A randomized placebo-controlled phase I clinical trial to evaluate the immunomodulatory activities of Atractylodes lancea (Thunb) DC. in healthy Thai subjects.
BACKGROUND
Atractylodes lancea (Thunb) DC. (AL) and bioactive compounds β-eudesmol and atractylodin have been demonstrated in the in vitro and in vivo studies for their potential clinical use in cholangiocarcinoma. The study was a randomized, double-blinded, placebo-controlled phase I clinical trial to evaluate the immunomodulatory effect of AL in human subjects.


METHODS
The modulatory effects of AL and β-eudesmol and atractylodin on TNFα and IL6 expression in PBMCs were measured using real-time PCR. Blood samples were collected from forty-eight healthy subjects following oral administration of a single or multiple dosing of capsule formulation of the standardized AL extract or placebo. Serum cytokine profiles, lymphocyte subpopulations (B lymphocytes, CD8+ cytotoxic T lymphocytes, CD4+ T-helper lymphocytes, and NK cells), and cytotoxic activity of PBMCs against the cholangiocarcinoma cell line CL-6 were evaluated using cytometric bead array (CBA) with flow cytometry analysis.


RESULTS
AL extract at almost all concentrations significantly inhibited both TNFα and IL6 expression in Con A-mediated inflammation in PBMCs. β-Eudesmol at all concentrations significantly inhibited only IL6 expression. Atractylodin at the lowest concentration significantly inhibited the expression of both cytokines, while the highest concentration significantly inhibited only IL6 expression. The administration of AL at a single oral dose of 1000 mg appeared to decrease IFNγ and IL10 and increase B cell, while significantly increase NK and CD4+ and CD8+ cells. A trend of increasing (compared with placebo) in the cytotoxic activity of PBMCs at 24 h of dosing was observed. AL at multiple dosing of 1000 mg for 21 days tended to decrease the production of all cytokines, while significantly inhibited IL17A production at 24 h of dosing. In addition, a significant increase in CD4+ and CD8+ cells was observed. A trend of increase in the cytotoxic activity of PBMCs was observed at 24 h but terminated at 48 h of dosing.


CONCLUSIONS
The results confirm the immunomodulatory activity of AL in humans. This activity, in complementary with the direct action of AL on inducing cholangiocarcinoma cell apoptosis, suggests its potential role for CCA control.


TRIAL REGISTRATION
Retrospectively registered on 17 October 2020 [Thai Clinical Trials Registry (TCTR: www.clinical trials.in.th ) Number TCTR20201020001 #].
['Kulma|Inthuon|I|', 'Panrit|Luxsana|L|', 'Plengsuriyakarn|Tullayakorn|T|', 'Chaijaroenkul|Wanna|W|', 'Warathumpitak|Siriprapa|S|', 'Na-Bangchang|Kesara|K|']
D000328:Adult D031174:Atractylodes D045744:Cell Line, Tumor D049109:Cell Proliferation D002478:Cells, Cultured D018281:Cholangiocarcinoma D016207:Cytokines D005260:Female D005663:Furans D006801:Humans D007155:Immunologic Factors D007963:Leukocytes, Mononuclear D008297:Male D012189:Retrospective Studies D045787:Sesquiterpenes, Eudesmane D013785:Thailand D055815:Young Adult
Immunomodulatory activity Atractylodes lancea β-Eudesmol Atractylodin Cholangiocarcinoma