BST106 Protects against Cartilage Damage by Inhibition of Apoptosis and Enhancement of Autophagy in Osteoarthritic Rats.

Chrysanthemum zawadskii var. latilobum (CZ) has been used as a traditional medicine in Asian countries for the treatment of inflammatory diseases. Recently, CZ extract was shown to inhibit differentiation of osteoclasts and provide protection against rheumatoid arthritis. The aim of this study was to investigate the molecular mechanisms of BST106, the ethanol extract of CZ, for cartilage protection in monosodium iodoacetate (MIA)-induced osteoarthritis (OA), particularly focusing on apoptosis and autophagy. BST106 (50, 100, and 200 mg/kg) was orally administered once daily to MIA-induced OA rats. Swelling, limping, roentgenography, and histomorphological changes were assessed 28 d after MIA injection. Biochemical parameters for matrix metalloproteinase (MMP), apoptosis, and autophagy were also assessed. BST106 ameliorated the severity of swelling and limping after MIA injection. Roentgenographic and histomorphological examinations revealed that BST106 reduced MIA-induced cartilage damage. BST106 decreased MIA-induced increases in MMP-2 and MMP-13 mRNA levels. Increased levels of serum cartilage oligomeric matrix protein and glycosaminoglycan release were attenuated by BST106. Furthermore, BST106 suppressed the protein expression of proapoptotic molecules and increased the protein expression of autophagosome- and autolysosome-related molecules. These findings indicate that BST106 protects against OA-induced cartilage damage by inhibition of the apoptotic pathway and restoration of impaired autophagic flux.

Effects of plant cell wall matrix polysaccharides on bacterial cellulose structure studied with vibrational sum frequency generation spectroscopy and X-ray diffraction.

The crystallinity, allomorph content, and mesoscale ordering of cellulose produced by Gluconacetobacter xylinus cultured with different plant cell wall matrix polysaccharides were studied with vibrational sum frequency generation (SFG) spectroscopy and X-ray diffraction (XRD). Crystallinity and ordering were assessed as the intensity of SFG signals in the CH/CH2 stretch vibration region (and confirmed by XRD), while Iα content was assessed by the relative intensity of the OH stretch vibration at 3240 cm(-1). A key finding is that the presence of xyloglucan in the culture medium greatly reduced Iα allomorph content but with a relatively small effect on cellulose crystallinity, whereas xylan resulted in a larger decrease in crystallinity with a relatively small decrease in the Iα fraction. Arabinoxylan and various pectins had much weaker effects on cellulose structure as assessed by SFG and XRD. Homogalacturonan with calcium ion reduced the SFG signal, evidently by changing the ordering of cellulose microfibrils. We propose that the distinct effects of matrix polysaccharides on cellulose crystal structure result, at least in part, from selective interactions of the backbone and side chains of matrix polysaccharides with cellulose chains during the formation of the microfibril.

The dorsal striatum expressing adenylyl cyclase-5 controls behavioral sensitivity of the righting reflex to high-dose ethanol.

High-dose ethanol inflicts sedation and loss of righting reflex (LORR). Recently, it was reported that AC5 knockout (AC5(-/-)) mice consumed more ethanol and showed reduced sensitivity to high-dose ethanol compared to wild-type mice. As an extension of the previous study, in the present study we examined the signaling mechanism regulating altered behavioral sensitivity of LORR in AC5(-/-) mice. AC5(-/-) mice had enhanced phosphorylation of the NR2B subunit of NMDA receptors in the dorsal striatum and a partial reduction of MK801 (NMDA receptor antagonist)/ethanol-induced LORR. AC5(-/-) mice showed increased levels of phospho-CaMKIIα, phospho-CREB, and BDNF in the dorsal striatum. CaMKIIα(+/-) or BDNF(+/-) mice displayed enhanced LORR, a behavioral phenotype opposite to that displayed by AC5(-/-) mice. Consistently with these results, stereotaxic infusion of KN62 (CaMKII inhibitor), siRNA-CaMKIIα, or siRNA-BDNF, within the dorsal striatum was sufficient to prolong LORR. These results suggest that neural mechanism is important for regulating behavioral sensitivity of LORR and that the signaling pathway(s) interplayed by AC5, CaMKIIα and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR.

Antinociceptive anti-inflammatory effect of Monotropein isolated from the root of Morinda officinalis.

The root of Morinda officinalis (Rubiaceae) is used to treat rheumatoid arthritis and impotence in the traditional Oriental medicine. To identify the antinociceptive anti-inflammatory components of this crude drug, we adopted an activity-directed fractionation approach. The active fraction of the BuOH extract of M. officinalis root was subjected to silica gel and ODS column chromatography to yield two diterpenes, compounds 1 and 2 and these were identified as monotropein and deacetylasperulosidic acid, respectively. The iridoid glycoside, monotropein, was tested for its anti-inflammatory antinociceptive effects using hot plate- and writhing antinociceptive assays and by using carrageenan-induced anti-inflammatory assays in mice and rats. Pretreatment with monotropein (at 20, 30 mg/kg/d, p.o.) significantly reduced stretching episodes and prolonged action time in mice. It also significantly reduced acute paw edema by carrageenan in rats. These results indicate that monotropein contributes to the antinociceptive and anti-inflammatory action of Morinda officinalis root.