JAK2, STAT3, TLR4

Atractylenolide I (40, 60, 80, 100, 120, 150 μM) dose- and time-dependently reduces the cell viability in human A375 melanoma cells after treatment for 24, 48 and 72 hours. Atractylenolide I (50 and 100 μM) induces apoptosis of A375 cells in a dose-dependent manner at 48 h of treatment. Atractylenolide I (100 μM) significantly reduces protein levels of phosphorylated JAK2 and STAT3 in A375 cells, without effect on total JAK2 and STAT3. Furthermore, Atractylenolide I inhibits the mRNA expression of STAT3-targeted genes, including Bcl-xL, MMP-2 and MMP-9. Atractylenolide I (up to 100 μM) shows no toxicity in normal cells. Atractylenolide I (25, 50 μM) decreases the Ox-LDL induced TNF-α, IL-6 and NO production in VSMCs. Atractylenolide I (12.5, 25 or 50 μM) significantly reduces the level of MCP-1 and inhibits Ox-LDL-induced VSMCs proliferation and migration. Atractylenolide I (25, 50 μM) inhibits positive staining of foam cells, and also significantly decreases lipid accumulation. Atractylenolide I (50 μM) suppresses p38MAPK and NF-κB p65 expression in VSMCs stimulated by Ox-LDL. Atractylenolide I (1, 10, 100 μM) downregulates paclitaxel-induced expression of VEGF and survivin via MyD88-dependent TLR4 signaling in EOC cells.

Atractylenolide I (5, 10 or 20 mg/kg, p.o.) restores the decreased body weight in mice subjected to chronic unpredictable mild stress (CUMS). Atractylenolide I alleviates CUMS-induced depressive-like behavior, attenuates CUMS-induced imbalances in hippocampal neurotransmitter levels and reduces CUMS-induced increases in hippocampal pro-inflammatory cytokine levels and in the NLRP3 inflammasome in the hippocampi of mice.