1.Multi-component Quality Consistency Evaluation of Leonuri Herba Granules Based on HPLC-DAD-CAD Multi-detector Technique and Chemometrics
Shuangyan LI ; Jun ZHANG ; Cong GUO ; Siyuan LI ; Jipeng DI ; Jiangmin SU ; An LIU ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):174-181
ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules, reveal the quality fluctuation patterns of products from the same and different manufacturers, providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector(HPLC-DAD-CAD) was employed to determine the contents of 4 components(syringic acid, leonurine hydrochloride, ferulic acid, and stachydrine hydrochloride) in samples from 19 manufacturers(53 batches, 159 boxes). Additionally, fingerprint profiles were constructed, and the fingerprint dissimilarity(PS) and relative standard deviation(RSD) of different samples from the same manufacturer were calculated. A principal component analysis(PCA) model was established with PS and the RSD values of the 4 components as variables to classify the manufacturers. Finally, samples from 5 manufacturers(M1-M5) covering three consistency groups were selected to calculate three quality consistency parameters, namely intra-batch consistency(PA), inter-batch consistency(PB), and PS. Then, PCA was performed with PA, PB, and PS of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them, the content of stachydrine hydrochloride(a pharmacopoeial quality control component) was 32.46-72.70 mg per bag, all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China, with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows:syringic acid of 1.43-41.92 mg per bag, leonurine hydrochloride of 0.67-11.85 mg per bag, and ferulic acid of 0.11-3.81 mg per bag. Notably, leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer(RSD of 4.8%-59.2%). PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers(M2, M6, M7, M8, M10, M15, M17, M18) demonstrated relatively high consistency, five manufacturers(M3, M9, M12, M13, M14) showed moderate consistency, six manufacturers(M1, M4, M5, M11, M16, M19) exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers, verifying the reliability of the proposed method. Among these, manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories, and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.
2.Multi-component Quality Consistency Evaluation of Leonuri Herba Granules Based on HPLC-DAD-CAD Multi-detector Technique and Chemometrics
Shuangyan LI ; Jun ZHANG ; Cong GUO ; Siyuan LI ; Jipeng DI ; Jiangmin SU ; An LIU ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):174-181
ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules, reveal the quality fluctuation patterns of products from the same and different manufacturers, providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector(HPLC-DAD-CAD) was employed to determine the contents of 4 components(syringic acid, leonurine hydrochloride, ferulic acid, and stachydrine hydrochloride) in samples from 19 manufacturers(53 batches, 159 boxes). Additionally, fingerprint profiles were constructed, and the fingerprint dissimilarity(PS) and relative standard deviation(RSD) of different samples from the same manufacturer were calculated. A principal component analysis(PCA) model was established with PS and the RSD values of the 4 components as variables to classify the manufacturers. Finally, samples from 5 manufacturers(M1-M5) covering three consistency groups were selected to calculate three quality consistency parameters, namely intra-batch consistency(PA), inter-batch consistency(PB), and PS. Then, PCA was performed with PA, PB, and PS of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them, the content of stachydrine hydrochloride(a pharmacopoeial quality control component) was 32.46-72.70 mg per bag, all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China, with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows:syringic acid of 1.43-41.92 mg per bag, leonurine hydrochloride of 0.67-11.85 mg per bag, and ferulic acid of 0.11-3.81 mg per bag. Notably, leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer(RSD of 4.8%-59.2%). PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers(M2, M6, M7, M8, M10, M15, M17, M18) demonstrated relatively high consistency, five manufacturers(M3, M9, M12, M13, M14) showed moderate consistency, six manufacturers(M1, M4, M5, M11, M16, M19) exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers, verifying the reliability of the proposed method. Among these, manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories, and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.
3.Lightweight end-to-end model-based korotkoff sounds phase identification and blood pressure measurement
Zhiyu JIANG ; Wenyi KOU ; Li LI ; Qijun ZHAO ; Yongjun QIAN ; Fan PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):248-254
Objective To propose a lightweight end-to-end neural network model for automated Korotkoff sound phase recognition and subsequent blood pressure (BP) measurement, aiming to improve measurement accuracy and population adaptability. Methods We developed a streamlined architecture integrating depthwise separable convolution (DSConv), multi-head attention (MHA), and bidirectional gated recurrent unit (BiGRU). The model directly processes Korotkoff sound time-series signals to identify auscultatory phases. Systolic BP (SBP) and diastolic BP (DBP) were determined using phase Ⅰ and phaseⅤdetections, respectively. Given the clinical relevance of phase Ⅳ for specific populations (e.g., children and pregnant women, denoted as DBPⅣ), BP values from this phase were also recorded.Results The study enrolled 106 volunteers with 70 males and 36 females at mean age of (40.0±12.0) years. The model achieved 94.25% phase recognition accuracy. Measurement errors were (0.1±2.5) mm Hg (SBP), (0.9±3.4) mm Hg (DBPⅣ), and (0.8±2.6) mm Hg (DBP). Conclusion Our method enables precise phase recognition and BP measurement, demonstrating potential for developing population-adaptive blood pressure monitoring systems.
4.Jianpi Xiaoai Prescription Ameliorates Chemotherapy Resistance in Colon Cancer by Targeting FGF2 to Inhibit PI3K/Akt Signaling Pathway
Xiaolan JIAN ; Kangwen NING ; Jiaxiang YANG ; Shenglan KOU ; Wanting KUANG ; Ziqi WANG ; Yuqin TAN ; Puhua ZENG ; Lingjuan TAN ; Wei PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):120-130
ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription (JPXA) in ameliorating the 5-fluorouracil (5-FU) resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations (10%, 15%, 20%) of JPXA-containing serum and drug-free serum were used for intervention, and 10% fetal bovine serum (10% FBS), fibroblast growth factor receptor (FGFR) inhibitor (AZD4547), and recombinant fibroblast growth factor 2 (FGF2) were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group, while HCT116/5-FU cells were used in other groups. Drug resistance, the level of FGF2 in the cell culture medium, the mRNA level of FGF2 in cells, and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model, JPXA (15 g·kg-1), 5-FU (0.02 g·kg-1), JPXA+5-FU (15 g·kg-1+0.02 g·kg-1), AZD4547 (0.012 5 g·kg-1), and AZD4547+5-FU (0.012 5 g·kg-1+0.02 g·kg-1) groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased, and the decrease was the most significant in the 20% group (P<0.01). HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 (p-FGFR1), but down-regulated protein level of FGFR1 (P<0.01). JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 (P<0.05). In addition, JPXA down-regulated the expression levels of phosphorylated protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR), while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter (Bad) (P<0.05). Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors, reduced the protein levels of FGF2, p-FGFR1, phosphorylated phosphatidylinositol-3-kinase (p-PI3K), p-Akt, and p-mTOR, and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.
5.Improvement effects and mechanism of Achyranthes bidentata total saponins extract on vascular endothelial dysfunction in spontaneously hypertensive rats
Ruifeng LIANG ; Wenjing GE ; Xiaobo KOU ; Ping TIAN ; Hongzhi AN ; Zheng WEI ; Mingli ZHANG
China Pharmacy 2026;37(3):331-337
OBJECTIVE To investigate the improvement effects and mechanism of Achyranthes bidentata total saponins (ABS) extract on vascular endothelial dysfunction in spontaneously hypertensive rat (SHR) based on cytochrome P450 4A (CYP4A)/20-hydroxyeicosatetetraenoic acid (20-HETE)/G protein-coupled receptor 75 (GPR75) axis. METHODS Ten Wistar- Kyoto rats were taken as the normal control group. Forty SHR were first stratified by systolic blood pressure and then, within each stratum, randomly assigned using a random-number table to the model group (MOD group), captopril positive control group (CAP group, 10 mg/kg), ABS low- and high-dose extract groups (ABS-L group, ABS-H group, 60 and 120 mg/kg), with 10 rats in each group. Animals in each group were given the corresponding drug or equal volume of pure water by gavage, once a day, for 28 consecutive days. After the last administration, systolic blood pressure of rats was measured. The levels of vasoactive substances, inflammatory factors and oxidative stress indicators in serum were measured. The pathological changes of rat thoracic aorta were observed. The level of reactive oxygen species (ROS) in aortic tissue was analyzed. The expressions of endothelial nitric oxide synthase (eNOS), CYP4A, GPR75, nuclear factor-κB p65 (NF-κB p65), phosphorylated NF-κB p65, p22phox, and reduced nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4) in thoracic aorta tissue were detected. RESULTS After 28 d of treatment, compared with MOD group, the systolic blood pressure of rats in the ABS-L and ABS-H groups decreased significantly. The levels of 20-HETE, angiotensin Ⅱ, interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular cell adhesion molecule-1 and malondialdehyde in serum were significantly reduced (P<0.05 or P<0.01), while the levels of nitric oxide, superoxide dismutase, glutathione peroxidase and catalase were significantly increased (P<0.05 or P<0.01). Intimal damage of thoracic aorta was reduced, and endothelial cell morphology was improved. The expressions of ROS, CYP4A, GPR75, p22phox, NOX4 and the phosphorylation level of NF-κB p65 protein in thoracic aorta were down-regulated or reduced (P<0.05 or P<0.01), while the expression of eNOS was up-regulated (P<0.05 or P<0.01). CONCLUSIONS ABS extract may alleviate the inflammatory response and oxidative stress in SHR effectively by down-regulating the expression of CYP4A, reducing the production of 20-HETE, inhibiting the activation of GPR75, and subsequently suppressing the activation of downstream NF-κB and NOX4, thereby improving hypertension-related vascular endothelial dysfunction.
6.Mechanism of Maimendong Yinzi in Alleviating Cough with Yin Deficiency and Lung Heat Syndrome by Modulating PAR1/Gαi/cAMP Signaling Pathway and TRPV1 Expression
Zihan ZHU ; Jiahui TANG ; Yuanyuan ZHANG ; Junping KOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):81-91
ObjectiveTo investigate the effects of Maimendong Yinzi (MMDYZ) on cough with Yin deficiency and lung heat syndrome and explore its potential mechanism of action. MethodsForty-eight Institute of Cancer Research (ICR) mice were randomly divided into a control group, a model group, a Baihe Gujin Tablet (BHGJP) group (1.36 g·kg-1), and low-dose, medium-dose, and high-dose MMDYZ groups (5, 10, 20 g·kg-1·d-1, based on the weight of crude drug), with eight mice in each group. The mouse model of cough with Yin deficiency and lung heat syndrome was prepared by a combination of smoke exposure, nasal drip of lipopolysaccharide (LPS), intragastric gavage with thyroxine, and capsaicin atomization. After successful modeling, drug interventions were administered for seven days. During modeling, the mice were observed for changes in general status, anal temperature, fecal water content, and water intake. After medication, the above indicators were evaluated again, along with assessments of spontaneous activity, cough sensitivity, lung function, lung index, and tracheal phenol red secretion. Bronchoalveolar lavage fluid (BALF) was analyzed for cell differential counts, and the level of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in serum was measured via enzyme linked immunosorbent assay (ELISA). Lung injury was assessed via hematoxylin-eosin (HE) staining. Network pharmacology was employed to predict the potential mechanism of MMDYZ in alleviation cough with Yin deficiency and lung heat syndrome. Western blot (WB) was used to measure protease-activated receptor1 (PAR1) and GTPhase αi subunit (Gαi) protein expressions in lung tissue. ELISA was used to determine lung cAMP content, and immunohistochemistry (IHC) was employed to evaluate transient receptor potential vanilloid subtype 1 (TRPV1) expression. ResultsCompared with the control group, the model group exhibited significantly increased water intake and anal temperature and significantly decreased fecal water content (P<0.05). The total distance traveled in 5 min and the central zone duration were reduced, while standing frequency significantly increased (P<0.05). Cough sensitivity and enhanced pause (PenH) were elevated. Peak expiratory flow (PEF) significantly declined (P<0.05). BALF neutrophil (NEU) and white blood cell (WBC) counts rose. Serum cAMP and cAMP/cGMP ratio significantly increased, and cGMP significantly decreased (P<0.05). Serum TNF-α and IL-6 levels were significantly elevated (P<0.05). The lung injury was obvious, and the lung index was significantly elevated (P<0.05). Compared with the model group, the medium-dose and high-dose MMDYZ groups and the BHGJP group showed significantly improved indicators mentioned above. Additionally, network pharmacology suggested that MMDYZ might alleviate cough with Yin deficiency and lung heat syndrome via cAMP, hypoxia inducible factor-1 (HIF-1), and TNF signaling pathways. WB, ELISA, and IHC revealed that, compared with the control group, the model group exhibited significantly upregulated PAR1, Gαi, and TRPV1 expressions and significantly downregulated cAMP in lung tissue (P<0.05). Compared with the model group, MMDYZ reduced PAR1 (P<0.01), Gαi (P<0.05), and TRPV1 (P<0.01) while increasing cAMP level (P<0.01). ConclusionMMDYZ may alleviate cough with Yin deficiency and lung heat syndrome by modulating the PAR1/Gαi/cAMP pathway and TRPV1 expression.
7.Curcumin extraction and preparation and optimization of curcumin nanoparticles
Yuhang WANG ; Han ZHANG ; Chaojing ZHANG ; Xurong KOU ; Tongtong JING ; Rimei LIN ; Xinyu LIU ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Tissue Engineering Research 2026;30(2):362-374
BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57%,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10%.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5%,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61%.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)%,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.
8.Curcumin extraction and preparation and optimization of curcumin nanoparticles
Yuhang WANG ; Han ZHANG ; Chaojing ZHANG ; Xurong KOU ; Tongtong JING ; Rimei LIN ; Xinyu LIU ; Shilei LOU ; Hui YAN ; Cong SUN
Chinese Journal of Tissue Engineering Research 2026;30(2):362-374
BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57%,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10%.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5%,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61%.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)%,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.
9.Drug‑drug interaction mechanisms and clinical challenges in antithrombotic therapy for acute ischemic stroke
Journal of Apoplexy and Nervous Diseases 2026;43(3):204-213
Objective To systematically summarize the pharmacological characteristics and clinical applications of antithrombotic medications in ischemic stroke, as well as their interactions with drugs used for common comorbidities, and to provide a reference for clinical medication. Methods Based on the UpToDate database and the integration with pharmacokinetic and pharmacodynamic mechanisms, this study systematically analyzed interactions between antithrombotic agents and between antithrombotics and drugs for comorbid conditions. Interactions were categorized and evaluated based on the level of evidence. Results The distinct pharmacological mechanisms of different antithrombotic drugs determine their patterns of drug-drug interactions. Combination antithrombotic therapy produces synergistic antithrombotic effects but increases the risk of hemorrhage. Extensive interactions exist when antithrombotics are co-administered with medications for cardiovascular diseases, metabolic disorders, neuropsychiatric conditions, and infectious diseases. These interactions primarily involve the cytochrome P450 enzyme system and P-glycoprotein pathways, which may compromise therapeutic efficacy or elevate the risk of bleeding and thrombosis. Conclusion Multiple drug interactions are present in antithrombotic therapy for ischemic stroke. In clinical practice, it is essential to consider the impact of pharmacokinetic and pharmacodynamic mechanisms. By integrating tools such as pharmacogenomics and therapeutic drug monitoring, individualized medication strategies should be implemented to achieve an optimal balance between antithrombotic efficacy and safety.
10.Effect of Quercetin on Cuproptosis in Rheumatoid Arthritis Rats and Its Mechanism via SLC31A1/FDX1 Pathway
Haoruo YANG ; Qiuai KOU ; Junhua REN ; Guo YUAN ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):121-130
ObjectiveTo observe the influence and therapeutic effect of quercetin on cuproptosis in rheumatoid arthritis rats and to explore its possible mechanism based on the solute carrier family 31 member 1 (SLC31A1)/ferredoxin 1 (FDX1) pathway. MethodsSixty male SD rats were divided into six groups: A control group, a model group, high- and low-dose quercetin groups (150 and 50 mg·kg-1), a cuproptosis inhibitor (tetrathiomolybdate, TTM) group (10 mg·kg-1), and a methotrexate group (2 mg·kg-1), 10 rats in each group. Except for the control group, the model of rheumatoid arthritis (CIA) rats was established by type Ⅱ collagen induction method. After successful modeling, each drug group was intervened according to the corresponding dose of drugs, and the control group and the model group were given the same amount of normal saline by gavage, once a day, which lasted for 4 weeks. The swelling degree of rats' feet was observed, and the clinical arthritis scores were determined. The levels of serum rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), and ceruloplasmin (Cp) were detected by enzyme-linked immunosorbent assay (ELISA). The content of copper ion (Cu), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in joint tissue was detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of joint tissue. The levels of reactive oxygen species (ROS) and dihydrolipoic acid transacetylase (DLAT) were detected by immunofluorescence (IF). The protein and mRNA expression of SLC31A1, FDX1, lipoic acid synthase (LIAS), heat shock protein 70 (HSP70), pyruvate dehydrogenase E1 subunit β (PDHB), and copper transporting P-type ATPase β (ATP7B) was detected by immunohistochemistry (IHC) and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared to the control group, the model group exhibited joint swelling and deformity, significantly increased clinical arthritis scores, obvious bone destruction, synovial hyperplasia, and inflammatory cell infiltration in joint tissue. In addition, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp showed significant elevation, while the level of IL-10 was significantly reduced. The levels of Cu, MDA, ROS, and DLAT in joint tissue were markedly increased, whereas SOD and GSH content was significantly decreased. The protein and mRNA expression of SLC31A1 and HSP70 was significantly up-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was significantly down-regulated (P<0.01). Compared to the model group, each treatment group exhibited varying degrees of improvement in joint swelling and deformation as well as clinical arthritis scores in rats. Additionally, there was a reduction in joint bone destruction, inflammatory cell infiltration, and synovial hyperplasia in rats. Furthermore, the serum levels of RF, MMP-3, TNF-α, IL-1β, and Cp significantly decreased, while the level of IL-10 increased significantly. In joint tissue, the levels of Cu, MDA, ROS, and DLAT showed significant decreases, while SOD and GSH content exhibited significant increases. The protein and mRNA expression of SLC31A1 and HSP70 was down-regulated, while the protein and mRNA expression of FDX1, LIAS, PDHB, and ATP7B was up-regulated (P<0.05). ConclusionQuercetin effectively reduces synovial hyperplasia and inflammatory infiltration in rats with rheumatoid arthritis, thereby alleviating pathological damage to joint tissue. This effect may be attributed to the blockade of the SLC31A1/FDX1 signaling pathway activation and inhibition of excessive cuproptosis.

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