The Anti-Tumor Effect and Mechanisms of Action of Penta-Acetyl Geniposide

Abstract

Gardenia, the fruit of Gardenia jasminoides Ellis, has been widely used to treat liver and gall bladder disorders in Chinese medicine. It has been shown recently that geniposide, the main ingredient of Gardenia Fructus, exhibits the anti-tumor effect. In this review, we discuss the anti-tumor effect and possible mechanisms of a derivative from Gardenia Fructus, penta-acetyl geniposide ((Ac)5GP). It has been demonstrated that (Ac)5GP plays more potent roles than geniposide in chemoprevention. (Ac)5GP decreased DNA damage and hepatocarcinogenesis induced by aflatoxin B1 (AFB1) by activating the phase II enzymes glutathione S-transferase (GST) and GSH peroxidase (GSH-Px). It reduced the growth and development of inoculated C6 glioma cells especially in pre-treated rats. In addition to the preventive effect, (Ac)5GP exerts its actions on apoptosis and growth arrest. Treatment of (Ac)5GP caused DNA fragmentation of glioma cells. (Ac)5GP induced sub- G1 peak through the activation of apoptotic cascades PKCdelta/JNK/Fas/caspase8 and caspase 3. Besides, p53/Bax signaling was suggested to be involved in (Ac)5GP-induced apoptosis, though its downstream cascades needs further clarified. (Ac)5GP has also been shown to inhibit DNA synthesis of tumor cells. It arrested cell cycle at G0/ G1 by inducing the expression of p21, thus suppressing the cyclin D1/cdk4 complex formation and the phosphorylation of E2F. The phosphorylation status of p53 on serine 392 correlated with the process of growth arrest. Evidences from the in vivo experiments showed that (Ac)5GP is not harmful to liver, heart and kidney. In conclusion, (Ac)5GP is highly suggested to be an anti-tumor agent for development in the future.

Monoamine Oxidase and Dopamine β-Hydroxylase Inhibitors from the Fruits of Gardenia jasminoides

“…The fruits of Gardenia jasminoides (Rubiaceae) (Korean herbal name is Chi Za) have been used as a natural yellow colorant in foods and also in traditional medicine for the treatment of liver and bladder disorders and inflammatory disease. The major effective constituents of Gardenia fruits, iridoid glycosides, flavonoids, and carotenoids, are responsible for the biological activities such as hypoglycemic activity, anti-tumor effect, anti-angiogenic activity, antithrombotic effect, and anti-oxidant activity (Miura et al , 1996; Pham et al , 2000; Suzuki et al , 2001; Koo et al , 2004; Peng et al , 2005). In our previous research, cold drugs inhibited the activity of MAO (Hwang et al , 1999) and especially, the total methanolic extract of the fruit of G. jasminoides exhibited a significant inhibition on MAO activity (IC 50 value of MAO-A is 1.23 mg/ml; MAO-B is 1.34 mg/ml) (Hwang, 2003).…”

Penta-Acetyl Geniposide Induce Apoptosis in C6 Glioma Cells by Modulating the Activation of Neutral Sphingomyelinase-Induced p75 Nerve Growth Factor Receptor and Protein Kinase Cδ Pathway

“…1] is an herbal derivative prepared from Gardenia geniposide. It has been suggested that (Ac) 5 GP plays more potent roles than geniposide in chemoprevention (Peng et al, 2005a). In addition, (Ac) 5 GP possesses the antitumor effect on apoptosis and growth arrest (Wang et al, 1993;Chang et al, 2002Chang et al, , 2004.…”

Protective Effects of Geniposide and Genipin against Hepatic Ischemia/Reperfusion Injury in Mice

“…The bioactivities of geniposide have been identified in numerous studies, including anti-oxidant (Yin et al ., 2010), antitumor (Peng et al ., 2005), and anti-inflammation bioactivities, however, the most important aspect of geniposide concerns its anti-oxidative capacity. Geniposide protected rat hippocampal slice cultures against oxygen and glucose deprivation-induced neuronal cell death (Lee et al ., 2006).…”