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Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis

  • Siqi Zhang (Natural Product Research Center, Korea Institute of Science and Technology) ;
  • Joonki Kim (Natural Product Research Center, Korea Institute of Science and Technology) ;
  • Gakyung Lee (Department of Integrative Biological Sciences and Industry, Sejong University) ;
  • Hong Ryul Ahn (Natural Product Research Center, Korea Institute of Science and Technology) ;
  • Yeo Eun Kim (Department of Integrative Biological Sciences and Industry, Sejong University) ;
  • Hee Ju Kim (Department of Integrative Biological Sciences and Industry, Sejong University) ;
  • Jae Sik Yu (Department of Integrative Biological Sciences and Industry, Sejong University) ;
  • Miso Park (Department of Pharmacy, Kangwon National University) ;
  • Keon Wook Kang (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Hocheol Kim (Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University) ;
  • Byung Hwa Jung (KIST-School, Korea University of Science and Technology (UST)) ;
  • Sung Won Kwon (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Dae Sik Jang (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Hyun Ok Yang (Department of Integrative Biological Sciences and Industry, Sejong University)
  • Received : 2024.04.12
  • Accepted : 2024.06.26
  • Published : 2024.11.01

Abstract

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumin-induced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Keywords

Acknowledgement

This research was funded by the Bio-Synergy Research Project [NRF2013M3A9C4078145] [NRF 2012M3A9C4048794] of the Ministry of Science, ICT, and Future Planning through the National Research Foundation of the Korea Institute of Science and Technology Institutional Program [2E31623].

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