Atractylenolide I is a sesquiterpene derived from the rhizome of Atractylodes macrocephala, possesses diverse bioactivities, such as neuroprotective, anti-allergic, anti-inflammatory and anticancer properties. Atractylenolide I reduces protein levels of phosphorylated JAK2 and STAT3 in A375 cells, and acts as a TLR4-antagonizing agent.
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[1]. 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[3]. Atractylenolide I (1, 10, 100 μM) downregulates paclitaxel-induced expression of VEGF and survivin via MyD88-dependent TLR4 signaling in EOC cells[4].
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[2].
References:
[1]. Atractylenolide I, et al. The JAK2/STAT3 pathway is involved in the anti-melanoma effects of atractylenolide I. Exp Dermatol. 2018 Feb;27(2):201-204.
[2]. Gao H, et al. Anti-depressant-like effect of atractylenolide I in a mouse model of depression induced by chronic unpredictable mild stress. Exp Ther Med. 2018 Feb;15(2):1574-1579.
[3]. Li W, et al. Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro. Exp Cell Res. 2017 Apr 1;353(1):26-34.
[4]. Huang JM, et al. Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking activation of TLR4/MyD88-dependent pathway. Sci Rep. 2014 Jan 23;4:3840.