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

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#].

The Role of Herbal Medicine in Cholangiocarcinoma Control: A Systematic Review

“…DC. extract was linked with suppression of the production of TNF- α and IL6 cytokines, which are involved in the pathogenesis and severity of CCA 137 . A phase II dose-finding study is underway to confirm efficacy, tolerability, and immunomodulatory activity of A. lancea (Thunb.)…”

A retrospective study of Pupingqinghua prescription versus Lianhuaqingwen in Chinese participants infected with SARS-CoV-2 Omicron variants

“…In addition, organic acid component, as the main active ingredient of pugongying, can improve acute tracheobronchitis by downregulating the protein expression levels of TNF-α and IL-6 (Yang et al, 2016). The main chemical constituents of Fuping, the flavones apigenin and luteolin, can suppress inflammatory responses by mediating neutrophil apoptosis (Lucas et al, 2013); In addition, Cangshu, Zhizi, and Huangqi have also been confirmed to have anti-inflammatory and anti-oxidant effects (Xiao et al, 2017;Kulma et al, 2021;Li et al, 2022). Combined with the aforementioned results, it may be suggested that PPQH plays an anti-SASR-COV-2 effect through its antiviral and anti-inflammatory cytokine storm functions; however, further research is still needed.…”

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice

“…Formulated AL and ATD are potential candidates and are currently under research and development for cholangiocarcinoma treatment [8,16,29]. Phase I clinical trial of AL showed promising safety and pharmacokinetic profiles [15], as well as immunomodulatory activity in healthy Thai subjects [30]. Phase II dose-finding study is currently in progress to find the most effective dose in patients with advanced stage cholangiocarcinoma.…”