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

BMC Complementary Medicine and Therapies

Luxsana Panrit¹  Wanna Chaijaroenkul²  Tullayakorn Plengsuriyakarn²  Siriprapa Warathumpitak²  Inthuon Kulma²  Kesara Na-Bangchang³ 

[1] Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University (Rangsit Campus), 12121, Pathumthani, Thailand;Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), 12121, Pathumthani, Thailand;Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), 12121, Pathumthani, Thailand;Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), 12121, Pathumthani, Thailand;Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), 12121, Pathumthani, Thailand;Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University (Rangsit Campus), 12121, Pathumthani, Thailand;

关键词: Atractylodes lancea;    β-Eudesmol;    Atractylodin;    Cholangiocarcinoma;    Immunomodulatory activity;   

DOI  :  10.1186/s12906-020-03199-6

来源: Springer

【 摘 要 】

BackgroundAtractylodes 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.MethodsThe 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.ResultsAL 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.ConclusionsThe 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 registrationRetrospectively registered on 17 October 2020 [Thai Clinical Trials Registry (TCTR: www.clinicaltrials.in.th) Number TCTR20201020001#].

【 授权许可】

CC BY