1.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
2.Screening of Antidepressant Active Components from Curcumae Rhizoma and Its Mechanism in Regulating Nrf2/GPX4/GSH Pathway
Yonggui SONG ; Delin DUAN ; Meixizi LAI ; Yali LIU ; Zhifu AI ; Genhua ZHU ; Huanhua XU ; Qin ZHENG ; Ming YANG ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):211-221
ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma, and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione(GSH) peroxidase 4(GPX4)/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma, including curcumol, curgerenone, curdione, curzerene, curcumenol, curcumenone, dehydrocurdione, isocurcumenol, furanodienone, furanodiene and zederone, were detected using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt(ABTS) radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress(CUMS), and W1118 wild-type male D. melanogaster were randomly divided into blank group, model group, curcumol group, curgerenone group, curdione group, curzerene group, curcumenol group,curcumenone group, dehydrocurdione group, isocurcumenol group, furanodienone group, furanodiene group, zederone group and fluoxetine group(10 μmol·L-1). The treatment groups received a dose of 0.1 g·L-1 of 11 characteristic components from Curcumae Rhizoma, while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test, climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry(LC-MS) was used to detect the levels of 5-hydroxytryptamine(5-HT) and dopamine(DA) in the brain of D. melanogaster, and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators, resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition, a mouse depression model was established by CUMS, and C57BL/6J mice were randomly divided into blank group, model group, low and high dose groups of curzerene(0.5, 1 mg·kg-1), and fluoxetine group(10 mg·kg-1) to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species(ROS) in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and GSH. Transmission electron microscope(TEM) was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein, and Nrf2 inhibitor(ML385) was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals, and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group, the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center(P<0.01), as well as a significant increase in immobility time in the forced swimming and tail suspension tests(P<0.01), and the ROS content in hippocampus significantly elevated(P<0.01), while the ATP content significantly reduced(P<0.01). In the hippocampal neurons of the model group, mitochondrial cristae were disordered, with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased(P<0.05), and the antioxidant enzymes SOD, CAT and GSH contents were also significantly reduced(P<0.05, P<0.01), and the gene expression levels of GPX1, GPX4 and GPX7 were significantly decreased(P<0.01). Compared with the model group, the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center(P<0.05), as well as a significant decrease in immobility time in the forced swimming and tail suspension tests(P<0.05, P<0.01). The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced(P<0.01), while the ATP content was significantly increased(P<0.05). The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated, and the expression level of Nrf2 protein was significantly increased(P<0.05). The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.01), while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.05), while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.
3.Exploring Therapeutic Effect of Yuejuwan on Depressed Mice Based on Lipidomics
Zhentao ZHANG ; Dan SU ; Huizhen LI ; Yonggui SONG ; Huanhua XU ; Meixizi LAI ; Zhifu AI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):85-94
ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum, prefrontal cortex and hippocampus of depressed mice based on lipidomics, and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group, model group, Yuejuwan group(3.6 g·kg-1) and fluoxetine group(10 mg·kg-1), and chronic unpredictable mild stress(CUMS) was used to establish the depression model. After 3 weeks of modeling, each administration group was gavaged with the corresponding drug solution according to the dose, and mice in the blank and model groups were given an equal volume of deionised water by gavage, one time/d for 2 weeks. After administration, the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test, open field test, tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in mouse serum. Lipidomic analysis of mouse serum, prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS), and the expression of mammalian target of rapamycin(mTOR), ribosomal protein S6 kinase(S6K), phosphorylation(p)-mTOR, p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group, mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test(P<0.01), the immobility times in the tail suspension test and forced swimming test were significantly increased(P<0.01), and serum levels of TC, TG, LDL-C, HDL-C, AST and ALT were significantly elevated(P<0.05, P<0.01). Compared with the model group, the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test(P<0.01), the immobility times in the tail suspension test and forced swimming test were significantly reduced(P<0.01), and the serum levels of TC, TG, LDL-C, AST and ALT were significantly decreased(P<0.05, P<0.01). Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum, prefrontal cortex and hippocampus of depressed mice, and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism, sphingolipid signaling, and glycosylphosphatidylinositol-anchored protein biosynthesis, among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group, the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased(P<0.01). In comparison with the model group, the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased(P<0.01). ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect, which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.
4.Effect of Different Fermentation Conditions on Fungal Community and Chemical Composition of Aurantii Fructus
Zhihong YAN ; Xiumei LIU ; Qiuyan GUAN ; Yonggui SONG ; Zhifu AI ; Genhua ZHU ; Yuhui PING ; Ming YANG ; Qin ZHENG ; Huanhua XU ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):254-262
ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus, in order to obtain the optimal fermentation conditions and flora structure, and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2(ITS2) high-throughput sequencing, combined with fungal community diversity analysis and fungal community structure analysis, were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7, 14, 21 d(numbered Y1-Y3 for the former, and numbered F1-F3 for the latter), respectively. At the same time, the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), combined with principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and compound retention time, parent ions, characteristic fragment ions and other information, the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method, while in the non-pressure-shelf natural fermentation method, there was a significant difference with the fermentation process, and at the genus level, the dominant genus of samples Y1, Y2, Y3 and F2 was Aspergillus, while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable, and the microbial community structure was more stable, which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis, including 70 flavonoids, 38 coumarins, 10 alkaloids, 34 organic acids and 3 other compounds. After fermentation, two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition, multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods, mainly including flavonoids, organic acids and coumarins. Comprehensively, the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable, the species richness was high and the overall content of differential compounds was high, which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation, the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds, and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus, as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.
5.Effect of Different Fermentation Conditions on Fungal Community and Chemical Composition of Aurantii Fructus
Zhihong YAN ; Xiumei LIU ; Qiuyan GUAN ; Yonggui SONG ; Zhifu AI ; Genhua ZHU ; Yuhui PING ; Ming YANG ; Qin ZHENG ; Huanhua XU ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):254-262
ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus, in order to obtain the optimal fermentation conditions and flora structure, and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2(ITS2) high-throughput sequencing, combined with fungal community diversity analysis and fungal community structure analysis, were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7, 14, 21 d(numbered Y1-Y3 for the former, and numbered F1-F3 for the latter), respectively. At the same time, the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), combined with principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and compound retention time, parent ions, characteristic fragment ions and other information, the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method, while in the non-pressure-shelf natural fermentation method, there was a significant difference with the fermentation process, and at the genus level, the dominant genus of samples Y1, Y2, Y3 and F2 was Aspergillus, while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable, and the microbial community structure was more stable, which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis, including 70 flavonoids, 38 coumarins, 10 alkaloids, 34 organic acids and 3 other compounds. After fermentation, two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition, multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods, mainly including flavonoids, organic acids and coumarins. Comprehensively, the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable, the species richness was high and the overall content of differential compounds was high, which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation, the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds, and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus, as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.
6.Mediation and latent variable analysis of new curriculum standard based physical education core literacy and subjective exercise experience among middle school students
YUAN Yuqing, HU Wenying, HU Chang, ZHANG Wen, SONG Chao
Chinese Journal of School Health 2025;46(7):941-945
Objective:
To examine the relationship among physical education core literacy, exercise self efficacy, physical self esteem and subjective exercise experience among middle school students, and to analyze the latent classes of exercise self efficacy, so as to provide evidence for enhancing adolescents subjective exercise experience.
Methods:
Using stratified cluster random sampling, 2 569 students from 12 provinces, autonomous regions or municipality directly under the central govement (Jiangxi, Guangdong, Hunan, Guizhou, Henan, Guangxi, Yunnan, Chongqing, Sichuan, Shandong, Hubei, Hebei) were surveyed from September to November in 2024 with Core Competency Scale of Physical Education, Subjective Exercise Experiences Scale, Exercise Self Efficacy Scale, and Physical Self esteem Scale. Pearson correlation analysis was conducted to explore the relationships among physical education core literacy, exercise self efficacy, physical self esteem, and subjective exercise experience. Mediation models with Bootstrap testing were employed to examine the mediating roles of exercise self efficacy and physical self esteem in the relationship between physical education core literacy and subjective exercise experience. Latent profile analysis (LPA) of exercise self efficacy was performed using Mplus 8.3.
Results:
Pearson correlation analysis revealed positive associations between physical education core literacy and exercise self efficacy ( r =0.21), physical self esteem ( r =0.38), and subjective exercise experience ( r =0.40); exercise self efficacy was positively correlated with physical self esteem ( r =0.25) and subjective exercise experience ( r =0.45); and physical self esteem was positively correlated with subjective exercise experience ( r =0.34) (all P <0.01). Mediation analysis indicated that physical education core literacy positively predicted subjective exercise experience ( β =0.41, P <0.05), with exercise self efficacy and physical self esteem serving as partial mediators (effect size=0.14, P <0.01), accounting for 34% of the total effect. LPA identified three latent classes of exercise self efficacy:low (14.71%, n =378), moderate (65.51%, n =1 683), and high (19.78%, n =508) exercise self efficacy groups.
Conclusion
Adolescents exercise self efficacy demonstrates heterogeneity, and both exercise self efficacy and physical self esteem mediate the relationship between physical education core literacy and subjective exercise experience.
7.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
8.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
9.Vonoprazan-based quadruple therapy is non-inferior to esomeprazole-based quadruple therapy for Helicobacter pylori eradication: A multicenter, double-blind, randomized, phase 3 study.
Zhiqiang SONG ; Qin DU ; Guoxin ZHANG ; Zhenyu ZHANG ; Fei LIU ; Nonghua LU ; Liqun GU ; Shingo KURODA ; Liya ZHOU
Chinese Medical Journal 2025;138(22):2938-2946
BACKGROUND:
Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China.
METHODS:
This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%.
RESULTS:
The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles.
CONCLUSION:
Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT04198363.
Humans
;
Esomeprazole/therapeutic use*
;
Double-Blind Method
;
Helicobacter Infections/drug therapy*
;
Male
;
Female
;
Middle Aged
;
Helicobacter pylori/pathogenicity*
;
Pyrroles/therapeutic use*
;
Sulfonamides/therapeutic use*
;
Adult
;
Clarithromycin/therapeutic use*
;
Amoxicillin/therapeutic use*
;
Aged
;
Anti-Bacterial Agents/therapeutic use*
;
Pyrrolidines/therapeutic use*
;
Drug Therapy, Combination
;
Proton Pump Inhibitors/therapeutic use*
10.Pain, agitation, and delirium practices in Chinese intensive care units: A national multicenter survey study.
Xiaofeng OU ; Lijie WANG ; Jie YANG ; Pan TAO ; Cunzhen WANG ; Minying CHEN ; Xuan SONG ; Zhiyong LIU ; Zhenguo ZENG ; Man HUANG ; Xiaogan JIANG ; Shusheng LI ; Erzhen CHEN ; Lixia LIU ; Xuelian LIAO ; Yan KANG
Chinese Medical Journal 2025;138(22):3031-3033


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