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To establish a quality evaluation method for Patrinia scabiosaefolia Fisch (PS), as well as to study the anti-inflammatory and hepatoprotective effects of the aqueous extract of Patrinia scabiosaefolia Fisch (APS). We used ultra performance liquid chromatography (UPLC) to establish fingerprint and content determination method for PS. The alcoholic liver injury model was prepared by feeding Lieber-DeCarli alcohol liquid feed to mice. We determined the levels of ALT, AST, TC, TG in serum, as well as GSH, MDA in the liver. The mRNA relative expression levels of TNF-α, IL-6, IL-1ß, INOS and COX-2 were detected by qRT-PCR, and liver tissues were taken for pathological examination. The fingerprints of 16 batches of PS were established, and 3 component peaks were identified, which were chlorogenic acid (CA), isochlorogenic acid A (ICAA) and isochlorogenic acid C (ICAC). The similarity of the 6 common peaks was between 0.924 and 1.000. A mice model of alcoholic liver injury was successfully made by mixing alcohol liquid feed. The levels of ALT, AST, TC and TG in serum and MDA, TNF-α, IL-1ß, LL-6, COX-2 and INOS mRNA in liver were effectively reduced in the drug administration group. The levels of GSH in mouse liver tissue were increased in the drug administration group. The method has good repeatability, stability and feasibility, and it meets the requirements for Quality evaluation. APS exhibits a protective effect against alcoholic liver injury (ALI) in mice.
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Patrinia , Camundongos , Animais , Patrinia/química , Fator de Necrose Tumoral alfa , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2 , Estrutura Molecular , Fígado , Etanol/farmacologia , RNA Mensageiro/farmacologiaRESUMO
Green tea is one of the main types of tea in China, and it has been widely consumed in the world. This study aims to investigate the potential mechanism by which the water extract of green tea (GTWE) may be effective in the treatment of alcohol-related hepatitis (ARH), utilizing a combination of network pharmacology, molecular docking, and experimental validation. Through network pharmacology analysis, seven active components and 45 potential targets were identified, with TLR4 being confirmed as the central target. Experimental findings demonstrate that GTWE exhibits significant efficacy in mitigating alcohol-induced liver inflammation and steatosis. Furthermore, the administration of GTWE has demonstrated significant efficacy in mitigating alcohol-induced intestinal inflammation and microbiota disturbance while concurrently restoring intestinal barrier function. Consequently, GTWE exhibits considerable potential as a pharmacological intervention and warrants further research and development as a lead compound for the treatment of ARH. Moreover, the prospective utilization of green tea in prolonged intakes exhibits potential as a prophylactic nutritive regimen against ARH.
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Microbioma Gastrointestinal , Hepatite , Camundongos , Animais , Chá , Simulação de Acoplamento Molecular , Estudos Prospectivos , Extratos Vegetais/farmacologia , InflamaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Verbenalin is a major compound in Verbena officinalis L. Verbena officinalis L was first recorded in the 'Supplementary Records of Famous Physicians.' Verbenalin (VE) is its active constituent and has been found to have many biological effects, including anti-obesity, anti-inflammatory, and antioxidant activities, removing jaundice, and treating malaria. It could treat lump accumulation, dysmenorrhea, throat obstruction, edema, jaundice, and malaria. Palmitic acid (PA), oleic acid (OA), ethanol, and acetaminophen liver injuries have been proven to benefit from verbenalin. AIM OF THE STUDY: To study the effects of verbenalin on the prevention of alcoholic steatohepatitis (ASH) through the regulation of oxidative stress and mitochondrial dysfunction by regulating MDMX (Murine double minute X)/PPARα (Peroxisome proliferator-activated receptor alpha)-mediated ferroptosis. MATERIAL AND METHODS: C57BL/6 mice treated with alcohol followed by the Gao-Binge protocol were administered verbenalin by gavage simultaneously. The mitochondrial mass and morphology were visualized using TEM. AML-12 cells were stimulated with ethanol to mimic ASH in vitro. Western blotting, co-immunoprecipitation, and kit determination were simultaneously performed. The target protein of verbenalin was identified by molecular docking, and cellular thermal shift assay (CETSA) further confirmed its interactions. RESULTS: Verbenalin alleviates oxidative stress and ferroptosis in alcohol-associated steatohepatitis. To elucidate the molecular mechanism by which verbenalin inhibits abnormal mitochondrial dysfunction, molecular docking was performed, and MDMX was identified as the target protein of verbenalin. CETSA assays revealed a specific interaction between MDMX and verbenalin. Co-immunoprecipitation demonstrated that PPARα played a critical role in promoting the ability of MDMX to affect ferroptosis. Verbenalin regulates MDMX/PPARα-mediated ferroptosis in AML-12 cells. CONCLUSION: Verbenalin regulates ferroptosis and highlights the therapeutic potential of verbenalin and ferroptosis inhibition in reducing alcoholic steatohepatitis.
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Fígado Gorduroso Alcoólico , Ferroptose , Leucemia Mieloide Aguda , Hepatopatia Gordurosa não Alcoólica , Animais , Feminino , Camundongos , Etanol/farmacologia , Fígado Gorduroso Alcoólico/metabolismo , Leucemia Mieloide Aguda/metabolismo , Fígado , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR alfa/metabolismo , Proteínas/metabolismoRESUMO
BACKGROUND: Hastatoside is an iridoid glycoside extracted from the herb, Verbena officinalis, that exerts various pharmacological effects, including anti-inflammatory, sleep-promoting, and analgesic effects. However, only a few studies have reported the efficacy of hastatoside in liver fibrosis. Liver fibrosis is a pathophysiological process, and its persistence can seriously affect the quality of life and well-being of the patients. HYPOTHESIS/PURPOSE: This study aimed to investigate the role of hastatoside on liver fibrosis and its possible underlying mechanisms. METHODS: C57BL/6 J mice with carbon tetrachloride (CCl4)-induced hepatic fibrosis were used as the in vivo models. Histological features of the liver were observed using Masson's trichrome and hematoxylin-eosin staining. Alanine aminotransferase and aspartate aminotransferase levels and the hepatic fibrosis indices (type 3 procollagen, laminin, and hyaluronic acid) were measured using corresponding assay kits. LX-2 human hepatic stellate cells (HSCs) stimulated with the transforming growth factor ß1 were used as the vitro models. Transfection of the glycogen synthase kinase (GSK)-3ß small interfering RNA (siRNA) and ß-catenin plasmids was also performed in vitro. Protein levels of GSK-3ß, phospho-GSK-3ß (Ser 9), α-smooth muscle actin, collagen type I alpha 1, c-Myc, cyclin D1, and ß-catenin were determined via western blotting. Moreover, the p-GSK-3ß:GSK-3ß ratio was calculated to determine the GSK-3ß activity. RESULTS: Hastatoside prevented CCl4-induced liver injury and histological damage. It inhibited the upregulation of α-SMA and Col1α1 levels in a CCl4-induced mouse hepatic fibrosis model. In vitro, hastatoside inhibited the proliferation and activation of HSCs by decreasing the expression levels of cyclin D1 and c-Myc and the proportion of LX-2 cells activated in the G0/G1 phase. Molecular docking results showed that hastatoside bound to GSK-3ß. Hastatoside significantly increased the GSK-3ß activity and inhibited the downstream effector expression of ß-catenin. CONCLUSION: These findings suggest that hastatoside can bind to GSK-3ß and promote its activity, while inhibiting the GSK-3ß downstream effector expression of ß-catenin, thereby inhibiting the activation and proliferation of HSCs, which further prevents the development of liver fibrosis. These results provide innovative insights into the underlying liver fibrosis. Moreover, hastatoside is a potential anti-fibrosis monomer that can potentially be used for the treatment of liver fibrosis.
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Doença Hepática Induzida por Substâncias e Drogas , Glicogênio Sintase Quinase 3 beta , Glicosídeos Iridoides , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Ciclina D1/metabolismo , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Estreladas do Fígado , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Qualidade de Vida , Transdução de Sinais , Glicosídeos Iridoides/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Shufeng Jiedu capsule (SFJDC) is a pure form of traditional Chinese medicine (TCM) that contains eight medicinal plants. Known for its anti-inflammatory and antipyretic effects, it is mostly used to treat upper respiratory tract infections and other infectious diseases, such as colds, pharyngitis, laryngitis, and tonsillitis. Both acute lung injury (ALI) and COVID-19 are closely related to lung damage, primarily manifesting as lung inflammation and epithelial cell damage. However, whether SFJDC can improve ALI and by what mechanism remain unclear. The purpose of this study was to explore whether SFJDC could be used as a prophylactic treatment for COVID-19 by improving acute lung injury. AIM OF THE STUDY: The purpose of this study was to determine whether SFJDC could protect against ALI caused by lipopolysaccharide (LPS), and we wanted to determine how SFJDC reduces inflammation and apoptosis pharmacologically and molecularly. MATERIALS AND METHODS: Preadministering SFJDC at 0.1 g/kg, 0.3 g/kg, or 0.5 g/kg for one week was followed by 5 mg/kg LPS to induce ALI in mice. Observations included the study of lung histomorphology, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) secretion, as well as the ratio of lung wet/dry weights. In addition, RAW264.7 cells were treated for 24 h with 1 µg/mL LPS after being pretreated for 1 h with 0.5 mg/mL SFJDC. In the samples, we detected TNF-α, IL-1ß, and IL-6. Cell apoptosis was detected by stimulating A549 cells for 24 h with RAW264.7 supernatant. Both in vitro and in vivo, the levels of A2A adenosine receptor (A2AAR), PKA, IκB, p-IκB, NF-κB P65 (P65), p-NF-κB P65 (p-P65), cleaved caspases-3 (Cc3), Bcl-2 associated X protein (Bax), and B-cell lymphoma-2 (Bcl-2) proteins were determined using Western blot analysis. RESULTS: Lung tissue morphology was improved as SFJDC decreased cytokine secretion, the ratio of lung wet/dry weights, and lung tissue secretion of proinflammatory cytokines. The expression of A2AAR was increased by SFJDC, and the phosphorylation of NF-κB was inhibited. TUNEL staining and flow cytometry showed that SFJDC inhibited apoptosis by reducing the expression of Cc3 and the ratio of Bax/Bcl-2. CONCLUSIONS: According to the results of this study, SFJDC can reduce inflammation and inhibit apoptosis. A2AAR activation and regulation of NF-κB expression are thought to make SFJDC anti-inflammatory and anti-apoptotic. A wide range of active ingredients may result in an anti-inflammatory and antipyretic effect with SFJDC.
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Lesão Pulmonar Aguda , COVID-19 , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios , Apoptose , Medicamentos de Ervas Chinesas , Inflamação/patologia , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão , Camundongos , NF-kappa B/metabolismo , Receptores Purinérgicos P1/metabolismo , Receptores Purinérgicos P1/uso terapêutico , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Alcoholic hepatitis is a serious form of liver damage. Inflammation is a key factor in alcoholic hepatitis and plays a key role in the progression of alcoholic liver disease. Adenosine receptor A2B (A2BAR) is a member of the adenosine receptor family and generally considered to be a negative regulator of the inflammatory response. We found that A2BAR was the most highly expressed adenosine receptor in ETOH-fed mouse liver tissue and was also highly expressed in primary Kupffer cells and ETOH-induced RAW264.7 cells. In addition, injection of BAY 60-6583 stimulated A2BAR, induced upregulation of the expression levels of cAMP, and reduced ETOH-induced steatosis and inflammation in mice. At the same time, knockdown of A2BAR in vitro increased the inflammatory response in RAW264.7 cells triggered by ETOH. After knockdown of A2BAR in vitro, the release of the inflammatory cytokines IL-6, IL-1ß and TNF-α was increased. After overexpression of A2BAR in vitro, the cAMP level was significantly increased, PKA expression was increased, the expression of phosphorylated proteins in the NF-kB signal transduction pathway was significantly affected, and the expression of the key phosphorylated protein p-P65 was decreased. However, after the simultaneous overexpression of A2BAR and inhibition of PKA, the expression of the key phosphorylated protein p-P65 was still significantly decreased. In addition, after the expression of A2BAR increased or decreased in RAW264.7 cells, AML-12 cells were cultured in the supernatant of RAW264.7 cells stimulated by ETOH, and the apoptosis rate was significantly changed by flow cytometry. These results suggest that A2BAR can reduce alcoholic steatohepatitis by upregulating cAMP levels and negatively regulating the NF-kB pathway. Overall, these findings suggest the significance of A2BAR-mediated inflammation in alcoholic liver disease.
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Hepatite Alcoólica/tratamento farmacológico , Células de Kupffer/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Receptor A2B de Adenosina/uso terapêutico , Receptores de AMP Cíclico/efeitos dos fármacos , Receptores de AMP Cíclico/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Hepatic fibrosis is the most common pathological feature of most chronic liver diseases, and its continuous deterioration gradually develops into liver cirrhosis and eventually leads to liver cancer. At present, there are many kinds of drugs used to treat liver fibrosis. However, Western drugs tend to only target single genes/proteins and induce many adverse reactions. Most of the mechanisms and active ingredients of traditional Chinese medicine (TCM) are not clear, and there is a lack of unified diagnosis and treatment standards. Natural products, which are characterized by structural diversity, low toxicity, and origination from a wide range of sources, have unique advantages and great potential in anti-liver fibrosis. This article summarizes the work done over the previous decade, on the active ingredients in natural products that are reported to have anti-hepatic fibrosis effects. The effective anti-hepatic fibrosis ingredients identified can be generally divided into flavonoids, saponins, polysaccharides and alkaloids. Mechanisms of anti-liver fibrosis include inhibition of liver inflammation, anti-lipid peroxidation injury, inhibition of the activation and proliferation of hepatic stellate cells (HSCs), modulation of the synthesis and secretion of pro-fibrosis factors, and regulation of the synthesis and degradation of the extracellular matrix (ECM). This review provides suggestions for the development of anti-hepatic fibrosis drugs.
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Produtos Biológicos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Humanos , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologiaRESUMO
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid loss of renal function, which may further develop into chronic kidney damage (CKD) or even end-stage renal disease (ESRD). AKI is a global health problem associated with high morbidity and costly treatments, and there is no specific or effective strategy to treat AKI. In recent years, Traditional Chinese Medicine (TCM) has attracted more attention, with lines of evidence showing that application of TCM improved AKI, and the mechanisms of action for some TCMs have been well illustrated. However, reviews summarizing the progress in this field are still lacking. In this paper, we reviewed TCM preparations and TCM monomers in the treatment of AKI over the last 10 years, describing their renal protective effects and mechanisms of action, including alleviating inflammation, programmed cell death, necrosis, and reactive oxygen species. By focusing on the mechanisms of TCMs to improve renal function, we provide effective complementary evidence to promote the development of TCMs to treat AKI. Moreover, we also summarized TCMs with nephrotoxicity, which provides a more comprehensive understanding of TCMs in the treatment of AKI. This review may provide a theoretical basis for the clinical application of TCMs in the future.
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Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment.
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Renal fibrosis, a common feature and leading cause for End Stage Renal Disease, still lacks effective therapy. In the current study, we detected and compared the anti-fibrotic effects of wogonin and wogonoside, two major components of Scutellaria baicalensis Georgi, in TGF-ß1-treated tubular epithelial cells of human and murine origins. Results consistently showed that compared with wogonoside, wogonin inhibits TGF-ß1-induced upregulated mRNA and protein levels of collagen I and α-SMA with more efficiency, which was further confirmed by the immunofluorescence results that wogonin decreased the percentage of collagen I and α-SMA positive cells in TGF-ß1-treated tubular epithelial cells. Mechanistically, wogonin mainly decreased Smad3 phosphorylation, but had marginal effect on non-canonical TGF-ß signaling pathways, such as p38 and ERK MAP Kinase. Furthermore, in the cells deficient for TGF-ß signaling or downstream Smad3, results demonstrated that even high concentration of wogonin failed to further decrease the level of collagen I and α-SMA, indicating the essential role of TGF-ß/Smad3 signaling inhibition in the therapeutic action of wogonin in TGF-ß1-stimulated tubular epithelial cells. Collectively, our results indicated that wogonin may be utilized as a potential anti-fibrotic Traditional Chinese Medicine monomer in the treatment of renal fibrosis.
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Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Flavanonas/farmacologia , Glucosídeos/farmacologia , Túbulos Renais Proximais/patologia , Proteína Smad3/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Fibrose , Flavanonas/uso terapêutico , Glucosídeos/uso terapêutico , Humanos , Camundongos , Fosforilação/efeitos dos fármacos , Ratos , Receptores de Fatores de Crescimento Transformadores beta/deficiência , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad3/deficiência , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
Two new dihydrostilbenoid glycosides, named 5-(2-phenylethyl)-3-hydroxyphenol-1-O-beta-D-glucopyranoside (1) and 6-(2-phenylethyl)-2,4-dihydroxy benzoic acid-2-O-beta-D-glucopyranoside (2), together with two known compounds, were isolated from the leaves of Litsea coreana Levl.. Their structures were established on the basis of NMR spectroscopic, MS and chemical data. Biological tests revealed that 1-3 exhibited moderate anti-inflammatory activity through an inhibitory effect on TNF-alpha, IL-1 production from RAW264.7 cell line activated with lipopolysaccharides (LPS).
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Anti-Inflamatórios/isolamento & purificação , Glucosídeos/isolamento & purificação , Litsea/química , Estilbenos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Células Cultivadas , Glucosídeos/química , Espectroscopia de Ressonância Magnética , Camundongos , Folhas de Planta/química , Estilbenos/químicaRESUMO
OBJECTIVE: The aim of this study was to investigate the prophylactic effect and some mechanisms of action of triterpene acids of loquat (TAL) on bleomycin A5-induced pulmonary fibrosis rats. METHODS: A model of pulmonary fibrosis was induced by injecting rats with a single dose of bleomycin A5 (5 mg/kg) into the trachea. From the second day, rats in the preventive groups were treated with TAL (50, 150 or 450 mg/kg) or dexamethasone (1.2 mg/kg). On the 28th day after medication, the rats were killed and haematoxylin-eosin or masson staining was used to evaluate the degree of pulmonary fibrosis. Tumour necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1) levels in alveolar macrophage culture supernatant were detected by ELISA. The mRNA expression of TNF-α and TGF-ß1 in alveolar macrophage was observed by RT-PCR. KEY FINDINGS: Lung histopathological examination showed TAL could ameliorate the structure of the lung and alleviate fibrogenesis. At the same time, TAL (150 or 450 mg/kg dose group) could reduce the expression of TNF-α and TGF-ß1 in alveolar macrophage of rats with pulmonary fibrosis at either the protein or mRNA level. CONCLUSIONS: TAL had a positive prophylactic effect on lung fibrosis, which might have been related to its reduction on TNF-α or TGF-ß1 expression in the alveolar macrophage of pulmonary fibrosis rats.
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Eriobotrya/química , Pulmão/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Fibrose Pulmonar/prevenção & controle , Triterpenos/uso terapêutico , Animais , Bleomicina , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Masculino , Extratos Vegetais/farmacologia , Folhas de Planta , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Traqueia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Alcoholic fatty liver (AFL) is a reversible condition, but it can potentiate the development of alcoholic hepatitis and even cirrhosis by increasing oxidant generation, which is one of the key pathogenic factors and could result in alcoholic liver disease (ALD). Total flavonoids from Litsea coreana (TFLC), an active component extracted from Litsea coreana leve, have been shown to have therapeutic effects on hyperlipidemia. The present study was to evaluate the protective effects of TFLC on alcoholic fatty liver (AFL) in rats, and investigate the potential mechanism. An AFL model in rats was established by intaking different doses of alcohol (concentration from 5% to 40%) over 12 weeks. Serum levels of TG, TC, LDL-C, HDL-C, TNF-α, insulin, and glucose were measured, histopathologic changes were determined, and expression of adipose differentiation-related protein (ADRP) in the liver were evaluated by Western blotting and immunohistochemistry, respectively. The results showed that treatment with TFLC resulted in decreased serum levels of TG, TC, LDL-C, TNF-α, glucose and insulin, as well as improved liver index. Morphological evaluation revealed rats in model group developed a severe steatosis, but the severities of liver steatosis were effectively ameliorated in TFLC (200 and 400 mg/kg) treated groups. Expression of hepatic ADRP were increased in model group, and suppressed in TFLC treated groups. These results suggest that TFLC had a protective effect on AFL rats; the mechanism may be involved in regulation serum lipid profiles via down-regulation of hepatic expression of ADRP in AFL rats.
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Etanol/efeitos adversos , Fígado Gorduroso Alcoólico/tratamento farmacológico , Flavonoides/uso terapêutico , Litsea/química , Fígado/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Fitoterapia , Animais , Glicemia/metabolismo , Regulação para Baixo , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Flavonoides/farmacologia , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Perilipina-2 , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVES: The study was to investigate the prevention effects and possible mechanism of Yu Ping Feng San fractioned polysaccharide (YPF-P) on CCl(4)-induced liver fibrosis in rats. METHODS: YPF-P was prepared from root of Astragalus membranaceus, rhizome of Atractylodes macrocephaia and root of Raidix saposhnikoviae, and compared with polysaccharide from root of Astragalus membranaceus (AP). Hepatic fibrosis was induced by subcutaneous injection with carbon tetrachloride twice weekly for 12 weeks in Sprague-Dawley rats. YPF-P, AP and colchicine were administered intragastrically daily to carbon tetrachloride-treated rats. Histopathological changes of the liver and hepatic stellate cells were evaluated by Masson staining and transmission electron microscopy, respectively. Markers of fibrosis were determined by radioimmunoassay, biochemistry assay and ELISA. The mRNA expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-13 (MMP-13), procollagen I and collagen III were detected by RT-PCR. KEY FINDINGS: YPF-P dose-dependently alleviated the degree of liver fibrosis and inhibited hepatic stellate cell transformation into myofibroblast-like cells, markedly reduced the elevated levels of hyaluronic acid, laminin, type IV collagen, type III procollagen, hydroxyproline and transforming growth factor beta-1, suppressed procollagen I, collagen III and TIMP-1 expression, and improved the TIMP-1/MMP-13 ratio. MMP-13 expression was only promoted moderately by YPF-P. Compared with AP, YPF-P showed more potency on most markers except laminin, type IV collagen and MMP-13 mRNA. CONCLUSIONS: YPF-P prevented the progress of rat liver fibrosis induced by carbon tetrachloride and had a more potent preventative effect. The preventative effect may be associated with the ability of YPF-P to inhibit the synthesis of matrix collagen and balance the TIMP/MMP system.
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Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática Experimental/prevenção & controle , Magnoliopsida , Polissacarídeos/uso terapêutico , Animais , Apiaceae , Astragalus propinquus , Atractylodes , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Ácido Hialurônico/metabolismo , Hidroxiprolina/metabolismo , Laminina/metabolismo , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Fitoterapia , Raízes de Plantas , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , RNA Mensageiro/metabolismo , Ratos , Rizoma , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVES: It was found that total flavonoids from Litsea coreana Levl. (TFLC), which is a traditional Chinese medicine, had a preventive effect against hepatic steatosis in our previous study. This study was designed to evaluate whether TFLC could improve liver fibrosis in rats. METHODS: The liver fibrosis model rats were treated with composite factors of high-fat emulsion (10 ml/kg) via gavage accompanied by a subcutaneous injection of low-dose CCl(4). Thirty rats were given composite factors plus TFLC (100, 200, 400 mg/kg), respectively, for 8 weeks. KEY FINDINGS: The results showed that TFLC (200 and 400 mg/kg) treatment significantly reduced the elevation of liver index (liver weight/body weight) and spleen index (spleen weight/body weight), alanine transaminase, aspartate aminotransferase, hyaluronic acid, laminin, procollagen III N-terminal peptide, procollagenase IV and hydroxyproline. In addition, TFLC treatment improved the morphologic changes of hepatic fibrosis, suppressed expression of alpha-smooth muscle actin, collagen I, transforming growth factor (TGF)-beta1 and TGFbeta receptor (TGFbetaR)1, and increased peroxisome proliferator-activated receptor-gamma expression in the liver of hepatic fibrosis rats. CONCLUSIONS: In conclusion, TFLC is able to ameliorate liver injury and protect rats from liver fibrosis. This process may be related to inhibiting the expression of transforming growth factor-beta1 and increasing the expression of peroxisome proliferator-activated receptor-gamma.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/uso terapêutico , Litsea/química , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Tetracloreto de Carbono/toxicidade , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Eletroforese em Gel de Ágar , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Immunoblotting , Fígado/enzimologia , Fígado/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/patologia , Testes de Função Hepática , Masculino , Estrutura Molecular , Tamanho do Órgão/efeitos dos fármacos , Folhas de Planta/química , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacosRESUMO
This study was designed to investigate the anti-inflammatory effect of Triterpenoic Acids from Eriobotrya japonica (Thunb.) Lindl. (TAL) on chronic bronchitis (CB) in rats. CB model was established by combination of Bacillus Calmette-Guerin (BCG, 5 mg/kg, injected through the caudal vein) and lipopolysaccharide (LPS, 1 g/L, injected through endotracheal intubation). Rats with CB model were treated with TAL (50, 150 and 450 mg/kg) for 3 weeks. The leukocytes in bronchoalveolar lavage fluid (BALF) were counted after Wright staining, the levels of cytokine tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-8, and IL-10 in the supernatants of lung homogenate were assessed by enzyme-linked immunosorbent assay (ELISA), and the protein expression of nuclear factor kappaB (NF-kappaB) and intercellular adhesion molecule-1 (ICAM-1) on bronchial epithelium were tested by immunohistochemical staining. As compared to the normal and sham groups, the total number of leukocyte, the differential counts of neutrophils and alveolar macrophage (AM) in BALF, the levels of TNF-alpha and IL-8 in the supernatants of lung homogenate, and the expression of NF-kappaB and ICAM-1 on bronchial epithelium in CB rats were significantly increased, while the level of IL-10 was decreased. TAL (50, 150 and 450 mg/kg) attenuated these alterations in model CB rats, which indicates that TAL has anti-inflammatory effect in the rats with CB.
Assuntos
Anti-Inflamatórios/uso terapêutico , Bronquite/tratamento farmacológico , Eriobotrya/química , Extratos Vegetais/uso terapêutico , Triterpenos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Bronquite/metabolismo , Líquido da Lavagem Broncoalveolar , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Triterpenos/farmacologiaRESUMO
OBJECTIVE: To study the effects and its mechanisms of total flavonoids of Litsea coreana (TFLC) on insulin resistance (IR) in rats with hyperlipidemia. METHODS: The rats were fed with high fat emulsion to make IR models. The effects of TFLC on the state of impaired glucose tolerance (IGT), fasting serum glucose (FSG), fasting serum insulin (FINS), fasting serum lipids (TC, TG, LDL-C, HDL-C), free fatty acid (FFA) and Leptin were observed,and the index of insulin sensitivity (ISI) was calculated. RESULTS: TFLC could significantly improve the state of IGT and depress the level of FSG, FINS, TC, TG, LDL-C, FFA and leptin of model rats, which could also increase the content of HDL-C and ISI significantly and enhance the sensitivity of insulin. CONCLUSION: TFLC has obvious effects on increasing insulin sensitivity and improving the insulin resistance in rats with hyperlipidemia,which may contribute to the regulating effects on the disturbance of lipid metabolism and the decrease of leptin level.
Assuntos
Flavonoides/farmacologia , Hiperlipidemias/tratamento farmacológico , Resistência à Insulina , Litsea/química , Animais , Glicemia/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/uso terapêutico , Teste de Tolerância a Glucose , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Insulina/sangue , Leptina/sangue , Lipídeos/sangue , Masculino , Plantas Medicinais/química , Ratos , Ratos Sprague-DawleyRESUMO
AIM OF THE STUDY: To evaluate the protective effects of total flavonoids of Litsea Coreana leve (TFLC) on rat high fat diet-induced hepatic steatosis model. MATERIALS AND METHODS: Rats were given either a high fat diet alone or the same diet plus TFLC for 4 weeks. RESULTS: TFLC improved liver histology with reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as decreased the over accumulation lipids in serum and liver. TFLC increased serum levels of leptin and insulin, while decreased serum TNFalpha level in high fat diet fed rat. Furthermore, TFLC was found increased the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in high fat diet fed rat liver. These benefits were associated with increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA) in high fat diet fed rat liver. CONCLUSIONS: TFLC exerts protective effects against hepatic steatosis in rats fed with high fat diet possibly through its antioxidant actions, improving the adipocytokines release and increasing the expression of PPARalpha.
Assuntos
Antioxidantes/uso terapêutico , Fígado Gorduroso/prevenção & controle , Flavonoides/uso terapêutico , Litsea/química , Fitoterapia , Alanina Transaminase/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado Gorduroso/enzimologia , Fígado Gorduroso/etiologia , Flavonoides/farmacologia , Insulina/sangue , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: To investigate the therapeutic effects and mechanisms of total flavonoids of Turpinia Arguta Seen (TFS) on adjuvant arthritis in rats. METHODS: The model of adjuvant arthritis was induced by injection of Freund's Complete Adjuvant (FCA). Secondary paw swelling of AA rats was measured with volume meter and polyarthritis index were scored. The splenocyte proliferation, (interleukin-1) IL-1 and interleukin-2 (IL-2) production were assayed by cell proliferation assay. Prostaglandin E(2) (PGE(2)) production was determined by radioimmunoassay. RESULTS: TFS (80, 160, 320 mg/kg, i.g.) could significantly inhibit secondary inflammatory reaction (secondary swelling, multiple arthritis, pathologic change of ankle arthritis) in AA rats. The results in vivo showed that the low response of splenocytes to concanavalin A (Con A) and lipopolysaccharide (LPS) and the decreased IL-2 synthesis were restored in AA rats treated with TFS (160, 320 mg/kg, i.g.), while the elevated IL-1 and PGE(2) released from peritoneal macrophages (PMphi) were also reduced. CONCLUSION: TFS has significant therapeutic effect on AA rats, which might be relate to its immunoregulatory actions.
Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/uso terapêutico , Animais , Dinoprostona/biossíntese , Flavonoides/farmacologia , Interleucina-1/biossíntese , Interleucina-2/biossíntese , Masculino , Medicina Tradicional Chinesa , Ratos , Ratos Sprague-DawleyRESUMO
The study was to evaluate the effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf (TAL) on expression of antioxidative mediators by alveolar macrophages (AM) in rats with chronic bronchitis (CB), CB was induced by endotracheal instillation of lipopolysaccharedes (LPS) followed by Bacillus Calmette-Guérin (BCG) injection through caudal vein 1 week later. Treatment groups received TAL at there different doses (50, 150, or 450 mg/kg daily, intragastrically (i.g.)) or dexamethasone (1.2 mg/kg daily i.g.) for 2 weeks, 7 days after LPS injection. AM were then isolated and incubated. Superoxide dismutase (SOD) and methylene dianiline (MDA) levels in AM were measured by commercial kits; meanwhile, heme oxygenase-1 (HO-1) expression and its mRNA expression in AM were detected by immunocytochemistry and RT-PCR, respectively. HO-1 activity of the lung was also detected by a specific biochemistry reaction. The levels of MDA and HO-1 expressed by cultured AM and the HO-1 activity in the lung of the TAL groups were significantly lower than those from the CB group without treatment (p < 0.01 and p < 0.05, respectively), while the SOD levels were increased in a dose-dependent manner by TAL treatment. These results suggest that TAL inhibits HO-1 expression and MDA production and up-regulates SOD expression in AM from CB rats, which might be one of molecular mechanisms of its anti-inflammatory effects in CB rats.