Alzheimer's disease (AD) is the most common form of dementia in the elderly. The number of people affected by AD is rapidly increasing. AD is characterized by cerebral atrophy, cerebral senile plaques, intraneuronal neurofibrillary tangles, and neuronal cell loss. Medical treatment of AD has a long history and differing results. We will review the effectiveness and limitations of the drugs used to treat AD.
Draper, a receptor responsible for the phagocytosis of apoptotic cells in Drosophila, possesses atypical epidermal growth factor (EGF)like sequences in the extracellular region and the two phosphorylatable motifs NPxY and YxxL in the intracellular portion. We previously suggested that Pretaporter, a ligand for Draper, binds to the EGF-like repeat and augments the tyrosine phosphorylation of Draper. In this study, we first tested the binding of Pretaporter to various parts of the extracellular region of Draper and found that a single EGF-like sequence is sufficient for the binding. We next determined roles of the two intracellular motifs by forcedly expressing Draper proteins, in which tyrosine residues within the motifs had been substituted with phenylalanine, in hemocytes of Draper-lacking flies. We found that Draper proteins with Y-to-F substitution in either motif still underwent tyrosine phosphorylation, suggesting the occurrence of phosphorylation at both motifs. The Draper protein with substitution in the YxxL motif rescued a defect of phagocytosis, as did intact Draper, but the Draper protein with substitution in the NPxY motif did not, indicating a role of the motif NPxY, but not YxxL, in Draper-mediated phagocytosis. This coincides with our previous finding that Ced-6, an NPxYbinding signaling adaptor, is required for Draper's actions in apoptotic cell clearance. In summary, we demonstrated that Draper binds to its ligand Pretaporter using EGF-like sequences, and that the NPxY motif in the intracellular region of Draper plays an essential role in its actions as an engulfment receptor.
Medicinal plants have played an important role in the treatment and prevention of diseases since ancient times. They are also potential sources of nutrients and drugs. This study evaluated Achyranthes aspera ethanolic extracts for their in vitro antioxidant activity and anti-hyperglycemic effects on alloxan-induced diabetic mice. Diabetes was induced in Swiss albino mice through intra-peritoneal administration of alloxan and their blood glucose levels and weight were measured weekly. At the end of the experiment, all animals were sacrificed and tissue samples were collected. A. aspera extracts had potent antioxidant activity compared to reference standard compounds. Treatment with an A. aspera extract at doses of 200 mg/kg and 400 mg/kg significantly reduced blood glucose levels in alloxan-induced diabetic mice. A. aspera extract also prevented lipid peroxidation as gauged by thiobarbituric acid reactive substances (TBARS) and hydroperoxides. Moreover, A. aspera extract increased the activity of catalase and reduced NO levels in alloxan-induced diabetic mice. Results revealed significant anti-hyperglycemic activity of A. aspera extracts in alloxan-treated mice that may be mediated by diminished oxidative stress.
Micronized purified flavonoid fraction (MPFF, Daflon®) is a phlebotonic drug widely used in chronic venous or lymphatic insufficiency. We aimed to investigate the effects of MPFF on hepatic and brain oxidative stress and on liver injury caused by lipopolysaccharide (LPS) in rats. MPFF (4.5, 9, or 18 mg/kg) or saline was administered orally for two days prior to intraperitoneal (i.p.) LPS (300 μg/kg) and at time of LPS administration. Rats were euthanized 4 h after LPS injection. The administration of LPS increased oxidative stress in brain and liver tissue. Malondialdehyde (MDA) increased by 193.5 and 191.8%, reduced glutathione (GSH) decreased by 73.8 and 70.8% and nitric oxide increased by 118.2 and 151.7% in the brain and liver, respectively. Serum paraoxonase 1 (PON1) activity decreased by 42.6%. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were raised by 101.8, 93.6, and 223.2%, respectively. Rats treated with MPFF at 9 and 18 mg/kg showed decreased brain MDA (27.5-34%), nitrite (25.5-41%) and increased GSH (27.2-74.1%). In the liver, MDA decreased by 16.4-59.8%, nitrite decreased by 54.7-56.7%, and GSH increased by 15.2-70.5% with MPFF at 4.5, 9, or 18 mg/kg, respectively. Serum PON1 activity showed 41-65.9% increments with MPFF. Significant reductions in serum AST, ALT, and ALP were seen after treatment with MPFF. Moreover, the degree of histological damage, expression of the inducible form of nitric oxide synthase and the apoptotic enzyme caspase-3 in the liver were substantially reduced. MPFF thus prevented the increased oxidative stress and inflammation in brain and liver as well as the liver dysfunction caused by endotoxemia in the rat.
Human osteosarcoma cell line SaOS-2 is an osteoblastic cell model that contains factors like bone morphogenetic proteins necessary for initiating bone formation. The cell line also expresses high levels of osteoinductive activity. In contrast to highly complicated and expensive ways to identify, purify, and separate specific bone-inducing agents from SaOS-2 cells, lysate can be used as an alternative to isolated bone-stimulating factors. Lysates of SaOS-2 stimulate the activity of the alkaline phosphatase of human osteoblastic cells HOS 58 in vitro. In other words, they probably possess osteoinductive activity. Different serial concentrations of substances like dexamethasoneand insulin were tested with and without a lysate of SaOS-2 cells to assay their synergistic action. Results showed that a lysate of the SaOS-2 cell line acts as a synergistic agent and increases the osteoinductive activity of known bone-inducing agents. SaOS-2 cell lysate could be used in the future as a clinical agent to promote bone repair and possibly enhance osteointegration. Using SaOS-2 total cellular extract offers the possibility of lowering the effective dose of other bone-inducing agents.
Naringenin and eriodictyol are chiral flavanones widely present in citrus fruits and herbal products. Pharmacological interest in the two flavanones is well known. Due to the chiral carbon atom, the compounds always exist in the racemic form. The present study reported a stereospecific HPLC method for the enantioseparation of naringenin and eriodictyol, which was performed on an amylose-based chiral stationary phase (CSP), Chiralpak AD-RH, in the reversed-phase mode. The effects of the mobile phase on retention, enantioseparation, and elution order were investigated. The different 3',4' substituent pattern of the two compounds affected the enantioselectivity. An online coupling HPLC-CD method was used for elution order determination. Both the CD sign of the eluted peaks at a single wavelength and complete CD spectra of the eluted enantiomers were obtained by the method.
Honokiol may exert significant antineoplastic effects in other systemic tumors besides skin cancers by virtue of modulation of other pathways. For instance, honokiol attenuates tumor growth in mammary malignancies. It mediates its anti-neoplastic role in these tumors by accentuating the phosphorylation of AMPK. As a result, honokiol causes significant mitigation of tumor proliferation and growth.
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