Chiisanoside, a triterpenoid saponin, exhibits anti-tumor activity by promoting apoptosis and inhibiting angiogenesis

The leaves of the Acanthopanax species have traditionally been used as a tonic and sedative, as well as in the treatment of rheumatism and diabetes, and one of their main active ingredients is a lupane triterpenoid chiisanoside which exhibits a series of significant pharmacological effects. However, the anti-tumor activity of chiisanoside on H 22 hepatocellular carcinoma and the pharmacokinetics study have not been mentioned. The aim of this study was to explore the anti-tumor efficacy, the potential mechanisms in a H 22 tumor-bearing mice model, and the pharmacokinetics properties and tissue distribution characteristics in a rat model. The results revealed that chiisanoside exhibited significant inhibition of tumor cell growth with no side effects on immune organs. The plasma cytokine levels of IL-2, TNF-α, and IFN-γ were enhanced, whereas the plasma VEGF level was decreased after chiisanoside treatment. Moreover, the results of H&E, TUNEL assay, immunohistochemistry showed that chiisanoside exhibited antitumor activity in vivo by promoting apoptosis and inhibiting angiogenesis. Additionally, further investigations on the pharmacokinetics revealed that chiisanoside had a trait of fast absorption and rapid elimination in rat. Furthermore, the results of tissue distribution showed that chiisanoside was mainly distributed in the liver, small intestine and other organs in rat, which indicated that chiisanoside exhibited good liver and small intestine-targeting efficiency. Chissanoside from Acanthopanax species exhibits anti-tumor activity by protecting liver function, regulating immunity, promoting apoptosis and inhibiting angiogenesis.