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Updated: Jun 5, 2025
Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice
Published on: January 7, 2019
Saikosaponins from Bupleurum scorzonerifolium Willd. alleviates microglial pyroptosis in depression by binding and
Yu Bi1, Mengmeng Li1, Yue Wang1
1Heilongjiang University of Chinese Medicine, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Traditional Chinese medicine (TCM) biological genetics (Heilongjiang province double first-class construction interdiscipline), Heilongjiang Touyan Innovation Team Program, 150040, China.
Background:
The major depressive disorder (MDD) is a heterogeneous condition and characterized by a high recurrence rate, with neuroinflammation playing a significant role in its various potential pathologies. In recent years, neuronal pyroptosis induced by neuroinflammation has garnered increasing attention in depression research. Bupleurum scorzonerifolium Willd. is depression research in traditional Chinese medicine prescriptions to treat depression and exhibits notable anti-inflammatory properties. Saikosaponins (SSs) are the primary active components of Bupleurum scorzonerifolium Willd., although their mechanism of action in relation to anti-depressive effects remains unclear.
Purpose:
The purpose is to evaluate the efficacy of Chinese herbal medicine in treating depression through the lens of modern pharmacology. Additionally, it aims to explore the potential value of new mechanisms in the treatment of depression.
Study Design And Methods:
An in vivo model of depression was established by intraperitoneal injection of LPS. HE staining, Nissl staining, and Golgi staining were used to evaluate the effectiveness of depression treatments in each group of mice. The activation of microglia was analyzed using immunofluorescence to evaluate the anti-inflammatory effects of drugs. In vitro models, N9 cells induced by LPS and ATP used CCK-8 assay, and lactate dehydrogenase assay were conducted to explore the therapeutic effect of the SSs. Western blot and immunohistochemical methods were employed to investigate the expression of P2X7 and apoptosis-related proteins. BzATP was introduced as a P2X7 agonist, and CETSA and CHX pulse-chase assay were utilized to verify the combined action and stability of the SSs with P2X7.
Results:
57 triterpenoid saponin compounds were identified by Unifi in Bupleurum scorzonerifolium Willd. In both in vivo and in vitro models, the SSs has been shown to significantly improve depression-like behavior, reduce central inflammation, and significantly inhibit neuronal pyroptosis in mice. The SSs can significantly decrease the expression of P2X7 in the brains of depressed mice and enhance the stability of P2X7 protein in N9 cells.
Conclusion:
SSs in Bupleurum scorzonerifolium Willd. bind and inhibit the P2X7 receptor to alleviate neuronal pyroptosis and improve symptoms of depression.
Insights
Saikosaponins from Bupleurum scorzonerifolium inhibit neuronal pyroptosis by targeting the P2X7 receptor, offering a new therapeutic strategy for major depressive disorder. This research explores novel mechanisms for depression treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Traditional Chinese Medicine
Background:
- Major depressive disorder (MDD) is complex and often recurrent, with neuroinflammation and neuronal pyroptosis implicated in its pathology.
- Bupleurum scorzonerifolium Willd. and its active compounds, saikosaponins (SSs), are used in traditional Chinese medicine for depression and possess anti-inflammatory properties.
- The precise anti-depressive mechanisms of SSs, particularly concerning neuroinflammation and pyroptosis, require elucidation.
Purpose of the Study:
- To evaluate the efficacy of Chinese herbal medicine, specifically SSs, in treating depression using modern pharmacological approaches.
- To investigate the potential of targeting neuronal pyroptosis and the P2X7 receptor as a novel mechanism for depression treatment.
Main Methods:
- Established in vivo (LPS-induced) and in vitro (LPS/ATP-induced N9 cells) depression models.
- Assessed depression-like behaviors, neuroinflammation (microglia activation), and neuronal damage (HE, Nissl, Golgi staining).
- Investigated the role of the P2X7 receptor and apoptosis-related proteins using Western blot, immunohistochemistry, and specific assays (CCK-8, LDH, CETSA, CHX pulse-chase).
Main Results:
- Identified 57 triterpenoid saponin compounds in Bupleurum scorzonerifolium Willd.
- SSs significantly ameliorated depression-like behaviors, reduced central inflammation, and inhibited neuronal pyroptosis in both in vivo and in vitro models.
- SSs decreased P2X7 receptor expression in depressed mice and enhanced P2X7 protein stability in N9 cells.
Conclusions:
- Saikosaponins (SSs) from Bupleurum scorzonerifolium Willd. demonstrate significant anti-depressive effects.
- SSs exert their therapeutic action by binding to and inhibiting the P2X7 receptor, thereby alleviating neuronal pyroptosis.
- This study highlights SSs and the P2X7 receptor pathway as a promising target for novel depression therapies.
