Kemin capsule ameliorates post-infectious cough by modulating the PI3K/AKT signaling pathway and TRPA1/TRPV1 channels.

Autor: Yang Z; School of Pharmacy, Shandong University of Traditional Chinese Medicine, 250355, China. Electronic address: yangzc007@163.com., Liang Y; School of Pharmacy, Shandong University of Traditional Chinese Medicine, 250355, China. Electronic address: lyx1202@163.com., Wu C; School of Pharmacy, Shandong University of Traditional Chinese Medicine, 250355, China. Electronic address: 1877662619@163.com., Xie H; School of Pharmacy, Shandong University of Traditional Chinese Medicine, 250355, China. Electronic address: 18870783345@163.com., Liu S; Shandong Kangzhonghong Pharmaceutical Technology Development Co., Ltd, 250014, China. Electronic address: kzyy88@126.com., Sun P; Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, 250355, China. Electronic address: sunpeng@sdutcm.edu.cn., Zhang Y; School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 250355, China. Electronic address: 60020129@sdutcm.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2025 Jan 30; Vol. 337 (Pt 1), pp. 118837. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1016/j.jep.2024.118837
Abstrakt: Ethnopharmacological Relevance: Kemin capsule (KMC), as an innovative traditional Chinese medicine (TCM), has shown excellent efficacy in treating PIC in China. The post-infectious cough (PIC) is a common condition in pediatrics, and the inflammatory responses to PIC are intricately linked to the immune mechanisms of the host. However, the precise mechanisms involved remain uncertain.
Aim of Study: The objective of this research is to investigate the mechanisms by which KMC treats PIC using a combination of UPLC-MS, bioinformatics, network pharmacology, and molecular docking. The study's findings will be corroborated through in vitro and in vivo experiments.
Materials and Methods: This study identified the main components of KMC using UPLC-MS. The mechanism by which these capsules treat PIC was explored through transcriptomics, network pharmacology, and molecular docking. PIC model in Balb/c mice was induced with respiratory syncytial virus (RSV) at a titer of 10^5.5 TCID 50 /mL. From day 14 post-infection, the mice were orally administered the capsules at doses of 0.3, 0.6, and 1.2 g/kg for two weeks. Cough was stimulated with capsaicin at 10^-4 mol/mL, and the effects on PIC mice were measured by cough frequency, latency, ELISA, and H&E staining. Expression levels of transient receptor potential (TRP) channel proteins and the PI3K/AKT signaling pathway were analyzed using RT-qPCR, immunohistochemistry (IHC), and western blot (WB). The effect of KMC on A549 cells proliferation in vitro was also assessed.
Results: The therapeutic efficacy of KMC is potentially exerted through its inherent bioactive constituents, including deoxyandrographolide, quercetin, and chryseriol. These compounds are hypothesized to modulate the PI3K/AKT signaling pathway and influence the function of TRP channel proteins, consequently mitigating the pathological state associated with PIC. In vivo experiments have demonstrated that KMC significantly reduces the frequency of coughs and extends the cough latency period in mice with PIC. KMC mitigates airway inflammation by suppressing the production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. The expression or phosphorylation levels of key regulators in the PI3K/AKT/TRP axis in mouse lung tissue, including PI3K, AKT, NF-κB p65, TLR4, STAT3, TRPV1, TRPA1 were significantly reduced.
Conclusion: KMC exerts its therapeutic effect on PIC by dampening the activation of the PI3K/AKT signaling pathway and the activity of TRPA1 and TRPV1 ion channels.
Competing Interests: Declaration of competing interest We declare that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We take full responsibility for the work being reported. It is the original study and has been neither published elsewhere nor submitted for publication.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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