RESUMEN
PURPOSE: In our previous study, we showed that Lycium chinense Miller fruit extract (LFE) exerted hepatoprotective effects in mice. In the current study, we examined the effect of LFE on liver enzyme levels in subjects with mild hepatic dysfunction. METHODS: A total of 90 subjects, aged 19 to 70 years old, with abnormal alanine aminotransferase (ALT) levels, were randomly placed into either an LFE (n = 45) treatment group or a placebo group (n = 45). During the 12-week clinical trial, subjects in each group received either LFE or placebo capsules, and were instructed to take four tablets per day (1760 mg/day). The primary outcome of the study was the changes of ALT and γ-glutamyltransferase (GGT) levels in each subject. The safety of LFE supplementation was assessed and adverse events were recorded. RESULTS: LFE supplementation for 12 weeks resulted in a significant reduction of ALT (P = 0.0498) and GGT (P = 0.0368) levels in comparison to the placebo. No clinically significant changes were observed in any safety parameters. CONCLUSION: These results suggest that LFE can be applied to subjects with mild hepatic dysfunction with no possible side effects. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRIS) as no. KCT0003985.
Asunto(s)
Hepatopatías , Lycium , Método Doble Ciego , Frutas , Hepatopatías/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Humanos , Adulto , Persona de Mediana Edad , AncianoRESUMEN
The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.
Asunto(s)
Suplementos Dietéticos , Memoria/efectos de los fármacos , Extractos Vegetales/farmacología , Aceite de Sésamo/farmacología , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/sangre , Péptidos beta-Amiloides/metabolismo , Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Dioxoles , Método Doble Ciego , Ingestión de Alimentos , Femenino , Furanos , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human TRAIL has been evaluated in clinical trials, however, various malignant tumors are resistant to TRAIL. Parthenolide (PT) has recently been demonstrated as a highly effective anticancer agent and has been suggested to be used for combination therapy with other anticancer agents. In this study, we investigate the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. HT-29 (TRAIL-resistant) and HCT116 (TRAIL-sensitive) cells were treated with PT and/or TRAIL. The results demonstrated that combined treatment induced apoptosis which was determined using MTT, cell cycle analysis, Annexin V assay and Hoechst 33258 staining. Interestingly, we confirmed that HCT116 cells have much higher death receptor (DR) 5 than HT-29 cells and PT upregulates DR5 protein level and surface expression in both cell lines. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, p53 cytochrome C release, and caspase cascades. These results suggest that PT sensitizes TRAIL-induced apoptosis via upregulation of DR5 and mitochondria-dependent pathway. Combination treatment using PT and TRAIL may offer an effective strategy to overcome TRAIL resistance of certain CRC cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Sesquiterpenos/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/uso terapéutico , Muerte Celular/efectos de los fármacos , Células Cultivadas , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Sinergismo Farmacológico , Células HCT116 , Células HT29 , Humanos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Parthenolide (PT), a principal active component in medicinal plants, has been used conventionally to treat migraine and inflammation. This component has recently been reported to induce apoptosis in cancer cells, through mitochondrial dysfunction. In the present study, we investigated PT-mediated cell death signaling pathway by focusing on the involvement of Bcl-2 family members in human colorectal cancer cells. We also investigated the inhibitory effect of PT on tumor growth in xenografts. Using the human colorectal cancer cell lines HT-29, SW620 and LS174T, we demonstrated that treatment of these cancer cells with PT induces apoptosis using MTT, Annexin V assay and Hoechst 33258 staining. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, cytochrome c release and caspase activation. Moreover, intraperitoneal injection of PT showed significant inhibition of tumor growth, angiogenesis in the xenograft model. These results demonstrate that PT exhibits anti-cancer activity in human colorectal cancer in vitro and in vivo. These findings may also provide a novel approach for the treatment of colorectal cancer.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Mitocondrias/patología , Sesquiterpenos/administración & dosificación , Carcinogénesis/efectos de los fármacos , Neoplasias Colorrectales/patología , Citocromos c/metabolismo , Genes bcl-2/genética , Células HT29 , Humanos , Mitocondrias/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cholangiocarcinomas are intrahepatic bile duct carcinomas that are known to have a poor prognosis. Sesquiterpene lactone parthenolide, which is the principal active component in medicinal plants, has been used to treat tumors. Parthenolide effectively induced apoptosis in all four cholangiocarcinoma cell lines in a dose-dependent manner. However, the sarcomatous SCK cells were more sensitive to parthenolide than the other adenomatous cholangiocarcinoma cells. Therefore, this study investigated whether or not the expression of p53, the Fas/Fas ligand (FasL), Bcl-2/Bcl-X(L) determines the enhanced drug susceptibility of SCK cells. The results showed that Bcl-2 family molecules, such as Bid, Bak, and Bax, are involved in the parthenolide-induced apoptosis and that the defective expression of Bcl-X(L) might contribute to the higher parthenolide sensitivity in the SCK cells than in the other adenomatous cholangiocarcinoma cells. SCK cells, which stably express Bcl-X(L), were resistant to parthenolide, whereas Bcl-X(L)-positive Choi-CK cells transfected with the antisense Bcl-X(L) showed a higher parthenolide sensitivity than the vector control cells. Molecular dissection revealed that Bcl-X(L) inhibited the translocation of Bax to the mitochondria, decreased the generation of intracellular reactive oxygen species, reduced the mitochondrial transmembrane potential (deltapsi(m)), decreased the release of cytochrome c, decreased the cleavage of poly(ADP-ribose) polymerase, and eventually inhibited apoptotic cell death. These results suggest that parthenolide effectively induces oxidative stress-mediated apoptosis, and that the susceptibility to parthenolide in cholangiocarcinoma cells might be modulated by Bcl-X(L) expression in association with Bax translocation to the mitochondria.