Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps

Abstract Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur me...

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Main Authors: Xu Wang, Hui-Ming Peng, Meng-Ru Zhang, Jing-Jing Li, Chuan-Peng Zhao, Ya-Li Zhang, Si-Yu Wang, Si-Ying Zhu, Jian-Kang Lu, Hai-Long Yin, Qiang Yin, Jin-Bo Fang
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Language:English
Published: BMC 2025-02-01
Series:Chinese Medicine
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Online Access:https://doi.org/10.1186/s13020-025-01069-2
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author Xu Wang
Hui-Ming Peng
Meng-Ru Zhang
Jing-Jing Li
Chuan-Peng Zhao
Ya-Li Zhang
Si-Yu Wang
Si-Ying Zhu
Jian-Kang Lu
Hai-Long Yin
Qiang Yin
Jin-Bo Fang
author_facet Xu Wang
Hui-Ming Peng
Meng-Ru Zhang
Jing-Jing Li
Chuan-Peng Zhao
Ya-Li Zhang
Si-Yu Wang
Si-Ying Zhu
Jian-Kang Lu
Hai-Long Yin
Qiang Yin
Jin-Bo Fang
author_sort Xu Wang
collection DOAJ
description Abstract Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.’s volatile oil (HVO) in SRA have not been fully elucidated. Methods This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism. Results HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA. Conclusion These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.
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spelling doaj-art-481fda67fffe4bb6b4cd5bc17b1b09202025-02-09T12:54:18ZengBMCChinese Medicine1749-85462025-02-0120111810.1186/s13020-025-01069-2Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular trapsXu Wang0Hui-Ming Peng1Meng-Ru Zhang2Jing-Jing Li3Chuan-Peng Zhao4Ya-Li Zhang5Si-Yu Wang6Si-Ying Zhu7Jian-Kang Lu8Hai-Long Yin9Qiang Yin10Jin-Bo Fang11School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Anatomy, Tongji Medical College, Huazhong University of Science and TechnologySchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologyHubei Shizhen Laboratory, School of Basic Medicine, Hubei University of Chinese MedicineSchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologySchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologySchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologySchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologySchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologyXinjiang Uygur Pharmaceutical Co., Ltd, No. 2, Shenyang Street, Urumqi Economic and Technological Development Zone (Toutunhe District), Xinjiang Uygur Autonomous RegionXinjiang Uygur Pharmaceutical Co., Ltd, No. 2, Shenyang Street, Urumqi Economic and Technological Development Zone (Toutunhe District), Xinjiang Uygur Autonomous RegionSchool of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.’s volatile oil (HVO) in SRA have not been fully elucidated. Methods This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism. Results HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA. Conclusion These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.https://doi.org/10.1186/s13020-025-01069-2Hyssopus cuspidatus Boriss.Volatile oilSteroid-resistant asthmaNeutrophil extracellular trapsNeutrophil elastase
spellingShingle Xu Wang
Hui-Ming Peng
Meng-Ru Zhang
Jing-Jing Li
Chuan-Peng Zhao
Ya-Li Zhang
Si-Yu Wang
Si-Ying Zhu
Jian-Kang Lu
Hai-Long Yin
Qiang Yin
Jin-Bo Fang
Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps
Chinese Medicine
Hyssopus cuspidatus Boriss.
Volatile oil
Steroid-resistant asthma
Neutrophil extracellular traps
Neutrophil elastase
title Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps
title_full Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps
title_fullStr Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps
title_full_unstemmed Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps
title_short Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps
title_sort hyssopus cuspidatus volatile oil a potential treatment for steroid resistant asthma via inhibition of neutrophil extracellular traps
topic Hyssopus cuspidatus Boriss.
Volatile oil
Steroid-resistant asthma
Neutrophil extracellular traps
Neutrophil elastase
url https://doi.org/10.1186/s13020-025-01069-2
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