RESUMEN
Osteoporosis is a common disease that increases the risk of fractures due to decreased bone density and weakens the bone microstructure. Preventing and diagnosing osteoporosis using the available drugs can be a costly affair with possible side effects. Therefore, natural product-derived therapeutics are promising alternatives. Our study demonstrated that the oat seedlings' extract (OSE) inhibited the receptor activator of the nuclear factor κB ligand (RANKL)-induced osteoclastogenesis from the bone marrow-derived macrophages (BMMs). The OSE treatment significantly attenuated the RANKL-mediated induction of the tartrate-resistant acid phosphatase (TRAP) activity as well as the number of TRAP-positive (TRAP+) multinucleated cells (MNCs) counted through the TRAP staining in a dose-dependent manner. It was also confirmed that the OSE suppressed the formation of the TRAP + MNCs in the early stage of differentiation and not in the middle and late stages. The results of the real-time quantitative polymerase chain reaction (qPCR) and the western blotting showed that the OSE dramatically inhibited the mRNA and protein expressions of the osteoclastogenesis-mediated transcription factors such as the c-Fos and the nuclear factor-activated T cells c1 (NFATc1). In addition, the OSE strongly attenuated the mRNA induction of the c-Fos/NFATc1-dependent molecules such as the TRAP, the osteoclast-associatedimmunoglobulin-like receptor (OSCAR), the dendritic cell-specific transmembrane protein (DC-STAMP), and the cathepsin K. These results suggest that the naturally derived OSE may be useful for preventing bone diseases.
RESUMEN
Policosanols is a health promoting aliphatic alcohol known as lipid-lowing agent. To enable maximising the functional properties of wheat, this research investigates the policosanol profiles and adenosine 5'-monophosphate-activated protein kinase (AMPK) activation potential of Korean wheat seedlings according to cultivars and growth times. GC-MS revealed six policosanols that differed markedly in content between 17 cultivars, especially, octacosanol (8) showed the most predominant component (49-83%), varying significantly in average concentrations with growth times as 361.4 (3 days) â 613.0 (6 days) â 203.1 (9 days) â 196.5 (12 days) â 50.9 mg/100 g (19 days). The highest average policosanol (738.7 mg/100 g) exhibited after 6 days, while the lowest was 104.4 mg/100 g on 19 days. Moreover, the wheat cultivars including Shinmichal 1, Anbaek, Namhae, and Joah at 6 days may be recommended as potential sources because of high policosanols (921.7-990.6 mg/100 g). Western blot analysis revealed markedly higher AMPK activation in cells treated with the hexane extracts (150-370% at 100 µg/ml) and octacosanol (8) possessed potent AMPK activator (control; 100 â 280% at 200 µg/ml). It is confirmed that the AMPK activation by wheat seedlings are positively related to the highest policosanol content at the 6 days of growth time, independent of the cultivar. Our results may be contributed to enhance the wheat value regarding development of new cultivars and functional foods.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Alcoholes Grasos/análisis , Extractos Vegetales/química , Triticum/química , Activación Enzimática , Cromatografía de Gases y Espectrometría de Masas , Hexanos , Plantones/química , Plantones/enzimología , Plantones/crecimiento & desarrollo , Triticum/enzimología , Triticum/crecimiento & desarrolloRESUMEN
Pancreatic cancer (PC) is one of the most aggressive malignancies in the world. Gemcitabine (Gem), a nucleoside pyrimidine analogue, is a first-line chemotherapeutic drug for PC, but the tumor response rate of Gem is very low and resistance to Gem has emerged as a major problem in the treatment of PC. Oat bran, used as animal and human food, has been found to be beneficial to health. In this study, effects of oat bran ethanol extract (OBE) on PC cells and Gem-resistant PC cells were investigated in vitro. OBE decreased cell survival and colony forming ability of PC cells, without any cytotoxicity on the normal pancreatic cells. Flow cytometry analysis and TUNEL assay showed that the OBE reduced G1/S phase transition and induced death in PC cells through AMPK activation and downregulation of JNK. Additionally, OBE could overcome Gem resistance through reduction in RRM1/2 expression and showed synergistic effect by combinatorial treatment with Gem on Gem-resistant PC cells. Additionally, LC-MS data showed that avenacoside A was a component of OBE. Thus, this study elucidated the anti-proliferative effect of OBE and synergistic effect of OBE with Gem on PC cells and Gem-resistant cells.
Asunto(s)
Avena/química , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos/efectos de los fármacos , Etanol/química , Neoplasias Pancreáticas/tratamiento farmacológico , Extractos Vegetales/farmacología , Línea Celular Tumoral , Desoxicitidina/farmacología , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Extractos Vegetales/química , GemcitabinaRESUMEN
The number of patients with bone metabolic disorders including osteoporosis is increasing worldwide. These disorders often facilitate bone fractures, which seriously impact the patient's quality of life and could lead to further health complications. Bone homeostasis is tightly regulated to balance bone resorption and formation. However, many anti-osteoporotic agents are broadly categorized as either bone forming or anti-resorptive, and their therapeutic use is often limited due to unwanted side effects. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aims to clarify the bone protecting effects of oat bran water extract (OBWE) and its mode of action. OBWE inhibited RANKL (receptor activator of nuclear factor-κB ligand)-induced osteoclast differentiation by blocking c-Fos/NFATc1 through the alteration of I-κB. Furthermore, we found that OBWE enhanced BMP-2-stimulated osteoblast differentiation by the induction of Runx2 via Smad signaling molecules. In addition, the anti-osteoporotic activity of OBWE was also evaluated using an in vivo model. OBWE significantly restored ovariectomy-induced bone loss. These in vitro and in vivo results showed that OBWE has the potential to prevent and treat bone metabolic disorders including osteoporosis.
Asunto(s)
Avena/química , Diferenciación Celular/efectos de los fármacos , Fibras de la Dieta , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Extractos Vegetales/farmacología , Agua/química , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Osteoblastos/citología , Osteoclastos/citología , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacosRESUMEN
The number of patients with osteoporosis is increasing worldwide, and a decrease in bone mass is a main risk factor for fracture. The prevention of bone loss is critical for improving the quality of life for patients. However, the long-term use of antiosteoporotic agents is limited due to their side effects. Barley has been traditionally ingested for thousands of years as a safe, natural food with pharmaceutical properties, and its seedling can enhance the biological activity of the medicinal components found in food. This study aimed to clarify the antiresorptive activity of barley seedling and its mode of action. Barley seedling extracts (BSE) dose-dependently inhibited RANKL-induced osteoclast differentiation with alteration of IκB degradation, c-Fos, and NFATc1 molecules in the early-to-middle stages of osteoclastogenesis. In the late phase of osteoclastogenesis, BSE also prevented DC-STAMP and cathepsin K, which are required for cell fusion and bone degradation, such as osteoclast function. In conclusion, barley seedling from natural foods may provide long-term safety and be useful for the prevention or treatment of osteoclast-mediated bone metabolic diseases, including osteoporosis.
RESUMEN
Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production.