Saikosaponin D Rescues Deficits in Sexual Behavior and Ameliorates Neurological Dysfunction in Mice Exposed to Chronic Mild Stress

Abstract

Often associated with sexual dysfunction (SD), chronic stress is the main contributing risk factor for the pathogenesis of depression. Radix bupleuri had been widely used in traditional Chinese medicine formulation for the regulation of emotion and sexual activity. As the main active component of Radix bupleuri, saikosaponin D (SSD) has a demonstrated antidepressant effect in preclinical studies. Herein, we sought to investigate the effect of SSD to restore sexual functions in chronically stressed mice and elucidate the potential brain mechanisms that might underly these effects. SSD was gavage administered for three weeks during the induction of chronic mild stress (CMS), and its effects on emotional and sexual behaviors in CMS mice were observed. The medial posterodorsal amygdala (MePD) was speculated to be involved in the manifestation of sexual dysfunctions in CMS mice. Our results revealed that SSD not only alleviated CMS-induced depressive-like behaviors but also rescued CMS-induced low sexual motivation and poor sexual performance. CMS destroyed astrocytes and activated microglia in the MePD. SSD treatment reversed the changes in glial pathology and inhibited neuroinflammatory and oxidative stress in the MePD of CMS mice. The neuronal morphological and functional deficits in the MePD were also alleviated by SSD administration. Our results provide insights into the central mechanisms involving the brain associated with sexual dysfunction. These findings deepen our understanding of SSD in light of the psychopharmacology of stress and sexual disorders, providing a theoretical basis for its potential clinical application.

Comprehensive comparison on the anti-inflammation and GC-MS-based metabolomics discrimination between Bupleuri chinense DC. and B. scorzonerifolium Willd

“…In clinical applications, BR has been widely used for treatment of fever, pain, and inflammation associated with influenza or the common cold ( Yang et al, 2017 ). The modern pharmacological investigations reported that BR presented broad biological activities including anti-influenza ( Yan et al, 2022 ), anti-tumor ( Zhao et al, 2019 ; Zhou et al, 2021 ), anti-inflammation ( Jiang et al, 2020 ), anti-depression ( Guo et al, 2020 ; Chen et al, 2021 ), anti-stress ( Wang P. et al, 2021 ; Wang Z. et al, 2021 )and antipyretic ( Wang et al, 2019 ), antiviral ( Du et al, 2018 ), antimicrobial ( Liu et al, 2016 ), immunomodulatory ( Tang et al, 2021 ) and hepatoprotective effects ( Ren et al, 2019 ). Although different types of chemicals have been reported to contain in BCH (saponins, volatile oils, flavonoids and polysaccharides) ( Xing et al, 2015 ) and NCH (saponins, lignans, fatty acids, volatile oils and polysaccharides) ( Jiang et al, 2020 ), the saponins and volatile oils have been investigated to be the most important parts for both BR species which are associated to their antipyretic ( Xing et al, 2015 ; Li et al, 2018 ) and anti-inflammatory effects ( Kim et al, 2015 ; Ma et al, 2016 ).…”

Aerobic Exercise Improves Methamphetamine-Induced Olfactory Dysfunction Through α-Synuclein Intervention in Male Mice

“…Immunohistochemistry assays were performed as previously described ( Wang et al, 2021b ), and mice were transcardially perfused with pre-cooled phosphate-buffered saline (PBS) and 4% paraformaldehyde. The brains were further fixed for 12 h at 4°C and dehydrated in 30% sucrose for cryoprotection.…”

Encore: Behavioural animal models of stress, depression and mood disorders

“…CUMS was recently used to elucidate the role of projections from lateral habenula (LHb) to VTA in driving TST immobility, showcasing the construct validity of the paradigm ( Bergström et al, 2007 ; Cerniauskas et al, 2019 ). Changes in aggressive and sexual behaviour have been reported, but require further quantification ( Gronli et al, 2005 ; Couch et al, 2016 ; Chen et al, 2018 ; Wang et al, 2021 ). Another reported effect is the potentiation of escape deficits in the LH test ( Willner, 2005 ).…”