PMID- 38367929
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240315
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 326
DP  - 2024 May 23
TI  - Xiaoyaosan promotes neurotransmitter transmission and alleviates CUMS-induced 
      depression by regulating the expression of Oct1 and Oct3 in astrocytes of the 
      prefrontal cortex.
PG  - 117923
LID - S0378-8741(24)00222-8 [pii]
LID - 10.1016/j.jep.2024.117923 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS) is a traditional prescription 
      for the treatment of liver depression and qi stagnation, and pharmacological 
      studies have shown that XYS has great potential to reverse depression. However, 
      anti-depression targets and the mechanism of XYS are still not entirely clear. 
      AIM OF THE STUDY: The present study aims to explore and verify the 
      anti-depression mechanism of XYS. MATERIALS AND METHODS: The antidepressant 
      effect of XYS was assessed in rats with depression induced by chronic 
      unpredictable mild stimulation (CUMS). The levels of 5-hydroxytryptamine (5-HT), 
      dopamine (DA), and norepinephrine (NE) in different brain regions were measured 
      using ELISA. The expression of organic cation transporters (Octs) were detected 
      by western blot and immunohistochemical techniques. Then, Decynium-22 (D22), an 
      Octs inhibitor, was injected into the prefrontal cortex (PFC) to verify the 
      correlation between Octs and depression-like behavior. Then, the effects of XYS 
      on the behavior, neurotransmitter concentration, and Octs expression in 
      D22-induced rats were examined. Finally, primary astrocytes were used to verify 
      the mechanism of XYS exerting anti-depressant activity by regulating Octs. 
      RESULTS: The result showed that XYS had a significant positive impact on the 
      behavior of depression rats induced by CUMS. XYS also improved the secretion of 
      5-HT, DA, and NE in the PFC, as well as the promotion of Oct1, Oct2, and Oct3 
      expression in the PFC. These results suggest that XYS has the potential to 
      alleviate depression by enhancing the secretion of neurotransmitters. This may be 
      related to XYS regulation of Oct's expression. When the expression of Octs was 
      inhibited in the PFC, rats exhibited behavior similar to depression, and XYS was 
      able to reverse this behavior, indicating that Octs play a significant role in 
      the development of depression and XYS may exert its antidepressant effects 
      through the regulation of Octs. Furthermore, the study also found that dopamine 
      uptake decreased after inhibiting the expression of Octs, and XYS-containing 
      serum could reverse the downregulation of Oct1 and Oct3 and promote intracellular 
      dopamine homeostasis in the astrocytes. Overall, XYS may exert antidepressant 
      effects by promoting dopamine uptake to improve neurotransmitter transport by 
      regulating the protein expression of Oct1 and Oct3 in astrocytes. CONCLUSIONS: 
      The antidepressant effect of XYS may be attributed to its ability to regulate the 
      expression of Oct1 and Oct3 in astrocytes of the PFC, thereby promoting 
      neurotransmitter transport.
CI  - Copyright (c) 2024. Published by Elsevier B.V.
FAU - Wu, Yayun
AU  - Wu Y
AD  - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second 
      Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 
      510120, PR China; Guangdong Provincial Hospital of Chinese Medicine, The Second 
      Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 
      University of Chinese Medicine, Guangdong, 510120, PR China; Guangdong Provincial 
      Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, 
      Guangzhou, 510120, PR China.
FAU - Liu, Lijuan
AU  - Liu L
AD  - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second 
      Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 
      510120, PR China; Guangdong Provincial Hospital of Chinese Medicine, The Second 
      Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 
      University of Chinese Medicine, Guangdong, 510120, PR China.
FAU - Zhao, Ya
AU  - Zhao Y
AD  - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second 
      Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 
      510120, PR China; Guangdong Provincial Hospital of Chinese Medicine, The Second 
      Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 
      University of Chinese Medicine, Guangdong, 510120, PR China; State Key Laboratory 
      of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of 
      Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
FAU - Li, Xiong
AU  - Li X
AD  - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second 
      Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 
      510120, PR China; Guangdong Provincial Hospital of Chinese Medicine, The Second 
      Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 
      University of Chinese Medicine, Guangdong, 510120, PR China.
FAU - Hu, Junhong
AU  - Hu J
AD  - School Pharmaceutical Science, Guangzhou University Chinese Medicine, Guangzhou, 
      510120, Guangdong, PR China.
FAU - Li, Hanlin
AU  - Li H
AD  - School Pharmaceutical Science, Guangzhou University Chinese Medicine, Guangzhou, 
      510120, Guangdong, PR China.
FAU - Zhao, Ruizhi
AU  - Zhao R
AD  - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second 
      Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 
      510120, PR China; Guangdong Provincial Hospital of Chinese Medicine, The Second 
      Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 
      University of Chinese Medicine, Guangdong, 510120, PR China; Guangdong Provincial 
      Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, 
      Guangzhou, 510120, PR China. Electronic address: zhaoruizhi@gzucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240216
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (xiaoyaosan)
RN  - VTD58H1Z2X (Dopamine)
RN  - 333DO1RDJY (Serotonin)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Drugs, Chinese Herbal)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Depression/drug therapy/etiology/metabolism
MH  - *Astrocytes
MH  - Dopamine
MH  - Serotonin
MH  - Behavior, Animal
MH  - Antidepressive Agents/pharmacology/therapeutic use
MH  - Prefrontal Cortex
MH  - Neurotransmitter Agents
MH  - *Drugs, Chinese Herbal
OTO - NOTNLM
OT  - Depression
OT  - Organic cation transporters
OT  - Prefrontal cortex
OT  - Xiaoyaosan
COIS- 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.
EDAT- 2024/02/18 00:42
MHDA- 2024/03/15 06:44
CRDT- 2024/02/17 19:18
PHST- 2024/01/16 00:00 [received]
PHST- 2024/02/12 00:00 [revised]
PHST- 2024/02/15 00:00 [accepted]
PHST- 2024/03/15 06:44 [medline]
PHST- 2024/02/18 00:42 [pubmed]
PHST- 2024/02/17 19:18 [entrez]
AID - S0378-8741(24)00222-8 [pii]
AID - 10.1016/j.jep.2024.117923 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2024 May 23;326:117923. doi: 10.1016/j.jep.2024.117923. Epub 
      2024 Feb 16.