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- Abstract：ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism.MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe2+ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot.ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）.ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe3+ uptake， leading to an imbalance in the antioxidant system.Keywords：hepatocarcinoma carcinoma;polyphyllin Ⅱ;ferroptosis;p53;mechanism334|312|5
<HTML><H-PDF><L-PDF>Updated：2024-07-31 Computer-aided Drug Design and Experimental Validation Reveal Molecular Mechanism of Saikosaponin D-induced Apoptosis of Bladder Cancer Cells Enhanced Publication
Abstract：ObjectiveTo explore the role of saikosaponin D （SSD） targeting signal transducer and activator of transcription 3 （STAT3） in inducing apoptosis of bladder cancer cells by computer-aided drug design and experimental verification.MethodThe druggability and biotoxicity of SSD were explored by Bayesian classifier modeling. The information about SSD， the active ingredient of Bupleuri Radix， was searched against the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform （TCMSP）. The targets of SSD were predicted by PubChem， TCMSP， a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）， Coremine， an Encyclopedia of Traditional Chinese Medicine （ETCM）， and SwissTargetPrediction. GeneCards， Therapeutic Target Database （TTD）， and Online Mendelian Inheritance in Man （OMIM） were employed to predict the potential therapeutic targets of bladder cancer. Then， the common targets shared by SSD and bladder cancer were selected for Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Molecular docking was adopted to explore the binding affinity and structural stability of SSD with target proteins. Cytoscape 3.9.1 was used to construct the STAT3-drug regulatory network and STAT3-apoptosis regulatory network. UM-UC-3 cells were treated with 0， 5， 10， 15 μmol·L-1 SSD for 24 h. Then， flow cytometry was used to detect the apoptosis of bladder cancer cells， and Western blot was employed to determine the protein levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Bcl-2-associated death promoter （Bad）， STAT3， and phosphorylation （p）-STAT3.ResultBayesian classifier modeling and molecular docking showed that SSD had low biotoxicity and bound well to the target protein STAT3 to form a stable protein-ligand complex. There were 282 common targets between bladder cancer and SSD， among which STAT3 was the most central target. The GO enrichment analysis showed that the potential core therapeutic targets involved 3 036 biological processes， 82 cellular components， and 171 molecular functions. The KEGG enrichment analysis showed that the potential core targets were mainly related to the C-type lectin receptor signaling pathway， Toll-like receptor signaling pathway， and cell apoptosis pathway. The STAT3-drug regulatory network and STAT3-apoptosis regulatory network showed that 29 drugs interacted with STAT3， and 27 apoptosis-related genes had a strong correlation with STAT3. Flow cytometry showed that the apoptosis rate increased with the increase in SSD concentration （P<0.05）. Western blotting results showed that SSD down-regulated the protein levels of p-STAT3 and Bcl-2 and up-regulated the protein levels of Bax and Bad in a concentration-dependent manner （P<0.05）.ConclusionSSD has good druggability and low biotoxicity. It may promote the apoptosis of bladder cancer cells by targeting STAT3.Keywords：saikosaponin D;network pharmacology;bladder cancer;apoptosis;signal transducer and activator of transcription 3 （STAT3）281|414|2<HTML><H-PDF><L-PDF>Updated：2024-07-31- Abstract：In order to implement the spirit of the 20th National Congress of the Communist Party of China， and the Opinions on Promoting the Inheritance， Innovation and Development of Traditional Chinese Medicine（TCM）， to regularly summarize the research results of TCM， to present the academic progress of TCM dynamically， and to give full play to the academic leadership of academic groups， the China Association of Chinese Medicine had organized the selection of the top 10 academic progress of TCM in 2023. The selection work adhered to the "four orientations"， eliminated the "four only"， highlighted the solution of clinical problems， answered scientific questions， led the development of the industry， reflected the exploratory and forward-looking， innovative and breakthrough， focused on new laws， new discoveries， new methods， new products， new theories in the field of basic research and applied basic research in TCM. After dynamic collection， preliminary examination， review and final judgment， the top 10 academic progress of TCM in 2023 were determined， including clinical studies have made important breakthroughs or achievements in the treatment of acute ST-segment elevation myocardial infarction（STEMI） by Tongxinluo， acupuncture treatment of refractory diseases such as chronic spontaneous urticaria and pregnancy vomiting， and Xuesaitong soft capsules to improve neurological function in patients with ischemic stroke. The mechanism of Huashi Baidusan， Pien Tze Huang， astragaloside Ⅳ， capsaicin was revealed. The application of technologies and methods such as spatial metabolomics， network medicine， multi-dimensional nucleic acid data resource platform of TCM， multi-unit transmission and information fusion provided new ideas for the research of TCM. The scientific system of TCM supervision was initially constructed and applied.Keywords：traditional Chinese medicine（TCM）;academic progress;acute myocardial infarction;spontaneous urticaria;pregnancy vomiting;acupuncture;intestinal flora;spatial metabolomics519|453|6<HTML><H-PDF><L-PDF>Updated：2024-07-12
Constitution Distribution and Clinical Data of 252 Patients with Allergic Asthma Enhanced Publication
Abstract：ObjectiveA cross-sectional study was conducted to analyze the constitution distribution characteristics of patients with allergic asthma， aiming to provide a basis for the regulation of constitution and the treatment of allergic asthma.MethodThe patients with allergic asthma treated in the outpatient clinic from December 2021 to September 2023 were selected. The clinical data of the patients were collected by a questionnaire survey. The composite constitution distribution characteristics of the patients and the correlations of constitution with gender， age， body mass index （BMI）， comorbid allergic diseases， history of allergy， family history， keeping pets， and fractional exhaled nitric oxide （FeNO） in the patients with special constitution were analyzed.ResultA total of 252 patients with allergic asthma were included in this study， with a male-to-female ratio of 1∶1.5， and the proportion of young people was the highest. The proportion of special constitution alone was the highest， and the proportions of other constitutions combined with special constitution followed the order of Yang deficiency， Qi deficiency， Qi depression， phlegm dampness， dampness heat， Yin deficiency， and blood stasis. There were 58 patients with special constitution combined with one other constitution， of which Yang deficiency accounted for the highest proportion. There were 38 patients with special constitution combined with two other constitutions， of which Qi deficiency + Yang deficiency was the most common. Among the patients， 116， 48， and 117 patients were overweight or obese， had a family history of allergic diseases， and had a history of allergy， respectively. Seventy patients kept pets， and there was a correlation between keeping pets and allergy to cat and dog hair （P<0.05）. Other allergic diseases complicated with allergic asthma occurred in 202 patients， being dominated by allergic rhinitis， urticaria， and eczema. There were 177 patients with eosinophilic airway inflammation. The patients with allergic asthma mainly presented the syndromes of wind asthma （134， 53.17%）， heat asthma （51， 20.24%）， cold asthma （32， 12.7%）， deficiency asthma （15， 5.95%）， Qi depression asthma （14， 5.56%）， and blood stasis asthma （6， 2.38%）. The results of binary logistic regression suggested that women were more likely have Yang deficiency and Qi depression than men. Older patients were less likely to present phlegm dampness and dampness heat. BMI was positively correlated with phlegm dampness and negatively correlated with Yang deficiency （P<0.05）.ConclusionThe patients with allergic asthma mainly present special constitution and wind asthma syndrome. The combination of special constitution and other constitutions （commonly Qi deficiency and Yang deficiency） leads to repeated attacks of allergic asthma. The incidence of allergic asthma is higher in women and young people， and women are more likely to have Yang-deficiency or Qi-deficiency constitution. Obesity may be a risk factor for allergic asthma. Obese people are more likely to have phlegm-dampness and dampness-heat constitutions. Pet contact and allergic rhinitis may lead to poor control of allergic asthma.Keywords：allergic asthma;characteristics of constitution;special constitution;composite constitution;clinical data343|285|6<HTML><H-PDF><L-PDF>Updated：2024-07-12- Abstract：ObjectiveTo observe the clinical efficacy and safety of Tinglu Yixin prescription in the treatment of patients with heart failure with preserved ejection fraction （HFpEF） combined with diabetes （syndromes of Qi and Yin deficiency and water retention and blood stasis） from taste-based compatibility and descending adverse Qi with bitter and pungent medicinals.MethodA total of 108 HFpEF patients with diabetes （syndromes of Qi and Yin deficiency and water retention and blood stasis） treated in the Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from May 2022 to March 2023 were enrolled in this study and randomized into an observation group （54 patients） and a control group （54 patients）. Both groups received conventional Western medicine treatment according to the guide recommendations for chronic heart failure and diabetes， and the observation group additionally received Tinglu Yixin prescription. The treatment course for both groups was 12 weeks. The New York Heart Association （NYHA） grading of cardiac function， left ventricular end diastolic diameter （LVEDD）， left atrium diameter （LAD）， the ratio of early diastolic maximum mitral flow velocity （E） to early diastolic mitral annular motion velocity （e'） （E/e'）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， hemoglobin A1c （HbA1c）， 6-minute walking test （6MWT）， Minnesota Living with Heart Failure Questionnaire， traditional Chinese medicine （TCM） syndrome scores， and safety indicators were determined before and after treatment.ResultFinally， 104 patients were included for analysis， including 52 patients in the observation group and 52 patients in the control group. After treatment， 35 and 47 patients in the control and observation groups showed improved cardiac function， which indicated the total response rates of 67.3% and 90.4%， respectively. The total response rate regarding the cardiac function in the observation group was higher than that in the control group （χ2=2.754， P<0.05）. The observation group outperformed the control group in reducing LVEDD and LAD （P<0.05）， decreasing the E/e' ratio （P<0.05）， lowering the NT-proBNP and HbA1c levels （P<0.05）， and recovering the 6MWT and Minnesota quality of life score TCM syndrome scores （P<0.05）. None of the safety indicators in the two groups showed abnormal values before and after treatment， and no serious adverse reaction was observed.ConclusionTinglu Yixin prescription can improve the heart function， exercise tolerance， and quality of life， lower the HbA1c level， and alleviate the TCM syndrome in the patients with HFpEF combined with diabetes （syndrome of qi and yin deficiency and water stagnation and blood stasis）.Keywords：heart failure with preserved ejection fraction;type 2 diabetes mellitus;Qi and Yin deficiency， water stagnation and blood stasis;Tinglu Yixin decoction;clinical effect261|172|3<HTML><H-PDF><L-PDF>Updated：2024-07-04
- Abstract：ObjectiveTo investigate the impact of icariin （ICA） on autophagy in glucocorticoid-induced bone microvascular endothelial cells （BMECs） mediated by the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway.MethodBMECs were isolated and cultured from femoral heads obtained during total hip arthroplasty and identified using immunofluorescence staining. The experimental cells were divided into four groups： A control group， a glucocorticoid group （100 mg·L-1 hydrocortisone）， an ICA group （100 mg·L-1 hydrocortisone+6.7×10-3 mg·L-1 ICA）， and a Rapamycin group （100 mg·L-1 hydrocortisone+6.7×10-3 mg·L-1 ICA+1 mg·L-1 rapamycin）. Autophagy in BMECs was induced using 100 mg·L-1 hydrocortisone. LC3 fluorescence staining was used to observe the peak of autophagy at different time points. Western blot analysis was employed to analyze the expression of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins in each group. Electron microscopy was used to observe autophagosomes and autolysosomes in the cells.ResultHydrocortisone at 100 mg·L-1 induced autophagy in BMECs， reaching a peak at around 5 hours， which then declined with further intervention. Compared to the control group， the glucocorticoid group showed cell membrane damage， disordered organelle arrangement， and a large number of autophagosomes and autolysosomes. Compared to the glucocorticoid group， the ICA group had more intact cell membranes， sparser organelle arrangement， and fewer autophagosomes and autolysosomes. Compared to the ICA group， the Rapamycin group showed cell membrane damage， disordered organelle arrangement， and more autophagosomes and autolysosomes. Compared to the control group， the glucocorticoid group had significantly increased expression of light chain 3B （LC3B）， Atg4B， and p62 （P<0.01）. Compared to the glucocorticoid group， the ICA group showed significantly decreased expression of LC3B， Atg4B， p62， and Beclin-1 （P<0.01）. Compared to the ICA group， the Rapamycin group had significantly increased expression of Atg4B and p62 （P<0.01）. Compared to the control group， the glucocorticoid group had significantly decreased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Compared to the glucocorticoid group， the ICA group showed significantly increased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Compared to the ICA group， the Rapamycin group had significantly decreased expression of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR （P<0.01）. Ubiquitination levels were significantly decreased in the glucocorticoid group compared to the control group （P<0.01）. Compared to the glucocorticoid group， ubiquitination levels were significantly increased in the ICA group （P<0.01）， and significantly decreased in the Rapamycin group compared to the ICA group （P<0.01）.ConclusionThe glucocorticoid-induced autophagy in BMECs is time-dependent. ICA inhibits glucocorticoid-induced autophagy in BMECs， and this effect may be related to the regulation of the PI3K/Akt/mTOR pathway.Keywords：icariin;steroid-osteonecrosis of the femoral head;bone microvascular endothelial cells;autophagy;phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） pathway281|316|6<HTML><H-PDF><L-PDF>Updated：2024-07-04
- Abstract：ObjectiveTo evaluate the efficacy and safety of Qingyusan capsules in the long-term treatment of mild to moderate active ulcerative colitis （UC） with the syndrome of large intestine dampness-heat.MethodA randomized， controlled design was adopted， and 88 patients with mild to moderate UC and syndrome of large intestine dampness-heat were randomized into a Qingyusan （Qingyusan capsules， 0.8 g·d-1） group and a control （mesalazine， 0.4 g·d-1） group， with 44 patients in each group. Three and one patients dropped out in the control and Qingyusan groups， respectively， during the 32 weeks of treatment. The clinical remission rate， mucosal healing rate， and modified Mayo score， TCM symptom score， and short inflammatory bowel disease questionnaire （SIBDQ） score before and after treatment were compared between the two groups. The colonoscopic and pathological changes were observed， and the clinical safety was compared between the two groups.ResultAfter treatment， the clinical remission rate and mucosal healing rate in the Qingyusan group were 72.1% （31/43） and 74.4% （32/43）， respectively， which were higher than those ［26.8% （11/41） and 41.5% （17/41）， respectively］ in the control group （χ2=17.200， χ2=10.843， respectively， both P<0.01）. The treatment in both groups decreased the modified Mayo score， partial Mayo score， and TCM symptom score （P<0.05）， and the decreases in the Qingyusan group were higher than those in the control group （P<0.01）. After treatment， the SIBDQ scores in both groups increased （P<0.05）， and the increase was more pronounced in the Qingyusan group than in the control group （P<0.01）. There was no difference in the incidence of adverse events between the two groups.ConclusionThe clinical efficacy of Qingyusan capsules is remarkable in the long-term treatment of UC with the syndrome of large intestine dampness-heat. Particularly， Qingyusan capsules demonstrates advantages in inducing and maintaining clinical remission， promoting mucosal healing， alleviating TCM symptoms， and enhancing the survival quality of patients， with high safety.Keywords：Qingyusan capsules;ulcerative colitis;syndrome of large intestine dampness-heat;clinical study396|263|1<HTML><H-PDF><L-PDF>Updated：2024-06-14
- Abstract：ObjectiveTo explore the mechanism of Jiawei Wendantang in preventing and treating diabetic atherosclerosis by observing the effect of this prescription on the nuclear factor-κB / NOD-like receptor protein 3（NF-κB/NLRP3） pathway and related inflammatory cytokines in rat model of diabetic atherosclerosis.MethodFifty-four SPF-grade rats were randomized into blank， model， atorvastatin （0.9 mg·kg-1·d-1）， and high-， medium-， low-dose （18.2， 9.1， 4.55 g·kg-1·d-1， respectively） Jiawei Wendantang groups. The rats in other groups except the blank group were modeled for diabetic atherosclerosis by intraperitoneal injection of streptozotocin and feeding with a high-sugar high-fat diet， and those in the blank group were injected with an equal dose of citric acid buffer and fed with a regular diet. The drug administration lasted for 4 weeks， and the blood glucose level in the tail vein was measured every 6 days. After the last administration， the rats were anesthetized for sample collection. Enzyme-linked immunosorbent assay was employed to measure the serum levels of interleukin-18 （IL-18）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1）. Western blot was employed to determine the relative protein levels of NF-κB p65， NLRP3， and ICAM-1 in the abdominal aorta. Real-time quantitative polymerase chain reaction was employed to determine the mRNA levels of NLRP3 and interleukin-1β （IL-1β） in the abdominal aorta. The pathological changes in the thoracic aorta were observed by hematoxylin-eosin staining.ResultCompared with the blank group， the model group showed elevated levels of IL-18， CRP， TNF-α， and ICAM-1 in the serum and blood glucose （P<0.05， P<0.01）， up-regulated protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and up-regulated mRNA levels of NLRP3 and IL-1β （P<0.05）. Compared with model group， Jiawei Wendantang lowered the levels of IL-18， CRP， TNF-α， ICAM-1 and blood glucose （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and down-regulated the mRNA levels of NLRP3 and IL-1β （P<0.05， P<0.01）. Moreover， Jiawei Wendantang alleviated the pathological injuries in the thoracic aorta.ConclusionJiawei Wendantang may modulate the NF-κB/NLRP3 signaling pathway to reduce the release and adhesion of inflammatory cytokines and regulate the blood glucose level to treat diabetic atherosclerosis.Keywords：Jiawei Wendantang;diabetic atherosclerosis;nuclear factor-
κ B （NF-κ B）;NOD-like receptor protein 3 （NLRP3）;inflammatory cytokines289|182|2<HTML><H-PDF><L-PDF>Updated：2024-06-14 - Abstract：ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）.MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot.ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）.ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.Keywords：Linggui Zhugantang;chronic bronchitis;airway mucus hypersecretion;inflammation;transient receptor potential （TRP） channel587|654|3<HTML><H-PDF><L-PDF>Updated：2024-06-14
- Abstract：ObjectiveTo observe the effect of Scutellariae Radix-Coptidis Rhizoma on plaque stability in atherosclerotic （AS） mice and to explore its possible mechanism of action based on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa B （NF-κB） signaling pathway.MethodTen normal C57BL/6J mice were used as the normal group， and the same strain of ApoE knockout （ApoE-/-） mice were fed with a high-fat diet for 12 weeks to construct an atherosclerosis model. Mice were randomly divided into five groups， namely the model group， the atorvastatin group， and the Scutellariae Radix-Coptidis Rhizoma low-， medium-， and high-dose groups， with ten mice in each group. Then normal and model groups were given equal volume of saline gavage， and the low-， medium-， high-dose Scutellariae Radix-Coptidis Rhizoma groups were given 1.95， 3.9， 7.8 g·kg-1 of the drug by gavage for 8 weeks， respectively. The general state of mice was observed. Hematoxylin-eosin staining was utilized to observe the pathology of aortic root plaques and calculate the percentage of plaque area. Masson staining and oil red O staining combined with immunohistochemistry of F4/80 and α-SMA were used to detect the plaque components of aortic root plaques and calculate the plaque vulnerability index. Enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was applied to detect the protein expression levels of matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， TLR4， MyD88， NF-κB p65， and phosphorylation （p） -NF-κB p65 in the aortic tissues of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） assay was employed to detect the expression levels of MMP-2， MMP-9， TLR4， and MyD88， NF-κB p65 mRNA.ResultCompared with the model group， the general state of the mice in each medication group was improved， and no obvious side effects were observed. Compared with the model group， the percentage of plaque area in the aortic root of AS mice was significantly reduced in the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The content of collagen fibers and smooth muscle cells in the plaques of the high-dose Scutellariae Radix-Coptidis Rhizoma group was significantly increased （P<0.01）， and the content of lipids and macrophages was significantly reduced （P<0.05）， the plaque vulnerability index of each dose group of Scutellariae Radix-Coptidis Rhizoma was significantly reduced， with significant reduction of the medium- and high-dose groups （P<0.01）. MMP-2 and MMP-9 protein and mRNA expression levels in aortic tissues were significantly reduced in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. The serum levels of TNF-α and IL-6 were significantly reduced in AS mice in medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups （P<0.05）. In the medium- and high-dose Scutellariae Radix-Coptidis Rhizoma groups， the levels of TLR4， MyD88 protein， and mRNA expression in aortic tissues were significantly reduced （P<0.05）， and the level of NF-κB p65 phosphorylation in aortic tissues was significantly reduced （P<0.05）.ConclusionScutellariae Radix-Coptidis Rhizoma may play an anti-inflammatory and stabilizing role by inhibiting the TLR4/MyD88/NF-κB signaling pathway.Keywords：Scutellariae Radix-Coptidis Rhizoma;atherosclerosis;inflammatory response;vulnerable plaque;Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa B （NF-
κ B）;mechanism of action417|154|4<HTML><H-PDF><L-PDF>Updated：2024-09-26
