Atractylenolide II

GW26-e1245 Atractylenolide II and Atractylenolide III Inhibit Platelets Activities and Thrombus Formation[Reference: WebLink]

J. Am. Coll. Cardiol., 2015, 66(16):C44-C44.

Atractylenolide II and Atractylenolide III Inhibit Platelets Activities and Thrombus Formation.

Determination of atractylenolide II in rat plasma by reversed-phase high-performance liquid chromatography.[Pubmed: 17236249]

Biomed Chromatogr. 2007 Mar;21(3):299-303.

METHODS AND RESULTS:
A method for quantitative determination of Atractylenolide II in rat plasma using reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with UV spectrometry was established. From a variety of compounds and solvents tested, Atractylenolide III was selected as the internal standard (IS) and ethyl acetate was found to be the best solvent for extracting Atractylenolide II from plasma samples. RP-HPLC analysis of the extracts was performed on an analytical column (DIKMA ODS, 150 x 4.6 mm; i.d., 5 microm) equipped with a security guard pre-column system. There was good linearity over the range 0.05-5.0 microg/mL (r > 0.99). The recoveries were more than 90.0% in plasma, and the intra- and inter-day coefficients of variation were less than 10.0% in all cases. The limit of detection (LOD) was 0.025 microg/mL and the lower limit of quantification (LLOQ) was 0.05 microg/mL.
CONCLUSIONS:
The RP-HPLC method was applied to quantitate Atractylenolide II in rat plasma within 24 h in a pharmacokinetics study where experimental rats received a single dose of Atractylenolide II (60 mg/kg).

Antiinflammatory Principles of Atractylodes Rhizomes.[Reference: WebLink]

Phytotherapy Research, 2007, 21(4):347-353.

The crude drug"jutsu"prepared from Atractylodes rhizomes has been used for antiinflammatory purposes in Oriental medicine.
METHODS AND RESULTS:
In fact, a preparation from A. japonica was found to show significant inhibition of the increased vascular permeability induced by acetic acid. Fractionation of the extract, monitoring by bioassay, resulted in the isolation of two active principles, (+)-eudesma-4 (14), 7 (11)-dien-8-one (VI) and atractylenolide I (VII).
CONCLUSIONS:
The structurally related principles Atractylenolide II and III (VIII and IX) also had the tendency to show antiinflammatory activity.

Inhibition of STAT3 signalling contributes to the antimelanoma action of atractylenolide II.[Pubmed: 25073716]

Exp Dermatol. 2014 Nov;23(11):855-7.

Our previous studies showed that Atractylenolide II (AT-II) has antimelanoma effects in B16 melanoma cells.
METHODS AND RESULTS:
In this study, we investigated the involvement of STAT3 signalling in the antimelanoma action of AT-II. Daily administration of AT-II (12.5, 25 mg/kg, i.g.) for 14 days significantly inhibited tumor growth in a B16 xenograft mouse model and inhibited the activation/phosphorylation of STAT3 and Src in the xenografts. In B16 and A375 cells, AT-II (20, 40 μm) treatment for 48 h dose-dependently reduced protein expression levels of phospho-STAT3, phospho-Src, as well as STAT3-regulated Mcl-1 and Bcl-xL. Overexpression of a constitutively active variant of STAT3, STAT3C in A375 cells diminished the antiproliferative and apoptotic effects of AT-II. These data suggest that inhibition of STAT3 signalling contributes to the antimelanoma action of AT-II.
CONCLUSIONS:
Our findings shed new light on the mechanism of action underlying the antimelanoma effects of AT-II and provide further pharmacological basis for developing AT-II as a novel melanoma chemopreventive/chemotherapeutic agent.

Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells.[Pubmed: 21524699]

J Ethnopharmacol. 2011 Jun 14;136(1):279-82.

Atractylenolide II (AT-II) is a sesquiterpene compound isolated from the dried rhizome of Atractylodes macrocephala (Baizhu in Chinese), which is traditionally prescribed for melanoma treatment by Chinese medicine practitioners. Our previous study showed that Atractylenolide II can inhibit B16 cells proliferation. Here we investigate the mechanistic basis for the anti-proliferative activity of Atractylenolide II in B16 melanoma cells.
METHODS AND RESULTS:
Cell viability was examined by MTT assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Protein expression was determined by Western blotting. Atractylenolide II treatment for 48 h dose-dependently inhibited cell proliferation with an IC(50) of 82.3 μM, and induced G1 phase cell cycle arrest. Moreover, treatment with 75 μM Atractylenolide II induced apoptosis. These observations were associated with the decrease of the expression of Cdk2, phosphorylated-Akt, phosphorylated-ERK and Bcl-2, the increase of the expression of phosphorylated-p38, phosphorylated-p53, p21, p27, and activation of caspases-8, -9 and -3. In addition, a chemical inhibitor of p53, PFTα, significantly decreased Atractylenolide II-mediated growth inhibition and apoptosis.
CONCLUSIONS:
We demonstrated that the G1-arresting and apoptotic effects of Atractylenolide II in B16 cells involve p38 activation as well as ERK and Akt inactivation, and the cytotoxic/apoptotic effects of Atractylenolide II are potentially p53 dependent.These findings provided chemical and pharmacological basis for the traditional application of Baizhu in melanoma treatment.