PURPOSE. We assess if a retinal ganglion cells (aRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma. METHODS. Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina were performed using antibodies against RNA-binding protein with multiple splicing (RBPMS), osteopontin, and melanopsin. Immunohistochemical analyses also were performed in adult mice with glutamate/aspartate transporter (GLAST) deletion (GLAST knockout [KO] mice), a mouse model of normal tension glaucoma. RESULTS. NMDA-induced loss of RBPMS-positive total RGCs was 58.4% 6 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive aRGCs was 5.0% 6 0.6% and that of melanopsin-positive ipRGCs was 7.6% 6 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% 6 0.9% compared to wild-type mice, whereas the loss of aRGCs and ipRGCs was 3.9% 6 0.4% and 9.3% 6 0.5%, respectively. The distribution of survived total RGCs, aRGCs, and ipRGCs was similar regardless of the location of the retina. CONCLUSIONS. These results suggest that aRGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.
Three new compounds, namely, 4-(4′-hydroxy-3′-methoxyphenyl)-3,5,7-trihydroxycoumarin
(1) and sulawesins A (2) and B (3), were isolated from the propolis of stingless bees (Tetragonula aff. biroi) collected on South Sulawesi, Indonesia.
In addition, five known compounds, glyasperin A, broussoflavonol F,
(2S)-5,7-dihydroxy-4′-methoxy-8-prenylflavanone,
(1′S)-2-trans,4-trans-abscisic acid, and (1′S)-2-cis,4-trans-abscisic acid, were identified. The structures
of the new compounds were determined by a combination of methods that
included mass spectrometry and NMR spectroscopy. The absolute configuration
of sulawesin A (2), a new podophyllotoxin derivative,
was determined by X-ray crystallography. The absolute configuration
of sulawesin B (3) was also determined by the ECD calculation.
4-(4′-Hydroxy-3′-methoxyphenyl)-3,5,7-trihydroxycoumarin
(1) and sulawesin A (2) were examined for
xanthine oxidase (XO) inhibitory activity; 1 exhibited
XO inhibitory activity, with an IC50 value of 3.9 μM.
The effect of antioxidant polyphenols and related phenolic compounds from plants on the reduction of metmyoglobin (MetMb) was investigated. Potent activity in the reduction of MetMb to oxymyoglobin (MbO2), a bright red protein in meat, was observed for three flavonols, kaempferol, myricetin, and quercetin, at 300 μmol/L against 60 μmol/L MetMb. Sinapic acid, catechin, nordihydroguaiaretic acid, taxifolin, morin, and ferulic acid promoted reduction at 600 μmol/L. A mechanism for the reduction by one of the active flavonols, quercetin, was proposed on the basis of analytical results for redox reaction products derived from quercetin. This suggested the importance of a high propensity toward reduction of the flavonol structure and rapid convertibility of the quinone form to the phenol form for the MbO2 reduction and the maintenance of the level of MbO2 produced.
Inhibitory activity of Fe-ion-catalyzed radical oxidation products from 22 types of phenolic compounds toward xanthine oxidase (XO) was investigated. Phenols are readily oxidizable compounds in nature and, thus, showed potent antioxidant activities. Among the phenols screened in this study, noticeable activity was observed in the oxidation product of caffeic acid, whereas almost no XO-inhibitory activity of caffeic acid was observed. Assay-guided purification of the oxidation product of caffeic acid afforded a highly potent XO inhibitor, with an IC50 value that was calculated to be 60 nmol L(-1), which indicated XO-inhibitory activity much stronger than that of allopurinol (IC50 = 1 μmol L(-1)), a potent XO inhibitor and excellent medicine for the treatment of gout. The chemical structure of this new XO inhibitor was investigated by one- and two-dimensional NMR and HR-ESI-MS analyses, and the unique tetracyclic structure was confirmed by synthesis starting from commercially available 1,2,4-trimethoxybenzene and 3,4-dimethoxylbenzoyl chloride.
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