Tinosporae Radix attenuates acute pharyngitis by regulating glycerophospholipid metabolism and inflammatory responses through PI3K-Akt signaling pathway

Lijie Lu; Chengfeng Huang; Yongfeng Zhou; Huajuan Jiang; Cuiping Chen; Jinyu Du; Tao Zhou; Feiyan Wen; Jin Pei; Qinghua Wu

doi:10.3389/fphar.2024.1491321

Tinosporae Radix attenuates acute pharyngitis by regulating glycerophospholipid metabolism and inflammatory responses through PI3K-Akt signaling pathway

Front Pharmacol. 2024 Nov 6:15:1491321. doi: 10.3389/fphar.2024.1491321. eCollection 2024.

Authors

Lijie Lu^#^{1

2}, Chengfeng Huang^#^{1

2}, Yongfeng Zhou^#³, Huajuan Jiang^{1

2}, Cuiping Chen^{1

2}, Jinyu Du^{1

2}, Tao Zhou^{1

2}, Feiyan Wen^{1

2}, Jin Pei^{1

2}, Qinghua Wu^{1

2}

Affiliations

¹ State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
³ Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.

^# Contributed equally.

Abstract

Introduction: With the onset of the COVID-19 pandemic, the incidence and prevalence of acute pharyngitis (AP) have increased significantly. Tinosporae Radix (TR) is a vital medication utilized in the treatment of pharyngeal and laryngeal ailments, especially AP. The study endeavors to explore unclear molecular mechanisms of TR in addressing AP.

Methods: Network pharmacology and metabolomics analyses of effect of TR on AP were conducted, and apossible pathway was validated both in vivo using the acute pharyngitis rat model and in vitro using the LPS-induced RAW264.7 cells model, through techniques such as histopathological examinations, immunohistochemical technology, ELISA, RT-qPCR, and Western blotting to systematically explore the possible mechanisms underlying the inhibition of AP by TR.

Results and discussion: Network pharmacology analysis identified several key targets, including PIK3CA, IL6, AKT1, TNF, and PTGS2, alongside pivotal signaling pathways such as IL-17, TNF, Hepatitis B, nuclear factor kappa B (NF-κB), Influenza A, and the PI3K-Akt pathway. Most of them are closely associated with inflammation. Then, wide-target metabolomics analysis showed that TR downregulated substances within the glycerophospholipid metabolic pathway, and modulated the PI3K-Akt pathway. The integrated findings from network pharmacology and metabolomics underscored the pivotal role of the PI3K-Akt signaling pathway and the attenuation of inflammatory responses. Finally, in vitro and in vivo experiments have shown that TR can inhibit inflammatory factors such as IL-6, TNF - α, and COX-2, downregulate targets such as PI3K and AKT on the PI3K-Akt signaling pathway, and thereby alleviate the inflammatory response of AP. Our study demonstrated that TR exerts an anti-AP effect through suppression of release of inflammatory factors and modulation of glycerophospholipid metabolism via suppressing the PI3K-Akt signaling pathway.

Keywords: PI3K-Akt signaling pathway; Tinosporae Radix; acute pharyngitis; glycerophospholipid metabolism; inflammatory responses.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supportes by National Natural Science Foundation of China (Grant no. 82274043), the Science and Technology Department of Sichuan Province (2023YFS0338), and the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202209).