ovatodiolide Chemical Properties

InChI

InChI=1S/C20H24O4/c1-12-5-4-6-15-11-16(23-20(15)22)9-13(2)10-18-17(8-7-12)14(3)19(21)24-18/h5,10-11,16-18H,3-4,6-9H2,1-2H3/b12-5+,13-10+/t16-,17-,18+/m0/s1

InChIKey

KTYZKXFERQUCPX-SIKGVNBJSA-N

SMILES

O1C(=O)C2=C[C@]1([H])CC(C)=C[C@@]1([H])OC(=O)C(=C)[C@]1([H])CCC(C)=CCC2 |t:10,25|

ovatodiolide Usage And Synthesis

Description

Ovatodiolide (OV) is a bioactive phytochemical purified from Anisomeles indica (L.) Kuntze (Labiatae) is a medicinal herb that has been widely used to treat a variety of inflammation-associated diseases. Ovatodiolide has been reported to exhibit many biological functions, including anti-cancer, anti-bacterial, and anti-HIV activities. Most importantly, the studies have demonstrated that ovatodiolide inhibited H. pylori-induced inflammation in gastric epithelial cells[1-2].

Biological Functions

Various oncogenic targets inhibited by ovatodiolide have been implicated; these include TNF-α, NF-κB, β-catenin, MMPs, and others to achieve anti-cancer effects such as the induction of cell cycle arrest, apoptosis, and reduction of metastatic potential. Ovatodiolide suppressed cell colony formation and induced apoptosis in the K562 and KU812 cells. Ovatodiolide enhanced the production of reactive oxygen species (ROS), activated Nrf2 signaling, and inhibited mTOR phosphorylation. Autophagic flux was enhanced after treatment with ovatodiolide in K562 cells. Furthermore, autophagy inhibition alleviated ovatodiolide-induced cell apoptosis, whereas autophagy promotion aggravated apoptosis in CML cells. These results demonstrated that ovatodiolide activates autophagy-mediated cell death in CML cells.
Additionally, ovatodiolide transcriptionally activated the expression of p62, and the p62 levels were negatively regulated by autophagy. Moreover, p62-Keap1-Nrf2 signaling was confirmed to be involved in ovatodiolide-induced cell death. Accordingly, LC3B knockdown augmented the ovatodiolide-induced p62 expression, increased the p62-Keap1 interaction, and enhanced the translocation of Nrf2 into the nucleus. In contrast, p62 inhibition abolished the effects induced through ovatodiolide treatment. Nrf2 inhibition with ML385 diminished the protective effect of autophagy inhibition in CML cells. Collectively, ovatodiolide induces oxidative stress and provokes autophagy, effectively decreasing the expression of p62 and weakening the protective effect of Nrf2 signaling activation, thus contributing to apoptosis in CML cells[2].

References

[1] Hsiu-Man Lien. “Antibacterial activity of ovatodiolide isolated from Anisomeles indica against Helicobacter pylori.” Scientific Reports (2019): 4205.
[2] Qingqing Xia . “Ovatodiolide induces autophagy-mediated cell death through the p62-Keap1-Nrf2 signaling pathway in chronic myeloid leukemia cells.” Chemico-Biological Interactions 387 (2023): Article 110819.