1.Study on the mechanism of N-acetylcysteine in alleviating cisplatin-induced liver injury
Biqian YANG ; Huiming HE ; Tingmei YIN ; Xiaoyan FU ; Guangmiao GAO ; Lingling YANG ; Jie LI ; Xiaolong LIAN ; Yi DENG
Journal of Chongqing Medical University 2025;50(6):815-820
Objective:To investigate the hepatoprotective effect of N-acetylcysteine(NAC)on rats with liver injury induced by cisplatin and its effect on intestinal flora and the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-kappa B(NF-κB).Methods:Male Sprague-Dawley rats were randomly divided into control group(CG),cisplatin group(CP),and NAC group.The rats in the NAC group were given NAC 15 mg/kg by gavage for 8 consecutive days.At half an hour after intragastric administration on the fifth day,all rats except those in the NC group were given intraperitoneal injection of 8 mg/kg cisplatin to induce acute liver injury.An automatic biochemical analyzer was used to measure the content of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),and total bilirubin(TBIL);liver index was calculated for the rats;Western blot was used to measure the relative expression levels of NF-κB,IL-6,and TNF-α in liver tissue;the 16S rDNA technique was used to measure and analyze the amplification information of the V3-V4 regions of each sample.Results:Compared with the NC group,the CP group had significant increases in the content of AST,ALT,ALP,and TBIL,while NAC reversed the abnormal liver function caused by cisplatin.Compared with the NC group,the CP group had a sig-nificant increase in liver index(P=0.000),while the NAC group had a significant reduction in liver index compared with the CP group(P=0.007).Compared with the NC group,the CP group had signifi-cant increases in the expression levels of IL-6,TNF-α,and NF-κB,while the NAC group showed reductions in the expression of these genes,with significant differences in the expression of IL-6 and TNF-α(P=0.006 and 0.000).Compared with the NC group,the CP group had a significant increase in the α-diversity index of intesti-nal flora,while compared with the CP group,the NAC group tended to have a reduction in the α-diversity index of intestinal flora.Com-pared with the CP group at the phylum level,the NAC group had an increase in the abundance of Actinobacteria and a reduction in the abundance of Firmicutes.Compared with the CP group at the genus level,the NAC group had a reduction in the abundance of Rumino-coccaceae and increases in the abundance of Bifidobacterium and Allobaculum.Conclusion:NAC can alleviate acute liver injury caused by cisplatin,possibly by downregulating the expression of IL-6,TNF-α,and NF-κB and regulating the abundance and diver-sity of intestinal flora.
2.Exploring the mechanism of Licorice in the treatment of liver injury induced by Semen Strychni based on network pharmacology,molecu-lar docking and animal experiments
Xiaoyan FU ; Zihan GONG ; Guangmiao GAO ; Biqian YANG ; Yi DENG ; Liping WANG ; Xiujuan YANG ; Zhijun YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1326-1341
AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P<0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P<0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P<0.05 or P<0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P<0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P<0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.
3.Exploring the mechanism of Licorice in the treatment of liver injury induced by Semen Strychni based on network pharmacology,molecu-lar docking and animal experiments
Xiaoyan FU ; Zihan GONG ; Guangmiao GAO ; Biqian YANG ; Yi DENG ; Liping WANG ; Xiujuan YANG ; Zhijun YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(10):1326-1341
AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P<0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P<0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P<0.05 or P<0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P<0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P<0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.
4.Visual analysis of the research progress and development trend of licorice anti-tumor
Tingmei YIN ; Biqian YANG ; Xiaoyan FU ; Yi DENG
China Pharmacist 2024;27(1):76-84
Objective To analyzes the Chinese and English literature of anti-tumor of licorice based on CiteSpace knowledge graph,and explores the research status,research hotspots and trends.Methods CiteSpace 6.2.R4 software was used to visually analyze the Chinese and English literature on licorice anti-tumor from January 2002 to September 2023 included in CNKI and Web of Science,and visually analyzed the research topics such as the number of publications,authors,institutions,journals,funds,and keywords.Results A total of 397 Chinese articles and 172 English articles were included after screening.The analysis of the authors of Chinese and English literature shows that Zheng Qiusheng and Jung are the authors with the largest number of anti-tumor articles in Chinese and English respectively,while Beijing University of traditional Chinese Medicine and Hallym University have the largest number of articles in Chinese and English respectively,and there is relatively more cooperation among research institutions in English literature.Chinese and English keyword analysis shows that the anti-tumor research of Glycyrrhiza uralensis mainly focuses on breast cancer,licorice and its active components,molecular mechanism and so on.Cluster analysis shows that research has focused on the active ingredients and clinical applications of licorice;Traditional Chinese Medicine treatment theory and commonly used compound medicines;Experimental research and mechanism of action of licorice on anti-tumor effects;Research on the mechanism of licorice in preventing and treating nephrotoxicity and other toxic side effects caused by chemotherapy drugs.Conclusion The study of anti-tumor mechanism of licorice and the combination of licorice and natural products may be the focus of future research.
5.Active Components and Compound Prescriptions of Glycyrrhizae Radix et Rhizoma in Treatment of Ulcerative Colitis: A Review
Guangmiao GAO ; Lingling YANG ; Xiujuan YANG ; Tingmei YING ; Biqian YANG ; Xiaolong LIAN ; Xiaoyan FU ; Jie LI ; Quhuan MA ; Yi DENG ; Zhijun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):264-274
Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease which primarily affects the colonic mucosa. The UC patients mainly present diarrhea, abdominal pain, tenesmus, and mucous bloody stools, and even malnutrition and systemic symptoms in severe cases, with rising incidence, which has a significant impact on the health and quality of life of patients. The pathogenesis of UC is not clear, and the Western medical therapies include sulfasalazine, glucocorticoids, and immunosuppressants, which, however, have side effects and unsatisfactory effects. Chinese medicine with high safety, mild adverse reactions, and a multi-component, multi-target, and multi-pathway treatment manner has garnering increasing attention. Therefore, finding the Chinese medicine to treat UC has become a hot spot. Glycyrrhizae Radix et Rhizoma is one of the commonly used Chinese herbal medicines, with the effects of tonifying spleen and reinforcing qi, clearing heat and detoxifying, dispelling phlegm and relieving cough, relieving pain, and harmonizing medicines. Glycyrrhizae Radix et Rhizoma mainly contains glycyrrhizic acid, glycyrrhetinic acid, diammonium glycyrrhizinate and other active ingredients. Modern pharmacological studies have shown that Glycyrrhizae Radix et Rhizoma has anti-inflammatory, antioxidant, antimicrobial, and immunomodulatory activities. According to statistics, Glycyrrhizae Radix et Rhizoma is among the top three Chinese herbal medicines for the treatment of UC. The recent years have witnessed progress in the treatment of UC with Glycyrrhizae Radix et Rhizoma and the related prescriptions. The present study summarized the mechanisms underlying the anti-inflammatory, immunomodulatory, intestinal flora-regulating, cell apoptosis-inducing, and oxidative stress-reducing effects of the key chemical constituents (glycyrrhetinic acid, diammonium glycyrrhizinate, polysaccharide, glycyrrhetinic acid, and isoglycyrrhizin) and compound prescriptions of Glycyrrhizae Radix et Rhizoma. The findings provide a solid foundation for further development and clinical application of Glycyrrhizae Radix et Rhizoma.
6.Comparison of intramedullary nailing combined with minimally invasive cerclage versus simple intramedullary nailing for femoral long oblique subtrochanteric fractures
Xuri TANG ; Anjun MA ; Chi FU ; Biqian YE ; Jibo FENG ; Yang WU
Chinese Journal of Orthopaedic Trauma 2017;19(11):994-998
Objective To compare intramedullary nailing assisted by minimally invasive cerclage with simple intramedullary nailing in the treatment of femoral long oblique subtrochanteric fractures.Methods From April 2010 to September 2015,our department treated 39 patients with femoral long oblique subtrochanteric fracture.Of them,16 were treated by cephalomedullary nailing combined with minimally invasive cerclage (observation group of 11 males and 5 females with an average age of 42.8 ± 13.2 years) and 23 by simple cephalomedullary nailing (control group of 17 males and 6 females with an average age of 46.2 ± 10.1 years).Their operation time,intraoperative blood loss,radiologic results (union time and alignment) and functional results [Visual Analog Scale (VAS) and Harris hip score] were compared between the 2 groups.Results The 39 patients were followed up from 12 to 30 months (average,15 months).For the observation group,the varus angle (2.2°± 1.4°) was significantly smaller than for the control group(4.1°±2.2°),the VAS scores at 1 and 3 months postoperatively (3.43 ± 1.54,1.13 ± 1.20) were significantly lower than for the control group (5.61 ± 1.41,3.34 ± 1.82),and the clinical union ratio at 3 months postoperatively(87.5%,14/16) significantly higher than for the control group (47.8%,11/23) (P < 0.05).There were no significant differences between the 2 groups in terms of operation time,intraoperative blood loss,Harris hip score at one year postoperatively,VAS score at 6 months postoperatively,or clinical union ratio at 6 or 12 months postoperatively(P > 0.05).Conclusions Cephalomedullary nailing is effective for the treatment of femoral long oblique subtrochanteric fractures no matter it is assisted by minimally invasive cerclage or not.However,since minimally invasive cerclage has the advantage of improving reduction and mechanical stability,combination of minimally invasive cerclage and cephalomedullary nailing may be more advantageous in early pain-relieving and functional recovery.
7.Effects of GIK on liver injury induced by lipopolysaccharide in rats
Yujiao YANG ; Youbo ZUO ; Yonggang HUI ; Biqian DONG ; Yong WAN
The Journal of Clinical Anesthesiology 2016;32(6):602-605
Objective To investigate if glucose-insulin-potassium (GIK)would relieve the liver injury induced by endotoxemia in rats.Methods Sixty SD male rats,weight 200-250g,were randomly divided into three groups (n = 20):control group (group C),lipopolysaccharide group (group LPS,LPS 8 mg/kg)and Glucose-insulin-potassium group(group GIK,8 mg/kg LPS+GIK 4 ml·kg-1 ·h-1 ).All the rats were injected with 20 mg/kg ketamine intraperitonealy before trial. Erythrocin was daubed on the wound to avoid infection.The rats of group LPS and group GIK were injected LPS 8 mg/kg intraperitoneal,then,rats in group LPS and group GIK received saline(4 ml·kg-1 ·h-1 )or GIK(Glucose 200 g/L,Insulin 60 IU/L,KCL 60 mmol/L)infusion continuously. Liver and serum samples were collected on before injection,3 days after injection and 5 days after in-jection.Serum concentrations of ALT and AST were measured.TNF-αlpha of liver homogenate was detected by ELISA.The severity of liver damage was assessed by an approprite histopathological sco-ring system and apoptosis of parenchymal cells were assessed by TUNEL immunofluorescence assay. Results Compared with group control,the level of serum ALT and AST in group LPS and group GIK were significantly higher at 3 days after injection.The level of hepatic TNF-α,the hepatic damage score and the index of hepatic apoptosis in group LPS and group GIK were significantly higher on 3 days after injection and 5 days after injection.(P<0.05).Compared with group LPS,the level of hepatic TNF-αand the hepatocyte apoptosis rates decreased significantly in group GIK on 3 days after injection.The level of serum ALT and AST,hepatic TNF-α,the hepatic damage score and the hepatocyte apoptosis rates decreased significantly in group GIK at 5 days after injection(P <0.05).Conclusion Intraperitoneal injection of endotoxin can cause liver injury in rats,resulting in the liver hepatdysfunction and hepatocyte damage.GIK has protective effects on LPS induced liver injury in rats.

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