Neuroprotection of paeoniflorin as antidepressant candidate

Yuh-Fung Chen, Department of Pharmacology, China Medical University, Taichung City 404328, Taiwan, R.O.C.Follow
Yi-Jui Chen, Department of Pharmacology, China Medical University, Taichung City 404328, Taiwan, R.O.C
Jai-Sing Yang, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan, R.O.C
Min-Min Lee, Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan, R.O.C.
Huei-Yann Tsai, Department of Pharmacy, China Medical University Hospital, Taichung 404327, Taiwan, R.O.C.

Abstract

Background: Depression is one of the common mental disorders worldwide, and currently used antidepressants have undesirable effects; therefore, the development of new antidepressants without side effects is urgently needed. Paeoniflorin (PF) exhibits various pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. NMDA receptors in the hippocampus play a vital role in the pathophysiology of depression. Due to the scarcity of reports on the neuroprotection of PF on NMDA-induced excitotoxicity in the hippocampus, the present study aims to investigate the effects of PF on NMDA-mediated EPSP and calcium influx in the hippocampus to evaluate the potential of PF as an antidepressant.

Methods: In order to investigate the effects of PF on the NMDA receptor in the hippocampus, the hippocampal slices, primary-cultured hippocampal neurons, and in silico molecular docking analysis of PF with the NMDA receptor were used.

Results: PF (2 mM) significantly depressed the NMDA-mediated EPSPs, resulting in a 50% inhibition. The intracellular calcium level in primary-cultured hippocampal neurons was 102.67 nM, and 520.36 nM after NMDA (125 mM) treatment. With NMDA and PF co-treatment, the calcium level was 204.58 mM, showing a 60.68% decrease. After NMDA was co-treated with 1 μM ruthenium red (RuR), the calcium level increased (from 534.58 nM to 665.68 nM). Additionally, co-treatment with PF significantly decreased the calcium level (468.05 nM, representing a 29.50% decrease). In the presence of NMDA and 1 mM w-conotoxin MVIIC (w-Cono) co-treatment, the calcium level was 496.29 nM. In the presence of NMDA, w-Cono, and RuR, the calcium level was 568.5 nM. Additionally, NMDA, w-Cono, RuR, and PF co-treatment significantly decreased the calcium level to 270.94 nM. In silico molecular docking analysis revealed a binding energy of -48.5188 Kcal/mol for PF with the NMDA receptor.

Conclusions: PF binds to the NMDA receptor, exhibits neuroprotection, and contributes to its potential as an antidepressant.

Recommended Citation

Chen, Yuh-Fung; Chen, Yi-Jui; Yang, Jai-Sing; Lee, Min-Min; and Tsai, Huei-Yann (2025) "Neuroprotection of paeoniflorin as antidepressant candidate," BioMedicine: Vol. 15 : Iss. 4 , Article 6.
DOI: 10.37796/2211-8039.1680