Elucidation of the mechanisms and therapeutic effects of Sini Decoction on anxiety induced by forced swimming stress in mice
- J Ethnopharmacol. 2026 Sep 15:368:121766. doi: 10.1016/j.jep.2026.121766.
- 1. Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, PR China.
- 2. Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical University, 710032, Xi'an, Shaanxi, PR China.
- 3. Department of Pharmacy, Xi'an Daxing Hospital, 710082, Xi'an, Shaanxi, PR China.
- 4. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Pharmacy, School of Stomatology, the Fourth Military Medical University, 710032, Xi'an, Shaanxi, PR China; Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, PR China. Electronic address: [email protected].
- 5. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Pharmacy, School of Stomatology, the Fourth Military Medical University, 710032, Xi'an, Shaanxi, PR China; Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, PR China. Electronic address: [email protected].
- 6. Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, PR China. Electronic address: [email protected].
Ethnopharmacological relevance: Sini Decoction (SND) is a famous prescription from the 'Treatise on Febrile Diseases,' composed of Aconitum carmichaeli Debx., Zingiber officinale Roscoe and Glycyrrhiza uralensis Fisch. It has been widely used in clinical practice within traditional Chinese medicine. According to in-depth studies, SND has demonstrated significant positive effects on psychiatric treatment. However, the efficacy and the mechanisms by which SND treats anxiety remain unclear.
Aim of the study: This study aimed to investigate the therapeutic effect and mechanisms of SND on anxiety induced by forced swimming (FS) stress in mice.
Materials and methods: Based on this, we first evaluated the safety of SND, and then used the anxiety model induced by FS to evaluate the therapeutic potential of SND. To further explore the molecular mechanism of SND in treating anxiety, we used network pharmacology combined with UHPLC-Q-Orbitrap-HRMS to predict the therapeutic targets and action pathways associated with SND. We then verified these predictions using molecular docking, CETSA experiments, immunofluorescence, and Western blotting. Finally, PI3K agonists are given to verify whether SND exerts anxiolytic effects through the PI3K/Akt pathway.
Results: The results of this study indicate that SND, at a maximum dose of 273.6 g/kg, does not cause acute toxicity in mice and has no significant effects on body weight, food intake, or histopathology of organs and tissues, demonstrating good safety. It can significantly increase the activity of anxious mice in the central area of the open field and the time spent in the open arms of the elevated plus maze, as well as improve hippocampal neuron damage, confirming its anxiolytic effects. Through network pharmacology and experimental validation, the study elucidated that its core mechanism involves regulating the PI3K/Akt signaling pathway, with 6-gingerol and Licochalcone B stably binding to core targets, experimental validation showed that SND downregulates the expression of PI3K and Akt proteins in this pathway, an effect that can be reversed by a PI3K agonist.
Conclusion: SND is a safe and effective anxiolytic formula, and its mechanism of action is related to the inhibition of the PI3K/Akt signaling pathway. Our research provides a pharmacological basis for the traditional use of SND and indicates that it is a promising candidate drug for the further development of treatments for anxiety.