1.Comparison of the efficacy and safety of vedolizumab versus infliximab in Bio-naive patients with ulcerative colitis
Duidui YAO ; Feixue LI ; Jiaqi WU ; Xiaobing LIU ; Hongping WEN
China Pharmacy 2026;37(10):1307-1312
OBJECTIVE To compare the efficacy and safety of vedolizumab (VDZ) versus infliximab (IFX) in biologic-naive(Bio-naive) patients with moderate-to-severe active ulcerative colitis (UC), and to analyze the factors influencing efficacy. METHODS Clinical data were retrospectively collected from Bio-naive patients with moderate-to-severe active UC who received treatment in the Department of Gastroenterology at Shanxi Provincial People’s Hospital from June 2023 to June 2024. Based on the type of biologic agent administered, the patients were divided into the IFX group (41 cases) and the VDZ group (30 cases). Patients in the two groups received IFX (5 mg/kg) or VDZ (300 mg) for induction and maintenance of remission therapy. The two groups were compared regarding modified Mayo score, serological indicators (hemoglobin, albumin, platelet count, erythrocyte sedimentation rate, C-reactive protein), combined medication, efficacy-related indexes (clinical response rate/remission rate, and endoscopic response rate/remission rate), and the occurrence of adverse drug reactions (ADR). Based on Logistic regression model, univariate and multivariate analyses were conducted to identify potential factors influencing clinical remission at week 14 and endoscopic remission at week 38. RESULTS There were no statistically significant differences in clinical response rate/remission rate, or endoscopic response rate/remission rate between the two groups at weeks 14 and 38 ( P >0.05). However, at week 14 of treatment, the proportion of patients using concomitant corticosteroids in VDZ group was 26.67%, significantly higher than the 7.50% in IFX group ( P <0.05). There was no statistical significance in the overall incidence of ADR between the two groups ( P >0.05); all ADRs in the IFX group were grade 3 and led to treatment discontinuation (6 cases), whereas ADR in the VDZ group was grade 2 and did not interrupt therapy (1 case). Univariate and multivariate regression analyses revealed that disease type (relapsing) was significantly associated with clinical remission at week 14 of treatment, and a history of smoking was significantly associated with endoscopic remission at week 38 of treatment (the odds ratios were 0.08 for both, with 95% confidence intervals of 0.01-0.77 and 0.01-0.91 respectively, P <0.05). CONCLUSIONS For Bio-naive patients with moderate-to-severe active UC, VDZ and IFX demonstrate comparable efficacy in inducing and maintaining clinical remission and promoting mucosal healing, as well as overall safety. Although IFX can achieve faster control of inflammation in the early stage of the disease, it causes more severe ADR. Disease type (relapsing) and smoking history are identified as independent negative predictors for short-term clinical remission and long-term endoscopic remission, respectively.
2.Study on the mechanism of Naozhenning granules in improving learning and memory impairment in multiple cerebral concussion model rats
Xinru WANG ; Yaozhou YAN ; Chunxue ZHANG ; Le ZHAO ; Li GAO ; Yonghui WANG
China Pharmacy 2026;37(11):1416-1421
OBJECTIVE To investigate the mechanism by which Naozhenning granules (NZN) improve learning and memory impairment in a rat model of multiple cerebral concussion (MCC). METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group (normal saline), a model group (normal saline), a piracetam group (positive control group, 0.324 g/kg), and high-, medium-, and low-dose NZN groups (5.4, 2.7, 1.35 g/kg), with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured; Evans blue (EB) extravasation in the cerebral cortex was detected; pathological changes of cortical neurons were observed; the levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) in the cerebral cortex were determined; and the phosphorylation levels of AMP-activated protein kinase (AMPK), glycogen synthase kinase 3β (GSK3β), and Tau protein were detected. RESULTS Compared with the blank group, the model group showed poor mental state, sluggish response to external stimuli, reduced food and water intake, decreased limb flexibility, and disheveled fur. Body weight, sucrose preference rate, and novel object recognition index were significantly decreased ( P <0.05); EB extravasation in the cerebral cortex was significantly increased ( P <0.05), with severe neuronal damage. The positive area ratio of Bax protein, IL-6 and TNF-α levels, and Tau protein phosphorylation level were all significantly increased ( P <0.05), whereas the positive area ratio of Bcl-2 protein, IL-10 level, and AMPK and GSK3β protein phosphorylation levels were significantly decreased ( P <0.05). Compared with the model group, all NZN dose groups showed improvements in general condition and pathological damage, with quantitative indices partially restored, and the differences in quantitative indices in high-dose NZN group were statistically significant ( P <0.05). CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway, inhibiting inflammatory response, reducing Tau protein phosphorylation level, and then repairing the neuronal injury.
3.Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD
Mengqi BAI ; Junhu LI ; Zhibo ZHAO ; Xiaoshuang ZHOU
China Pharmacy 2026;37(11):1428-1433
OBJECTIVE To investigate the mechanism of cordycepin in delaying the transformation from acute kidney injury (AKI) to chronic kidney disease (CKD) (short for “AKI-CKD”). METHODS Network pharmacology and bioinformatics were used to analyze and predict the signaling pathways of cordycepin in delaying AKI-CKD progression and its relationship with the ferroptosis pathway. Cell experiments were performed to verify the predicted results. Human renal tubular epithelial HK-2 cells were divided into blank group, cordycepin group, model group, and H 2 O 2 +cordycepin group. Except for the blank group and cordycepin group, all other groups were treated with 150 μmol/L H 2 O 2 for 72 h to induce persistent oxidative stress injury in cells. After 72 h of cordycepin (40 μmol/L) intervention, the protein and mRNA expression levels of glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4),nuclear factor-erythroid 2-related factor 2(Nrf2), and heme oxygenase-1 (HO-1) in cells were detected. Furthermore, the Nrf2 inhibitor ML385 was added on the basis of H 2 O 2 +cordycepin to verify the role of the Nrf2/HO-1 pathway. RESULTS Network pharmacology and bioinformatics analysis showed that there were 42 overlapping genes related to AKI-CKD and ferroptosis that interact with cordycepin ferroptosis, among which 38 were annotated as ferroptosis-related genes. HO-1 and Nrf2 might be important targets for cordycepin to inhibit ferroptosis. The binding energies of cordycepin with Nrf2 and HO-1 proteins were -8.5 and -6.7 kcal/mol, respectively. Cell experiments showed that compared with the model group, the protein and mRNA expression levels of GPX4, Nrf2 and HO-1 were significantly increased ( P <0.05),while the protein and mRNA expression levels of ACSL4 were significantly decrease d ( P <0.05) in the H 2 O 2 +cordycepin group. After the addition of the Nrf2 inhibitor ML385, the effects of cordycepin on the above proteins and mRNA were significantly reversed ( P <0.05). CONCLUSIONS Cordycepin can inhibit ferroptosis by activating the Nrf2/HO-1 pathway, reduce persistent oxidative stress injury of renal tubular epithelial cells, and delay the progression of AKI-CKD.
4.The mechanism of magnoflorine in inhibiting colon cancer based on network pharmacology and in vitro experiment
Lulu TAN ; Lina ZHU ; Shujin ZHANG ; Yuxuan WANG ; Huimei LI ; Yuke WANG ; Jiayi HOU ; Qilong FENG ; Jianyun SHI
Acta Universitatis Medicinalis Anhui 2026;61(6):1021-1031
ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology, molecular docking, and in vitro cell experiments. MethodsIn this study, the canonical SMILES of magnoflorine was obtained from the PubChem database, and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database, while the disease targets of colon cancer were obtained from the DisGeNET, GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken, and a protein-protein interaction (PPI) network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology (GO) and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally, cellular experiments including CCK-8 assays, EdU experiments, cell scratch assays, and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 (STAT3) in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.
5.Mechanism of Herbal Cake-separated Moxibustion in Improving Neuroimmune Inflammation in Rats with Chronic Fatigue Syndrome by Interfering TLR4/MyD88/NF-κB Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Wei LI ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):140-149
ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome (CFS) rats, based on the regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups: Normal group, model group, sham herbal cake moxibustion group, Chinese medicine intragastric administration group, and herbal cake-separated moxibustion group, with 10 rats in each group. Except for the normal group, all other groups underwent a 21-day modeling process, followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14) acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), as well as hippocampal levels of IL-1β, IL-6, TNF-α, and NF-κB, were detected by enzyme-linked immunosorbent assay (ELISA). Morphological changes in the hippocampus were observed using hematoxylin-eosin (HE) staining. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of TLR4, MyD88, and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4, MyD88, NF-κB, and p65 proteins in the hippocampus. ResultsCompared with the normal group, the model group showed a significant decrease in upright times during the open field test (P<0.01), as well as significant reductions in total movement distance, resting time, and center region duration (P<0.01). In the tail suspension test, immobility time increased (P<0.01), and struggle times decreased (P<0.01). Serum and hippocampal levels of IL-1β, IL-6, and TNF-α, as well as hippocampal NF-κB levels and TLR4, MyD88, and NF-κB mRNA expression, were significantly elevated (P<0.01). After treatment, compared with the model group, the total movement distance and upright times in the open field test were significantly increased in all treatment groups (P<0.01), while resting time and center region duration were notably prolonged (P<0.05, P<0.01). Immobility time in the tail suspension test was significantly shortened (P<0.01), and struggle times significantly increased (P<0.05). Serum and hippocampal levels of IL-1β, IL-6, TNF-α, hippocampal NF-κB levels, and TLR4 and NF-κB mRNA expression were significantly reduced (P<0.05, P<0.01). Compared with the sham herbal cake moxibustion group, the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test (P<0.05) and a significant increase in upright times (P<0.01). In the tail suspension test, immobility time was reduced (P<0.01), and struggle times increased (P<0.01). Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced (P<0.01), while serum IL-6 levels, as well as hippocampal levels of IL-1β, TNF-α, NF-κB, and TLR4, MyD88, and NF-κB mRNA expression, were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group (P<0.05, P<0.01). Compared with the Chinese medicine intragastric administration group, the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test (P<0.01). In the tail suspension test, immobility time was reduced (P<0.01), and struggle times increased (P<0.01). Serum IL-1β, hippocampal TNF-α levels, and TLR4, MyD88, and NF-κB mRNA expression were significantly decreased (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats, regulates neuroimmune inflammatory responses, and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.
6.Pharmacokinetics and anti-inflammatory activity of cannabidiol/ γ-polyglutamic acid-g-cholesterol nanomicelles.
Rui LI ; Li-Yan LU ; Chu XU ; Rui HAO ; Xiao YU ; Rui GUO ; Jue CHEN ; Wen-Hui RUAN ; Ying-Li WANG
China Journal of Chinese Materia Medica 2025;50(2):534-541
In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals
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Cannabidiol/administration & dosage*
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Polyglutamic Acid/analogs & derivatives*
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Humans
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Male
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Rats
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Rats, Sprague-Dawley
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Anti-Inflammatory Agents/administration & dosage*
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Micelles
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Caco-2 Cells
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Cholesterol/pharmacokinetics*
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Tissue Distribution
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Nanoparticles/chemistry*
7.Network pharmacology, molecular docking, and animal experiments reveal mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children.
Yong-Kai YIN ; Chang-Miao NIU ; Li-Ting LIANG ; Mo DAN ; Tian-Qi GAO ; Yan-Hong QIN ; Xiao-Ning YAN
China Journal of Chinese Materia Medica 2025;50(1):228-238
Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals
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Drugs, Chinese Herbal/pharmacology*
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Molecular Docking Simulation
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Adipose Tissue/immunology*
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Mice
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Male
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Humans
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Network Pharmacology
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Macrophages/immunology*
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Mice, Inbred C57BL
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Child
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Protein Interaction Maps/drug effects*
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Obesity/genetics*
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Inflammation/drug therapy*
8.Effect and mechanism of combined use of active components of Buyang Huanwu Decoction in ameliorating neuronal injury induced by OGD/R.
Cun-Yan DAN ; Meng-Wei RONG ; Xiu LOU ; Tian-Qing XIA ; Bao-Guo XIAO ; Hong GUO ; Cun-Gen MA ; Li-Juan SONG
China Journal of Chinese Materia Medica 2025;50(4):1098-1110
Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry*
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Apoptosis/drug effects*
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Animals
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Neurons/cytology*
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Mice
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Molecular Docking Simulation
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Cell Line
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Glucose/metabolism*
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Humans
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Neuroprotective Agents/pharmacology*
9.Fourth national survey of traditional Chinese medicine resources and protection of traditional knowledge of medication use among ethnic minorities.
Jiang-Wei DU ; Xiao-Bo ZHANG ; Jian-Zhi CUI ; Shao-Hua YANG ; Hai-Tao LI ; Zhi-Yong LI ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2025;50(9):2349-2355
Traditional Chinese medicine(TCM) resources are the essential material foundation for the development of TCM. The national survey of TCM resources serves as a periodic summary of these resources, ensuring the continuity, prosperity, and development of TCM in China. Since 1949, four national surveys of TCM resources have been conducted. The fourth survey incorporated an investigation into traditional knowledge related to TCM resources, including the traditional medicinal knowledge of Chinese ethnic minorities, with the goal of systematically exploring, preserving, and inheriting this knowledge. This manuscript provides an overview of the basic findings from the first three national surveys of TCM resources, while also clarifying the concepts, categories, forms, carriers, and acquisition pathways of traditional knowledge related to TCM resources. A preliminary summary of the findings from traditional knowledge investigations reported in current literature is also presented. Based on the fourth survey, this manuscript emphasizes the urgency of developing public medical knowledge through empirically-based investigations, the excavation, and compilation of traditional knowledge. It also outlines the potential for conducting "precise" investigations based on first-hand data obtained from the survey, as well as facilitating the discovery and evaluation of new medicines using traditional knowledge related to ethnic minority medicinal practices. This manuscript is expected to provide valuable insights for promoting the health and industrial development of ethnic minority populations in the post-"survey" phase.
Humans
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Medicine, Chinese Traditional
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China/ethnology*
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Minority Groups
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Ethnicity
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Drugs, Chinese Herbal/therapeutic use*
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Health Knowledge, Attitudes, Practice/ethnology*
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Surveys and Questionnaires
10.Effects of combined use of active ingredients in Buyang Huanwu Decoction on oxygen-glucose deprivation/reglucose-reoxygenation-induced inflammation and oxidative stress of BV2 cells.
Tian-Qing XIA ; Ying CHEN ; Jian-Lin HUA ; Qin SU ; Cun-Yan DAN ; Meng-Wei RONG ; Shi-Ning GE ; Hong GUO ; Bao-Guo XIAO ; Jie-Zhong YU ; Cun-Gen MA ; Li-Juan SONG
China Journal of Chinese Materia Medica 2025;50(14):3835-3846
This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects*
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Drugs, Chinese Herbal/pharmacology*
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Animals
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Mice
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Glucose/metabolism*
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Cell Line
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Inflammation/genetics*
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Oxygen/metabolism*
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Pyrazines/pharmacology*
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Microglia/metabolism*
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NF-E2-Related Factor 2/immunology*
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NF-kappa B/immunology*
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Toll-Like Receptor 4/immunology*
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Anti-Inflammatory Agents/pharmacology*
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Humans

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