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The mixed lineage kinase 3 (MLK3) is a recently described member of MLK subfamily of mammalian serine/threonine protein kinases that function as mitogen-activated protein kinases (MAPK) kinase kinases (MAPKKKs) [6]. Studies on neuronal cell types suggest that MLK3 predominantly activates the JNK pathway and plays a pivotal role in neuronal cell death evoked by NGF-deprivation or ischemia injury [7] and [8]. Cdc42, a member of Rho family GTPase, induces activation loop Bazedoxifene acetate and membrane targeting of MLK3 [9] and promotes neuronal apoptosis through activating MLK3-JNK3 cascade during ischemic reperfusion in rat hippocampus [10]. However, an implication of ROS in MLK3 signaling cascade that mediates apoptosis has never been reported.
Geniposide is one of the main irioid-glyco compounds in Gardenia jasminoides Ellis fruits used as an oriental folk medicine, and is converted to the aglycone genipin by bacterial enzymes, β-d-glycosidases in the digestive organs and then observed into the blood [11] and [12]. Although genipin was not studied in detail, its pharmacological activities have been documented in recent years. Genipin shows the anti-fibrogenic effect by decreasing TGF-β1 expression in human subconjunctional fibroblasts [13]. In PC12h cells, genipin exerts neuritogenic effect by activating mitogen-activated protein kinase (MAPK) through the soluble guanylate cyclase-cGMP-dependent protein kinase-signaling pathway [14] and [15]. In addition to these actions, genipin has also been proved to possess antioxidant and anti-inflammatory activities [16] and [17].