Ecliptasaponin II alleviates the radiation enteritis by activating PPARγ to inhibit the apoptosis of endothelial cells

Ecliptae Herba is a well-known traditional Chinese medicine, and used for the bleeding and immunity-related diseases in China. This study was aimed to explore the alleviation and mechanisms of eclipta total saponins (ETS) on radiation enteritis (RE). ETS were extracted using the percolation method, and the main active components, Ecl1 and Ecl2, were quantified with HPLC analysis to be 20.39 % and 50.42 %, respectively. Subsequently, a mouse model of RE was established to evaluate the therapeutic effect of ETS and reveal the main active components. The results demonstrated that ETS and Ecl2, but not Ecl1, significantly ameliorated RE in mice, as evidenced by reduced disease activity index scores, shortened colon length, and the down-regulated MPO activity and histopathological injury in colons. Furthermore, ETS and Ecl2 also reversed the increased intestinal permeability and crypt damage. In vitro, Ecl2 obviously inhibited ionizing radiation (IR)-induced apoptosis in HUVECs. This effect was associated with a down-regulated Bax/Bcl2 ratio, release of Cyt-C, and subsequent inhibition of the Caspase-3/PARP cascade. Molecular docking results revealed that Ecl2 potentially binds to the anti-apoptotic proteins PPARγ, but not Bcl2. Additionally, Ecl2 was found to increase the nuclear translocation of PPARγ and the transcription of its downstream target genes CAV1 , aP2 , and CD36. GW9662 abolished Ecl2-mediated anti-apoptosis effects in HUVECs. Collectively, ETS possesses the ability to ameliorate RE, and Ecl2 may act as the main effector component. Ecl2 regulates the Bax/Bcl2-Caspase-3/PARP cascade to inhibit IR-induced apoptosis of endothelial cells by activating PPARγ.