Background: Guizhi Gancao Decoction (GGD), a classic formula in Traditional Chinese Medicine (TCM), is composed of Ramulus Cinnamomi (RC) and Radix Glycyrrhizae (RG). It is traditionally used to restore heart Yang and promote Qi transformation. However, its anti-cold effects, underlying mechanisms, and primary active components remain to be fully elucidated.
Objective: To investigate the anti-cold activity of GGD, identify its primary active components, and further explore its underlying mechanisms.
Methods: Mice were randomized into six groups (n = 10): control (no cold exposure), model (cold exposure), Miglitol (50 mg/kg, cold exposure), and three GGD groups (1, 2, 4 g/kg, cold exposure). After 21 days of treatment, body temperature and athletic performance were assessed. The main components of GGD were identified using HPLC-Q-TOF-MS, and network pharmacology was employed to analyze key compounds, targets, and biological processes. The pivotal signaling pathway was experimentally validated.
Results: GGD significantly alleviated hypothermia induced by cold exposure, while reducing total cholesterol, lipid droplets, mitochondrial membrane potential, and Adenosine
Triphosphate (ATP) production in brown adipose tissue (BAT). Additionally, GGD significantly upregulated the expression of Uncoupling protein 1 (UCP1) and its upstream regulator, Peroxisome proliferatoractivated receptor γ (PPARγ).
Conclusions: Administration of GGD maintains core body temperature during cold exposure by activating BAT via the PPARγ signaling pathway. The key compounds licochalcone D, hispaglabridin A, and cinnamic acid target PPARγ, UCP1, and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) respectively, regulating fatty acid oxidation and lipid metabolism. These compounds contribute to enhanced thermogenesis via PPARγ pathway. The prescription has the potential to be developed as a medicine for increasing thermogenesis in cold conditions.
Declarations
Not applicable.
CRediT authorship contribution statement
Zexu Shen: Writing - original draft, Validation, Data curation. Xiang Li: Methodology, Conceptualization. Chenghui Yan: Methodology, Conceptualization. Tianshu Ren: Methodology. Bo Xing: Methodology. Yingying Qu: Formal analysis. Dong Yao: Data curation. Zihua Xu: Writing - review & editing, Supervision. Yaling Han: Writing - original draft, Resources. Qingchun Zhao: Writing - review & editing, Supervision, Project administration, Methodology, Conceptualization.
Ethics approval and consent to participate
We minimized the number of animals used and all experiments were considered to reduce animal suffering. All procedures involving animals were in accordance with the ethical standards of the Committee on the Ethics of Animal Experiments of the General Hospital of Northern Theater Command (NO. 2023-54, NO. 2025-21).
Consent for publication
This work is original and has not been published nor is it currently under consideration for publication elsewhere. All authors have read and approved the final manuscript. We consent to the publication of this manuscript in Precision Medication and agree to transfer copyright to the publisher. Any materials reproduced from other sources are properly licensed or fall under fair use.
Availability of data and materials
All experimental materials are available from the corresponding author upon reasonable request.
Funding
Not applicable.
Declaration of Competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
Not applicable.
Authors' other information
Not applicable.
Appendix A. Supporting information
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.prmedi.2026.100077.
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