1.Establishment and Evaluation of Mouse Model of Ischemic Heart Disease with Qi and Yin Deficiency Syndrome Based on Proteomics
Qiuyan ZHANG ; Ying LI ; Yunxiao GAO ; Longxiao HU ; Yue YUAN ; Xiaoxiao CHEN ; Yali SHI ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):52-61
ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease(IHD) with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol(ISO). MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass, with 12 mice in each group. The model groups 1, 4, and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg-1·d-1 for four consecutive days, the model groups 2, 5, and 8 received ISO at a dose of 10 mg·kg-1·d-1 for seven consecutive days, while the model groups 3, 6, and 9 were given ISO at a dose of 15 mg·kg-1·d-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process, body mass, 24-hour food and water intake, grip strength, and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography, the serum levels of norepinephrine(NE), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP) were determined via enzyme-linked immunosorbent assay(ELISA). The content of adenosine triphosphate(ATP) in myocardial tissue was measured by biochemical analysis, while histopathological changes in myocardial tissue were observed via hematoxylin-eosin(HE) staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition(DDA) proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment, and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg-1·d-1 for 14 consecutive days. Under this condition, compared with the normal group, the model group demonstrated significant reductions in body mass, food intake, water intake, grip strength, total distance and average speed of exercise, ejection fraction(EF), fractional shortening(FS), serum levels of NE and cGMP, and myocardial ATP content(P<0.01), while immobility time, cAMP level, and the cAMP/cGMP value were significantly increased(P<0.05, P<0.01). HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement, inflammatory cell infiltration, myocardial fiber rupture, and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group, with 52 up-regulated and 89 down-regulated. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the cellular components(CC) were mainly related to mitochondria and the inner mitochondrial membrane, the biological processes(BP) were associated with complement activation, platelet activation, and responses to metal ions, suggesting that the potential functional pathways involved the complement and coagulation cascade, as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome, and the underlying mechanisms may be related to the regulation of iron ions by complement C3, C5 and Cp, and plays a role in the regulation through the BP of complement activation, platelet activation, and responses to metal ions, and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.
2.Establishment and Evaluation of Mouse Model of Ischemic Heart Disease with Qi and Yin Deficiency Syndrome Based on Proteomics
Qiuyan ZHANG ; Ying LI ; Yunxiao GAO ; Longxiao HU ; Yue YUAN ; Xiaoxiao CHEN ; Yali SHI ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):52-61
ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease(IHD) with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol(ISO). MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass, with 12 mice in each group. The model groups 1, 4, and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg-1·d-1 for four consecutive days, the model groups 2, 5, and 8 received ISO at a dose of 10 mg·kg-1·d-1 for seven consecutive days, while the model groups 3, 6, and 9 were given ISO at a dose of 15 mg·kg-1·d-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process, body mass, 24-hour food and water intake, grip strength, and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography, the serum levels of norepinephrine(NE), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP) were determined via enzyme-linked immunosorbent assay(ELISA). The content of adenosine triphosphate(ATP) in myocardial tissue was measured by biochemical analysis, while histopathological changes in myocardial tissue were observed via hematoxylin-eosin(HE) staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition(DDA) proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment, and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg-1·d-1 for 14 consecutive days. Under this condition, compared with the normal group, the model group demonstrated significant reductions in body mass, food intake, water intake, grip strength, total distance and average speed of exercise, ejection fraction(EF), fractional shortening(FS), serum levels of NE and cGMP, and myocardial ATP content(P<0.01), while immobility time, cAMP level, and the cAMP/cGMP value were significantly increased(P<0.05, P<0.01). HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement, inflammatory cell infiltration, myocardial fiber rupture, and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group, with 52 up-regulated and 89 down-regulated. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the cellular components(CC) were mainly related to mitochondria and the inner mitochondrial membrane, the biological processes(BP) were associated with complement activation, platelet activation, and responses to metal ions, suggesting that the potential functional pathways involved the complement and coagulation cascade, as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome, and the underlying mechanisms may be related to the regulation of iron ions by complement C3, C5 and Cp, and plays a role in the regulation through the BP of complement activation, platelet activation, and responses to metal ions, and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.
3.Preliminary Efficacy of Growth Hormone Therapy in Children With Congenital HeartDisease and Short Stature: A Six-case Report and Literature Review
Xi YANG ; Siyu LIANG ; Qianqian LI ; Hanze DU ; Shuaihua SONG ; Yue JIANG ; Huijuan MA ; Shi CHEN ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):641-646
Congenital heart disease (CHD) is a congenital malformation resulting from abnormal embryonic development of the heart and great vessels, accounting for approximately 25% of all congenital malformations. Children with CHD are often complicated by short stature. Although surgical treatment can improve their growth and development to a certain extent, some children still experience growth retardation after surgery. Recombinant human growth hormone (rhGH) is the main drug for treating short stature, but its efficacy and safety in the treatment of patients with concomitant CHD warrant further investigation. This article reports six cases of children with CHD and short stature who were treated with rhGH. Through a literature review, we summarize and discuss the therapeutic efficacy, follow-up experiences, and adverse reactions of rhGH treatment, aiming to provide references for clinicians in applying rhGH to treat patients with CHD and short stature.
4.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
5.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
6.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
7.Chemical composition and efficacy of warming lung and resolving fluid retention of Asarum forbesii grown under different shading conditions.
Lu LIAO ; Li-Xian LU ; Hong-Zhuan SHI ; Qiao-Sheng GUO ; Cheng-Hao FEI ; Kun ZHAO ; Yuan-Yuan XING ; Yong SU ; Chang LIU ; Xin-Yue YUAN
China Journal of Chinese Materia Medica 2025;50(2):384-394
Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals
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Mice
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Lung/pathology*
;
Drugs, Chinese Herbal/administration & dosage*
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Male
;
Light
;
Cytokines/genetics*
;
Humans
8.Tanreqing Capsules protect lung and gut of mice infected with influenza virus via "lung-gut axis".
Nai-Fan DUAN ; Yuan-Yuan YU ; Yu-Rong HE ; Feng CHEN ; Lin-Qiong ZHOU ; Ya-Lan LI ; Shi-Qi SUN ; Yan XUE ; Xing ZHANG ; Gui-Hua XU ; Yue-Juan ZHENG ; Wei ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2270-2281
This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified_f_Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Lung/metabolism*
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Mice, Inbred C57BL
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Capsules
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Orthomyxoviridae Infections/virology*
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Gastrointestinal Microbiome/drug effects*
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Male
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Humans
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Female
;
Influenza A virus/physiology*
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Influenza, Human/virology*
9.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
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Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Surveys and Questionnaires
10.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
;
Rats

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