Geniposide and geniposidic acid, modified forms of genipin, attenuate genipin-induced mitochondrial apoptosis without altering the anti-inflammatory ability in KGN cell line

Genipin has been demonstrated to induce apoptosis in various cell lines, but in this paper, the apoptosis effect was found attenuated significantly in KGN cell line after when its functional groups was modified, which is a reliable tumor cell line of granulosa cell. Furthermore, geniposide and geniposidic acid, chemicals modified from genipin, were discovered to retain the anti-inflammatory effect of genipin. The apoptosis induced by genipin was considered related to mitochondrial pathway with altered expression of Bcl-2 family, P53, elevated activities of caspase 3 and caspase 9, andactivated mitogen-activated protein kinase members. To evaluate the anti-inflammatory effect and anti-oxidant effect of chemicals modified from genipin, expression of iNOS, IL members, and activities of superoxide dismutase, catalase were investigated. Genipin, geniposide, and geniposidic acid all showed efficient anti-inflammatory effect by inhibiting expression of iNOS and most IL members. Different from genipin, geniposide and geniposidic acid could not inhibit superoxide dismutase activity, showing better antioxidant effects than genipin. In conclusion, genipin was suggested applied after structural modification, retaining anti-inflammatory ability without inducing apoptosis or oxidative stress, and the apoptosis induced by genipin was considered derived from the activated mitogen-activated protein kinase members and mitochondrial pathway.