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This study demonstrated the feasibility of evaluating the effect of the antiosteoporotic agents within 2 weeks after ovariectomy in mice. The muCT analysis may serve as a valuable tool, specifically in a high-throughput pharmacological screening test, offering useful information regarding the effects of test compounds on both bone resorption and formation.

ABSTRACT-Aconiti tuber, roots of aconite (Aconitum japonicum), has been used for centuries in Japan and China to increase peripheral body temperature. We previously reported that mesaconitine, an alkaloid from Aconitum japonicum, elicits endothelium-dependent and nitric oxide-mediated relaxation in isolated rat aorta. In the present study, we investigated the effect of mesaconitine on isolated rat small gastric arteries. Mesaconitine elicited a concentration-dependent (10, 30, 100 mM) vasorelaxation in isolated rat gastric artery precontracted with norepinephrine, which was resistant to N M -nitro-L-arginine (L-NNA) (an inhibitor of nitric oxide synthase) and indomethacin (an inhibitor of cyclooxygenase). The L-NNA-and indomethacinresistant relaxation by mesaconitine was mainly endothelium-dependent, inhibited by high K + (30 mM), and inhibited by a combination of Ca 2+-dependent K + channel blockers, charybdotoxin and apamin. The relaxation by mesaconitine was proportional to the external Ca 2+ concentration. These results suggest that mesaconitine elicits vasorelaxation of isolated rat small gastric artery mainly via release of endothelium-derived hyperpolarizing factor.Keywords: Mesaconitine, Vasorelaxation, Gastric artery, Endothelium-derived hyperpolarizing factor, Aconitum japonicumAconiti tuber, roots of aconite (Aconitum japonicum or Aconitum carmichaeli), is an oriental herbal medicine traditionally used for centuries in Japan and China for analgesic, antirheumatic and neurological indications. The pharmacological effects of aconite alkaloids, including aconitine, have been described as positive inotropic effects (1). The main active constituents are the C19 diterpene alkaloids, mesaconitine being pharmacologically the most active. Mesaconitine is described as the most potent analgesic constituent in Aconiti tuber (2) Preparations of Aconiti tuber have been therapeutically used to increase peripheral body temperature. It can be anticipated that the effect of Aconiti tuber preparations on peripheral body temperature might be the consequence of improvement of the low blood flow by aconite alkaloids. Indeed, in a previous study we found that mesaconitine elicits a strong relaxation in isolated rat aorta. This relaxation is mainly endothelium-dependent and mediated by nitric oxide (NO) (3). Considering that smaller resistance rather than big conductance vessels are responsible for improvements in peripheral blood circulation, the potential vasodilatory influence of mesaconitine on smaller resistance vessels was investigated in the present study. In addition, the role of the endothelium in this relaxation was studied.The endothelium modulates vascular tone by releasing NO, but also by releasing other mediators such as prostacyclin and endothelium-derived hyperpolarizing factor(s) (EDHF). While prostacyclin is only involved in a limited number of preparations, the relative contributions of NO and EDHF is likely to be dependent on the size of the vessels; the contribution of NO is the largest in large-diameter...

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Abstract:The purpose of this study was to investigate the potential effects of the anti-bone resorptive agent alendronate (ALN) and the steroidal anti-inflammatory agent prednisolone (PL) on rheumatoid arthritis (RA) in mice with an antitype II collagen (CII) antibody-induced model of arthritis. Arthritis was induced in female BALB/c mice with anti-CII antibody and LPS. ALN (1 mg/kg) was subcutaneously and PL (0.3, 3 mg/kg) orally administered once a day for 12 days. Severity of arthritis was evaluated on Days 6, 10 and 12, and paws and femoral bone were collected on Day 12 for histopathological examination and microcomputed tomography (micro-CT) analysis. ALN significantly inhibited bone destruction in the paws, but did not inhibit paw edema, synovial proliferation, or inflammatory cell infiltration. On the other hand, PL inhibited paw edema, synovial proliferation and inflammatory cell infiltration, but had no effect on bone destruction in the paws or bone loss in the femoral bone. ALN inhibited bone destruction in this RA model, with prominent amelioration of bone destruction and osteoclast reduction. PL inhibited inflammation, but not bone destruction in the paws. In addition, PL induced bone loss in the femoral bone as determined by micro-CT analysis. Our findings suggest that not only anti-inflammation effects but also direct inhibition of bone destruction is important for the treatment of arthritis. (J Toxicol Pathol 2007; 20: 21-27)

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