PMID- 37059253
OWN - NLM
STAT- MEDLINE
DCOM- 20230508
LR  - 20230508
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 312
DP  - 2023 Aug 10
TI  - Zuojinwan ameliorates CUMS-induced depressive-like behavior through inducing 
      ubiquitination of MyD88 via SPOP/MyD88/NF-kappaB pathway.
PG  - 116487
LID - S0378-8741(23)00355-0 [pii]
LID - 10.1016/j.jep.2023.116487 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Zuojinwan (ZJW) is a traditional Chinese medicine 
      compound, which is often used clinically to treat gastritis and has 
      anti-inflammatory activity. It was found that ZJW is involved in suppressing the 
      expression of inflammatory factors, and neuroinflammation is thought to be 
      associated with the development of depression. AIM OF THE STUDY: In this study, 
      we investigated whether ZJW could exert antidepressant effects by regulating 
      MyD88 ubiquitination in depressed mice and attempted to elucidate the possible 
      mechanisms. MATERIALS AND METHODS: Six active compounds of Zuojinwan (ZJW) were 
      identified by HPLC. Then, the effects of ZJW on depression-like behavior in mice 
      were investigated by constructing a chronic unpredictable mild stimulation (CUMS) 
      mouse model. Meanwhile, the effect of ZJW on hippocampal neurons was investigated 
      by Nissl staining. In addition, western blotting, PCR, ELISA, 
      co-immunoprecipitation and immunostaining were used to explore whether ZJW could 
      inhibit neuroinflammation through SPOP/MyD88/NF-kappaB pathway and thus produce 
      antidepressant effects. Finally, we constructed the AAV-Sh-SPOP virus vector to 
      silence SPOP and verify the mechanism of ZJW's antidepressant action. RESULTS: 
      ZJW could dramatically ameliorate the depressive behavior induced by CUMS 
      stimulation and alleviate hippocampal neuronal damage. CUMS stimulation resulted 
      in decreased SPOP expression, impaired MyD88 ubiquitination, and activation of 
      downstream NF-kappaB signaling, which could be reversed by ZJW. In addition, ZJW 
      could significantly ameliorate the abnormal activation of microglia, and the 
      excessive levels of pro-inflammatory factors were inhibited. By blocking the 
      expression of SPOP, we found that ZJW exerted anti-inflammatory and 
      antidepressant effects mainly by promoting the ubiquitination of MyD88 and 
      inhibiting the activation of downstream inflammatory signals. CONCLUSION: In 
      conclusion, ZJW possesses alleviating effects on depression induced by CUMS 
      stimulation. ZJW can inhibit neuroinflammation and improve 
      neuroinflammation-induced depression-like behaviors through SPOP/MyD88/NF-kappaB 
      pathway.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Tao, Weiwei
AU  - Tao W
AD  - Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China; 
      School of Chinese Medicine, School of Integrated Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210023, China.
FAU - Su, Kunhan
AU  - Su K
AD  - Department of Gastroenterology, Nanjing Integrated Traditional Chinese and 
      Western Medicine Hospital, Nanjing, 210014, China.
FAU - Huang, Yuzhen
AU  - Huang Y
AD  - Department of Gastroenterology, Nanjing Integrated Traditional Chinese and 
      Western Medicine Hospital, Nanjing, 210014, China.
FAU - Lu, Zihan
AU  - Lu Z
AD  - China Pharmaceutical University, Nanjing, 210009, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Gastroenterology, Nanjing Integrated Traditional Chinese and 
      Western Medicine Hospital, Nanjing, 210014, China; Nanjing University of Chinese 
      Medicine, Nanjing, 210023, China.
FAU - Yang, Lu
AU  - Yang L
AD  - Department of Gastroenterology, Nanjing Integrated Traditional Chinese and 
      Western Medicine Hospital, Nanjing, 210014, China; Nanjing University of Chinese 
      Medicine, Nanjing, 210023, China.
FAU - Zhang, Guoying
AU  - Zhang G
AD  - School of Chinese Medicine, School of Integrated Chinese and Western Medicine, 
      Nanjing University of Chinese Medicine, Nanjing, 210023, China.
FAU - Liu, Wanli
AU  - Liu W
AD  - Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China; 
      Department of Gastroenterology, Nanjing Integrated Traditional Chinese and 
      Western Medicine Hospital, Nanjing, 210014, China. Electronic address: 
      njzxjh001@njucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230412
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (NF-kappa B)
RN  - 0 (SPOP protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Myd88 protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *NF-kappa B/metabolism
MH  - *Myeloid Differentiation Factor 88/metabolism
MH  - Neuroinflammatory Diseases
MH  - Antidepressive Agents/pharmacology/therapeutic use
MH  - Anti-Inflammatory Agents/pharmacology/therapeutic use
MH  - Ubiquitination
MH  - Depression/drug therapy/etiology
MH  - Hippocampus/metabolism
MH  - Stress, Psychological/complications
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - CUMS
OT  - MyD88
OT  - Neuroinflammation
OT  - SPOP
OT  - Ubiquitination
OT  - Zuojinwan
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- 2023/04/15 06:00
MHDA- 2023/05/08 06:41
CRDT- 2023/04/14 19:26
PHST- 2023/02/09 00:00 [received]
PHST- 2023/03/24 00:00 [revised]
PHST- 2023/04/09 00:00 [accepted]
PHST- 2023/05/08 06:41 [medline]
PHST- 2023/04/15 06:00 [pubmed]
PHST- 2023/04/14 19:26 [entrez]
AID - S0378-8741(23)00355-0 [pii]
AID - 10.1016/j.jep.2023.116487 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2023 Aug 10;312:116487. doi: 10.1016/j.jep.2023.116487. Epub 
      2023 Apr 12.