Gracillin, as a natural steroidal saponin component of D. quinqueloba, has antitumour, antimicrobial, antioxidant, pro‐apoptotic and anti‐inflammatory properties[1].
In vitro, Gracillin markedly inhibited the viability of RKO, SW480 and HCT116 cells, with IC50 of 3.118, 2.671 and 5.473μM, respectively. Gracillin (0, 2.5, 5 or 10μM; 36h) also stimulated apoptosis in human CRC cells in a dose-dependent manner[1]. Gracillin obviously inhibited the proliferation of A549 cells with IC50 of 2.54μmol/L in a concentration-dependent and time-dependent manner and induced morphological changes[2]. Gracillin inhibited the gastric tumor BGC823 cell proliferation in a concentration-dependent manner with IC50 of 8.3μM and gastric tumor SGC7901 cell proliferation with IC50 of 8.9μM in the range of 0-15μM[3]. Gracillin (0-12μM; 12h) induced TIPE2 expression in BGC-823 cells in a concentration-dependent manner[3]. Gracillin had dose-dependent inhibitory effects on the mitochondrial function in various human cancer cell lines derived from lung, colorectum, prostate, pharynx, and liver with IC50 of ~1-5μM[4].
In vivo, Gracillin (1 or 2mg/kg; i.p.; administered 8 times over 14 days) dose-dependently inhibited the growth of HCT116 cell-derived xenograft tumors in BALB/c nude mice while maintaining stable body weight[1]. Fish treated with 1mg/kg Gracillin carried significantly fewer parasites than the control, and the acute toxicity LD50 of Gracillin for grass carp was 1.64mg/kg[5].
References:
[1] Yang L, et al. Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway. J Cell Mol Med. 2021 Jan;25(2):801-812.
[2] Yang J, et al. Gracillin Isolated from Reineckia carnea Induces Apoptosis of A549 Cells via the Mitochondrial Pathway. Drug Des Devel Ther. 2021 Jan 20;15:233-243.
[3] Liu W, et al. Beneficial Effects of Gracillin From Rhizoma Paridis Against Gastric Carcinoma via the Potential TIPE2-Mediated Induction of Endogenous Apoptosis and Inhibition of Migration in BGC823 Cells. Front Pharmacol. 2021 Sep 24;12:669199.
[4] Min HY, et al. The natural compound gracillin exerts potent antitumor activity by targeting mitochondrial complex II. Cell Death Dis. 2019 Oct 24;10(11):810.
5[5] Zheng W, et al. Antiparasitic efficacy of Gracillin and Zingibernsis newsaponin from Costus speciosus (Koen ex. Retz) Sm. against Ichthyophthirius multifiliis. Parasitology. 2015 Mar;142(3):473-9.