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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2025-02-01
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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 |
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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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institution | Kabale University |
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language | English |
publishDate | 2025-02-01 |
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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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