RESUMEN
This study aimed to examine the chemical and anti-aging properties of chicken essence (CE) prepared with Sesamum indicum, Angelica acutiloba, and Zingiber officinale (HCE). HCE was analyzed for nutritional and phytochemical composition, and its anti-aging effects were investigated on the D-galactose (Gal)-induced aging mice. Results showed that HCE possessed significantly higher calories and contents of valine and total phenols than CE; it also contained significant amounts of ferulic acid, sesamin, and sesamolin. HCE significantly decreased MDA and NO levels in serum and liver and increased liver GSH levels in the D-Gal-induced mice. HCE greatly enhanced SOD and CAT activities in serum and liver, and liver GPx activity, as well as upregulating SIRT1 expression and downregulating TNF-α, IL-1ß, IL-6, iNOS, Cox-2, and MCP-1 expression in liver tissues. This study demonstrates that HCE was effective in suppressing the aging process through enhancing antioxidant and anti-inflammatory activities and modulating the aging-related gene expression.
RESUMEN
Adlay (Coix lacryma-jobi var. ma-yuen (Rom. Caill.) Stapf) seeds are edible crop classified as Traditional Chinese Medicine (TCM). Adlay bran (AB) is one of the wastes generated during adlay refining processes. In this work, supercritical fluid extract of AB (AB-SCF) was investigated to reveal its lipid regulating potential and decode its bifunctional ingredients. AB-SCF×0.5 (30.84 mg/kg/body weight), AB-SCF×1 (61.67 mg/kg/BW), AB-SCF×5 (308.35 mg/kg/BW) and AB-SCF×10 (616.70 mg/kg/BW) were administrated to high fat-diet (HFD) induced hyperglycemic hamsters for 8 weeks. The results indicates that AB-SCF displays a prevention of dramatic body weight gains, lower levels of serum TG, TC, LDL-C and higher in HDL-C, amelioration of cardiovascular risk, alleviation of hepatic TG, TC and lipid peroxidation, and enhancement on cholesterol metabolism with higher bile acid excretion. Investigations on energy metabolic mechanism demonstrates that the hyperlipidemia mitigating capacities of AB-SCF are up-regulated on lipoprotein lipase, AMPK, p-AMPK and down-regulated at fatty acid synthase. Major bio-functional lipid compositions are identified as linoleic acid (28.59%) and oleic acid (56.95%). Non-lipid chemical and active markers are confirmed as 3-O-(trans-4-feruloyl)-ß-sitostanol (1463.42 ppm), 3-O-(cis-4-feruloyl)-ß-sitostanol (162.60 ppm), and ß-sitosterol (4117.72 ppm). These compositions might synergistically responsible for the mentioned activities and can be regarded as analytical targets in quality control. AB-SCF may be considered as a promising complementary supplement, and developed as a functional food or new botanical drug in the future.
RESUMEN
Objective: Harmonizing formulas are associated with beneficial renal outcomes in chronic kidney disease (CKD), but the therapeutic mechanisms are unclear. The study aims to explore the associations of intentions and independent factors with harmonizing formulas prescriptions for patients with CKD. Methods: We conducted a population-based cross-sectional study to explore factors associated with harmonizing formulas prescription. Patients who had been prescribed harmonizing formulas after CKD diagnosis was defined as the using harmonizing formulas group. Disease diagnoses when having harmonizing formula prescriptions and patient characteristics related to these prescriptions were collected. Results: In total, 24,971 patients were enrolled in this analysis, and 5,237 (21%) patients were prescribed harmonizing formulas after CKD diagnosis. The three most frequent systematic diseases and related health problems for which harmonizing formula prescriptions were issued in CKD were symptoms, signs, and ill-defined conditions (24.5%), diseases of the digestive system (20.67%), and diseases of the musculoskeletal system (12.9%). Higher likelihoods of harmonizing formula prescriptions were associated with young age (adjusted odds ratio: 0.98, 95% confidence interval: 0.97-0.98), female sex (1.79, 1.68-1.91), no diabetes (1.20, 1.06-1.36), no hypertension (1.38, 1.27-1.50), no cerebrovascular disease (1.34, 1.14-1.56), less disease severity (0.85, 0.83-0.88), using nonsteroidal anti-inflammatory drugs (NSAIDs) (1.65, 1.54-1.78), and using analgesic drugs other than NSAIDs (1.47, 1.35-1.59). Conclusion: Harmonizing formulas are commonly used for treating symptoms of the digestive and musculoskeletal systems in CKD cases. Further research on harmonizing formula effectiveness with regard to particular characteristics of CKD patients is warranted.
RESUMEN
Dengue virus (DENV) is a mosquito-borne pathogen that is becoming a serious global threat, owing to its rising incidence in inter-tropical regions that yield over 50 million annual infections. There are currently no approved antiviral agents for the management of dengue, and recent shortcomings in its immunization called for immediate action to develop effective drugs with prophylactic ability to better manage its infection. In an attempt to discover novel antiviral sources, we identified the medicinal herb Polygonum cuspidatum (PC) as a bioactive botanical material against DENV infectivity. Specifically, the methanolic extract from PC rhizomes (PCME) potently inhibited DENV infection without causing significant cytotoxicity. Further examination on the viral life cycle demonstrated that PCME particularly targeted the initial stages of DENV infection, while pre- and post-infection treatments had no effect. More importantly, the PCME could efficiently inactivate DENV free virus particles and block the viral attachment and entry/fusion events without apparently influencing viral replication, egress, and cell-to-cell spread. The antiviral effect of PCME was also recapitulated in infection analysis using DENV pseudoparticles displaying viral structural proteins that mediate DENV particle entry. Besides, PCME treatment also inhibited direct DENV entry into several cell types relevant to its infection and reduced viral infectivity of other members of the Flaviviridae family, including the hepatitis C virus (HCV) and Zika virus (ZIKV). Due to its potency against DENV entry, we suggest that the phytobioactive extract from PC is an excellent starting point as an antiviral source material for further development of therapeutic strategies in the prophylactic management of DENV infection.
Asunto(s)
Antivirales/farmacología , Virus del Dengue/efectos de los fármacos , Dengue/tratamiento farmacológico , Fallopia japonica/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Internalización del Virus/efectos de los fármacos , Animales , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Hepacivirus/efectos de los fármacos , Humanos , Fitoquímicos/química , Plantas Medicinales/química , Células Vero , Acoplamiento Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: Despite the advent of direct-acting antivirals (DAAs), HCV remains an important public health problem globally. There is at present no effective vaccine against the virus, and the DAAs in current use cannot prevent de novo infection, including in liver transplant setting wherein donor livers inevitably become re-infected. Developing inhibitors to HCV entry using nature-derived small molecules may help to expand/complement the current treatment options. PURPOSE: In this study, we explored the effect of the plant alkaloid berberine (BBR) on HCV early viral entry. METHODS: Cell culture-derived HCV (HCVcc), viral pseudoparticles bearing HCV glycoproteins (HCVpp), and entry-related assays were employed to assess BBR's bioactivity. Molecular docking was used to predict BBR-HCV glycoproteins interaction, and the compound's antiviral activity was confirmed against HCVcc infection of primary human hepatocytes (PHHs). RESULTS: BBR specifically impeded HCVcc attachment and entry/fusion steps without inactivating the free virus particles or affecting the expression of host cell entry factors and post-entry viral replication. BBR also effectively inhibited infection by viral pseudoparticles expressing HCV E1/E2 glycoproteins and molecular docking analysis pointed at potential interaction with HCV E2. Finally, BBR could suppress HCVcc infection of PHHs. CONCLUSIONS: We identified BBR as a potent HCV entry inhibitor, which merits further evaluation particularly for use in transplant setting against graft re-infection by HCV.
Asunto(s)
Antivirales/farmacología , Berberina/farmacología , Hepacivirus/efectos de los fármacos , Proteínas del Envoltorio Viral/metabolismo , Antivirales/química , Berberina/química , Células Cultivadas , Hepacivirus/patogenicidad , Hepacivirus/fisiología , Hepatitis C/tratamiento farmacológico , Hepatocitos/efectos de los fármacos , Hepatocitos/virología , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Terapia Molecular Dirigida , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia that can lead to long-term complications including heart diseases, stroke, retinopathy, and renal failure. Treatment strategies include stimulating glucose uptake and controlling blood glucose level. Bofutsushosan (BOF) and Daisaikoto (DAI) are two herb-based kampo medicines that have been demonstrated to improve metabolism-associated disorders including obesity, hyperlipidemia, and nonalcoholic fatty liver. Given their bioactivities against metabolic syndromes, we explored in this study the effect of BOF and DAI extracts on glucose absorption and used them as source to identify phytochemical stimulator of glucose absorption. Glucose uptake and mechanistic studies were evaluated in differentiated C2C12 skeletal muscle cells, and HPLC analysis was used to determine the molecular bioactive constituents. Our results indicated that the ethanolic extracts of BOF and DAI (BOFEE and DAIEE, respectively) enhanced the glucose uptake ratio in the differentiated C2C12 cells, and further analysis identified the flavone baicalin as a major constituent capable of efficiently stimulating glucose absorption. Mechanistic studies revealed that the effect from baicalin involved the activation of IRS-1 and GLUT-4, and implicated the AMPK, PI3K/Akt, and MAPK/ERK signaling cascades. Due to its potency, we suggest that baicalin merit further evaluation as a potential candidate anti-hyperglycemic agent for the treatment and management of T2DM.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Glucosa/metabolismo , Hipoglucemiantes/farmacología , Insulina/metabolismo , Animales , Línea Celular , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Hipoglucemiantes/química , Ratones , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Hepatitis C Virus (HCV) remains an important public health threat with approximately 170 million carriers worldwide who are at risk of developing hepatitis C-associated end-stage liver diseases. Despite improvement of HCV treatment using the novel direct-acting antivirals (DAAs) targeting viral replication, there is a lack of prophylactic measures for protection against HCV infection. Identifying novel antivirals such as those that target viral entry could help broaden the therapeutic arsenal against HCV. Herein, we investigated the anti-HCV activity of the methanolic extract from Rhizoma coptidis (RC), a widely used traditional Chinese medicine documented by the WHO and experimentally reported to possess several pharmacological functions including antiviral effects. Using the cell culture-derived HCV system, we demonstrated that RC dose-dependently inhibited HCV infection of Huh-7.5 cells at non-cytotoxic concentrations. In particular, RC blocked HCV attachment and entry/fusion into the host cells without exerting any significant effect on the cell-free viral particles or modulating key host cell entry factors to HCV. Moreover, RC robustly suppressed HCV pseudoparticles infection of Huh-7.5 cells and impeded infection by several HCV genotypes. Collectively, our results identified RC as a potent antagonist to HCV entry with potential pan-genotypic properties, which deserves further evaluation for use as an anti-HCV agent.
Asunto(s)
Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Hepacivirus/fisiología , Hepatitis C/virología , Extractos Vegetales/farmacología , Ranunculaceae/química , Internalización del Virus/efectos de los fármacos , Antivirales/química , Línea Celular , Genotipo , Humanos , Extractos Vegetales/química , Replicación Viral/efectos de los fármacosRESUMEN
Artemisia capillaris (A. capillaris) is a common herbal drug used for thousands years in ancient China. A. capillaris has been empirically used to manage hand-foot-mouth disease (HFMD), which is commonly caused by enterovirus 71 (EV71). EV71 can cause meningoencephalitis with mortality and neurologic sequelae without effective management. It is presently unknown whether A. capillaris is effective against EV71 infection. To test the hypothesis that it could protect cells from EV71-induced injury, a hot water extract of A. capillaris was tested in human foreskin fibroblast cells (CCFS-1/KMC) and human rhabdomyosarcoma cells (RD cells) by plaque reduction assay and flow cytometry. Inhibition of viral replication was examined by reverse quantitative RT-PCR (qRT-PCR). Its effect on translations of viral proteins (VP0, VP1, VP2, protease 2B and 3AB), and apoptotic proteins were examined by western blot. A. capillaris was dose-dependently effective against EV71 infection in both CCFS-1/KMC cells and RD cells by inhibiting viral internalization. However, A. capillaris was minimally effective on viral attachment, VP2 translation, and inhibition of virus-induced apoptosis. Further isolation of effective molecules is needed. In conclusion, A. capillaris has anti-EV71 activity mainly by inhibiting viral internalization. A. capillaris would be better to manage EV71 infection in combination with other agents.
Asunto(s)
Antivirales/farmacología , Artemisia/química , Enterovirus Humano A/efectos de los fármacos , Regulación Viral de la Expresión Génica , Extractos Vegetales/farmacología , Internalización del Virus/efectos de los fármacos , Antivirales/aislamiento & purificación , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Enterovirus Humano A/genética , Enterovirus Humano A/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibroblastos/virología , Prepucio/citología , Humanos , Masculino , Extractos Vegetales/aislamiento & purificación , Biosíntesis de Proteínas/efectos de los fármacos , Proteínas Virales/antagonistas & inhibidores , Proteínas Virales/genética , Proteínas Virales/metabolismo , Acoplamiento Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Enterovirus 71 (EV71) infection can cause airway symptoms, brainstem encephalitis, neurogenic shock, and neurogenic pulmonary edema with high morbidity and mortality. There is no proven therapeutic modality. Flos Farfarae is the dried flower bud of Tussilago farfara L. that has been used to manage airway illnesses for thousands of years. It has neuro-protective activity and has been used to manage neuro-inflammatory diseases. However, it is unknown whether Flos Farfarae has activity against EV71-induced neuropathy. The current study used both human foreskin fibroblast (CCFS-1/KMC) and human rhabdomyosarcoma (RD) cell lines to test the hypothesis that a hot water extract of Flos Farfarae could effectively inhibit EV71 infection. The authenticity of Flos Farfarae was confirmed by HPLC-UV fingerprint. Through plaque reduction assays and flow cytometry, Flos Farfarae was found to inhibit EV71 infection ([Formula: see text]). Inhibition of viral replication and protein expression were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR), and western blot, respectively. The estimated IC[Formula: see text]s were 106.3[Formula: see text][Formula: see text]g/mL in CCFS-1/KMC, and 15.0[Formula: see text][Formula: see text]g/mL in RD cells. Therefore, Flos Farfarae could be beneficial to inhibit EV71 infection by preventing viral replication and structural protein expression.
Asunto(s)
Enterovirus Humano A/genética , Enterovirus Humano A/fisiología , Fibroblastos/virología , Expresión Génica/efectos de los fármacos , Fármacos Neuroprotectores , Extractos Vegetales/farmacología , Tussilago , Proteínas Estructurales Virales/genética , Proteínas Estructurales Virales/metabolismo , Replicación Viral/efectos de los fármacos , Línea Celular Tumoral , Depresión Química , Relación Dosis-Respuesta a Droga , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/tratamiento farmacológico , Prepucio/citología , Células Hep G2 , Humanos , Masculino , Extractos Vegetales/uso terapéuticoRESUMEN
Without a vaccine, hepatitis C virus (HCV) remains a global medical and socio-economic burden, predisposing about 170 million carriers worldwide to end-stage liver diseases including cirrhosis and hepatocellular carcinoma. Although the recently developed direct-acting antivirals (DAAs) have revolutionized hepatitis C treatment, most of them are unsuitable for monotherapy due to risks of resistance, thus necessitating combination with interferon (IFN)-alpha, ribavirin, or additional DAAs. More importantly, the high cost associated with the DAAs restricts their accessibility to most parts of the world. Developing novel cost-effective anti-HCV therapeutics may help expand the scope of antivirals and treatment strategies against hepatitis C. Herein, we applied an activity-based and fraction-guided analysis of extracts from the medicinal plant Phyllanthus urinaria (P. urinaria), which yielded fraction 13 (F13) as possessing the most potent inhibitory activity against early viral entry of cell-culture HCV infection. Chemical analysis (silica gel chromatography followed by ESI LC-MS plus (1)H and (13)C NMR) of F13 identified loliolide (LOD), a monoterpenoid lactone, as a novel inhibitor of HCV entry. Specifically, LOD could efficiently inactivate HCV free virus particles, abrogate viral attachment, and impede viral entry/fusion, with minimal effect on viral replication/translation, particle production, and induction of type I IFN host antiviral immune response. ELISA-based binding analysis confirmed the monoterpenoid's ability in efficiently blocking HCV particle attachment to the host cell surface. Furthermore, LOD could inhibit infection by several genotypic strains of HCV. This is the first report characterizing P. urinaria and its bioactive compound LOD as potent HCV entry inhibitors, which merit further evaluation for development as candidate antiviral agents against hepatitis C.
Asunto(s)
Antivirales/farmacología , Benzofuranos/farmacología , Hepacivirus/efectos de los fármacos , Hepacivirus/fisiología , Phyllanthus/química , Extractos Vegetales/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Línea Celular , Células Cultivadas , Fraccionamiento Químico , Relación Dosis-Respuesta a Droga , Genotipo , Humanos , Concentración 50 Inhibidora , Extractos Vegetales/química , Ensamble de Virus/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Replicación ViralRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Gan-Lu-Siao-Du-yin (GLSDY) is a prescription of traditional Chinese medicine. GLSDY contains 11 ingredients and is commonly used for endemic diseases. Enterovirus 71 (EV71) is an endemic disease that can cause meningoencephalitis with mortality and neurologic sequelae without any effective management. It is unknown whether GLSDY is effective against EV71 infection. AIM OF THE STUDY: To test the hypothesis that GLSDY can protect cell from EV71-induced injury. MATERIALS AND METHODS: Effects of a hot water extract of GLSDY on EV71 were tested in human foreskin fibroblast cells (CCFS-1/KMC) and human rhabdomyosarcoma cells (RD cells) by plaque reduction assay and flow cytometry respectively. Inhibition of viral replication was further examined by reverse quantitative RT-PCR (qRT-PCR). Its effect on viral protein translation and virus-induced apoptosis were examined by western blot. RESULTS: GLSDY was dose-dependently effective against EV71 infection (p<0.0001) in both CCFS-1/KMC cells and RD cells. GLSDY was highly effective when supplemented after viral inoculation (P<0.0001) with an IC50 of 8.7µg/mL. GLSDY inhibited viral RNA replication (P<0.0001), formation of viral structural proteins (VP0, VP1, VP2 and VP3) and non-structural proteins (protease 2B and 3AB). Furthermore, 300µg/mL GLSDY is effective to inhibit virus-induced apoptosis possibly through direct inhibition of caspase-8 and indirectly by inhibition of Bax. CONCLUSIONS: GLSDY is cheap and readily available to manage EV71 infection by inhibiting viral replication, viral protein formations, and EV71-induced apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Enterovirus Humano A/efectos de los fármacos , Fibroblastos/virología , Rabdomiosarcoma/virología , Replicación Viral/efectos de los fármacos , Línea Celular Tumoral , Humanos , Análisis de Matrices TisularesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense is a traditional Chinese medicinal herb which has been used to treat various inflammatory and infectious diseases, while Bupleurum kaoi is an endemic plant in Taiwan. We determined whether B. chinense and B. kaoi and their biologically active saikosaponin compounds possess anti-melanoma activity. In addition, we developed a novel saikosaponin-d nanoparticle system to improve its solubility, and evaluated its antiproliferative effects and molecular mechanisms in melanoma cells. MATERIALS AND METHODS: Ethanolic extracts from B. chinense and B. kaoi were prepared, and their saikosaponin contents were determined by high performance liquid chromatography analysis. Saikosaponin-d nanoparticles were synthesized, and their physicochemical properties were evaluated by particle size analyzer, transmission electron microscopy, differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy. Human A375.S2 melanoma cells were cultured, and cell viability determined by the MTT assay. Apoptosis was evaluated by determination of mitochondrial membrane potential, and signal transduction pathways investigated by Western blotting. RESULTS: Ethanolic extracts from B. kaoi showed more potent antiproliferative effect on human A375.S2 melanoma cells compared to B. chinense. The saikosaponin-a, -c and -d contents were higher in B. kaoi compared to B. chinense. Saikosaponin-d was the most potent compound in terms of anti-melanoma activity, and saikosaponin-d nanoparticles exhibited increased water solubility due to lowered particle size, amorphous transformation and intermolecular hydrogen bond formation with the excipient. Furthermore, saikosaponin-d nanoparticles showed enhanced antiproliferative activity against melanoma cells, and induced apoptosis through the mitochondrial pathway. The anti-melanoma activity was mediated by phosphorylation of JNK and p38, phosphorylation of p53, increased level of cytochrome c, and activation of caspase 9. CONCLUSIONS: B. kaoi contains higher saikosaponin content and shows greater anti-melanoma activity than B. chinense. Saikosaponin-d nanoparticles have improved solubility, and may have potential use in the future as a form of treatment for melanoma.
Asunto(s)
Bupleurum/química , Medicamentos Herbarios Chinos/farmacología , Melanoma/patología , Nanopartículas/química , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melanoma/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Nanopartículas/ultraestructura , Ácido Oleanólico/análisis , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Tamaño de la Partícula , Raíces de Plantas/química , Saponinas/análisis , Saponinas/química , SolubilidadRESUMEN
Enterovirus 71 (EV71) can cause central nervous system infections with mortality and neurologic sequelae. At present, there is no effective therapeutic modality for EV71 infection. The infection is more common in families with poor socioeconomic status. Therefore, finding a readily available, cost-effective therapeutic modality would be very helpful to these socioeconomically disadvantaged families. Yakammaoto is a cheap and readily available traditional prescription that is proven to have antiviral activity against coxsackievirus B4 (CVB4). CVB4 and EV71 are enteroviruses. In this study, we evaluated the antiviral activity of hot water extract of yakammaoto against EV71. The results of plaque reduction assay and flow cytometry demonstrated that yakammaoto dose dependently inhibited EV71 infection. In addition, reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR results showed that yakammaoto reduced viral replication. Western blotting analysis showed that yakammaoto can inhibit viral protein production. Thus, our results suggest that yakammaoto should be considered to manage EV71 infection in the future.
Asunto(s)
Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Enterovirus Humano A/fisiología , Evaluación Preclínica de Medicamentos , Enterovirus Humano A/efectos de los fármacos , Genes Virales , Células Hep G2 , Humanos , Biosíntesis de Proteínas , Proteínas Estructurales Virales/genética , Proteínas Estructurales Virales/metabolismo , Acoplamiento Viral , Internalización del Virus , Replicación Viral/efectos de los fármacosRESUMEN
For centuries, natural plant extracts have played an important role in traditional medicine for curing and preventing diseases. Studies have revealed that Artocarpus communis possess various bioactivities, such as anti-inflammation, anti-oxidant, and anticancer activities. A. communis offers economic value as a source of edible fruit, yields timber, and is widely used in folk medicines. However, little is known about its molecular mechanisms of anticancer activity. Here, we demonstrate the antiproliferative activity of A. communis methanol extract (AM) and its dichloromethane fraction (AD) in two human hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay showed the long-term inhibitory effect of both extracts on cell growth. DNA laddering and immunoblotting analyses revealed that both extracts did not induce apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated different cell cycle distribution compared to UV-treated cells, which presented apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining revealed that AM and AD triggered autophagosome accumulation. Immunoblotting showed a significant expression of autophagy-related proteins, which indicated the autophagic cell death (ACD) of hepatoma cell lines. This study therefore demonstrates that A. communis AM and its dichloromethane fraction can induce ACD in HCC cells and elucidates the potential of A. communis extracts for development as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating cancer cell death.
Asunto(s)
Antineoplásicos Fitogénicos , Artocarpus , Autofagia/efectos de los fármacos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Células Hep G2 , Humanos , Metanol , Cloruro de Metileno , Estimulación QuímicaRESUMEN
One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1-3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 13-15, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor α and/or ß as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.
Asunto(s)
Estrógenos/farmacología , Liriope (Planta)/química , Fitoquímicos/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Cromanos/química , Cromanos/aislamiento & purificación , Cromanos/farmacología , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Estrógenos/química , Estrógenos/aislamiento & purificación , Humanos , Isocumarinas/química , Isocumarinas/aislamiento & purificación , Isocumarinas/farmacología , Células MCF-7 , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
BACKGROUND & AIMS: A vaccine against hepatitis C virus (HCV) is unavailable and cost-effective antivirals that prevent HCV infection and re-infection, such as in the transplant setting, do not exist. In a search for novel and economical prophylactic agents, we examined the antiviral activity of saikosaponins (SSa, SSb2, SSc, and SSd) from Bupleurum kaoi root (BK) as entry inhibitors against HCV infection. METHODS: Infectious HCV culture systems were used to examine the effect of saikosaponins on the complete virus life cycle (entry, RNA replication/translation, and particle production). Antiviral activity against various HCV genotypes, clinical isolates, and infection of primary human hepatocytes were also evaluated. RESULTS: BK and the saikosaponins potently inhibited HCV infection at non-cytotoxic concentrations. These natural agents targeted early steps of the viral life cycle, while leaving replication/translation, egress, and spread relatively unaffected. In particular, we identified SSb2 as an efficient inhibitor of early HCV entry, including neutralization of virus particles, preventing viral attachment, and inhibiting viral entry/fusion. Binding analysis, using soluble viral glycoproteins, demonstrated that SSb2 acted on HCV E2. Moreover, SSb2 inhibited infection by several genotypic strains and prevented binding of serum-derived HCV onto hepatoma cells. Finally, treatment with the compound blocked HCV infection of primary human hepatocytes. CONCLUSIONS: Due to its potency, SSb2 may be of value for development as an antagonist of HCV entry and could be explored as prophylactic treatment during the course of liver transplantation.
Asunto(s)
Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Hepacivirus/fisiología , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Internalización del Virus/efectos de los fármacos , Animales , Antivirales/aislamiento & purificación , Antivirales/toxicidad , Bupleurum , Línea Celular , Hepatitis C/prevención & control , Hepatocitos/efectos de los fármacos , Hepatocitos/virología , Humanos , Trasplante de Hígado , Masculino , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Ácido Oleanólico/toxicidad , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Saponinas/aislamiento & purificación , Saponinas/toxicidad , Virión/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose-dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract.
Asunto(s)
Antineoplásicos/farmacología , Artocarpus/química , Lectinas de Unión a Manosa/farmacología , Extractos Vegetales/farmacología , Lectinas de Plantas/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Células Hep G2 , Humanos , Lectinas de Unión a Manosa/análisis , Extractos Vegetales/química , Lectinas de Plantas/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Yakammaoto is a prescription of traditional Chinese medicine (TCM) containing nine ingredients, including Ephedra sinica, Pinellia ternate, Zingiber officinale, Tussilago farfara, Aster tataricus, Ziziphus jujube, Belamcanda chinensis, Asarum sieboldii, and Schisandra chinensis. Yakammaoto has been used against flu-like symptoms for more than two thousand years in China and Japan. Coxsackievirus B4 (CVB4) causes not only flu-like symptoms but life-threatening diseases, such as pneumonia, acute kidney injury, and so forth with severe morbidity and mortality. There is no effective therapeutic modality against CVB4 infection. It is unknown whether yakammaoto is effective against CVB4 infection. We tested the hypothesis that yakammaoto can effectively inhibit CVB4-induced plaque formation in human airway and renal tubular cell lines by preventing viral attachment, internalization, and replication. MATERIALS AND METHODS: The fingerprint of yakammaoto was assessed by HPLC. Effects of yakammaoto on CVB4 infection were tested by plaque reduction assay, reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA). RESULTS: Yakammaoto dose-dependently inhibited CVB4-induced plaque formation in HK-2, A549, and HEp-2 cells (p<0.0001). Yakammaoto was both effective when supplemented prior to and after viral inoculation (p<0.0001) by preventing viral attachment (p<0.0001), internalization (p<0.0001), and replication (p<0.0001). Yakammaoto could decrease NGAL secretion before cytolysis to protect against viral injury. CONCLUSIONS: Yakammaoto had antiviral activity against CVB4-induced cellular injuries in airway mucosa and renal tubular epithelia by preventing viral attachment, internalization, and replication. The current study provides a basic support of its potential use against CVB4-induced airway and concomitant renal injuries.
Asunto(s)
Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Enterovirus Humano B/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Infecciones por Coxsackievirus/tratamiento farmacológico , Enterovirus Humano B/fisiología , Humanos , Interferón beta/metabolismo , Túbulos Renales/citología , Sistema Respiratorio/citología , Factor de Necrosis Tumoral alfa/metabolismo , Acoplamiento Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: Many natural products used in preventive medicine have also been developed as cosmeceutical ingredients in skin care products, such as Scutellaria baicalensis and Gardenia jasminoides. Norartocarpetin is one of the antioxidant and antityrosinase activity compound in Artocarpus communis; however, the cytotoxicity, skin irritation and antimelanogenesis mechanisms of norartocarpetin have not been investigated yet. METHODS: In the present study, cell viability in vitro and skin irritation in vivo are used to determine the safety of norartocarpetin. The melanogenesis inhibition of norartocarpetin was determined by cellular melanin content and tyrosinase in B16F10 melanoma cell. Moreover, we examined the related-melanogenesis protein by western blot analysis for elucidating the antimelanogenesis mechanism of norartocarpin. RESULTS: The result of the present study demonstrated that norartocarpetin not only present non-cytotoxic in B16F10 and human fibroblast cells but also non-skin irritation in mice. Moreover, our result also first found that norartocarpetin downregulated phospho-cAMP response element-binding (phospho-CREB) and microphthalmia-associated transcription factor (MITF) expression, which in turn decreased both synthesis of tyrosinases (TRP-1 and TRP-2) and cellular melanin content. This process is dependent on norartocarpetin phosphorylation by mitogen-activated protein kinases such as phospho-JNK and phospho-p38, and it results in decreased melanogenesis. CONCLUSION: The present study suggests that norartocarpetin could be used as a whitening agent in medicine and/or cosmetic industry and need further clinical study.