摘要:ObjectiveTo investigate the anti-inflammatory effect and mechanism of Danggui Shaoyaosan (DSS) in ameliorating vascular dementia (VaD).MethodsSeventy 8-week-old C57BL/6J male mice were randomized into 7 groups: control, model, sham, positive control (donepezil, 10 mg·kg-1), and low-, medium-, and high-dose (12, 24, 36 g·kg-1, respectively) DSS groups (n=10). After drug administration, behavioral tests and cerebral blood flow detection were carried out. Enzyme-linked immunosorbent assay was used to assess the levels of interferon (IFN)-α, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and CXC motif chemokine ligand 10 (CXCL10) in the brain tissue. Hematoxylin-eosin staining was employed to observe the changes in hippocampal morphology. Transcriptomics was used to predict the potential signaling mechanisms of DSS in ameliorating neuroinflammation, and Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were conducted to verify the expression changes of related genes.ResultsCompared with the control group and the sham group, the model group showed deceases in recognition index in the new object recognition test, movement distance and time in the target quadrant, and number of crossings in the Morris water maze test (P<0.01). In addition, the model group showed slow cerebral blood flow and down-regulated protein levels of postsynaptic density protein 95 (PSD95) and occludin (P<0.05, P<0.01), and there was no significant difference between the control group and the sham group. Compared with the model group, the DSS at each dose increased the new object recognition index, the distance and time in the target quadrant, the number of crossings, and cerebral blood flow (P<0.05, P<0.01). In terms of brain tissue injury-related protein expression and inflammatory factor content, the medium-dose DSS group had the best effect, with higher protein levels of PSD95 and occludin (P<0.05) and lower levels of IFN-α, TNF-α, and IL-6 (P<0.01) than the model group. The hippocampus of model mice showed pathological manifestations such as cell loss and disarrangement, which were alleviated after administration of DSS at each dose. Transcriptomic results indicated that interferon regulatory factor 7 (IRF7), signal transducer and activator of transcription 3 (STAT3), and bone marrow stromal cell antigen 2 (BST2) were differentially expressed genes (down-regulated) in control group and medium-dose DSS group compared with the model group. The KEGG pathway enrichment analysis showed that RIG-Ⅰ-like receptor signaling pathway, Toll-like receptor signaling pathway, cytosolic DNA-sensing pathway, and downstream stimulator of interferon genes (STING) were both upstream signaling pathways affecting IFN expression. Real-time PCR results indicated that the mRNA levels of cyclic good manufacturing practice(GMP)-adenosine monophosphate(AMP) synthase (cGAS), STING, IRF7, STAT3, and BST2 in the model group were higher than those in the sham group (P<0.05, P<0.01). The mRNA levels of all the genes in the medium-dose DSS group were down-regulated compared with those in the model group after administration (P<0.05, P<0.01). Western blot results indicated that the relative expression levels of cGAS, STING, p-IRF7, p-STAT3, and BST2 in the model group were higher than those in the sham group (P<0.05, P<0.01). The protein levels of cGAS, STING, p-IRF7, p-STAT3, and BST2 in the medium-dose DSS group were decreased compared with those in the model group (P<0.05, P<0.01).ConclusionDSS ameliorates cognitive impairment in the VaD model mice by inhibiting the cGAS-STING/IRF7/STAT3-mediated neuroinflammation.
关键词:Danggui Shaoyaosan;neuroinflammation;vascular dementia;cyclic good manufacturing practice(GMP)-adenosine monophosphate(AMP) synthase (cGAS)-stimulator of interferon genes (STING)
摘要:ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells.MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR.ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01).ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
摘要:ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma (HMG) on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism.MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses (1.56, 3.12 g∙kg-1, respectively) or metformin (0.26 g∙kg-1) by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test (OGTT) was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)], liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], non-esterified fatty acids (NEFA), glycosylated serum protein (GSP), serum glucose (GLU), fasting insulin (FINS), and renal function indicators [creatinine (Crea) and blood urea nitrogen (BUN)] were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma (PPARγ), acetyl coenzyme A carboxylase (ACC), and sterol regulatory element-binding protein-1 (SREBP-1) were determined by Western blot. The pathological changes in the liver and pancreas were examined.ResultsCompared with the normal group, the model group presented increased body weight, elevated levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, GSP, and HDL-C, up-regulated protein levels of ACC and SREBP-1, and down-regulated protein level of PPARγ (P<0.01). Meanwhile, the model group presented a large amount of lipid droplets and steatosis in the liver, as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group, the high- and low-dose HMG groups showed decreased body weight, declined levels of blood glucose, TG, TC, AST, ALT, GLU, NEFA, and GSP, and elevate level of HDL-C (P<0.05, P<0.01). Moreover, the two groups showcased reduced lipid droplets and steatosis in the liver, as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ (P<0.01).ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ, SREBP-1, and ACC.
关键词:Mori Folium;Ginseng Radix et Rhizoma;type 2 diabetes mellitus;glucose and lipid metabolism;peroxidase proliferator-activating receptor gamma (PPARγ);sterol regulatory element-binding protein-1 (SREBP-1);acetyl coenzyme A carboxylase (ACC)
摘要:ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia (OAS) and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.MethodsThirty-five male SD rats were randomized into a blank group (n=7) and a modeling group (n=28). The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups: model, Cuscutae Semen-Lycii Fructus granules (3.2 g·kg-1), Cuscutae Semen-Lycii Fructus total flavonoids (0.34 g·kg-1), and L-carnitine (0.38 g·kg-1), and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase (SOD), malondialdehyde (MAD), and glutathione peroxidase (GSH-Px) in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of SIRT1, Nrf2, Occludin, zonula occludens-1 (ZO-1), connexin 43 (CX43), and β-catenin.ResultsCompared with the blank group, the model group showed decreased total sperm count and motility (P<0.05, P<0.01), obvious damage in the testicular tissue and blood-testis barrier structure, reduced score of spermatogenic function (P<0.01), declined levels of GSH-Px and SOD in the testicular tissue (P<0.05), elevated level of MDA, and down-regulated protein levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin (P<0.05, P<0.01) and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, and β-catenin in the testicular tissue (P<0.05, P<0.01). After treatment, the testicular tissue, blood-testis barrier structure, and score of spermatogenic function (P<0.01) were improved in the Cuscutae Semen-Lycii Fructus granules group, Cuscutae Semen-Lycii Fructus total flavonoids group, and L-carnitine group. Compared with the model group, the treatment groups presented lowered levels of GSH-Px and SOD (P<0.05, P<0.01), and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group (P<0.05, P<0.01).ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage, thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.
摘要:Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear, and its pathogenesis is complex and refractory, collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment, traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis, and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis, this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu (stagnation) and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore, it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex, such as external wind and cold pathogens, emotional injuries, internal accumulation of dampness, and deficiency of healthy Qi, all of which can disrupt the ascending and descending movement of Qi, impede the circulation of Qi and fluids, close the pores and skin texture, and subsequently lead to stagnation. Based on the above understanding, "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind, warming cold, regulating Qi, eliminating dampness, tonifying deficiency, and external treatment, aiming to remove the causes, promote the circulation of Qi and fluids, and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms, reduce recurrence rate, and improve quality of life, which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu", enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.
关键词:psoriasis;Fuyu;Liu Wansu;traditional Chinese medicine;theoretical discussion
摘要:ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription (KXJD) and investigate its effective components and therapeutic targets in the treatment of common psoriasis.MethodsUltra-performance liquid chromatography-high resolution mass spectrometry (UPLC-Q-TOF MS) was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then, all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM, GEO, GeneCards, and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING, and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated, and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently, the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group, a model group, a positive drug methotrexate group, and a KXJD group. In the model group, the methotrexate group, and the KXJD group, imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage, while the methotrexate group and the KXJD group were respectively administered 1 mg·kg-1 suspension and 30.42 g·kg-1 decoction of traditional Chinese medicine by gavage. Five days after administration, the mice were sacrificed, and samples were collected. Hematoxylin-eosin (HE) staining was used to observe the skin tissue samples of mice, and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α (TNF-α), cyclooxygenase 2 (PTGS2), interleukin (IL)-1β, and IL-6 in the skin tissue of mice were detected by immunohistochemistry (IHC). The mRNA expressions of TNF-α, IL-1β, IL-6, and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR).ResultsIn this study, 208 compounds in KXJD were identified by UPLC-Q-TOF MS, and 44 compounds were detected in serum, including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened, and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α, IL-1β, IL-6, PTGS2, and ALB were the key target proteins. The results of molecular docking showed that the binding ability of (+)-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable, and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group, the stratum corneum and epidermis in the model group mice were significantly thickened, and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group (P<0.01). The expression areas of PTGS2, TNF-α, IL-1β, and IL-6 proteins in the skin tissue of the model group mice were significantly increased (P<0.01), and the expression levels of PTGS2, TNF-α, IL-1β, and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated (P<0.01). Compared with the model group, the pathological Baker scores of the methotrexate group and the KXJD group were both decreased (P<0.01), and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced (P<0.05, P<0.01). The expression levels of PTGS2, TNF-α, IL-1β, and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased (P<0.01).ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α, IL-1β, IL-6, and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction, which may be a key target for the treatment of psoriasis. The compound (+)-hexylphenylglycolic acid may play a key role.
关键词:Kaixuan Jiedu;cyclooxygenase 2 (PTGS2);psoriasis;network pharmacology;traditional Chinese medicine (TCM) compound
摘要:ObjectiveTo explore the effects of Kaixuan Jiedu core prescription (KXJD) on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions.MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups: healthy control (n=11), model (n=11), methotrexate (MTX, n=5), low-dose (15.21 g·kg-1) KXJD (n=5), and high-dose (30.42 g·kg-1) KXJD (n=5). Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX, respectively, by gavage daily, while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment, back skin lesions were collected. Firstly, healthy control and model mice were selected for tandem mass tag (TMT) quantitative proteomics (control vs model=3 vs 3) and targeted lipid metabolomics (control vs model=11 vs 11). Then, the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally, an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate (S1P), and Western blot was employed to determine the expression levels of sphingosine kinase 2 (SPHK2) and monocyte chemotactic protein-1 (MCP-1).ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin, and key proteases [serine palmitoyltransferase, long chain base subunit 2 (SPTLC2), SPHK2, delta(4)-desaturase sphingolipid 1 (Degs1), and ceramide synthase 4 (CerS4)] and 8 sphingolipid metabolites (including ceramides, sphingol, sphingomyelin, and glycosphingolipid) expressed abnormally (P<0.05) compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components (quercetin, kaempferol, and luteolin) in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol-1. Further experimental verification showed elevated expression levels of SPHK2, S1P, and MCP-1 in psoriatic skin compared with healthy skin (P<0.05), and KXJD down-regulated the expression levels of SPHK2, S1P, and MCP-1 compared with the model group (P<0.05).ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.
摘要:ObjectiveTo use bioinformatics technology to screen the molecular patterns and diagnostic biomarkers of ferroptosis closely related to psoriasis, observe the therapeutic effect of Kaixuan Jiedu core prescription on psoriasis and explore its potential mechanism through animal experiments.MethodsPsoriasis microarray data from GEO were analyzed to identify differentially expressed genes (DEGs). Intersection with a ferroptosis gene set yielded psoriasis ferroptosis-related genes (FRGs), which underwent correlation, consensus clustering, enrichment, and immune infiltration analyses. Core diagnostic FRGs (Hub-FRGs) were identified using random forest (RF), support vector machine (SVM), LASSO regression, Nomogram, and ROC analyses. In vivo, imiquimod (5% cream) induced psoriasis in mice (except controls). Drug treatment groups received respective doses, while control and model groups received saline via daily gavage for 7 days. Back skin changes were recorded and PASI scored. Hematoxylin-eosin (HE) staining assessed histopathology. The levels of ferrous ion (Fe2+), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and free fatty acid (FFA) in skin tissue were detected. The level of reactive oxygen species (ROS) in skin tissue was detected by immunofluorescence. Immunohistochemistry was used to detect the expression of ChaC glutathione-specific γ-glutamyl transferase 1 (CHAC1), arachidonic acid 12-lipoxygenase β (ALOX12B), trimotif protein 21 (TRIM21), proliferation marker (Ki67) and nuclear transcription factor-κB (NF-κB) protein.ResultsAnalysis of GSE30999 identified 2 100 DEGs and 24 FRGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed 1 000 biological functions and 75 pathways. After cluster analysis, combined with three machine learning algorithms, Nomogram and ROC curve analysis, the core Hub-FRGs (CHAC1, ALOX12 B, TRIM21) were obtained. Immunoinfiltration showed inactive memory CD4+T cells and activated dendritic cells abundance significantly correlated with Hub-FRGs. In vivo, model group vs. control showed significantly increased PASI/Baker scores (P<0.05), epidermal hyperkeratosis, inflammatory infiltration, and elevated levels of Fe2+, MDA, 4-HNE, FFA, ROS, CHAC1, ALOX12B, TRIM21, Ki67, and NF-κB (P<0.05). Drug groups vs. model group exhibited significantly reduced scores (P<0.05), alleviated skin lesions, and decreased levels of Fe2+, MDA, 4-HNE, FFA, ROS, Hub-FRGs, Ki67, and NF-κB (P<0.05).ConclusionKaixuan Jiedu core prescription can significantly improve the skin pathological injury of psoriasis mice, showing good therapeutic and repair effects, and its mechanism may be related to regulating the expression of ferroptosis genes CHAC1, ALOX12B and TRIM21, which are closely related to the pathogenesis of psoriasis.
摘要:ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis.MethodsThirty Balb/c mice were randomly grouped as follows (n=6): normal, model, Kaixuan Jiedu (KXJD, 15.21 g·kg-1), Kaixuan (KX, 3.08 g·kg-1), and Jiedu (JD, 12.13 g·kg-1). Except the normal group, the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod, and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index (PASI) was calculated. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor (VEGF), platelet-endothelial cell adhesion molecule (CD31), proliferating cell nuclear antigen (Ki67), and cytokeratin 10 (CK10) in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A (IL-17A) and interleukin-23 (IL-23). The spleen and thymus were photographed and weighed, and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum, liver, and kidney functions and by HE staining of the liver, kidney and spleen.ResultsCompared with that of the normal group, the skin of the model group showed erythema, infiltration, and typical psoriasis-like changes, tortuous dilation of dermal capillaries, hyperkeratosis in epidermal cells, acanthosis, massive lymphocytic infiltration in the dermis, impaired barrier function, increased expression of VEGF, CD31, Ki67, and CK10 (P<0.01), reduced expression of Claudin-1 and Occludin (P<0.01) in the epidermis, and up-regulated mRNA levels of IL-17A and IL-23 (P<0.01). In addition, the mice in the model group showed spleen enlargement, thymus atrophy, increased spleen index, and decreased thymus index (P<0.01). Compared with the model group, KXJD and JD reduced psoriasis-like skin lesions, inhibited the tortuous dilation of dermal capillaries, reduced the expression of VEGF, CD31, Ki67, and CK10 (P<0.01), increased the expression of claudin-1 (P<0.01), and down-regulated the mRNA levels of inflammatory factors (P<0.01). Moreover, the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index, thymus index, and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group.ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis, which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells, tortuous dilation of dermal capillaries, and inflammatory reactions, as well as the protection of the skin barrier. Moreover, KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective, causing no obvious liver and kidney injuries.
摘要:ObjectiveTo investigate the target proteins directly bound by neochlorogenic acid (NA) and the molecular mechanisms that ameliorate the proliferation and inflammatory response of psoriatic keratinocytes.MethodsM5-induced HaCaT cells were used as a psoriatic keratinocyte proliferation and inflammatory cell model. The synthesized NA probe (NA-P) and NA prodrug were first evaluated for cell viability using a cell proliferation/cell counting kit-8(CCK-8). The potency of NA and NA-P was evaluated in the safe concentration range, and the effects of 0-100 μmol·L-1 NA and probe on M5-induced proliferation of HaCaT cells were detected using CCK-8. The effects of 20, 40, 80 μmol·L-1 NA and 80 μmol·L-1 NA-P on the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-23 (IL-23), and interleukin-17A (IL-17A) inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to measure the effects of NA on the mRNA expression of keratin 16 (K16) in HaCaT cells, S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A7 (S100A7), IL-6, IL-17A, and chemokine 1 (CXCL1). In vitro fluorescence labeling and competition experiments using NA-P were performed, and target protein angling and analysis using pull-down experiments combined with liquid chromatography-mass spectrometry (Pull-down/LC-MS/MS) were conducted. Target validation was performed using pull-down experiments combined with protein immunoblotting (Pull down-WB), cellular heat transfer analysis combined with protein immunoblot (CETSA-WB) experiments, and molecular docking. Finally, Real-time PCR was utilized to detect the effects of 20, 40, 80 μmol·L-1 NA and 80 μmol·L-1 NA-P on the mRNA expression of IL-1β, nucleotide-binding oligomeric structural domain-like receptor protein 3 (NLRP3), apoptosis-associated speckled-like protein (ASC), and cysteine protease-1 (Caspase-1) in HaCaT cells. Protein immunoblot (Western blot) was used to detect the effects of phosphorylated p65 (p-p65), p65, phosphorylated human nuclear factor-κB inhibitory protein α (p-IκBα), human nuclear factor κB inhibitory protein α (IκBα), and heat shock protein 90 (HSP90) expression.ResultsIn the 200 μmol·L-1 safe concentration range, HaCaT cell proliferation, increased expression of TNF-α, IL-1β, IL-23, and IL-17A inflammatory factors, and increased mRNA expression of K16, S100A9, S100A7, IL-6, IL-17A, and CXCL1 were observed in the M5 group compared with the blank group. Cell proliferation in 5-100 μmol·L-1 NA and NA-P groups was inhibited, and the expression of TNF-α, IL-1β, IL-23, and IL-17A inflammatory factors was decreased in the NA-L, NA-M, NA-H, and NA-P-H groups. The mRNA expression of K16, S100A9, S100A7, IL-6, IL-17A, and CXCL1 was decreased (P<0.05). High-confidence targets were screened for HSP90 protein by Pull-down/LC-MS/MS using 200 μmol·L-1 NA competing with 100 μmol·L-1 NA-P. Compared with that in the blank group, the mRNA expression of NLRP3, IL-1β, ASC, and Caspase-1, as well as the expression of p-p65/p65, p-IκBα/IκBα, and HSP90 protein, were increased in HaCaT cells in the M5 group (P<0.05). Compared with that in the M5 group, the mRNA expression of NLRP3, IL-1β, ASC, and Caspase-1 of cells in the NA-L group, the NA-M group, the NA-H group, and the NA-P-H group was decreased (P<0.05). p-p65/p65 and p-IκBα/IκBα were decreased in the NA-M and NA-H groups (P<0.05), and there was no change in HSP90 protein. Pull down-WB showed that NA could directly target HSP90 protein, and NA binding to HSP90 protein enhanced its thermal stability. Molecular docking of NA with HSP90 family proteins HSP90AA1, HSP90B1, and HSP90AB1 all resulted in highly stable binding.ConclusionNA can inhibit the proliferation and inflammatory response of psoriatic keratinocytes by a mechanism that may be achieved by targeting HSP90 to modulate the NF-κB/NLRP3 signaling pathway.
关键词:neochlorogenic acid;HSP90;nuclear factor-κB/nucleotide-binding oligomeric structural domain-like receptor protein 3(NF-κB/NLRP3) signaling pathway;proliferation of psoriatic keratinocyte;inflammation
摘要:ObjectiveTo explore the effect of gypenosides (GPs) on liver lipid deposition in metabolism-associated fatty liver disease (MAFLD) mice and its mechanism based on classical/non-classical ferroptosis.MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout (ApoE-/-) mice were randomly divided into a model group, a low-dose GPs (GPs-L) group, a high-dose GPs (GPs-H) group, and a simvastatin (SV) group. Starting from the second week, mice in the blank group were given a maintenance diet, and the other four groups were fed a high-fat diet daily. After eight weeks of feeding, mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg-1·d-1 and 2.973 mg·kg-1·d-1, respectively, and mice in the SV group were given simvastatin of 2.275 mg·kg-1·d-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid (NEFA) and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin (HE) and oil red O staining. The levels of coenzyme Q10 (CoQ10), glutathione (GSH), malondialdehyde (MDA), and Fe2+ in serum, as well as nicotinamide adenine dinucleotide phosphate [NAD(P)H] in the liver were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ferroptosis suppressor protein 1 (FSP1) in the liver of mice was observed by the immunohistochemical (IHC) method, and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction (Real-time PCR) and Wes automated protein expression analysis system.ResultsCompared with those in the blank group, the levels of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver in the model group were significantly increased, and the level of HDL-C in serum was significantly decreased (P<0.01). The liver tissue structure changed, and there were fat vacuoles of different sizes and a large number of red lipid droplets, with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased, while the level of MDA and Fe2+ in serum was significantly increased (P<0.01). The mRNA and protein expressions of cystine/glutamate transporter (xCT/SLC7A11), glutathione peroxidase (GPX4), p62, nuclear factor E2-related factor 2 (Nrf2), and FSP1 were significantly decreased, and the mRNA and protein expressions of tumor antigen (p53), spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonate 15-lipoxygenase (ALOX15), and Kelch-like epichlorohydrin-associated protein-1 (Keap1) were significantly increased (P<0.01). Compared with those in the model group, the level of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver of mice in the GPs-L, GPs-H, and SV groups were decreased, while the level of HDL-C in serum was significantly increased (P<0.05, P<0.01). The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased, while the levels of MDA and Fe2+ in serum were significantly decreased (P<0.05, P<0.01). The mRNA and protein expressions of xCT, GPX4, p62, Nrf2, and FSP1 were significantly increased, while the mRNA and protein expressions of p53, SAT1, ALOX15, and Keap1 were significantly decreased (P<0.05, P<0.01).ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.
摘要:ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy (DN) by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/sirtuin-3 (SIRT3)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway.MethodsSixty-five SD rats were randomized into a sham group (10 rats) and a modeling group (55 rats), and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin (35 mg·kg-1) to prepare a DN model. After successful modeling, the rats were randomized into model, empagliflozin (10 mg·kg-1), and low-, medium-, and high-dose (7.656, 15.312, 30.624 g·kg-1, respectively) Shenxiao Tongluo prescription groups. The urine microalbumin (UmAlb), blood urea nitrogen (BUN), and serum creatinine (SCr) levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate, superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissue. Hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 (DRP1) and pyruvate kinase M2 (PKM2) in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α, SIRT3, HIF-1α, dynamin-related protein 1 (Drp1), optic atrophy 1 (OPA1), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2) in the kidney tissue.ResultsCompared with the sham group, the model group showed elevated levels of UmAlb, BUN, SCr, lactate, and MDA, decreased SOD level (P<0.05), glomerular hypertrophy, thickening of the mesangial basement membrane, vacuolar degeneration of renal tubular epithelial cells, and infiltration of renal interstitial inflammatory cells, oval mitochondria with disordered, blurred or disappearing cristae, down-regulated protein levels of PGC-1α, SIRT3, and OPA1, and up-regulated protein levels of HIF-1α, DRP1, HK2, and PKM2 (P<0.05). Compared with the model group, the treatment in all the groups increased the body weight, lowered the levels of GLU, UmAlb, BUN, and MDA, raised the level of SOD, alleviated the pathological damage in the kidney tissue and mitochondrial damage, up-regulated the expression of PGC-1α, SIRT3, and OPA1, and down-regulated the expression of HIF-1α, DRP1, and PKM2 (P<0.05). Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 (P<0.05), which had no statistical significance in the low-dose Shenxiao Tongluo prescription group.ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway, thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.
摘要:ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue.ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05).ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
摘要:ObjectiveTo study the tumor inhibition and T helper cell (Th)1/Th2 balance regulation effect of modified Wenyang Sanjie prescription on lung cancer tumor-bearing mice and to elaborate its mechanism.MethodsA mouse model bearing a lung cancer tumor was established by subcutaneous injection of Lewis lung cancer cells into the armpit and was randomly divided into lung cancer model group, low-dose, medium-dose, and high-dose groups of modified Wenyang Sanjie prescription, and positive control group, with 12 mice per group. The low-dose, medium-dose, and high-dose groups of modified Wenyang Sanjie prescription were given modified Wenyang Sanjie prescription by dosing at 2.5, 5, 10 g·kg-1, once a day, respectively. The positive control group was intraperitoneally injected with cisplatin (2 mg·kg-1), once every other day, for a total of 30 days. Serum interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA), and spleen index, thymus index, and tumor growth inhibition rate were calculated. Tumor microvascular density was determined by immunohistochemistry, and tumor hypoxia inducible-factor (HIF)-1α, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) mRNA were determined by Real-time quantitative polymerase chain reaction (PCR). The protein levels of HIF-1α, EGFR, and VEGF were determined by Western blot.ResultsCompared with lung cancer model group, IFN-γ and IL-2 were increased in the modified Wenyang Sanjie prescription groups and positive control group, while IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). Compared to the low-dose group of modified Wenyang Sanjie prescription, IFN-γ and IL-2 were increased in the medium-dose and high-dose groups of modified Wenyang Sanjie prescription, while IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). IFN-γ and IL-2 were increased in the high-dose group of modified Wenyang Sanjie prescription compared to the medium-dose group of modified Wenyang Sanjie prescription, and IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05).ConclusionModified Wenyang Sanjie prescription can significantly inhibit microangiogenesis, regulate Th1/Th2 balance, inhibit tumor growth, and significantly inhibit the progression of lung cancer in mice.
摘要:ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis.MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay.ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB.ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
关键词:mitotically-associated long non-coding RNA;microRNA-50-5p;non-metastatic melanoprotein B;gastric cancer;proliferation;migration;epithelial mesenchymal transition
摘要:ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm turbidity obstructing lung syndrome, and to investigate its effects on inflammatory factors, immune function, and the programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway.MethodsA randomized controlled study was conducted, enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital, Beijing University of Chinese Medicine, from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table, with 45 patients in each group. The control group received conventional Western medical treatment, while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy, COPD Assessment Test (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walk test (6MWT), serum inflammatory factors, T lymphocyte subsets, and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment.ResultsThe total clinical effective rate was 78.57% (33/42) in the control group and 95.35% (41/43) in the observation group, with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant (χ2 = 5.136, P<0.05). After treatment, both groups showed significant reductions in CAT and mMRC scores (P<0.05, P<0.01) and significant increases in 6MWT compared to baseline (P<0.01). The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1(MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were significantly reduced in both groups (P<0.05, P<0.01), with greater reductions in the observation group (P<0.05, P<0.01). CD8+ levels were significantly reduced (P<0.01), while CD3+, CD4+, and CD4+/CD8+ levels were significantly increased in both groups after treatment (P<0.05, P<0.01), with more significant improvements observed in the observation group (P<0.05, P<0.01). Serum PD-1 levels were reduced (P<0.05, P<0.01), and PD-L1 levels were increased significantly in both groups after treatment (P<0.05, P<0.01), with more pronounced changes in the observation group (P<0.05).ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors, improving immune function, and regulating the PD-1/PD-L1 signaling pathway.
摘要:ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure (ADHF) with the traditional Chinese medicine (TCM) pattern of Qi and Yin deficiency, Yang deficiency, and blood stasis.MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency, Yang deficiency, and blood stasis type were randomly assigned to an observation group (34 cases) and a control group (34 cases). Both groups received conventional Western medical treatment, while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included: TCM syndrome score, TCM syndrome efficacy, New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk distance (6MWD), hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor A (VEGF-A), Caspase-3, and the number of rehospitalizations for heart failure within one month after discharge.ResultsThere were no significant differences in sex, age, vital signs, or underlying diseases between the two groups. Compared with baseline, both groups exhibited significant reductions in TCM syndrome scores, NT-proBNP, and HIF-1α levels (P<0.01), as well as significant increases in 6MWD, LVEF, VEGF-A, and Caspase-3 levels (P<0.05, P<0.01). After treatment, the observation group showed significantly greater reductions in TCM syndrome score, NT-proBNP, HIF-1α, and Caspase-3 levels compared with the control group (P<0.05) and significantly greater increases in 6MWD, TCM syndrome efficacy, and VEGF-A levels (P<0.05). No significant differences were observed between the groups in NYHA functional classification, LVEF, or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period.ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency, Yang deficiency, and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α, VEGF-A, and Caspase-3.
关键词:Shengmai Jiuxin decoction;acute decompensated heart failure;Qi and Yin deficiency, Yang deficiency, and blood stasis type;hypoxia-inducible factor-1 (HIF-1) signaling pathway
摘要:ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes.MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum.ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms.ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.
摘要:ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality.MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei, Anhui and Guangdong, and their diameter range, epidermis color and producing areas were recorded. Total flavonoids, total phenols, volatile oils, 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry, ultra performance liquid chromatography-photodiode array detector(UPLC-PDA) and gas chromatography-mass spectrometry(GC-MS). Then the differences between the contents of these components were analyzed by principal component analysis(PCA) and non-parametric test. According to the weights of the index components determined by PCA model, entropy weight-technique for order preference by similarity to ideal solution(TOPSIS) model was constructed to evaluate the quality of Perillae Caulis with different characters and origins.ResultsThere were significant differences in the composition of Perillae Caulis with different diameters, epidermis colors and producing areas, and 9 differential components were screened out, including 6 index constituents(total flavonoids, total phenols, caffeic acid, scutellarin, rosmarinic acid and luteolin) and 3 volatile components(caryophyllene oxide, (-)-humulene epoxide Ⅱ, 14-hydroxycaryophyllene), of which 6 index constituents were higher in samples with small diameter, purple-brown epidermis and southern origin, while the contents of 3 volatile components were higher in samples with large diameter, dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters, epidermis colors and origins(P<0.05), and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area, especially Guangdong, had a high score.ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters, epidermal colors and production areas of Perillae Caulis, samples showing small diameter, owing purple-brown epidermis, and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.
关键词:appearance;origin;entropy weight-technique for order preference by similarity to ideal solution(TOPSIS);chemometrics;quality difference;Perillae Caulis
摘要:ObjectiveTo systematically investigate the identification characteristics of medicinal amber, elucidate its microscopic features, crystal structural properties, and elemental composition, and thereby provide a scientific foundation for quality control and authenticity verification.MethodsThirty-nine batches of amber samples were collected and analyzed through integrated techniques including morphological analysis, microscopic identification, powder X-ray diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and inductively coupled plasma mass spectrometry (ICP-MS) to evaluate their morphological attributes, phase composition, molecular vibrational modes, and trace element profiles. Among them, the XRD experiment used Cu Kα radiation (λ=1.540 6 Å), with a scanning angle range of 10° to 70° (2θ) and a step size of 0.02°, the Raman spectroscopy experiment employed a 785 nm laser, with a spectral measurement range of 3 400 to 50 cm-1, a laser power of 300 mW, a laser intensity of 30%, and a scanning time of 100 to 1 000 ms, the infrared spectroscopy experiment used a carbon-sulfur lamp, with a scanning range of 4 000 to 500 cm-1, a resolution of 4 cm-1, and 3 scans, the ICP-MS experiment utilized frequency power of 1.2 kW, a double-pass cyclonic spray chamber, a sample introduction system flow rate of 0.7-1.0 L·min-1, and an auxiliary gas flow of 0.2 L·min-1.ResultsUnder orthogonal polarized light microscopy, medicinal amber exhibited an isotropic homogeneous structure, with partial samples containing inorganic impurities such as AsS and SiO₂. FTIR spectra revealed characteristic absorption peaks at 2 932-2 939 cm-1 (C-H stretching vibrations), 1 705-1 728 cm-1 (C=O stretching vibrations), and 880-887 cm-1 (C=C deformation vibrations), confirming the oxidative polymerization of terpenoid resin. Raman spectroscopy further identified distinctive peaks at 2 925 cm-1, 2 870 cm-1 (saturated C-H stretching), and 1 648 cm-1 (C=C stretching), consistent with the structural features of oxidized-polymerized resin. ICP-MS analysis demonstrated that S, Al, Si, Fe, Na, and Ca were the predominant trace elements in medicinal amber.ConclusionThis study comprehensively evaluated medicinal amber's morphological attributes, phase composition, molecular vibrational modes, and trace elements through multimodal analytical techniques. The findings establish data support for establishing quality standards for medicinal amber and distinguishing it from synthetic resin imitations.
TIAN Xiurong, WANG Hao, PANG Kejing, YU Penglong, LIU Xia, SHEN Mengyue, JIANG Xianglin, LI Yonghua, LI Zhihong, DING Hongqiong, YANG Qin, LI Xingying, XIONG Qian, WAN Guochao, MA Yuexiang, LIU Zhenping
摘要:ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan, providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product.MethodsSamples of Foeniculi Fructus were collected from eight producing areas, including Minqin (Gansu), Bozhou (Anhui), Qingdao (Shandong), Dezhou (Shandong), Urumqi (Xinjiang), Nujiang (Yunnan), Gutuo (Inner Mongolia), and Haiyuan (Ningxia). Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect the volatile organic compounds (VOCs) in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology (NIST) mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform, VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted, and 97 VOCs detected via GC-IMS were subjected to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection (VIP) values greater than 1.ResultsA total of 97 VOCs were identified, including alcohols, aldehydes, ketones, esters, organic acids, terpenoids, ethers, alkenes, and benzenes. The PLS-DA model, based on VOCs data obtained by GC-IMS, effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation, the model achieved a prediction parameter (Q2) of 0.976 and a goodness-of-fit parameter (R2) of 0.936, with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin.ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology, PLS-DA, and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.
关键词:gas chromatography-ion mobility spectrometry technology;volatile organic compounds;Foeniculi Fructus from Haiyuan;chemometric methods;geographical origin discrimination model
摘要:This article systematically analyzes the historical evolution of the name, origin, academic name, medicinal parts, origin, harvesting, processing and other aspects of Abri Herba and Abri Mollis Herba by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the modern literature, so as to provide a basis for the development of famous classical formulas containing this type of medicinal materials. According to the herbal textual research, Abri Herba was first recorded in Lingnan Caiyaolu, with other aliases such as Huangtoucao and Xiye Longlincao. It originates from the dried whole plant of Abrus cantoniensis, a Fabaceae plant, which can be used medicinally except for its fruits. Currently, this species is mainly distributed in Guangdong and Guangxi, and also found in Hunan and Thailand, it can be harvested throughout the year, mainly in spring and autumn. The roots, stems, and leaves can be used for medicinal purposes, but the pods are toxic and need to be removed. After harvesting, impurities and pods are removed, and it is dried and processed for medicinal use. Abri Herba has a sweet and slightly bitter taste, is cool in nature, and is associated with the liver and stomach meridians, it is used for clearing heat and relieving dampness, dispersing blood stasis and relieving pain, and is mainly used to treat jaundice-type hepatitis, stomach pain, rheumatic bone pain, contusion and ecchymosis pain, and mastitis. Abri Mollis Herba was first recorded in the 1982 edition of Zhongyaozhi as another origin for Abri Herba, and was singled out in some monographs such as Xinhua Bencao Gangyao in 1988 for use, while some other monographs use it as a local habitual products or confused products of Abri Herba with aliases such as Daye Jigucao, Qingtingteng, and Maoxiangsi. It comes from the dried whole herb of A. mollis without pods, and is mainly produced in Guangxi and Guangdong, and occasionally found in Hong Kong, Hainan and Fujian. The collection and processing are similar to Abri Herba, after harvesting, impurities and pods are removed, and it is dried and cut for medicinal use. Abri Mollis Herba has a sweet and light taste, is cool in nature, and is associated with the liver and stomach meridians, with the efficacy of clearing heat and detoxifying, and promoting dampness, it is mainly used to treat infectious hepatitis, mastitis, furuncles, burns and scalds, and pediatric malnutrition. Based on the research, A. mollis was first recorded to be used as a medicine in the same origin as A. cantoniensis, and as plants of the same genus, have similar morphological characteristics, and their medicinal parts, collection and processing, properties and flavors, and meridian affiliations are consistent. And in the folk, Abri Mollis Herba is often used as Abri Herba, which has been used for a long time and is now dominated by the cultivation of A. mollis. So it is recommended that the subsequent version of Chinese Pharmacopoeia should include A. mollis in the origin of Abri Herba, and it is also recommended that in famous classical formulas refered to Jiguccao can use A. cantoniensis and A. mollis as the sources of the herb, refered to Mao Jiguccao can use A. mollis as the sources of the herb. Processing is carried out according to the requirements specified in the original formulas, and raw products are recommended to be included in the medicine if there are no requirements.
关键词:famous classical formulas;Abri Herba;Abri Mollis Herba;origin;medicinal parts;processing;herbal textual research
摘要:Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by erosive arthritis, with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years, challenges such as suboptimal efficacy, drug resistance, severe side effects, and high costs of long-term treatment remain, especially for patients in the early stages of RA, as well as those with RA complications, comorbidities, and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine, the 27th session of the Clinical Dominant Disease Series (Rheumatoid Arthritis) Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine (TCM), western medicine, and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA, especially during the early stage, periods of low to moderate disease activity, remission phase, and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA, refractory cases, and stages with severe complications, by rapidly controlling disease progression, alleviating symptoms, enhancing the quality of life, and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA, TCM shows potential in regulating immunity, alleviating symptoms, and improving physical constitution, which provides new insights into the comprehensive treatment of RA with comorbidities. However, high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future, individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.
关键词:rheumatoid arthritis;clinical dominant disease;traditional Chinese medicine;integrated traditional Chinese and western medicine;expert recommendation
摘要:Based on the etiology and clinical diagnostic criteria of type 2 diabetes mellitus (T2DM), identification and typing of treatment from the perspective of traditional Chinese and western medicine, the criteria for evaluating the clinical compatibility of traditional Chinese and western medicine in animal models of T2DM were set up. The literature was reviewed to sort out and analyze the existing commonly used modeling methods, summarize the mechanism, compare the advantages and disadvantages, and calculate the consistency between the animal model and the clinical symptoms, syndromes, and indicators from the perspective of traditional Chinese and western medicine. The authors found that spontaneous animal models and high-fat diets combined with multiple low-dose streptozotocin (STZ) induction models were more in line with modern medical pathogenesis of T2DM. However, it fails to form some special syndromes required for traditional Chinese medicine (TCM) research. In addition, there are many methods of combining the etiology and pathogenesis of TCM, which can be divided into three categories: intervention carried out by drug administration, behavioral stimulation, or environmental changes according to TCM, or use of hormones according to clinical evidence and combination of the two methods mentioned above. All of them can successfully establish different types of animal models. However, different methods of establishing syndrome models have their own advantages and disadvantages, and there is no unified standard for the stability and evaluation of syndrome models. As for the clinical consistency criteria of traditional Chinese and western medicine established in this paper, the animal model with 100% consistency has not been calculated due to the conditions of incomplete symptoms and syndromes described in the studies and different selection indicators. Consequently, the establishment of a simple, easy-to-use, and affordable T2DM animal model with both traditional Chinese and western medicine disease characteristics and the improvement of the Chinese and western medicine evaluation system for different evidence types are of great significance for the future development of TCM research on T2DM.
关键词:type 2 diabetes mellitus;animal model;evaluation criteria;disease and syndrome combination of traditional Chinese and western medicine
摘要:ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea (PD) in both traditional Chinese medicine (TCM) and western medicine, providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine.MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed, CNKI, and Wanfang Data. According to the diagnostic criteria of TCM and western medicine, the modeling methods in the literature were summarized, evaluated for strengths and weaknesses, and systematically assessed for clinical concordance rates to identify suitable reference models.ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine, respectively. Commonly used modeling methods included estrogen administration, physical stimulation, and surgical intervention, with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate.ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation, but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover, except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome, no animal models for other TCM syndromes have been reported, which limits comprehensive TCM research on this disease to a certain extent.
摘要:Liver being substantial Yin and functional Yang maintain normal function of Qi, blood and meridians. In clinical practice, it is often found that pan-vascular lesions with atherosclerosis as the predominant pathological change often co-occur with metabolic dysfunction-associated fatty liver disease(MAFLD). MAFLD leads to increased risk and worse prognosis for many pan-vascular diseases, including cardiovascular disease. Dysregulation of energy homeostasis disrupts the hepatic homeostasis of body use, and representative drugs to improve metabolism, such as metformin, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 agonists, not only have a clear cardiovascular benefit, potential improvement of MAFLD has also been demonstrated. The liver stores blood and the heart pumps blood, and liver diseases affect the heart, that's why the unsmoothness of vessels appears. So the treatment should from the standpoint of liver, restoring liver function, soothing the liver and nourishing heart, activating blood and dredging meridian. It is of great significance to explore in depth the pathogenesis and treatment of pan-vascular lesions caused by MAFLD, and to restore the energy homeostasis by adjusting the balance of liver Yin and Yang.
关键词:liver being substantial Yin and functional Yang;metabolic dysfunction-associated fatty liver disease;panvasculopathy;energy metabolism;imbalance of Yin and Yang;atherosclerosis;traditional Chinese medicine pathogenesis
摘要:Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model, this paper used multiple databases to search for the keywords "heart and spleen deficiency", "insomnia", "sleepless", "disease syndrome-combined animal model", "model evaluation", etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment, modeling factors, syndrome model, disease model, macro characterization & macro characterization evaluation scale, micro indicators, etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method, the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease, and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation, which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine (TCM) syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome, along the specific related ideas of "prescription and syndrome, treatment principle and selection of prescription, treatment principle and selection of acupoints, as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice, so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.
关键词:heart and spleen deficiency;insomnia;sleepless;disease syndrome-combined animal model;model evaluation
摘要:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis as its pathological basis. Although current therapeutic drugs can alleviate symptoms, they are often accompanied by a high risk of side effects. In recent years, the use of flavonoids from traditional Chinese medicine (TCM) in the treatment of RA has garnered significant attention. Studies have shown that the mechanisms by which flavonoids treat RA include inhibiting the release of pro-inflammatory factors, regulating multiple cellular signaling pathways, alleviating oxidative stress, modulating immune system functions, inhibiting bone destruction, and suppressing angiogenesis. Due to their notable anti-inflammatory, antioxidant, and immunomodulatory activities, flavonoids hold promise as potential therapeutic agents for RA. A substantial number of articles in this field have been published. By reviewing Chinese and international literature and applying bibliometric and visual analysis using CiteSpace, this paper explored research hotspots and frontiers in this field, systematically reviewed the structures and anti-RA mechanisms of TCM flavonoids, provided a theoretical basis for their use in RA treatment and clinical applications, and offered new perspectives and references for the discovery of novel TCM-based anti-RA drugs.
关键词:flavonoid compound;rheumatoid arthritis;mechanism of action;signaling pathway;fibroblast-like synoviocyte
摘要:Central nervous system(CNS) disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier(BBB), which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration, intravenous injection and transdermal delivery, which have certain advantages, but it is difficult for the drugs to effectively cross the BBB. Therefore, it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery, as a non-invasive method, can realize the targeted delivery of drugs to the CNS via three pathways, including olfactory neurons, trigeminal neurons and blood circulation, and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers, nanoparticles, nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine(TCM), and significantly increase drug concentration in the brain, which provides new strategies for the treatment of CNS diseases. In this paper, the current status of drug delivery for CNS diseases was systematically sorted out, the characteristics of nasal drug delivery were discussed in depth, and the research progress of passive targeting, active targeting, and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed, which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.
关键词:traditional Chinese medicine;nasal drug delivery;central nervous system diseases;blood-brain barrier;drug delivery system;guide medicine upwards;research progress
摘要:Asthma is a chronic inflammatory respiratory disease involving multiple cells and cellular components, characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing, significantly impacting patients' quality of life. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, as a crucial hub in intracellular signaling, is widely involved in the regulation of cell growth, proliferation, survival, metabolism, and a series of pathophysiological processes. Its regulatory role in the pathological progression of asthma is particularly significant, specifically in promoting airway inflammation, mediating epithelial mesenchymal transition, accelerating airway remodeling, regulating cell autophagy, inducing mucus hypersecretion, and influencing immune response balance. This study analyzed potential molecular targets of the PI3K/Akt pathway, including activators such as cysteine proteinase inhibitor 1(CST1), found in inflammatory zone 1(FIZZ1) and free fatty acid receptor 1(FFAR1), and inhibitors such as human β-defensin-3(hBD-3), disintegrins, metalloproteinase 33(ADAM33) and interleukin-27(IL-27), and initially revealed the potential molecular mechanisms of traditional Chinese medicine(TCM) in asthma intervention. Based on this, the authors systematically summarized the efficacy and specific mechanisms of TCM monomers, compounds, and external treatments for asthma by regulating the PI3K/Akt signaling pathway through literature review and analysis, aiming at establishing a robust foundation for the wide application and advanced development of TCM in asthma treatment, offering innovative insights for clinical research and drug development of asthma.
摘要:Heart failure (HF), as the terminal stage of most cardiovascular diseases, manifests with primary symptoms including dyspnea, fatigue, edema, and palpitations. With recurrent episodes and a protracted clinical course, HF imposes a substantial global disease burden. PANoptosis represents a distinctive form of programmed cell death (PCD) that integrates features of pyroptosis, apoptosis, and necroptosis, yet cannot be fully attributed to any single pathway among these three PCD modalities. Recent studies demonstrate significant dysregulation of PANoptosis-related genes during HF progression, positioning PANoptosis as both an emerging mechanism mediating HF pathogenesis and a novel therapeutic target. In recent years, traditional Chinese medicine (TCM) has gained substantial recognition for its therapeutic potential in HF management, offering advantages such as flexible compatibility, multi-target effects, and minimal adverse reactions. Astragali Radix, a representative Qi-invigorating and blood-activating herbal medicine, has demonstrated remarkable clinical efficacy in the treatment for various HF subtypes. Research reveals that its major bioactive components—including astragaloside Ⅳ, polysaccharide, quercetin, and calycosin—exhibit significant associations with the regulation of apoptosis, pyroptosis, and necroptosis pathways. This review systematically explores the therapeutic feasibility of Astragali Radix in the prevention and treatment of HF through the lens of PANoptosis mechanisms. By synthesizing recent advances in the mechanisms of Astragali Radix-derived bioactive compounds and Astragali Radix-containing compound prescriptions in modulating PANoptosis, this paper aim to provide critical insights for advancing the diagnosis and therapeutic strategies of HF.
摘要:Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease that primarily affects the mucosal layer of the rectum and colon. Its pathogenesis is complex and remains incompletely understood. Endoplasmic reticulum stress (ERS) plays a critical role in cellular responses to external stress and the maintenance of homeostasis, and its abnormal activation is closely associated with the development of various inflammatory diseases, particularly in the pathological process of UC. ERS maintains cellular homeostasis by activating the unfolded protein response (UPR). However, when ERS is prolonged or excessive, UPR fails to alleviate the stress, leading to epithelial cell death and aggravating the progression of UC. Modulating ERS may serve as a key target for the prevention and treatment of UC, and it is one of the current research hotspots. Traditional Chinese medicine (TCM) has shown significant efficacy in regulating ERS, offering unique therapeutic advantages through multi-target and multi-pathway mechanisms. Recent studies have confirmed that TCM can alleviate ERS, inhibit apoptosis, regulate autophagy, reduce inflammatory responses, and maintain intestinal barrier function to prevent and treat UC. This review summarized the relationship between ERS and UC and discussed the intervention of TCM in regulating ERS for the treatment of UC, aiming to provide new insights and approaches for the treatment of UC with TCM.
关键词:traditional Chinese medicine;ulcerative colitis;endoplasmic reticulum stress;apoptosis;autophagy
摘要:“Inflammation-cancer” transformation of chronic atrophic gastritis (CAG) refers to the process in which the gastric mucosa, in the context of CAG, progresses through stages of precancerous lesions of gastric cancer (PLGC), such as intestinal metaplasia and dysplasia, and eventually develops into gastric cancer (GC). In China, the incidence and mortality rates of GC rank among the highest in the world, and the proportion of GC cases caused by gastric mucosal infection and inflammation has been increasing. Modern medical treatments for CAG and PLGC mainly rely on drug therapy, endoscopic resection, and regular surveillance. Although these disease management strategies are relatively mature, they present limitations in early lesion prevention and recurrence risk control. Therefore, it is imperative to identify therapeutic approaches for CAG and PLGC that offer preventive, reversible, and recurrence-reducing benefits. With advances in research on the mechanisms underlying inflammation-cancer transformation and the integration of traditional Chinese and Western medicine, the advantages of TCM in preventing and even reversing early-stage CAG and PLGC have gradually become apparent. This review explored the mechanisms of inflammation-cancer transformation in CAG from five aspects: inflammatory microenvironment, autophagy, glycolysis, bile acids, and ferroptosis. In conjunction with TCM theory and a deeper understanding of the distinct mechanisms involved in the inflammation-cancer transformation of CAG, this review further discussed the specific mechanisms through which TCM intervened in treating CAG and PLGC, with the aim of providing theoretical support and therapeutic insights for future clinical applications.
关键词:chronic atrophic gastritis;inflammation-cancer transformation;pathogenesis;traditional Chinese medicine;review
摘要:Ulcerative colitis (UC) is a refractory disease of the digestive system characterized by diverse etiologies, complex pathogenesis, a prolonged course, and frequent relapses. In recent years, the incidence of UC has been increasing annually, severely impairing patients' quality of life, posing a risk of malignant transformation that may threaten patients' lives, and resulting in a substantial medical burden. Traditional Chinese medicine (TCM) compound formulas, with their advantages of multi-component and multi-target actions, have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is a core component of innate immunity, and its aberrant activation is closely associated with the onset and progression of UC, involving multiple processes such as inflammation and oxidative stress, and exhibiting crosstalk with pathways including nuclear factor-κB (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and thioredoxin-interacting protein (TXNIP). At present, NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment, challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM, hindering the realization of precision therapy. In this context, by reviewing literature from the past decade, this paper summarizes the activation process of NLRP3 and its relationship with UC, and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways, with a view to providing a reference for further research into the pathogenesis of UC, TCM treatment strategies, and their mechanisms of action.