Abstract
Kampo medicines are important drugs in Japan. However, the mechanism of action has not yet been clarified. In rare cases, Kampo medicines cause serious adverse effects, which mechanism and therapeutic discipline have not been established. Recently, the Ministry of Health, Labor, and Welfare has reported that mesenteric vein sclerosis, occurs in patients who have been taking Kampo medicines containing Gardenia Fruit for a long time. However, the risk factors and mechanism of this adverse effect are unknown.
We identified Kampo medicines at high risk for the onset of this adverse effect using the Japanese Adverse Drug Event Report (JADER) database. The results suggest that there may be an increased risk of occurrence in elderly women taking Kamishoyosan and Orengedokuto, which contain Gardenia Fruit.
We also studied the effects of geniposide and crocin, the main components of Gardenia Fruit on human umbilical vein endothelial cells (HUVECs) and found that crocin inhibited the cell proliferation. Because calcification in intestinal veins is a characteristic of this adverse effect and the elderly were at higher risk, calcium deposition and cellular senescence were examined. There was no difference in calcium deposition between geniposide and crocin treated HUVECs. On the other hand,β-galactosidase, a typical indicator of cellular senescence, was increased in crocin treated HUVECs. Although further studies are needed to determine the relationship between these data and mesenteric venous sclerosis, this finding suggests that crocin may have some effect on the adverse effect.
