1.Diabetic Kidney Disease and Gut-kidney Axis: A Review
Yingchao WANG ; Yexin CHEN ; Hua ZHANG ; Jiangteng LIU ; Zhichao RUAN ; Xingru PAN ; Weijun HUANG ; Jinxi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):310-320
With the rising incidence of diabetes, diabetic kidney disease (DKD) has become a significant global health burden. Although current prevention and treatment strategies can partially delay the progression of DKD, the risk of patients advancing to end-stage renal disease remains high. Since the concept of the "gut-kidney axis" was first introduced at the International Congress on Dialysis in 2011, research on the role of gut microbiota in the pathogenesis of DKD has received increasing attention. This review summarizes the current research on gut microbiota, explores the mechanisms through which it contributes to DKD development, and outlines clinical approaches for DKD prevention and treatment based on the "gut-kidney axis" theory. Evidence indicates that dietary interventions, intake of probiotics or prebiotics, use of metformin and novel antidiabetic drugs, and application of traditional Chinese medicine (TCM) compound formulas can effectively improve gut microbiota composition, influence metabolite production, and restore the intestinal mucosal barrier. These interventions can further regulate intestinal innate immunity and inflammatory responses, thereby modulating the progression of DKD. Despite challenges posed by the traditional oral administration of water-decocted TCM compound formulas and the complexity of their ingredients, increasing evidence suggests that TCM may indirectly affect the occurrence and development of DKD by modulating gut microbiota. This finding provides a new perspective on the potential mechanisms of TCM in DKD treatment and may offer novel strategies for DKD prevention and therapy.
2.Mechanisms of Mahuang Lianqiao Chixiaodoutang in Improving Obesity-type Polycystic Ovary Syndrome in Rats Based on PI3K/Akt Signaling Pathway
Shiwei HU ; Biran ZHU ; Jinrong ZHANG ; Luyao RUAN ; Ji KUANG ; Jianghuan HUA ; Zhe LIU ; Yanyue YAO ; Ji WANG ; Min ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):21-31
ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang (MLC) improves obesity-type polycystic ovary syndrome (PCOS) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsThirty-six female Sprague-Dawley (SD) rats were randomly divided into a blank control group (Con) and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole (1 mg·kg-1) combined with a high-fat diet (HFD). After model establishment, the obesity-type PCOS model preparation group was further divided into the model group (Mod, normal saline), metformin group (Met, 0.3 g·kg-1), low-dose MLC group (MLC-L, 4.3 g·kg-1), medium-dose MLC group (MLC-M, 8.6 g·kg-1), and high-dose MLC group (MLC-H, 17.2 g·kg-1). Active components of MLC and targets of obesity-type PCOS were screened from databases, a protein-protein interaction (PPI) network was constructed, and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin (HE) staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), testosterone (T), and estradiol (E2). Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K (p-PI3K/PI3K), phosphorylated Akt/Akt (p-Akt/Akt), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing, the abundances of Lachnospiraceae, Lachnoclostridium, and Dorea were increased in the MLC groups (P<0.05), while the abundance of Veillonella was decreased (P<0.05). KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that, compared with the Mod group, body weight decreased to normal levels in the Met, MLC-M, and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T, FSH, and LH/FSH were reduced (P<0.05, P<0.01), while the E2 level was increased (P<0.01). Ovarian cell apoptosis was reduced (P<0.01), and the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 in ovarian tissue were significantly increased, whereas Bax protein expression was significantly decreased (P<0.05, P<0.01). ConclusionMLC can regulate gut microbiota structure, effectively improve ovarian pathology in rats with obesity-type PCOS, and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.
3.Mechanisms of Mahuang Lianqiao Chixiaodoutang in Improving Obesity-type Polycystic Ovary Syndrome in Rats Based on PI3K/Akt Signaling Pathway
Shiwei HU ; Biran ZHU ; Jinrong ZHANG ; Luyao RUAN ; Ji KUANG ; Jianghuan HUA ; Zhe LIU ; Yanyue YAO ; Ji WANG ; Min ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):21-31
ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang (MLC) improves obesity-type polycystic ovary syndrome (PCOS) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsThirty-six female Sprague-Dawley (SD) rats were randomly divided into a blank control group (Con) and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole (1 mg·kg-1) combined with a high-fat diet (HFD). After model establishment, the obesity-type PCOS model preparation group was further divided into the model group (Mod, normal saline), metformin group (Met, 0.3 g·kg-1), low-dose MLC group (MLC-L, 4.3 g·kg-1), medium-dose MLC group (MLC-M, 8.6 g·kg-1), and high-dose MLC group (MLC-H, 17.2 g·kg-1). Active components of MLC and targets of obesity-type PCOS were screened from databases, a protein-protein interaction (PPI) network was constructed, and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin (HE) staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), testosterone (T), and estradiol (E2). Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K (p-PI3K/PI3K), phosphorylated Akt/Akt (p-Akt/Akt), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing, the abundances of Lachnospiraceae, Lachnoclostridium, and Dorea were increased in the MLC groups (P<0.05), while the abundance of Veillonella was decreased (P<0.05). KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that, compared with the Mod group, body weight decreased to normal levels in the Met, MLC-M, and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T, FSH, and LH/FSH were reduced (P<0.05, P<0.01), while the E2 level was increased (P<0.01). Ovarian cell apoptosis was reduced (P<0.01), and the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 in ovarian tissue were significantly increased, whereas Bax protein expression was significantly decreased (P<0.05, P<0.01). ConclusionMLC can regulate gut microbiota structure, effectively improve ovarian pathology in rats with obesity-type PCOS, and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.
4.Clinical Efficacy and Mechanisms of Qigui Didang Decoction in Treatment of Stage Ⅲ-Ⅳ Diabetic Kidney Disease with Kidney Collateral Stasis Syndrome in Real World
Yingchao WANG ; Jiaqi WANG ; Zongjiang ZHAO ; Hua ZHANG ; Jiannan ZHOU ; Jiangteng LIU ; Zhichao RUAN ; Weijun HUANG ; Jinxi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):162-169
ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease (DKD) in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods, patients were divided into the Qigui Didang decoction group (Qigui Didang decoction + conventional treatment) and the control group (conventional treatment alone). A 1∶1 propensity score matching (PSM) method was used to reduce bias caused by confounding factors. Clinical efficacy, traditional Chinese medicine (TCM) symptom scores, renal function indicators, mRNA expression related to pathway mechanisms, glycolipid metabolism indices, and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included, including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching, there were statistically significant differences between the two groups in DKD stage, baseline urinary albumin-to-creatinine ratio (UACR), 24-hour urine total protein (24 h-UTP), and estimated glomerular filtration rate (eGFR) (P<0.05). After matching, 47 cases were included in each group, and there was no statistically significant difference in baseline data between the two groups. After matching, the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group (χ2=4.681, P<0.05). Compared with data before treatment, the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased (P<0.05). Compared with data before treatment, serum creatinine (SCr), 24 h-UTP, and UACR levels were significantly decreased, while eGFR was significantly increased in the Qigui Didang decoction group (P<0.05). Compared with data before treatment, the mRNA expression of silent information regulator 1 (Sirt1) was significantly upregulated, while the mRNA expression of nuclear factor-kappa B (NF-κB) and tumor suppressor protein p53 (p53) was significantly downregulated in the Qigui Didang decoction group (P<0.05). Compared with data before treatment, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2 hPG), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels were decreased, while high-density lipoprotein cholesterol (HDL-C) levels were increased (P<0.05). There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function, glycolipid metabolism, and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome, with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.
5.Clinical Efficacy and Mechanisms of Qigui Didang Decoction in Treatment of Stage Ⅲ-Ⅳ Diabetic Kidney Disease with Kidney Collateral Stasis Syndrome in Real World
Yingchao WANG ; Jiaqi WANG ; Zongjiang ZHAO ; Hua ZHANG ; Jiannan ZHOU ; Jiangteng LIU ; Zhichao RUAN ; Weijun HUANG ; Jinxi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):162-169
ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease (DKD) in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods, patients were divided into the Qigui Didang decoction group (Qigui Didang decoction + conventional treatment) and the control group (conventional treatment alone). A 1∶1 propensity score matching (PSM) method was used to reduce bias caused by confounding factors. Clinical efficacy, traditional Chinese medicine (TCM) symptom scores, renal function indicators, mRNA expression related to pathway mechanisms, glycolipid metabolism indices, and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included, including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching, there were statistically significant differences between the two groups in DKD stage, baseline urinary albumin-to-creatinine ratio (UACR), 24-hour urine total protein (24 h-UTP), and estimated glomerular filtration rate (eGFR) (P<0.05). After matching, 47 cases were included in each group, and there was no statistically significant difference in baseline data between the two groups. After matching, the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group (χ2=4.681, P<0.05). Compared with data before treatment, the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased (P<0.05). Compared with data before treatment, serum creatinine (SCr), 24 h-UTP, and UACR levels were significantly decreased, while eGFR was significantly increased in the Qigui Didang decoction group (P<0.05). Compared with data before treatment, the mRNA expression of silent information regulator 1 (Sirt1) was significantly upregulated, while the mRNA expression of nuclear factor-kappa B (NF-κB) and tumor suppressor protein p53 (p53) was significantly downregulated in the Qigui Didang decoction group (P<0.05). Compared with data before treatment, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2 hPG), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels were decreased, while high-density lipoprotein cholesterol (HDL-C) levels were increased (P<0.05). There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function, glycolipid metabolism, and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome, with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.
6.Allogeneic lung transplantation in miniature pigs and postoperative monitoring
Yaobo ZHAO ; Ullah SALMAN ; Kaiyan BAO ; Hua KUI ; Taiyun WEI ; Hongfang ZHAO ; Xiaoting TAO ; Xinzhong NING ; Yong LIU ; Guimei ZHANG ; He XIAO ; Jiaoxiang WANG ; Chang YANG ; Feiyan ZHU ; Kaixiang XU ; Kun QIAO ; Hongjiang WEI
Organ Transplantation 2026;17(1):95-105
Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO2) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.
7.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
8.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
9.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*
;
Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
;
Rats
10.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C

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