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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Cholangiocarcinoma | Research article

A randomized placebo-controlled phase I clinical trial to evaluate the immunomodulatory activities of Atractylodes lancea (Thunb) DC. in healthy Thai subjects

Authors: Inthuon Kulma, Luxsana Panrit, Tullayakorn Plengsuriyakarn, Wanna Chaijaroenkul, Siriprapa Warathumpitak, Kesara Na-Bangchang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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Abstract

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.​clinicaltrials.​in.​th) Number TCTR20201020001#].
Appendix
Available only for authorised users
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Metadata
Title
A randomized placebo-controlled phase I clinical trial to evaluate the immunomodulatory activities of Atractylodes lancea (Thunb) DC. in healthy Thai subjects
Authors
Inthuon Kulma
Luxsana Panrit
Tullayakorn Plengsuriyakarn
Wanna Chaijaroenkul
Siriprapa Warathumpitak
Kesara Na-Bangchang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-03199-6

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