台灣新冠一號刺激人類單核球生長，細胞週期調控和細胞移行的相關表現

Taiwan Chingguan Yihau-NRICM101 Stimulates Monocyte Proliferation, Cell Cycle Propagation and Migration

目的：台灣清冠一號（NRICM-01）由台灣衛生福利部國家中醫藥研究所開發，用在減緩新冠肺炎病程。NRICM-01的配方包含薄荷、荊芥、桑葉、歐洲防風草、黃芩、魚腥草、板藍根、白茅根、厚樸和甘草。NRICM-01被廣泛用於治療新冠肺炎病人，擁有理想的安全性和有效性，對自體免疫患者也是如此。然而，使用NRICM-01對類風濕性關節炎（RA）患者的免疫系統影響尚不清楚。
方法：本研究採用人類THP-1細胞研究NRICM-01的藥效。評估其對單核細胞存活、細胞週期增殖和細胞遷移能力的影響。將健康個體和接受Simponi治療的類風濕性關節炎（RA）患者的血清分別與THP-1細胞和NRICM101共培養。
結果：MTT實驗顯示，NRICM101從1 mg/mL到20 mg/mL的組別在24小時後顯著促進單核細胞增殖，且呈現劑量依賴性。流式細胞儀分析顯示，10 mg/mL NRICM101顯著降低了THP-1細胞的細胞週期G1期，增加了S期，提示細胞週期延長。Transwell實驗顯示，20 mg/mL NRICM101刺激了單核細胞的移動，並伴隨相關的遷移蛋白上調。在使用Simponi治療的RA患者血清和健康個體血清進行的共培養實驗中，THP-1細胞增殖並無顯著差異。
結論：NRICM101被證實可以對抗SARS-CoV-2病毒感染（引發的細胞激素風暴。我們的初步結果揭示了其對單核細胞存活和移動能力有潛在影響。NRICM101與健康個體及接受Simponi治療的類風濕性關節炎（RA）患者的血清共培養時，均能刺激THP-1增生。基於這些發現，我們建議風濕病學家謹慎考慮NRICM101對類風濕性關節炎患者單核細胞存活和運動能力的潛在影響。

Objectives: Taiwan Chingguan Yihau (NRICM-01) were developed by Department Of Traditional Chinese Medicine Of Taiwan launched to combat COVID-19 pandemic. The formula of NRICM-01 contained mint, nepeta, mulberry leaf, parsnip, skullcap, houttuynia cordata, northern Isatis root, cogongrass, magnolia bark, and licorice. NRICM-01 was widely used to ameliorate COVID-19 infection with ideal patient safety and efficacy, including autoimmune patients. However, the cellular effect of NRICM-01 on rheumatoid arthritis (RA) patients remained obscure.
Methods: Human THP-1 Cells were applied to investigate pharmaceutical effect of NRICM101. The capacity of monocyte cell viability, cell cycle propagation and cell motility were evaluated. Serum obtained from healthy individuals and etanercept-treated RA patients were incubated with THP-1 Cells and NRICM101, respectively.
Results: NRICM101 significantly promoted monocyte proliferation in dose-dependent manner from 1mg/mL to 20mg/mL at 24 hr in MTT assay. From flowcytometry analysis, NRICM101 10mg/mL significantly decreased cell cycle G1 phase and increased S phase in THP-1 cells, suggesting cell cycle propagation. In transwell assay, NRICM101 20mg/mL stimulated the invasive behavior of monocytes with associated migratory protein upregulation. No significant difference in THP-1 cell proliferation was observed between co-culture experiments using serum from etanercept-treated RA patients and those using serum from healthy individuals.
Conclusions: NRICM101 was designated to combat cytokine storm triggered by SARS-CoV-2 virus infection, especially lung parenchyma. Our preliminary results revealed its potential impact on monocyte viability and motility. NRICM101 was capable of stimulating THP-1 proliferation when co-cultured with serum from both healthy individuals and etanercept-treated RA patients. Based on these findings, we recommend that rheumatologists exercise caution regarding the potential effects of NRICM101 on monocyte viability and motility in RA patients.