Antidepressant and Anti-Neuroinflammatory Effects of Bangpungtongsung-San

Abstract

Bangpungtongsung-san (BTS) is a traditional Korean medicine consisting of 18 herbs, some which have antidepressant effects. Here, we used an animal model of reserpineinduced depression and lipopolysaccharide (LPS)-stimulated BV2 microglia to assess the antidepressant and anti-neuroinflammatory effects of BTS. Aside from a control group, C57BL/6 mice were administered reserpine (0.5 mg/kg) daily for 10 days via intraperitoneal injection. BTS (100, 300, or 500 mg/kg), vehicle (PBS), or fluoxetine (FXT, 20 mg/kg) was administered orally 1 h before reserpine treatment. Following treatment, a forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed, and immobility time and total travel distance were measured. Administration of BTS not only reduced immobility time in the FST and TST but also significantly increased the total travel distance in the OFT. Furthermore, reserpine-treated mice showed significantly elevated serum levels of corticosterone, a stress hormone; however, treatment with BTS significantly reduced corticosterone levels, similar to FXT treatment. Serotonin in reserpine-treated mice was significantly reduced compared to that in control mice, while BTS mice exhibited increased serotonin levels. BTS mice showed increased expression of brain-derived neurotrophic factor (BDNF) and a higher ratio of phosphorylated cAMP response element-binding protein (p-CREB) to CREB (p-CREB/ CREB) in the hippocampus. Additionally, reserpine-treated mice exhibited significantly elevated mRNA levels of pro-inflammatory cytokines, but BTS mice showed reduced mRNA levels of interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in the hippocampus. To further demonstrate the anti-neuroinflammatory effects of BTS in vitro, we examined its anti-neuroinflammatory and neuroprotective effects in lipopolysaccharide (LPS)-stimulated BV2 microglia. BTS significantly reduced the levels of NO, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, TNF-a, IL-1b, and IL-6 in a dose-dependent manner via a decrease in the expression of nuclear factor (NF)-kB p65. Furthermore, the neuroprotective factor heme oxygenase-1 (HO-1) was upregulated via the nuclear factor-E2-related factor 2 (NRF2)/CREB pathway. Taken

Antidepressant and Anxiolytic-Like Effects of the Stem Bark Extract of Fraxinus rhynchophylla Hance and Its Components in a Mouse Model of Depressive-Like Disorder Induced by Reserpine Administration

“…Reserpine administration improves anxiety and depressive-like behaviors shown by mice staying at the edge of the space in OFT and maintaining immobility in TST and FST (Chang et al, 2015). This induced symptom effectively relieves anxiety and depressive symptoms, such as increased crossing and decreased immobility by antidepressant-like PSAP and herbal medicines (Sousa et al, 2018;Park et al, 2020). This study found that reserpineadministered mice exhibited reduced central dwelling time and entry frequency in the OFT as well as increased immobility in the TST and FST.…”

“…This evidence has been applied to animal models showing depressive symptoms, and reserpine-administered animal models are being used to study the pathological symptoms of depression (Uriguen et al, 2008). Reserpine administration may affect neuroinflammation by damaging rodent nerve tissues and releasing proinflammatory cytokines such as IL-1β, IL-12, IL-6, TNF-α, and IFN-γ from the hippocampus, liver, and serum (Huang et al, 2004;Zhou et al, 2014;Park et al, 2020). In addition, brain-derived neurotrophic factor (BDNF)-Tropomyosin receptor kinase B (TrkB) signaling participates in emotional, learning, and memory regulation in the hippocampus and activates neurotrophic pathways.…”

Onjisaponin B Attenuates Experimental Reserpine-Induced Depression in Mice

“…Reserpine (purchased from Sigma-Aldrich, St Louis, MO, USA) was dissolved in the vehicle (phosphatebuffered saline (PBS) containing 0.1 % dimethyl sulfoxide (DMSO) and 0.3 % Tween-80) to a final concentration of 1 mg/kg. Reserpine was administered to mice intraperitoneally with a dose of 1 mg/kg/d for 3 consecutive days, according to a published paper [14] .…”

High Serum Levels of iNOS and MIP-1α are Associated with Post-Stroke Depression

“…13 Another study found that after antidepressant treatment in a vivo model of depression, the production of NO was decreased by inhibiting the expression of iNOS. 14 The possible mechanism is that inhibiting iNOS signaling pathway may alleviate depressive symptoms by exerting anti-inflammatory and neuroprotective effects. 15 Macrophage inflammatory protein 1α (MIP-1α) belongs to a member of the CC subfamily of chemokines and its release is considered a crucial process in the recruitment of inflammatory cells during initiation and subsequent maintenance of inflammatory responses.…”

“…21 The 80 patients diagnosed with depression after the first-ever acute ischemic stroke were enrolled in PSD group. The PSD group was divided into mild PSD group (8)(9)(10)(11)(12)(13)(14)(15)(16), moderate PSD group (17)(18)(19)(20)(21)(22)(23) and severe PSD group (≥ 24) according to HAMD scores. 22 During the same period, 40 non-depressed patients after the first-ever acute ischemic stroke and 40 healthy control subjects were recruited as non-PSD group and normal group, respectively.…”