Journal of ethnopharmacology · 2025
Multi-omics elucidation of HDRSD alleviating allergic rhinitis via IL-1β/TRPV1 pathway regulation.
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Li Yunong, Yang Jianing, Liu Ruobai, Xiang Yedong, Zhang Yulian, Zheng Mingyu, Yan Guanghai, Wang Chongyang, Chai Jingmei
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Han-Duo-Re-Shao Decoction (HDRSD), a traditional Korean medicine, effectively treats cold-pattern allergic rhinitis (AR). Its mechanism is rooted in addressing the lung-spleen-kidney qi-yang deficiency triad, which heightens rhinitis susceptibility. Guided by the principle of 'warming yang to dissipate cold', HDRSD fortifies body resistance and applies the 'cultivating earth to generate metal' theory to nourish the lungs. This study integrates ethnopharmacology with network pharmacology to elucidate HDRSD's "multi-component, multi-target, multi-pathway" mechanisms against AR.
AIM OF THE STUDY: The purpose of this study was to systematically reveal the active ingredients, targets and molecular mechanisms of HDRSD in the treatment of AR through in vivo and in vitro experiments.
MATERIALS AND METHODS: This study employed network pharmacology, molecular docking, transcriptome sequencing, protein-protein docking, molecular dynamics simulation, metabolomics, Western blot, and immunofluorescence to investigate how the main components of HDRSD regulate the IL-1β/TRPV1 pathway. In vivo, using HDM-induced AR mouse models, we assessed how HDRSD components alleviate symptoms via transcriptomics, flow cytometry, ELISA, HE staining, PAS staining, untargeted metabolomics and TUNEL assay. In vitro, using human nasal epithelial cells (HNEpCs), we verified the core IL-1β/TRPV1 regulation mechanism of HDRSD components through immunofluorescence, Western blot, metabolomics, transmission electron microscopy, JC-1 staining, mitoSOX staining and TUNEL assay.
RESULTS: The results showed that compared with the model group, the high-dose HDRSD group exhibited significant reductions in mice: a 42.3 % decrease in TNF-α (P < 0.01), along with decreases of 38.7 % in IL-4 (P < 0.05), 57.1 % in IL-5 (P < 0.05), 62.5 % in IL-6 (P < 0.05), and 59.5 % in IL-13 (P < 0.05). Furthermore, eosinophil infiltration in the nasal mucosa was reduced by 56.1 % (P < 0.01). Transcriptome sequencing revealed significant enrichment of the NLRP3 and NF-κB pathways. Network pharmacology identified IL-6 and IL-1β as core targets, corroborated by Western blot analysis showing decreased protein expression of IL-6, IL-1β, TRPV1, and NLRP3. Metabolomic analysis indicated that HDRSD primarily modulates AR through lipid metabolism pathways, with HDRSD-Pro demonstrating significant enrichment in metabolic pathways. Furthermore, HDRSD reduced eosinophil infiltration and goblet cell hyperplasia in the nasal mucosa. Mechanistically, HDRSD components downregulated IL-1β expression, thereby reducing its binding to the TRPV1 E600 site. This inhibition suppressed Ca2+ influx, alleviated mitochondrial damage in HNEpCs, and decreased apoptosis, ultimately mitigating AR.
CONCLUSION: This study revealed that the main components of HDRSD reduce mitochondrial damage and alleviate the process of AR through the IL-1β/TRPV1 signaling pathway.
AIM OF THE STUDY: The purpose of this study was to systematically reveal the active ingredients, targets and molecular mechanisms of HDRSD in the treatment of AR through in vivo and in vitro experiments.
MATERIALS AND METHODS: This study employed network pharmacology, molecular docking, transcriptome sequencing, protein-protein docking, molecular dynamics simulation, metabolomics, Western blot, and immunofluorescence to investigate how the main components of HDRSD regulate the IL-1β/TRPV1 pathway. In vivo, using HDM-induced AR mouse models, we assessed how HDRSD components alleviate symptoms via transcriptomics, flow cytometry, ELISA, HE staining, PAS staining, untargeted metabolomics and TUNEL assay. In vitro, using human nasal epithelial cells (HNEpCs), we verified the core IL-1β/TRPV1 regulation mechanism of HDRSD components through immunofluorescence, Western blot, metabolomics, transmission electron microscopy, JC-1 staining, mitoSOX staining and TUNEL assay.
RESULTS: The results showed that compared with the model group, the high-dose HDRSD group exhibited significant reductions in mice: a 42.3 % decrease in TNF-α (P < 0.01), along with decreases of 38.7 % in IL-4 (P < 0.05), 57.1 % in IL-5 (P < 0.05), 62.5 % in IL-6 (P < 0.05), and 59.5 % in IL-13 (P < 0.05). Furthermore, eosinophil infiltration in the nasal mucosa was reduced by 56.1 % (P < 0.01). Transcriptome sequencing revealed significant enrichment of the NLRP3 and NF-κB pathways. Network pharmacology identified IL-6 and IL-1β as core targets, corroborated by Western blot analysis showing decreased protein expression of IL-6, IL-1β, TRPV1, and NLRP3. Metabolomic analysis indicated that HDRSD primarily modulates AR through lipid metabolism pathways, with HDRSD-Pro demonstrating significant enrichment in metabolic pathways. Furthermore, HDRSD reduced eosinophil infiltration and goblet cell hyperplasia in the nasal mucosa. Mechanistically, HDRSD components downregulated IL-1β expression, thereby reducing its binding to the TRPV1 E600 site. This inhibition suppressed Ca2+ influx, alleviated mitochondrial damage in HNEpCs, and decreased apoptosis, ultimately mitigating AR.
CONCLUSION: This study revealed that the main components of HDRSD reduce mitochondrial damage and alleviate the process of AR through the IL-1β/TRPV1 signaling pathway.