Back

Suppressive effects of oroxylin A on intracellular proliferation of Toxoplasma gondii via host cell ERK phosphorylation inhibition

Zhang, Z. Z.; Norose, K.; Shinjyo, N.; Lin, X. X.; Suganami, A.; Tamura, Y.; Sakamoto, H.; Hikosaka, K.

2024-03-17 microbiology
10.1101/2024.03.17.585380 bioRxiv
Show abstract

Toxoplasma gondii poses a significant threat to immunocompromised patients, resulting in high mortality rates. Considering the side effects of anti-Toxoplasma drugs, we focused on a potential candidate, oroxylin A (OA), a common component extracted from Astragalus membranaceus and Scutellaria baicalensis which suppressed the growth of T. gondii in vitro and in vivo. Our result demonstrated that OA suppressed T. gondii intracellular proliferation and downregulated phosphorylation of ERK1/2 of T. gondii-infected host cells very similar to the MEK1 specific inhibitor PD98059. Our in silico analysis showed that OA interacts sufficiently with the mammalian MEK1 region where established MEK1 inhibitors like PD98059 and trametinib bind. Moreover, OA improved the survival rate in T. gondii-infected mice. This study proposes that host MEK1 is a novel potential target for anti-Toxoplasma drugs with a new mechanism of action.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.