological interventions for PMD. Traditional Chinese medicine (TCM), as a treasure of motherland medicine, integrates thousands of years of TCM experience and wisdom and has the advantages of holistic regulation, low toxicity, and mild adverse reactions in the prevention and treatment of PMD. In recent years, more and more studies have been conducted on the active ingredients, extracts, and compound formulas of TCM for treating PMD via multi-components and multi-directions, achieving fruitful results. A large number of studies have shown that TCM treats PMD by reducing inflammation, inhibiting oxidation, and modulating monoamine neurotransmitter levels, which mainly involve NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1), brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) and other signaling pathways. This article reviews the clinical and basic studies about TCM treatment of PMD to analyzes the pathogenesis of PMD and the therapeutic targets of TCM, aiming to provide basic theoretical support and new approaches for the TCM treatment of PMD.
关键词:Perimenopausal Depression;pathogenesis;active ingredients of traditional Chinese medicine(TCM);extracts of TCM;compound formula of TCM;research progress
摘要:Malignant tumors, a group of serious diseases in China, endangers the health of the people. They are mainly treated by surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. With the development of precision medicine, targeted anti-tumor drugs have garnered increasing attention from researchers and gradually applied in clinical treatment. The mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathway plays a key role in the occurrence and development of tumors, participating in the regulation of tumor microenvironment and the invasion, migration, proliferation, apoptosis, and drug resistance of tumor cells. Therefore, the key effectors targeting the regulation of the MAPK/NF-κB signaling pathway have become potential targets for the treatment of tumors. In China, traditional Chinese medicine (TCM) has become a key approach of tumor treatment since it can exert anti-tumor effects in a multi-component, multi-effect, multi-target, and multi-pathway manner, demonstrating definite clinical efficacy in tumor treatment. The available studies published in recent years have shown that the active components, herb pairs, and compound prescriptions of TCM can play an anti-tumor role by interfering with the MAPK/NF-κB signaling pathway, promoting apoptosis, inhibiting cell proliferation, blocking the cell cycle, inhibiting tumor invasion and metastasis and tumor stem cell characteristics, improving the immune function, and reversing tumor multi-drug resistance. However, a systematic review of the relevant studies remains to be conducted. This paper introduces the mechanism of tumor management via the MAPK/NF-κB pathway and reviews the research progress in TCM treatment of tumors via this pathway in recent years, aiming to provide a theoretical basis for the clinical application of anti-tumor TCM, drug development, and in-depth mechanism research.
关键词:mitogen-activated protein kinase (MAPK);nuclear factor-κB (NF-κB);traditional Chinese medicine;tumor;mechanism
摘要:Tumor-associated macrophages (TAMs), as the main immune cells in the human body, are key factors in maintaining the homeostasis of the tumor microenvironment. With high plasticity, they can polarize into the classically activated (M1) macrophages or alternatively activated (M2) macrophages under different conditions. M1 macrophages can inhibit tumor growth by phagocytosis, and M2 can inhibit the immune microenvironment to promote tumorigenesis and immune escape. Small molecules of traditional Chinese medicine have been widely studied in gastrointestinal tumors. These small molecules exert anti-tumor activity by enhancing TAM activity and promoting the polarization of macrophages. Targeted intervention in TAMs with these molecules has the potential to inhibit the development of gastrointestinal tumors. This article summarizes the research status and significance of small molecules of traditional Chinese medicine targeting TAMs against gastrointestinal tumors, aiming to provide reference for the future studies in this field.
关键词:small molecules of traditional Chinese medicine(TCM);tumor-associated macrophages(TAMs);gastrointestinal tumors;tumor microenvironment;immune microenvironment;research progress
摘要:Insomnia is the most common sleep disorder in clinical practice, and prolonged insomnia can significantly impact daily life and work. Currently, the clinical treatment of insomnia primarily relies on sedative and hypnotic drugs, which, although fast-acting, come with numerous adverse reactions. Traditional Chinese medicine (TCM) approaches the treatment of insomnia by employing syndrome differentiation and focusing on addressing the root cause of the disease. This approach is characterized by fewer adverse reactions, stable long-term effects, and better patient compliance. Huanglian Ejiaotang was first recorded in Zhang Zhongjing's Treatise on Febrile and Miscellaneous Diseases(《伤寒杂病论》) during the Han dynasty. It has the effects of nourishing Yin, reducing fire, eliminating irritability, and calming the nerves. Clinical studies have shown that Huanglian Ejiaotang is frequently used to treat insomnia and, when combined with other classic prescriptions, Western medicine, or other therapies, it can have a synergistic effect, thereby enhancing therapeutic outcomes. Research indicates that the mechanism of action of Huanglian Ejiaotang in treating insomnia may be related to the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), central neurotransmitters, gut microbiota, and the inhibition of inflammatory factors. The active components of Huanglian Ejiaotang that are effective in treating insomnia include berberine, baicalin, baicalein, total glucosides of paeony, and collagen. This article discussed the treatment of insomnia with Huanglian Ejiaotang from several perspectives, including its theoretical foundation, clinical research, and mechanisms of action, and also summarized the latest research progress on Huanglian Ejiaotang for insomnia, with the aim of providing more comprehensive ideas for the clinical diagnosis and treatment of insomnia.
摘要:Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function over a short period due to various etiologic factors. If left untreated, AKI can progress to chronic kidney disease (CKD) or even end-stage renal disease (ESRD). Although continuous renal replacement therapy (CRRT) can manage severe AKI, effective pharmacological treatments for AKI remain largely unavailable. Chinese medicine, with its multi-target and multi-pathway approaches, has accumulated substantial theoretical and practical knowledge in treating AKI and related complications. Rehmanniae Radix is a commonly used Chinese medicinal, known for its functions in clearing heat, cooling blood, nourishing yin, and promoting fluid production. The primary active ingredients of Rehmanniae Radix include catalpol, acteoside, and aucubin. In this study, we summarized recent research on the effect of the active ingredients of Rehmanniae Radix in preventing and treating AKI. We found that the key mechanisms underlying its anti-AKI effects include amelioration of inflammation, alleviation of oxidative stress, and inhibition of apoptosis. Additionally, the antifibrotic properties of the active ingredients of Rehmanniae Radix suggest its potential in slowing CKD progression. We reviewed the mechanisms of Rehmanniae Radix in treating AKI and its antifibrotic effects to provide a scientific basis for developing new AKI drugs, promoting the utilization of Rehmanniae Radix resources, and reducing the transition from AKI to CKD.
关键词:Rehmanniae Radix;acute kidney injury;fibrosis;mechanism of action;research progress