Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy

Zhang, Yamin; Lin, Jiajia; Xu, Xiaomei; Lu, Xuehua; Li, Lisha; Yang, Yuezhen; Lin, Wenjin

doi:10.3390/ijms26178678

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Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy

by

Yamin Zhang

^1,*,†,

Jiajia Lin

^2,†,

Xiaomei Xu

¹,

Xuehua Lu

¹,

Lisha Li

¹,

Yuezhen Yang

² and

Wenjin Lin

^2,3,*

¹

Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, China

²

School of Pharmacy, Fujian Medical University, Fuzhou 350122, China

³

College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou 350002, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(17), 8678; https://doi.org/10.3390/ijms26178678

Submission received: 28 May 2025 / Revised: 3 September 2025 / Accepted: 4 September 2025 / Published: 5 September 2025

(This article belongs to the Special Issue The Role of Bioactive Compounds in Human Health and Disease: 3rd Edition)

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Abstract

This study aimed to compare the therapeutic effects of fresh (CMF) and dried (CMD) Centipeda minima against allergic rhinitis (AR), elucidate their underlying molecular mechanisms, and identify the bioactive compounds responsible for their immunomodulatory actions. An ovalbumin-induced AR mouse model was treated with CMF or CMD extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components, which were further validated in RAW264.7 and RBL-2H3 cells. CMF and CMD exhibited distinct anti-AR mechanisms: CMF predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas CMD enhanced Th1 activity (increasing IFN-γ). Metabolomic analysis revealed CMF was rich in amino acids while CMD contained higher flavonoids, with neocnidilide and 6-gingerol identified as key bioactive compounds that modulated TNF-α, IL-6, and IL-10 via NF-κB and JAK-STAT pathways. These findings demonstrate that CMF and CMD exert complementary anti-inflammatory effects through Th2 inhibition and Th1 activation, respectively, providing a molecular basis for the traditional use of Centipeda minima and highlighting its bioactive compounds as potential therapeutics for inflammatory diseases.

Keywords: Centipeda minima; fresh and dried products; allergic rhinitis; transcriptomics; widely targeted metabolomics

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MDPI and ACS Style

Zhang, Y.; Lin, J.; Xu, X.; Lu, X.; Li, L.; Yang, Y.; Lin, W. Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy. Int. J. Mol. Sci. 2025, 26, 8678. https://doi.org/10.3390/ijms26178678

AMA Style

Zhang Y, Lin J, Xu X, Lu X, Li L, Yang Y, Lin W. Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy. International Journal of Molecular Sciences. 2025; 26(17):8678. https://doi.org/10.3390/ijms26178678

Chicago/Turabian Style

Zhang, Yamin, Jiajia Lin, Xiaomei Xu, Xuehua Lu, Lisha Li, Yuezhen Yang, and Wenjin Lin. 2025. "Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy" International Journal of Molecular Sciences 26, no. 17: 8678. https://doi.org/10.3390/ijms26178678

APA Style

Zhang, Y., Lin, J., Xu, X., Lu, X., Li, L., Yang, Y., & Lin, W. (2025). Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy. International Journal of Molecular Sciences, 26(17), 8678. https://doi.org/10.3390/ijms26178678

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Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy

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