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Objective: The purpose of this study was to evaluate the protective effect of Shengmai Zhenwu decoction on patients with chronic heart failure (CHF) based on the levels of soluble interleukin 1 receptor-like 1 (ST2). Methods: We included a total of 80 outpatients and inpatients with CHF who were undergoing treatment at the Shanghai Municipal Hospital of Traditional Chinese Medicine between March 2020 and March 2022. We randomly divided them into the observation group (n = 40) and the control group (n = 40). Patients in the control group received treatments as per conventional Western medicine, while those in the observation group were treated with the Shengmai Zhenwu decoction in conjunction with Western medicine for eight consecutive weeks. We then compared the pre- and post-treatment levels of ST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) of the patients in the two groups. Results: There were no significant differences in the pre-treatment levels of ST2 and NT-proBNP indexes between the two groups (P > 0.05), while the post-treatment comparison between the two groups in terms of ST2 and NT-proBNP levels suggested that the effect in the observation group was better, with statistical significance (P < 0.05). Conclusion: Shengmai Zhenwu decoction was beneficial in patients with CHF, suggesting that it could be a promising and effective method for the treatment of CHF.
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BACKGROUND: Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process. METHODS: Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α. RESULTS: Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups. CONCLUSIONS: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.
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Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Actinas , Inibidores da Angiogênese/uso terapêutico , Animais , Tetracloreto de Carbono , Colágeno/efeitos adversos , Hidroxiprolina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática Experimental/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice. METHODS: High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively. RESULTS: Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 µg/mL, 50 µg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05). CONCLUSIONS: XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.
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Medicamentos de Ervas Chinesas/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Actinas/metabolismo , Animais , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Endotélio/efeitos dos fármacos , Endotélio/patologia , Células Estreladas do Fígado/patologia , Células Estreladas do Fígado/ultraestrutura , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , Miofibroblastos/ultraestrutura , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Cultura Primária de Células , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. MATERIAL AND METHODS: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4) in C57BL/6 mice for 6 weeks. From week 4 to week 6, the CCl4-injected mice were randomly divided into three groups, followed by oral administration of Sorafenib, XFZY and water for 3 weeks. Biochemical parameters, hydroxyproline (Hyp) content and histological changes of the liver were determined. The expressions of alpha smooth muscle actin (α-SMA), collagen I, CD31 and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and western blot. The protein expressions of VEGFR-2, hypoxia inducing factor (HIF)-1α, asymmetric dimethylarginine (ADMA) and dimethylarginine hydrolase (DDAH) 1 were determined by western blot. The mRNA levels of α-SMA, VEGF and HIF-1α were measured by RT-PCR. RESULTS: Both Sorafenib and XFZY improved biochemical parameters of the liver fibrosis mice. A significant reduction in Hyp content was found in the XFZY-treated mice as well as the Sorafenib-treated mice. Changes in histopathology showed that Sorafenib and XFZY decreased inflammatory and fibrotic stages of the liver in fibrosis mice. Compared to CCl4 model group, Sorafenib and XFZY decreased α-SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1α and ADMA, and increased the expression of DDAH1. CONCLUSION: XFZY inhibits liver fibrosis not only through inhibiting collagen deposition but also through an antiangiogenic effect on the fibrotic liver. Moreover, the antiangiogenic mechanism of XFZY involves alleviating hypoxia and protecting liver sinusoidal endothelial cell function.
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Inibidores da Angiogênese/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fitoterapia , Actinas/genética , Actinas/metabolismo , Amidoidrolases/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Tetracloreto de Carbono , Colágeno Tipo I/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the effects of three classical anti-jaundice formulas Yinchenhao Decoction (YCHD). Yinchen Wuling San (YCWLS) and Zhizi Baipi Decoction (ZZBPD) on liver fibrosis induced by dimethylnitrosamine (DMN) in rats and explore the formula-syndrome relationship. METHODS: Forty-eight rats were weighted, and divided into five groups: normal control, DMN, YCHD, YCWLS and ZZBPD groups using stratified random method. Liver fibrosis in rats was induced by intraperitoneal injection of DMN for 4 weeks at the dosage 10 mg/kg body weight, once per day for 3 consecutive days in each week. Each groups was gavaged with distilled water (control or model group), YCHD, YCWLS and ZZBPD respectively in the last 2-week modeling period. At the end of the 4th week, rats were sacrificed and their blood sample and liver tissue were taken for detecting pathology and analyzing of hydroxyproline (Hyp) and liver function. RESULTS: Compared with the normal control group, DMN model group showed liver damage and liver fibrosis with remarkably increased Hyp content (P<0.01) and abnormal liver function (P<0.01). Liver fibrosis induced by DMN in rats was improved by administration of YCHD. Compared with DMN model group, content of Hyp was decreased remarkably (P<0.01) and liver function and hepatic histology were improved significantly after 2 weeks of YCHD treatment (P<0.05 or P<0.01)., and content of hepatic Hyp was decreased in the ZZBPD groups. Comparison of various parameters between groups showed that content of serum total bilirubin was decreased significantly in the YCWLS group (P<0.01), and content of hepatic Hyp was decreased in the ZZBPD group. CONCLUSION: Efficacy of YCHD in inhibition of liver fibrosis induced by DMN in rats is far better than YCWLS and ZZBPD. The pathogenesis of the liver fibrosis induced by DMN is mainly damp-heat. In addition, both damp and heat pathogenic factors play very important role in this model. The syndrome is highly correlated with the prescription YCHD.
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Dimetilnitrosamina/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/tratamento farmacológico , Fitoterapia , Animais , Hidroxiprolina/análise , Fígado/patologia , Cirrose Hepática Experimental/patologia , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To explore the intervention effects of Xiaopi Pill (XPW), a compound traditional Chinese herbal medicine, on the development progress of dimethylnitrosamine (DMN)-induced liver fibrosis in rats. METHODS: Liver fibrosis model was established by intraperitoneal injection of 0.5% DMN 2 mL/kg thrice a week for 4 weeks. Rats were divided into control group given saline and treatment group given XPW during the 3rd week of DMN injections. Rats were sacrificed at the end of the experiment, and then liver histological changes, liver function and mRNA expression of the liver fibrosis-associated markers were observed. RESULTS: (1) At the end of the 2nd and 4th weeks of DMN injection, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) increased significantly in rats (P<0.01 or P<0.05); content of total bilirubin (TBil) increased significantly compared with the normal group until the end of the 4th week (P<0.05); compared with the model group after 4 weeks of DMN injection, the serum levels of ALT, AST, ALP and TBil were decreased remarkably in the XPW-treated group (P<0.01 or P<0.05). (2) The hepatic inflammation and collagen deposition in hepatic tissues increased by different degrees in experimental rats. Parts of pathological changes in the rat liver were found at the end of the 4th week, including a complete round structure of false flocculus round, meantime, the hydroxyproline content of hepatic tissue was increased significantly at the end of the 2nd and 4th weeks (P<0.05). Compared with the 4-week model group, the hepatic inflammation, collagen deposition and hydroxyproline content in hepatic tissues were alleviated dramatically (P<0.05). (3) Compared with the normal and 2nd week groups, protein expression of alpha-smooth muscle actin (α-SMA) was gradually increased, and that of the 4th week group were aggrandized significantly (P<0.01). Compared with the normal group, the mRNA expression of α-SMA, transforming growth factor-ß1 (TGF-ß1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and heme oxygenase-1 (HO-1) was gradually increased. Further changes in above-mentioned abnormalities were found in the model rats at the end of the 4th week (P<0.01); while compared to the 4th week group, protein and mRNA levels of α-SMA and mRNA levels of TGF-ß1, TIMP-1, and HO-1 were decreased significantly in the XPW group (P<0.01 or P<0.05). CONCLUSION: Progressive DMN-induced liver fibrosis in rats can be suppressed by XPW; the mechanism may be associated with inhibition of the activated hepatic stellate cells.