A new phenolic acid isolated from Salvia miltiorrhiza ameliorates OVA-induced allergic asthma by regulation of Th17/Treg cells and inflammation through the TLR4 pathway

IF 7.5 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines Pub Date : 2025-12-01 Epub Date: 2025-12-13 DOI:10.1016/j.cjnm.2025.100007

Zeng Mengnan , Wu Yuanyuan , Ren Yingjie , Jiao Xianmian , Chang Fangzhuo , Wang Yuanyuan , Feng Weisheng , Zheng Xiaoke

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引用次数: 0

Abstract

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1’s effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg⁻¹) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21−25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L⁻¹), a specific TLR4 blocker, against S1 (10 µmol·L⁻¹) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL⁻¹) to elucidate the TLR4 pathway’s mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1’s positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1’s therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

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从丹参中分离的一种新的酚酸通过TLR4通路调节Th17/Treg细胞和炎症，改善ova诱导的过敏性哮喘

丹参（S. miltiorrhiza）是一种重要的中药成分，具有活血化瘀的作用，被广泛应用于哮喘的治疗。本研究首次从丹参中分离到一种新型酚酸（S1），并对其抗哮喘活性及其机制进行了初步研究。采用卵清蛋白（OVA）建立过敏性哮喘（AA）模型。采用多因素联合分析、流式细胞术、共培养等方法探讨S1对AA的作用机制，为哮喘临床治疗提供依据。在第21 ~ 25天，每天给ova诱导AA （OVA-AA）小鼠S1（10或20 mg·kg−1）。该研究检查了气道反应性、肺损伤、炎症以及免疫球蛋白E （IgE）、PGD2、白细胞介素（il - 4,5,10,13,17a）、肿瘤坏死因子α (TNF-α)、GM-CSF、CXCL1、CCL11和mMCP-1的水平。此外，肥大细胞（MC）激活和脱颗粒，以及T辅助型17 (Th17)/Treg免疫细胞和TLR4途径生物标志物也进行了研究。在共培养的16HBE细胞和LPS（1µg·mL−1）诱导的骨髓源性细胞（bmdc）或脾淋巴细胞（SLs）中，研究了TLR4特异性阻滞剂TLR4 (TAK-242)（1µmol·L−1）对S1（10µmol·L−1）的拮抗活性，以阐明TLR4通路的介导作用。S1表现出气道反应性降低、肺损伤和炎症，IgE、PGD2、白细胞介素、TNF-α、GM-CSF、CXCL1、CCL11和mMCP-1下调。它还阻碍了MC的激活和脱颗粒，上调了IL-10，并影响了卵细胞攻击后Th17/Treg免疫细胞的转化。此外，S1在OVA-AA小鼠中抑制TLR4通路，TLR4拮抗增强了S1的积极作用。OVA-AA小鼠模型分析表明，S1可缓解AA临床症状，恢复肺功能，抑制气道反应。S1的治疗作用通过调节Th17/Treg免疫细胞和炎症发生，至少部分归因于TLR4途径。该研究为S1在AA治疗中的应用提供了分子依据。

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来源期刊

Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.50

自引率

4.30%

发文量

2235

期刊介绍： The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.