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.

doi:10.1101/2024.03.17.585380

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bioRxiv · 10.1101/2024.03.17.585380

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.

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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.

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Zhang, Z. Z., Norose, K., Shinjyo, N., Lin, X. X., Suganami, A., Tamura, Y., Sakamoto, H., Hikosaka, K.. 2024-03-17. Suppressive effects of oroxylin A on intracellular proliferation of Toxoplasma gondii via host cell ERK phosphorylation inhibition. https://doi.org/10.1101/2024.03.17.585380

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