人参皂苷Rb1通过促进调节性T细胞（Treg）增殖和抑制炎症T细胞缓解哮喘
2025/04/30
摘要
背景：调节性T细胞（Treg）是一种具有可行性、耐受性和治疗效益的活性药物。尽管Treg通过调节炎症与哮喘预后相关，但迄今为止还没有专门设计用于通过上调Treg来治疗哮喘的药物。
方法：利用流式微球阵列技术筛选250种天然产物的文库。在筛选出的候选基因中，我们选取了gRb1进行进一步研究。通过流式细胞术和细胞因子分析评估gRb1对小鼠哮喘模型和健康人PBMCs中Treg和Th17细胞的影响。
结果：在炎症条件下，人参皂苷Rb1 （gRb1，人参的主要成分）增加了表达IL-10和TGF-β的Treg细胞群，降低了Th17细胞群；激活了Treg细胞中磷酸化STAT 5和NFAT1；抑制常规T细胞（Tconvs）中NFAT1的活化；增加Treg增殖和Tconv-Treg分化，抑制Tconv增殖；和减少Tconvs的炎性细胞因子分泌。在哮喘模型小鼠中，gRb1抑制哮喘症状与升高的Treg和降低的Th17、Th1和Th2计数有关。gRb1刺激哮喘患者和健康供者的PBMCs后，表达IL-10和TGF-β的Treg细胞数量增加，表达IL-17A、IL-22、IFN-γ和TNF-α的t细胞数量减少。
结论：gRb1通过改变Treg-炎性T细胞平衡减轻哮喘。这些发现提示了一种通过gRb1治疗增强Treg活性的策略。这可能为哮喘及相关疾病提供一种新的治疗方法。
Asthma Alleviation by Ginsenoside Rb1 via Promotion of Treg Proliferation and Inflammatory T Cell Inhibition
Susanna Choi, Seung-Ah Yoo, Kon-Young Ji, Dong Ho Jung, Saseong Lee, Kang-Gu Lee, Ki-Myo Kim, Joo Young Lee, Myung-A Jung, Bo-Jeong Pyun, Jung Hur, Joon Young Choi, Chin Kook Rhee, Wan-Uk Kim , Taesoo Kim
Abstract
Background: Regulatory T cells (Tregs) are living drugs with feasibility, tolerability, and therapeutic benefits. Although Tregs are linked to asthma prognosis through inflammation regulation, no therapeutic agents specifically designed to manage asthma by upregulating Tregs have been developed to date.
Methods: We screened a library of 250 natural products using a cytometric bead array. Among the selected candidates, gRb1 was identified for further investigation. The effects of gRb1 on Treg and Th17 populations were evaluated in mouse asthma models and human PBMCs from both healthy donors and asthma patients using flow cytometry and cytokine analysis.
Results: In inflammatory conditions, ginsenoside Rb1 (gRb1, a major ginseng component) increased IL-10- and TGF-β-expressing Treg populations and decreased the Th17 population; activated phospho-STAT5 and NFAT1 in Tregs; inhibited NFAT1 activation in conventional T cells (Tconvs); increased Treg proliferation and Tconv-Treg differentiation, inhibiting Tconv proliferation; and reduced inflammatory cytokine secretion by Tconvs. In asthma model mice, suppression of asthma symptoms by gRb1 was associated with elevated Treg and lower Th17, Th1, and Th2 counts. gRb1 treatment of stimulated PBMCs from patients with asthma and healthy donors increased IL-10- and TGF-β-expressing Treg populations and decreased IL-17A-, IL-22-, IFN-γ-, and TNF-α-expressing T-cell populations.
Conclusions: gRb1 alleviate asthma by shifting the Treg-inflammatory T cell balance. These findings suggest a strategy for enhancing Treg activity through treatment with gRb1. This may provide a novel therapeutic approach for asthma and related disorders.
背景：调节性T细胞（Treg）是一种具有可行性、耐受性和治疗效益的活性药物。尽管Treg通过调节炎症与哮喘预后相关，但迄今为止还没有专门设计用于通过上调Treg来治疗哮喘的药物。
方法：利用流式微球阵列技术筛选250种天然产物的文库。在筛选出的候选基因中，我们选取了gRb1进行进一步研究。通过流式细胞术和细胞因子分析评估gRb1对小鼠哮喘模型和健康人PBMCs中Treg和Th17细胞的影响。
结果：在炎症条件下，人参皂苷Rb1 （gRb1，人参的主要成分）增加了表达IL-10和TGF-β的Treg细胞群，降低了Th17细胞群；激活了Treg细胞中磷酸化STAT 5和NFAT1；抑制常规T细胞（Tconvs）中NFAT1的活化；增加Treg增殖和Tconv-Treg分化，抑制Tconv增殖；和减少Tconvs的炎性细胞因子分泌。在哮喘模型小鼠中，gRb1抑制哮喘症状与升高的Treg和降低的Th17、Th1和Th2计数有关。gRb1刺激哮喘患者和健康供者的PBMCs后，表达IL-10和TGF-β的Treg细胞数量增加，表达IL-17A、IL-22、IFN-γ和TNF-α的t细胞数量减少。
结论：gRb1通过改变Treg-炎性T细胞平衡减轻哮喘。这些发现提示了一种通过gRb1治疗增强Treg活性的策略。这可能为哮喘及相关疾病提供一种新的治疗方法。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
（Allergy. 2025 Apr 19. doi: 10.1111/all.16551.）
Asthma Alleviation by Ginsenoside Rb1 via Promotion of Treg Proliferation and Inflammatory T Cell Inhibition
Susanna Choi, Seung-Ah Yoo, Kon-Young Ji, Dong Ho Jung, Saseong Lee, Kang-Gu Lee, Ki-Myo Kim, Joo Young Lee, Myung-A Jung, Bo-Jeong Pyun, Jung Hur, Joon Young Choi, Chin Kook Rhee, Wan-Uk Kim , Taesoo Kim
Abstract
Background: Regulatory T cells (Tregs) are living drugs with feasibility, tolerability, and therapeutic benefits. Although Tregs are linked to asthma prognosis through inflammation regulation, no therapeutic agents specifically designed to manage asthma by upregulating Tregs have been developed to date.
Methods: We screened a library of 250 natural products using a cytometric bead array. Among the selected candidates, gRb1 was identified for further investigation. The effects of gRb1 on Treg and Th17 populations were evaluated in mouse asthma models and human PBMCs from both healthy donors and asthma patients using flow cytometry and cytokine analysis.
Results: In inflammatory conditions, ginsenoside Rb1 (gRb1, a major ginseng component) increased IL-10- and TGF-β-expressing Treg populations and decreased the Th17 population; activated phospho-STAT5 and NFAT1 in Tregs; inhibited NFAT1 activation in conventional T cells (Tconvs); increased Treg proliferation and Tconv-Treg differentiation, inhibiting Tconv proliferation; and reduced inflammatory cytokine secretion by Tconvs. In asthma model mice, suppression of asthma symptoms by gRb1 was associated with elevated Treg and lower Th17, Th1, and Th2 counts. gRb1 treatment of stimulated PBMCs from patients with asthma and healthy donors increased IL-10- and TGF-β-expressing Treg populations and decreased IL-17A-, IL-22-, IFN-γ-, and TNF-α-expressing T-cell populations.
Conclusions: gRb1 alleviate asthma by shifting the Treg-inflammatory T cell balance. These findings suggest a strategy for enhancing Treg activity through treatment with gRb1. This may provide a novel therapeutic approach for asthma and related disorders.
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