Inhibition of the activation of hepatic stellate cells by arundic acid via the induction of cytoglobin.

Background: The activation of hepatic stellate cells plays a central role in the development of liver fibrosis during chronic liver trauma. The aim of the present study was to identify a compound that inhibits the activation process of stellate cells.

Methods: Rat primary cultured stellate cells and a human stellate cell line (LX-2) were used.

Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of dopaminergic neurons as seen in Parkinson's disease. Oxidative stress has been as one of several pathogenic hypotheses for Parkinson's disease. Here we investigated whether arundic acid, an astrocyte-modulating agent, can protect against alterations of nitric oxide synthase (NOS) and superoxide dismutase (SOD) expression on MPTP neurotoxicity in mice, utilizing an immunohistochemistry.

Effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model: comparison with nifedipine, ticlopidine and cilostazol.

The systemic treatment effects of OP-1206 alpha-CD (17S-20-dimethyl-trans-delta 2-PGE1 alpha-cyclodextrin clathrate), a prostaglandin E1 (PGE1) analogue, on walking dysfunction, spinal cord blood flow (SCBF) and skin blood flow (SKBF) were assessed in the rat neuropathic intermittent claudication (IC) model in comparison with nifedipine (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate), ticlopidine (5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-C]pyridine hydrochloride) and cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone). Two pieces of silicone rubber strips were placed in the lumbar (L4 and L6) epidural space in rats. After surgery, walking function was measured using a treadmill apparatus.

Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.

An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat.

Structure-activity study of L-amino acid-based N-type calcium channel blockers.

Synthesis and structure-activity relationship (SAR) study of L-amino acid-based N-type calcium channel blockers are described. The compounds synthesized were evaluated for inhibitory activity against both N-type and L-type calcium channels focusing on selectivity to reduce cardiovascular side effects due to blocking of L-type calcium channels. In the course of screening of our compound library, N-(t-butoxycarbonyl)-L-aspartic acid derivative 1a was identified as an initial lead compound for a new series of N-type calcium channel blockers, which inhibited calcium influx into IMR-32 human neuroblastoma cells with an IC(50) of 3.

L-Cysteine based N-type calcium channel blockers: structure-activity relationships of the C-terminal lipophilic moiety, and oral analgesic efficacy in rat pain models.

This study was performed to determine the structure-activity relationships (SAR) of L-cysteine based N-type calcium channel blockers. Basic nitrogen was introduced into the C-terminal lipophilic moiety of L-cysteine with a view toward improvement of its physicochemical properties. L-Cysteine derivative 9 was found to be a potent and selective N-type calcium channel blocker with IC(50) of 0.

The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model.

Unlabelled: IV prostaglandin E1 improves clinical symptoms in patients with spinal canal stenosis. In the present study, we assessed the effects of OP-1206 alpha-CD, an orally active prostaglandin E1 analog, on walking dysfunction in the rat neuropathic intermittent claudication model. To induce spinal stenosis, two pieces of silicon rubber were placed in the lumbar (L4-6) epidural space in rats.

Structure-activity study of L-cysteine-based N-type calcium channel blockers: optimization of N- and C-terminal substituents.

Synthesis and structure-activity relationship (SAR) studies of L-cysteine-based N-type calcium channel blockers are described. In the course of exploring SAR of the N- and C-terminal substituents, the L-cysteine derivative was found to be a potent N-type calcium channel blocker with an IC(50) value of 0.14 microM on IMR-32 assay.

Involvement of cathepsin E in exogenous antigen processing in primary cultured murine microglia.

We have attempted to elucidate an involvement of cathepsin E (CE) in major histocompatibility complex class II-mediated antigen presentation by microglia. In primary cultured murine microglia, CE was localized mainly in early endosomes and its expression level was markedly increased upon stimulation with interferon-gamma. Pepstatin A, a specific inhibitor of aspartic proteases, significantly inhibited interleukin-2 production from an OVA-(266-281)-specific T helper cell hybridomas upon stimulation with native OVA presented by interferon-gamma-treated microglia.