Bupleurum chinense DC improves CUMS-induced depressive symptoms in rats through upregulation of the cAMP/PKA/CREB signalling pathway

Chang, Bai-Jin; Liu, Yanru; Hu, Jianfeng; Tang, Zhishu; Qiu, Zhidong; Song, Zhong-Xing; Jia, Ailing; Zhang, Yuru

doi:10.1016/j.jep.2022.115034

Cited by 16 publications

(2 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, is a common component of Chinese herbal prescriptions such as Xiaoyaosan [ 6 ] and Chaihu-Shugan-San [ 7 ], which are administered clinically to improve symptoms of depression . Saikosaponin D (SSD) is a pharmacologically active ingredient extracted from Radix Bupleuri [ 8 , 9 ], which is capable of ‘dispersing stagnated liver qi for relieving qi stagnation’ according to traditional Chinese Medicine (TCM) theory. Several researches reported that SSD was founded to have the effect to inhibit neuronal apoptosis and microglia activation as well as neuroinflammation in LPS-induced mice [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress

et al. 2022

View full text Add to dashboard Cite

Background Many studies about depression have focused on the dysfunctional synaptic signaling in the hippocampus that drives the pathophysiology of depression. Radix Bupleuri has been used in China for over 2000 years to regulate liver-qi. Extracted from Radix Bupleuri, Saikosaponin D (SSD) is a pharmacologically active substance that has antidepressant effects. However, its underlying mechanism remains unknown. Materials and methods A chronic unpredictable mild stress (CUMS) paradigm was used as a rat model of depression. SD rats were randomly assigned to a normal control (NC) group or one exposed to a CUMS paradigm. Of the latter group, rats were assigned to four subgroups: no treatment (CUMS), fluoxetine-treated (FLU), high-dose and low-dose SSD-treated (SSDH and SSDL). SSD was orally administrated of 1.50 mg/kg and 0.75 mg/kg/days for three weeks in the SSDH and SSDL groups, respectively. Fluoxetine was administrated at a dose of 2.0 mg/kg/days. SSD’s antidepressant effects were assessed using the open field test, forced swim test, and sucrose preference test. Glutamate levels were quantified by ELISA. Western blot and immunochemical analyses were conducted to quantify proteins in the Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) pathways in the hippocampal CA1 region. To measure related gene expression, RT-qPCR was employed. Results CUMS-exposed rats treated with SSD exhibited increases in food intake, body weight, and improvements in the time spent in the central are and total distance traveled in the OFT, and less pronounced pleasure-deprivation behaviors. SSD also decreased glutamate levels in CA1. In CA1 region of CUMS-exposed rats, SSD treatment increased mGluR5 expression while decreasing Homer1 expression. SSD also increased expressions of postsynaptic density protein 95 (PSD95) and synapsin I (SYP), and the ratios of p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 in the CA1 region in CUMS-exposed rats. Conclusions SSD treatment reduces glutamate levels in the CA1 region and promotes the expression of the synaptic proteins PSD-95 and SYP via the regulation of the Homer1-mGluR5 and downstream mTOR signaling pathways. These findings suggest that SSD could act as a natural neuroprotective agent in the prevention of depression.

show abstract

Section: Introductionmentioning

confidence: 99%

Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress

et al. 2022

View full text Add to dashboard Cite

show abstract

“…ZZKZ contains four botanical drugs, including Aurantii Fructus Immaturus , Rhizoma Atractylodis Macrocephalae , Radix Bupleuri Chinensis, and Fructus Crataegi Pinnatifidae ( Zhang et al, 2012 ). More and more effective components and functions of each ingredients of ZZKZ have been elucidated by phytochemical and pharmacological studies ( Jurikova et al, 2012 ; Feng et al, 2020 ; Chang et al, 2022 ; Jia et al, 2022 ). As the preferred TCM in regulating gastrointestinal motility and psychiatric symptoms, ZZKZ has been widely used in patients with FD ( Guo et al, 2011 ; Lin et al, 2018 ; Wen et al, 2019 ; Xiao et al, 2022 ; Xu et al, 2022 ), especially those with the PDS subtype, with the differentiation of TCM syndrome being Spleen-deficiency and Qi-stagnation ( Lin et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia

Xiao

Tan

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD).Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats.Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.

show abstract

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study

Yang

Liu

Sun

et al. 2023

Chin. J. Integr. Med.

View full text Add to dashboard Cite

Bupleurum chinense DC improves CUMS-induced depressive symptoms in rats through upregulation of the cAMP/PKA/CREB signalling pathway

Cited by 16 publications

References 62 publications

Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress

Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress

Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study

Contact Info

Product

Resources

About