The therapeutic effects of saikosaponins on depression through the modulation of neuroplasticity: From molecular mechanisms to potential clinical applications

Chen, Shen; Wang, Ke; Wang, Hongzhan; Gao, Yang; Nie, Kexin; Jiang, Xinyue; Su, Hao; Tang, Yueheng; Lu, Fuer; Dong, Hui; Wang, Zhi

doi:10.1016/j.phrs.2024.107090

Cited by 5 publications

(2 citation statements)

References 200 publications

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“…These results predicted the potential molecular interactions between the active compounds and the 11 core targets [TNF, CXCL8 (IL-8), IL-1β, NFKBIA, PTGS2, GABBR2, GABRA1, GABRG2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), and estrogen receptor 1 (ESR1)], supporting their antipyretic effects. Many of these interactions, including baicalin–GABBR [ 48 ], saikosaponin A–GABBR [ 49 ], saikosaponin A–TNF, saikosaponin C–TNF [ 50 ], saikosaponin C–VEGFA, saikosaponin A–VEGFA [ 51 ], and glycyrrhizic acid–NFKBIA [ 52 ], have been experimentally described in the literature. Compared to other compounds, saikosaponin C had the lowest binding energies towards GABBR2, GABRA1, NFKBIA, and EGFR.…”

Section: Resultsmentioning

confidence: 99%

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Chen,

Wu,

et al. 2024

Pharmaceuticals

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Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

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Section: Resultsmentioning

confidence: 99%

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Chen,

Wu,

et al. 2024

Pharmaceuticals

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“…Unlike other natural medicines, Bupleurum is rich in a large number of saikosaponins. As a class of triterpene saponins, saikosaponins have been reported to have therapeutic potential in improving neuroplasticity [ 67 , 68 , 69 ]. However, the depressive effects of bupleurum have not been well summarized.…”

Section: Multiple Pharmacological Effects Of Bupleurummentioning

confidence: 99%

Bupleurum in Treatment of Depression Disorder: A Comprehensive Review

Ran,

Peng,

Guo

et al. 2024

Pharmaceuticals

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The incidence of depression has been steadily rising in recent years, making it one of the most prevalent mental illnesses. As the pursuit of novel antidepressant drugs captivates the pharmaceutical field, the therapeutic efficacy of Traditional Chinese Medicine (TCM) has been widely explored. Chaihu (Bupleurum) has been traditionally used for liver conditions such as hepatitis, liver inflammation, liver fibrosis, and liver cancer. It is believed to have hepatoprotective effects, promoting liver cell regeneration and protecting against liver damage. In addition, Bupleurum has also been used as a Jie Yu (depression-relieving) medicine in China, Japan, Republic of Korea, and other Asian countries for centuries. This review article aims to summarize the research conducted on the antidepressant properties and mechanisms of Bupleurum, as well as discuss the potential of TCM formulas containing Bupleurum. This review highlights various antidepressant ingredients isolated from Bupleurum, including saikosaponin A, saikosaponin D, rutin, puerarin, and quercetin, each with distinct mechanisms of action. Additionally, Chinese herb prescriptions and extracts containing Bupleurum, such as Chaihu Shugansan, Xiaoyaosan, and Sinisan, are also included due to their demonstrated antidepressant effects. This review reveals that these Bupleurum compounds exhibit antidepressant effects through the regulation of neurotransmitter mechanisms (such as 5-HT and DA), the NMDA (N-methyl-D-aspartate) system, brain-derived neurotrophic factor (BDNF), and other intracellular signaling pathways. Collectively, this comprehensive review provides insights into the multiple applications of Bupleurum in the treatment of depression and highlights its potential as an alternative or complementary approach to traditional therapies. However, it is essential to consider the potential adverse effects and clinical restrictions of Bupleurum despite its promising potential. Further research is needed to elucidate its specific mechanisms of action and evaluate its effectiveness in human subjects.

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KeYu ShuShen Granule alleviates symptoms of depression by targeting the mTOR pathway in a rat model of depression induced by chronic unpredictable mild stress

Pei,

Zhang,

Liu

et al. 2024

Brain Behavior and Immunity Integrative

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The therapeutic effects of saikosaponins on depression through the modulation of neuroplasticity: From molecular mechanisms to potential clinical applications

Cited by 5 publications

References 200 publications

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Bupleurum in Treatment of Depression Disorder: A Comprehensive Review

KeYu ShuShen Granule alleviates symptoms of depression by targeting the mTOR pathway in a rat model of depression induced by chronic unpredictable mild stress

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