Quantitative proteomics reveals the therapeutic effects of RFAP against depression via pathway regulation of long-term depression and potentiation

Yang Wu; Ying Hao; Guohua Yu; Li Li; Shanglong Wang; Xin Li; Zengliang Zhang; Shengcan Zou; Zimin Liu; Pengcheng Fan; Yuanyuan Shi

doi:10.1016/j.heliyon.2023.e13429

Quantitative proteomics reveals the therapeutic effects of RFAP against depression via pathway regulation of long-term depression and potentiation

Heliyon. 2023 Feb 15;9(3):e13429. doi: 10.1016/j.heliyon.2023.e13429. eCollection 2023 Mar.

Authors

Yang Wu¹, Ying Hao^{1

2}, Guohua Yu¹, Li Li³, Shanglong Wang³, Xin Li³, Zengliang Zhang⁴, Shengcan Zou³, Zimin Liu³, Pengcheng Fan⁵, Yuanyuan Shi^{1

6}

Affiliations

¹ School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.
² Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, 10065, USA.
³ Chenland Nutritionals, Inc., Irvine, CA, 92614, USA.
⁴ Traditional Chinese Medicine College, Inner Mongolia Medical University, Jinshan Development Zone Hohhot, Inner Mongolia, 010110, China.
⁵ State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Institute of Lifeomics, Beijing 102206, China.
⁶ Shenzhen Research Institute, Beijing University of Chinese Medicine, Shenzhen, Guangdong, 518118, China.

Abstract

Ethnopharmacological relevance: RFAP is a compound extraction complex of four Traditional Chinese Medicine (TCM), including the dry bark of Paeonia lactiflora Pall. (Radix Paeoniae Alba), Gardenia jasminoides J. Ellis (Fructus Gardeniae), Albizia julibrissin Durazz. (Albizia julibrissin Durazz), and Paeonia × suffruticosa Andrews (Peony bark). Not only RFAP but also the individual ingredients have been commonly used for the treatment of depression in the clinic. However, the underlying mechanism of pharmacology is difficult to interpret since its holistic and multidrug nature.

Aim of the study: This study aimed to elucidate the potential antidepressant mechanism of RFAP in the treatment of chronic unpredictable mild stress (CUMS) rats' model via the quantitative proteomics approach.

Materials and methods: We established the CUMS rats' model and evaluated the efficacy of RFAP using multiple behavior assays, including the sugar preference test, open field test, and forced swimming test. Then label-free quantitative proteomics analyses were performed to evaluate the integrated changes of proteome profiling in control, CUMS, RFAP low dose, and RFAP high dose groups. Finally, we validated the critical changed proteins in the pathways of long-term depression and potentiation via RT-PCR and Western blotting assays.

Results: We successfully established the CUMS rats' model. The behavior assays indicated that the rats demonstrated a tendency to behavioral despair after four weeks. Label-free quantitative proteomics showed that 107 proteins were significantly upregulated and 163 proteins were downregulated in the CUMS group compared to the control group. These differentially expressed proteins were involved in long-term potentiation, long-term depression, nervous system development, neuronal synaptic structural constituent of ribosome, ATP metabolic process, learning or memory, and cellular lipid metabolic process. RFAP treatment partially restored the differentially expressed protein profile. The protective effect of RFAP on behavioral assessment were consistent with the results of proteomics.

Conclusions: The results indicated that RFAP exerted a synergistic effect on CUMS by regulating long-term inhibition and potentiation-related proteins.

Keywords: CUMS; Depression; Quantitative proteomics; Traditional Chinese medicine.