抗COVID - 19中草药金花清肝颗粒诱导中性粒细胞/淋巴细胞比率和血浆IL - 6和IFN - γ水平的快速变化:一项开放标签、单臂试点研究

Y. Kageyama, K. Aida, K. Kawauchi, M. Morimoto, T. Ebisui, T. Akiyama, Tsutomu Nakamura
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引用次数: 7

摘要

传统中草药为中国感染冠状病毒2019 (COVID - 19)的患者提供了临床益处。金花清肝颗粒(JHQGG)是先前为治疗H1N1流感而开发的中草药配方,已被鼓励用于临床疑似COVID - 19感染的患者。然而,JHQGG作用的免疫药理学机制尚未得到证实。为了深入了解这一问题,本研究以未感染的个体为研究对象,研究了摄入JHQGG对血液和免疫参数的急性影响。为此,招募了18名健康志愿者,他们之前和现在的严重急性呼吸综合征冠状病毒感染检测均为阴性。单次口服JHQGG 1 h后采集外周血,进行血液学、生化和细胞因子检测。JHQGG迅速诱导血浆白细胞介素(IL)‐6水平显著降低(P=0.00309),血浆干扰素(IFN)‐γ水平显著升高(P=0.0268)。IL - 6水平降低,IFN - γ水平升高,分别出现在14名(77.8%)和13名(72.2%)受试者中。JHQGG显著降低中性粒细胞比例(P=0.00561),显著提高淋巴细胞比例(P=0.00485);因此,JHQGG显著降低了中性粒细胞/淋巴细胞比率(NLR) (P=0.00649)。这些发现表明,使用JHQGG治疗COVID - 19的临床益处至少部分与其对IL - 6、IFN - γ和NLR的快速调节作用有关。考虑到IL - 6和NLR是严重COVID - 19感染的关键生物标志物,JHQGG可能不仅适用于抑制疑似和无症状病例的疾病发作,而且适用于预防轻至重度感染患者的疾病进展。目前的开放标签单臂研究已在大学医院医学信息网络临床试验注册中心(UMIN - CTR)前瞻性注册,试验号为:2020年5月15日,UMIN000040407。
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Jinhua Qinggan granule, a Chinese herbal medicine against COVID‑19, induces rapid changes in the neutrophil/lymphocyte ratio and plasma levels of IL‑6 and IFN‑γ: An open‑label, single‑arm pilot study
Traditional Chinese herbal medicine has provided clinical benefits to patients infected with coronavirus 2019 (COVID‐19) in China. Jinhua Qinggan granule (JHQGG) is a Chinese multi‐herbal formula previously developed for the treatment of H1N1 influenza and has been encouraged for use in patients with clinically suspected COVID‐19 infection. However, the immunopharmacological mechanism for the efficacy of JHQGG has not yet been confirmed. To obtain insight into this issue, the present study examined the acute effects of JHQGG ingestion on hematological and immunological parameters using uninfected individuals as subjects. For this purpose, 18 healthy volunteers were enrolled, all of whom tested negative for prior and current severe acute respiratory syndrome coronavirus 2 infection. Peripheral blood samples were collected 1 h after a single oral JHQGG administration and subjected to hematological, biochemical and cytokine tests. JHQGG rapidly induced a significant decrease in the plasma level of interleukin (IL)‐6 (P=0.00309) and an increase in the plasma level of interferon (IFN)‐γ (P=0.0268). A decrease in IL‐6 and an increase in IFN‐γ levels were observed in 14 (77.8%) and 13 (72.2%) subjects, respectively. Notably, JHQGG significantly decreased the proportion of neutrophils (P=0.00561) and increased that of lymphocytes (P=0.00485); accordingly, the neutrophil/lymphocyte ratio (NLR) was significantly reduced by JHQGG (P=0.00649). These findings suggest that the clinical benefits of the use of JHQGG against COVID‐19 are, at least in part, associated with its rapid modulatory effects on IL‐6, IFN‐γ and NLR. Considering that IL‐6 and NLR are critical biomarkers for severe COVID‐19 infection, JHQGG may thus be suitable not only for suppressing disease onset in suspected and asymptomatic cases, but also for preventing disease progression in patients with mild to severe infection. The present open‐label, single‐arm study has been prospectively registered on the University Hospital Medical Information Network‐Clinical Trials Registry (UMIN‐CTR) under the trial no. UMIN000040407 on May 15, 2020.
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