1.Multidimensional Analysis of Mechanisms of Nuciferine Against Cerebral Ischemia Based on Transcriptomic Data
Yingying QIN ; Peng LI ; Sha CHEN ; Yan LIU ; Jintang CHENG ; Qingxia XU ; Guohua WANG ; Jing ZHOU ; An LIU ; Chang CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):184-191
ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect, but the specific mechanism of action has not been elaborated. Based on the transcriptome results, the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue, cell, pathological process, biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group, model group and nuciferine group(40 mg·kg-1) according to weight. Except for the sham group, the model of middle cerebral artery occlusion(MCAO) was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery, transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue, and gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue, cell, pathological process, biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform(TMNP). ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response, ion transport, cell proliferation and differentiation, and synaptic function. TMNP research found that at the tissue level, nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels, nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells, mobilizing immune cells, regulating inflammation. And at the level of biological processes and signaling pathways, nuciferine mainly acted on the processes such as vascular remodeling, inflammation-related signaling pathways, and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing, gene quantitative analysis and TMNP, the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation, affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.
2.Research and prospect of integrated traditional Chinese and western medicine in treatment of bronchiectasis.
Qing MIAO ; Zi YANG ; Bo XU ; Sha-Sha YUAN ; Yu-Chen WEI ; Jin-Zhi ZHANG ; Rui LI ; Chang-Zheng FAN
China Journal of Chinese Materia Medica 2025;50(13):3692-3698
Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy*
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Humans
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Drugs, Chinese Herbal/therapeutic use*
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Medicine, Chinese Traditional/methods*
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Animals
3. Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats
Rui-Ying TIAN ; Wen-Xin MA ; Zi-Yu LIU ; Hui-Ming MA ; Sha-Sha XING ; Na HU ; Chang LIU ; Biao MA ; Jia-Yang LI ; Hu-Jun LIU ; Chang-Cai BAI ; Dong-Mei CHEN
Chinese Pharmacological Bulletin 2024;40(3):490-498
Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.
4.Mechanism of Gualou Xiebai Baijiu Decoction for regulating the intestinal microflora and its metabolites to improve atherosclerosis in mice
Zhifan CHEN ; Yulin CHEN ; Sha NIE ; Wenhao SUN ; Chang LI ; Zishan MA ; Kai HU ; Yingying HE ; Ying LIU ; Yaoping TANG
Chinese Journal of Comparative Medicine 2024;34(7):10-19
Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction(GXB)in improving atherosclerosis(AS)in mice by regulating the gut microbiota(GM)and its metabolites.Methods Thirty-two male ApoE-/-mice were divided randomly into a Blank group,Model group,atorvastatin(Ato)group,and GXB group(n=8 mice per group).AS was established in all mice,except the Blank group,and the respective treatments were administered by gavage.Aortic plaques were detected by Oil red O staining and pathological changes in aortic tissue were detected by hematoxylin and eosin staining.The GM was analyzed using 16S rRNA gene sequencing technology,and mouse GM metabolites,including trimethylamine oxide(TMAO),short-chain fatty acids(SCFA),and serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)were determined.Results Compared with the Blank group,mice in the Model and Ato groups showed an increase in AS plaque area(P<0.05).Serum levels of TG,TC,and LDL-C were increased(P<0.001)while levels of HDL-C and NO were decreased(P<0.01,P<0.001)in the Model group compared with the Blank group.The plaque area was decreased(P<0.05),serum levels of TG,TC,and LDL-C were decreased(P<0.001),and NO levels were increased(P<0.01)in the Ato and GXB groups,while HDL-C levels were increased in the GXB group(P<0.05)compared with the Model group.Plaque area was decreased(P<0.05)and the NO level was increased(P<0.01)in the GXB group compared with the Ato group.A total of 6345 characteristic sequences were obtained from 16S rRNA analysis.α-Diversity analysis indicated that GXB reduced the richness of the GM in AS mice(P<0.001)and improved its uniformity(P<0.05).β-Diversity analysis suggested that the microbial community structure in the GXB group was similar to that in the Blank group.The abundance of microbial communities differed among the groups at the phylum and genus levels.At the phylum level,the abundance of Proteobacteria was increased(P<0.01)in AS mice,while GXB intervention reduced the abundance of Proteobacteria(P<0.01)and increased the abundance of Verrucomimicrobiota(P<0.05).At the genus level,GXB effectively increased the abundance of Akkermansia(P<0.05).SCFAs were significantly increased(P<0.01)and TMAO levels were significantly decreased(P<0.01)in the GXB group compared with the Model group.Conclusions GXB can regulate the intestinal flora and intestinal flora metabolites SCFA and TMAO to improve AS.Akkermansia may be a key bacterial genus of the gut microbiota through which GXB may improve AS.
5.Clinical trial of Sacoharomyces boulardii with ursodeoxycholic acid in the treatment of neonatal hyperbilirubinemia
Xiao-heng GUO ; Sha-sha XU ; Hai-zhi WANG ; Yang LI ; Chang-geng ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(22):3244-3248
Objective To investigate the effects of Sacoharomyces boulardii combined with ursodeoxycholic acid on serum levels of gamma-glutamate transpeptidase(γ-GT),insulin like growth factor-1(IGF-1)and retinol binding protein(RBP)in neonates with hyperbilirubinemia.Methods Neonatal hyperbilirubinemia children were divided into control group and treatment group by cohort method.The control group was given ursodeoxycholic acid,5 mg·kg-1 each time,twice a day,and took the tablet powder in warm water;the treatment group was additionally treated with Sacoharomyces boulardii on the basis of the control group,1 bag each time,orally once every 24 h.The clinical efficacy,yellows regression,serum total bilirubin(TBIL),indirect bilirubin(IBIL),transferrin(TRF)levels and serum γ-GT,IGF-1 and RBP levels before and after treatment were compared between the two groups.And evaluated the safety.Results 152 cases in treatment group and 148 cases in control group were enrolled.After treatment,the clinical efficacy of the treatment group and control group was 94.08%(143 cases/152 cases)and 81.76%(121 cases/148 cases);the re-phototherapy rate was 8.55%(13 cases/152 cases)and 20.95%(31 cases/148 cases),the difference was statistically significant(all P<0.05).The duration of phototherapy in the treatment group and control group were(20.17±5.32)and(26.39±7.69)h;the decolorization time were(3.97±0.60)and(5.59±0.83)d;the hospital stay were(7.17±0.66)and(9.16±0.90)d;the TBIL were(133.26±15.69)and(179.15±17.65)μmol·L-1;the IBIL were(141.88±18.19)and(198.65±19.26)μmol·L-1;the γ-GT were(38.19±3.75)and(50.87±4.25)U·L-1;the RBP were(20.42±3.21)and(25.50±3.43)mg·L-1;the IGF-1 were(20.43±3.06)and(26.51±3.38)ng·L-1;the TRF were(1.98±0.27)and(1.65±0.20)g·L-1,the difference was statistically significant(all P<0.05).The adverse drug reactions of treatment group and control group were diarrhea,nausea and vomiting,rash.The total incidence of adverse reactions in treatment group and control group was 8.52%(13 cases/152 cases)and 9.46%(14 cases/148 cases),there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion The treatment of neonatal hyperbilirubinemia with yeast burra combined with ursodeoxychonic acid can effectively improve the levels of serum γ-GT,IGF-1 and RBP,and the clinical efficacy is good.
6.Clinical trial of Sacoharomyces boulardii with ursodeoxycholic acid in the treatment of neonatal hyperbilirubinemia
Xiao-heng GUO ; Sha-sha XU ; Hai-zhi WANG ; Yang LI ; Chang-geng ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(22):3244-3248
Objective To investigate the effects of Sacoharomyces boulardii combined with ursodeoxycholic acid on serum levels of gamma-glutamate transpeptidase(γ-GT),insulin like growth factor-1(IGF-1)and retinol binding protein(RBP)in neonates with hyperbilirubinemia.Methods Neonatal hyperbilirubinemia children were divided into control group and treatment group by cohort method.The control group was given ursodeoxycholic acid,5 mg·kg-1 each time,twice a day,and took the tablet powder in warm water;the treatment group was additionally treated with Sacoharomyces boulardii on the basis of the control group,1 bag each time,orally once every 24 h.The clinical efficacy,yellows regression,serum total bilirubin(TBIL),indirect bilirubin(IBIL),transferrin(TRF)levels and serum γ-GT,IGF-1 and RBP levels before and after treatment were compared between the two groups.And evaluated the safety.Results 152 cases in treatment group and 148 cases in control group were enrolled.After treatment,the clinical efficacy of the treatment group and control group was 94.08%(143 cases/152 cases)and 81.76%(121 cases/148 cases);the re-phototherapy rate was 8.55%(13 cases/152 cases)and 20.95%(31 cases/148 cases),the difference was statistically significant(all P<0.05).The duration of phototherapy in the treatment group and control group were(20.17±5.32)and(26.39±7.69)h;the decolorization time were(3.97±0.60)and(5.59±0.83)d;the hospital stay were(7.17±0.66)and(9.16±0.90)d;the TBIL were(133.26±15.69)and(179.15±17.65)μmol·L-1;the IBIL were(141.88±18.19)and(198.65±19.26)μmol·L-1;the γ-GT were(38.19±3.75)and(50.87±4.25)U·L-1;the RBP were(20.42±3.21)and(25.50±3.43)mg·L-1;the IGF-1 were(20.43±3.06)and(26.51±3.38)ng·L-1;the TRF were(1.98±0.27)and(1.65±0.20)g·L-1,the difference was statistically significant(all P<0.05).The adverse drug reactions of treatment group and control group were diarrhea,nausea and vomiting,rash.The total incidence of adverse reactions in treatment group and control group was 8.52%(13 cases/152 cases)and 9.46%(14 cases/148 cases),there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion The treatment of neonatal hyperbilirubinemia with yeast burra combined with ursodeoxychonic acid can effectively improve the levels of serum γ-GT,IGF-1 and RBP,and the clinical efficacy is good.
7.Comparative chemical characters of Ziziphi Spinosae Semen from geographical origins of China
Pengwang WANG ; Miao SHA ; Weimei ZHANG ; Hongyue TIAN ; Xu LIANG ; Wei TIAN ; Bo XU ; Guanglu CHANG ; Xia LI ; Wenyuan GAO
Science of Traditional Chinese Medicine 2024;2(1):37-47
Background: Ziziphi Spinosae Semen (ZSS) contains a wide range of active components. Because existing methods cannot fully evaluate these components, a new quantitative method needs to be established for component characterization. Objective: Ziziphi Spinosae Semen has gained increasing attention in recent years, primarily as a medicinal and edible plant. The content determination of ZSS is not specified in the Chinese Pharmacopeia (2020 edition). Environmental conditions in different production areas can influence the quality of ZSS. This study aims to identify ZSS collected from various geographical origins in China. Materials and methods: High-performance liquid chromatography (HPLC) fingerprints were established using optimized HPLC-photo-diode array methods. Subsequently, similarity analysis and quantification of ZSS from different sources were conducted. Metabolites of ZSS were identified and evaluated using the UHPLC-Q Exactive HF Orbitrap MS system. Principal component analysis, hierarchical cluster analysis, and orthogonal partial least squares discriminant analysis were performed based on all peak areas. Results: In this study, the components of ZSS against insomnia were screened through network pharmacology. As revealed by the results of protein-protein interaction network analysis, Gene Ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, 14 core components, 10 core targets, and 25 pathways were identified. Thirty-four batches of ZSS fingerprints were established through the HPLC method, which identified 12 characteristic peaks, with 6 being qualitatively identified. An identification method for assessing differences in the chemical composition of ZSS from different origins was developed by using UHPLC-Q Exactive HF Orbitrap MS. Differential markers from various origins were screened and identified. Through multiple analyses such as principal component analysis and orthogonal partial least squares discriminant analysis, it was concluded that there were differences in ZSS metabolites from Hebei, Shandong, and Shaanxi provinces. Seventeen differential metabolites of different origins were identified. Conclusions: This study confirmed that ZSS played a synergistic role in improving insomnia through multiple components, targets, and pathways. The content of all 5 components was high, except for jujuboside B. In addition, 6 compounds in ZSS extracts from different origins differed in content, indicating that different growth environments might impact the quality of ZSS.
8.Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish.
Ling-Jie RUAN ; Li-Na HUANG ; Xin-Yi GAO ; Chang-Jie LAI ; Lin-Jing ZHANG ; Yu-Fan WU ; Mei SHA ; Miao YE
China Journal of Chinese Materia Medica 2023;48(6):1558-1567
Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.
Animals
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Zebrafish
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Rhus/chemistry*
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Triterpenes/analysis*
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Coronary Disease
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Thrombosis
9.Mechanisms of Yangxin Tongmai Formula for blood stasis syndrome in coronary heart disease rats based on untargeted plasma metabolomics and intestinal flora 16S rRNA sequencing
LIU Yinxing ; CHEN Zijun ; WANG Yiqin ; CHENG Xihua ; LI Jie ; CHEN Lingli
Digital Chinese Medicine 2023;6(2):198-209
【Objective】 To investigate the correlations between intestinal flora, plasma metabolites, and
blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin
Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats.
【Methods】 A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used
to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed.
【Results】 The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine,
and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05).
【Conclusion】 YXTMF could alleviate blood stasis syndrome in CHD rats through improving
their plasma metabolisms achieved by regulating the intestinal flora.
10.Analysis on research hotspots and trends in the field of TCM for cervical cancer based on CiteSpace
Min WANG ; Hanzhu NIE ; Fang LI ; Xiaoyan PANG ; Yuehan DUAN ; Ting LIU ; Tiantian WU ; Sha GONG ; Wei CHANG
International Journal of Traditional Chinese Medicine 2023;45(5):620-625
Objective:To analyze the research hotspots and trends in the field of Traditional Chinese Medicine (TCM) for cervical cancer at home and abroad in recent 30 years through visualization method.Methods:By setting "cervical cancer" and "TCM" as the research subjects, the articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Web of Science Core database (WoS) from January 1, 1992 to January 1, 2022. Citespace 5.8 R3 software was used to conduct visual analysis on the authors, institutions and keywords included in the articles.Results:A total of 1 123 Chinese articles and 573 English articles were included. The number of articles issued showed a gradual upward trend; the author with the largest number of Chinese publications was Jin Zhe, and the author with the largest number of English publications was Chen Guo. The institution with the largest number of Chinese publications was Beijing University of Chinese Medicine; the institution with the largest number of English publications was Chinese Academy of Medical Sciences. Keywords co-occurrence of the top 3 Chinese keywords in the network frequency (excluding the search words) were "cervical erosion", "urinary retention" and "Yunnan Baiyao"; English keywords were "HeLa cell", "bibliometric", and "information monitoring system". Chinese keywords formed 11 clusters and 25 emergent words; English keywords formed 9 clusters and 17 emergent words.Conclusions:The research content in the field of TCM of cervical cancer about knowledge map in the past 30 years at home and abroad is rich. TCM can play the role of antagonizing human papillomavirus, enhancing immune function, regulating TCM constitution, improving quality of life and so on. At present, the research hotspot is the mechanism exploration of cervical cancer and the curative effect research of clinical complications, and the research trend is clinical curative effect research.

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