Osthole Improves Spatial Memory Deficits in Rats via Hippocampal α 1-Adrenergic and D 1 /D 2 Receptors.

The present study evaluated the effect of osthole, an active ingredient isolated from Cnidium monnieri L. Cusson, on spatial memory deficits caused by central neurotoxins using the Morris water maze in rats. The involvement of catecholaminergic receptors on the memory-enhancing effect of osthole in rat hippocampus was further investigated by intrahippocampal injection of catecholaminergic receptor antagonists. Intracisternal injection of osthole (10 µ g/brain) improved the spatial performance and working memory impairments caused by the catecholaminergic neurotoxin 6-hydroxydopamine. No significant differences in swimming speeds were observed among sham, neurotoxin-induced, and osthole-treated groups. Intracisternal osthole injection also attenuated the spatial performance and working memory impairments caused by the α 1 receptor antagonist phenoxybenzamine, the D1 receptor antagonist SCH 23390, and the D2 receptor antagonist sulpiride. Therefore, we demonstrated that the effect of osthole on improving spatial memory deficits may be related to the activation of hippocampal α 1 and D1/D2 receptors.

Antioxidant phenolic profile from ethyl acetate fraction of Fructus Ligustri Lucidi with protection against hydrogen peroxide-induced oxidative damage in SH-SY5Y cells.

In this study, we demonstrated the antioxidant and protective properties of crude extract and fractions from Fructus Ligustri Lucidi (FLL) against hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells. The contents of their phytochemical profiles were determined by spectrophotometric methods and high performance liquid chromatography using a photodiode array detector. FLL crude extract possessed appreciable scavenging capacity against 1,1-diphenyl-2-picrylhydrazyl and H2O2. The ethyl acetate (EtOAc) fraction was the most active fraction in scavenging free radicals and H2O2. Following exposure of cells to H2O2, there was a marked decrease in cell survival and intracellular antioxidant enzymes, and then intracellular oxidative stress, the level of lipid peroxidation, and caspase-3 activity were increased. Simultaneous treatment with the EtOAc fraction blocked these H2O2-induced cellular events. Hydroxytyrosol and salidroside are major components of the EtOAc fraction. These results show that the phenolic-enriched EtOAc fraction of FLL contains tyrosol-related derivatives and exerts the protective effects against H2O2 toxicity via its free radical scavenging activity and ability to elevate the levels of antioxidant enzymes.

Oculopharyngeal somatic myopathy in a patient with a novel large-scale 3,399 bp deletion and a homoplasmic T5814C transition of the mitochondrial DNA.

We report a 65-year-old woman with a sporadic form of progressive oculopharyngeal somatic myopathy due to a novel large-scale 3,399 base pair (bp) deletion of the mitochondrial DNA (mtDNA) and co-occurrence of a homoplasmic T5814C transition. The onset of myopathy began from chronic progressive external ophthalmoplegia (CPEO) at age of 20 years. Bulbar weakness, neck and proximal limb paralysis, slowly progressed to eventual respiratory failure. The plasma levels of pyruvate (1.5 mg/dL) and lactate (20.2 mg/dL) were elevated. Muscle biopsy showed decreased enzymatic activity of cytochrome c oxidase, but no ragged-red fibers. Electron microscopy showed "parking-lot" paracrystalline inclusions in the enlarged mitochondria suggestive for mitochondrial myopathy. Sequencing of the whole mitochondrial genome of the patient's muscle and leukocytes showed 3,399 bp deletion of the mtDNA from nucleotide position 8,024 to 11,423 and a homoplasmic thymidine to cytosine transition at nucleotide position 5,814 of the tRNA(Cys) gene of mtDNA (T5814C). T5814C was absent in the white blood cells of the patient's daughter and in 205 normal controls. We conclude that a large-scale deletion may coexist with T5814C transition in patients with sporadic form of mitochondrial cytopathy manifested by slowly progressive oculopharyngeal somatic myopathy.

Melas with point mutations involving tRNALeu (A3243G) and tRNAGlu(A14693g).

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) is typically associated with a single point mutation in the mitochondrial genome (mtDNA). Because mtDNA is known to have a higher mutation rate than nuclear DNA, we speculate that some patients with MELAS syndrome may harbor more than one mutation in mtDNA. For this purpose, mtDNA extracted from muscle containing dysmorphic mitochondria from a 32-year-old man with MELAS was sequenced in its entirety to identify all possible mutations. The result showed a homoplasmic A14693G and a heteroplasmic A3243G. The A14693G transition was not present in 205 unrelated control individuals, was not seen in 76 species randomly selected from GenBank, and appears to disrupt the base pairing within the T-loop of mtDNA tRNA(Glu). His asymptomatic siblings' blood showed wild-type at these positions, whereas the blood of the patient's oligosymptomatic diabetic mother had a heteroplasmic A14693G and an apparent homoplasmic wild-type A3243, suggesting an association of A14693G with diabetes mellitus. This case demonstrates the importance of sequencing the mtDNA in its entirety to evaluate the molecular basis of mitochondriopathy.

Ultrastructural 'fingerprint' in cryoprecipitates and glomerular deposits: a clinicopathologic analysis of fingerprint deposits.

Organized glomerular electron-dense deposits with a fingerprint pattern are well known in some patients of lupus nephritis or cryoglobulinemia. In general, these two diseases are always discussed separately as the causes of such deposits. However, 3 of our 5 lupus patients with glomerular fingerprint deposits also had cryoglobulinemia. One of the remaining 2 patients died and the other was lost to follow-up. The purpose of our study was to seek an appropriate clinicopathologic assessment of fingerprint deposits. All these patients showed overt proteinuria, active urinary sediment, a high degree of activity of lupus nephritis, and diffuse proliferative glomerulonephritis (WHO class IV). Their cryoprecipitates and renal biopsy specimens were investigated by means of immunochemistry, immunofluorescence and electron microscopy. The ultrastructural 'fingerprint' structures were exactly the same in the cryoprecipitates and in the glomerular deposits in 2 of 3 lupus patients with cryoglobulinemia, as were IgG, IgM and IgA. Therefore, these observations furnish emerging morphologic evidence for the glomerular deposition of immune complexes of circulating cryoglobulins in lupus nephritis. In addition, electron microscopic fingerprint deposits on renal biopsy or cryoprecipitate can be regarded as a very sensible marker of concomitant or subsequent development of diffuse lupus nephritis. If the patient is accompanied by nephritic syndrome, an early trial of immunosuppressive therapy may be warranted.