Deguelin is a naturally occuringAkt inhibitor purified from the herbs of Derris robusta, which downregulatesAkt phosphorylation and shows anticancer effect.
Deguelin is one of four major naturally occurring rotenoids isolated from root extracts and is best recognized as a NADH: ubiquinone oxidoreductase (complex I) inhibitor, resulting in significant alterations in mitochondrial function, and it is also a potential PI3K/AKT inhibitor[3]. As a natural agent for chemotherapy, deguelin remarkably suppresses proliferation in numerous solid cancers. Nevertheless, the molecular mechanisms of its suppression are still insufficient[4]. In the mouse skin study, deguelin reduced tumor incidence from 60% in the control group to 10% in the group treated with a dose of 33 µg, and multiplicity was reduced from 4.2 in the control group to 0.1 in the treatment group. When the dose was increased 10-fold to 330 µg, no tumors were observed in the treatment group[5]. Deguelin has been reported to elicit PD-like symptoms (degeneration of the dopaminergic pathway) in rats administered with deguelin (6 mg/kg/day for 6 days), possibly through the inhibition of mitochondrial complex I[3].
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