Hepatoprotective Limonoids from Andiroba (Carapa guianensis)

International Journal of Molecular Sciences

Takashi Kikuchi¹  Takeshi Yamada¹  Reiko Tanaka¹  Seiya Miyazawa²  Osamu Muraoka²  Toshio Morikawa²  Kaiten Ozeki²  Kiyofumi Ninomiya²  Natsuko Matsuo² 

[1] Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan;Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan;

关键词: hepatoprotective effect;    limonoid;    andiroba;    Carapa guianensis;    Meliaceae;    structural requirement;   

DOI  :  10.3390/ijms17040591

来源: DOAJ

【 摘 要 】

Three gedunin-type limonoids, gedunin (1), 6α-acetoxygedunin (2), and 7-deacetoxy-7-oxogedunin (3), which were isolated from the seed and flower oils of andiroba (Carapa guianensis Aublet, Meliaceae), exhibited hepatoprotective effects at doses of 25 mg/kg, p.o. against d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. To characterize the mechanisms of action of 1–3 and clarify the structural requirements for their hepatoprotective effects, 17 related limonoids (1–17) isolated from the seed and/or flower oils of C. guianensis were examined in in vitro studies assessing their effects on (i) d-GalN-induced cytotoxicity in primary cultured mouse hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. The mechanisms of action of 1–3 are likely to involve the inhibition of LPS-induced macrophage activation and reduced sensitivity of hepatocytes to TNF-α; however, these compounds did not decrease the cytotoxicity caused by d-GalN. In addition, the structural requirements of limonoids (1–17) for inhibition of LPS-induced NO production in mouse peritoneal macrophages and TNF-α-induced cytotoxicity in L929 cells were evaluated.

【 授权许可】

Unknown