一项评价苍术（白术） DC. 在健康泰国受试者中的免疫调节活性的随机安慰剂对照 I 期临床试验。
A randomized placebo-controlled phase I clinical trial to evaluate the immunomodulatory activities of Atractylodes lancea (Thunb) DC. in healthy Thai subjects.
机构信息
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12121, Thailand.
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani, 12121, Thailand.
出版信息
BMC Complement Med Ther. 2021 Feb 12;21(1):61. doi: 10.1186/s12906-020-03199-6.
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 #].
背景
白术（Thunb）DC.（AL）和生物活性化合物β-桉叶醇和苍术素已在体外和体内研究中证明具有在胆管癌的临床应用潜力。这项研究是一项随机、双盲、安慰剂对照的 I 期临床试验，旨在评估 AL 在人体中的免疫调节作用。
方法
采用实时 PCR 法测定 AL、β-桉叶醇和苍术素对 PBMCs 中 TNFα 和 IL6 表达的调节作用。四十八名健康受试者口服标准化 AL 提取物胶囊制剂或安慰剂后，采集血液样本。采用流式细胞术分析细胞因子微珠阵列（CBA）检测血清细胞因子谱、淋巴细胞亚群（B 淋巴细胞、CD8 细胞毒性 T 淋巴细胞、CD4 T 辅助淋巴细胞和 NK 细胞）和 PBMCs 对胆管癌细胞系 CL-6 的细胞毒性。
结果
AL 提取物在几乎所有浓度下均显著抑制 ConA 介导的 PBMCs 炎症中 TNFα 和 IL6 的表达。β-桉叶醇在所有浓度下均显著抑制 IL6 的表达。苍术素在最低浓度下显著抑制两种细胞因子的表达，而最高浓度仅显著抑制 IL6 的表达。单次口服 1000mg AL 似乎会降低 IFNγ 和 IL10，并增加 B 细胞，同时显著增加 NK 和 CD4 和 CD8 细胞。在 24 小时给药时观察到 PBMCs 细胞毒性活性增加的趋势（与安慰剂相比）。AL 多剂量 1000mg 连续给药 21 天，细胞因子的产生呈下降趋势，而在给药 24 小时时，IL17A 的产生受到显著抑制。此外，CD4 和 CD8 细胞显著增加。在 24 小时观察到 PBMCs 细胞毒性活性增加的趋势，但在 48 小时终止。
结论
这些结果证实了 AL 在人体中的免疫调节活性。这种活性与 AL 诱导胆管癌细胞凋亡的直接作用互补，提示其在胆管癌控制中的潜在作用。
试验注册
于 2020 年 10 月 17 日回顾性注册[泰国临床试验注册中心（TCTR：www.clinical trials.in.th）编号 TCTR20201020001 #]。
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