Evidence map›Paper›PMID 41925791›Full record

ArticleMetabolic brain disease2026

Saikosaponin-d attenuates postpartum estrogen withdrawal-induced depressive symptoms by modulating glucocorticoid metabolism and inhibiting hippocampal NLRP3 inflammatory vesicle activation.

Xuejia Zhai, Qianfeng Yang, Yao Zhao, Xin Zeng, Yajie He, Qiuyun You

Abstract read
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Article in Metabolic brain disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xuejia ZhaiDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic Of China. zhaixuejia@hust.edu.cn.
Qianfeng YangSchool of Pharmacy, Hubei University of Chinese Medicine, 430065, Wuhan, People's Republic Of China.
Yao ZhaoDepartment of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic Of China.
Xin ZengSchool of Pharmacy, Hubei University of Chinese Medicine, 430065, Wuhan, People's Republic Of China.
Yajie HeDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic Of China.
Qiuyun YouEngineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, People's Republic Of China.

Funding

Chinese Pharmaceutical Association CPA-Z05-ZC-2022-002Natural Science Foundation of Hubei Province 2024AFB645
6 · The paper itself

Abstract

Postpartum depression (PPD) is a prevalent mental disorder affecting women worldwide. Radix Bupleuri, a traditional Chinese herb frequently used in PPD treatment formulations, contains saikosaponin-d (SSd) as one of its major bioactive constituents. Dysregulation of glucocorticoid metabolism and activation of the NLRP3 inflammasome have been implicated in the pathophysiology of depression. However, whether SSd alleviates PPD through modulation of these pathways remains unclear. In this study, we investigated the therapeutic effects and underlying mechanisms of SSd in a hormone-simulated PPD rat model. Following model establishment, anhedonia-like behavior was assessed using the sucrose preference test, while locomotor activity and anxiety-like behavior were evaluated using the open field test. Serum inflammatory cytokines levels were measured by ELISA, and hippocampal NLRP3 inflammasome-related proteins were examined by Western blot. SSd treatment significantly ameliorated PPD-induced behavioral deficits, as evidenced by increased sucrose preference and locomotor activity. Both SSd and fluoxetine (FLU) markedly suppressed the expression of NLRP3 inflammasome components (NLRP3, caspase-1) and reduced serum levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Notably, SSd—but not FLU—significantly decreased plasma corticosterone (CORT) and 11-dehydrocorticosterone (11-DHCORT) levels and was associated with altered 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, suggesting differential modulation of glucocorticoid metabolism. Additionally, SSd treatment coincided with increased estrogen receptor (ERα/ERβ) expression in key brain regions. Comprehensive analysis of these data suggests that SSd is associated with reduced neuroinflammation, restoration of glucocorticoid metabolic balance, and increased estrogen receptor expression, which may collectively contribute to the amelioration of PPD-like behaviors.

Indexed as

DepressionEstrogensGlucocorticoidsHippocampusNLR Family, Pyrin Domain-Containing 3 ProteinOleanolic AcidSaponinsAnimalsFemaleInflammasomesPostpartum PeriodRatsRats, Sprague-DawleyEstrogensGlucocorticoidsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratOleanolic Acidsaikosaponin DSaponinsGlucocorticoidNeuroinflammationNLRP3 inflammasomePostpartum-depressionSaikosaponin-d

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.