Baicalin (BA), a major polyphenol compound isolated from the extracts of Scutellaria radix, has been previously reported to ameliorate depressive-like behaviors in mice with chronic unpredictable mild stress (CUMS). However, its underlying antidepressant mechanisms remain unclear. This study was designed to confirm the antidepressant-like effects of BA on CUMS induced behavioral abnormalities in mice, and sought to explore the pharmacological mechanisms in vivo and in vitro. The CUMS procedure was carried out to induce depression in mice. Afterwards, the tail suspension test (TST), forced swim test (FST), and open field test (OFT) were performed within 24 h, then sucrose preference test (SPT) was conducted. Additionally, PC12 cells were pretreated with BA for 2 h, then further stimulated with corticosterone for 24 h. The levels of Interleukin-1β (IL-1β), IL-6 and Tumor Necrosis Factor-α (TNF-α) in serum, hippocampus homogenate and cell culture medium were determined using the enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of inhibition of high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathways in hippocampus and PC12 cells were detected. Our results showed that CUMS-treated mice presented notable depressive-like symptoms, such as decreased sucrose consumption, increased FST and TST immobility time. While BA (25, 50 mg/kg) significantly attenuated these changes. Besides, BA treatment considerably inhibited inflammatory cytokinesl (IL-1β, IL-6, TNF-α) levels in serum, hippocampus homogenate and cell culture medium. Western blot analysis indicated that BA inhibited the expressions of HMGB1, TLR4, and p-NF-κBp65 both in vivo and in vitro. In conclusion, the present study confirmed that BA possessed efficient antidepressant effects on depression, which was possibly related to the inhibition of HMGB1/TLR4/NF-κB pathways.

A response surface methodology was applied to optimize the variables affecting the supercritical fluid carbon dioxide extraction of oil from the fruit of Gardenia jasminoides using the Box–Behnken design. The optimum extraction parameters were an extraction temperature of 49.94 °C, an extraction pressure of 29.89 MPa and an extraction time of 93.82 min. Through a GC/MS analysis, we revealed 16 major components of the oil extract, which showed potent antidepressant effects in both of two behavior despair models in mice: tail suspension test and forced swimming test. Our results suggest that the oil extract of Gardenia jasminoides prepared using the supercritical fluid carbon dioxide extraction may contain effective constituents to be used for depression therapy.

Objective. To study the protective effect of Echinacoside for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopaminergic (DA) neurons injury in the subacute mouse model of Parkinson’s disease (PD) and to explore its mechanism of action. Methods. We chose 10 weeks of healthy wild type C57BL/6 male mice, hypodermic MPTP 30 mg/kg/day, five days, to prepare PD subacute mouse model. Behavior indexes of open field test and pole test were applied to examine the function of ECH to PD subacute mice model of PD sample action. The effects of ECH on dopaminergic neurons and astrocyte were examined using Immunohistochemistry including tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression. The total numbers of TH-positive neurons and GFAP-positive cells in the substantia nigra pars compacts (SNpc) and ventral tegmental area (VTA) were obtained stereologically using the optical fractionator method. Enzyme-linked immunosorbent assay (ELISA) method was used to detect the inflammatory cytokines in the serum, including TNF-α (Ttumor necrosis factor alpha) and IFN-γ (interferon gamma). Protein expressions of ionized calcium binding adaptor molecule 1 (IBA-1), TNF-α, Cleaved caspase-3, glial derived neurotrophic factor (GDNF), and phosphorylated and total extracellular signal-regulated kinase (p-ERK and ERK) in the anatomical region of substantia nigra (SN) were tested by protein immunoblot method (i.e., Western blotting). Results. ECH reversed the reduction of total distance in open field test in MPTP-induced PD model mice (P < 0.01), shortened the return time and total time of PD subacute model mice in pole test (P < 0.01, P < 0.05), significantly reversed the reduction of TH positive neurons induced by MPTP (P < 0.05), and reduced the activation of astrocytes (P < 0.05). Meanwhile, ECH significantly inhibited the expression of IBA-1, Cleaved caspase-3, and TNF-α in midbrain of MPTP model mice (P < 0.05, P < 0.05, and P < 0.05) and upregulated the expression of GDNF (P < 0.05). And ECH lowered the level of TNF-α and IFN-γ in serum (P < 0.05, P < 0.05). Conclusion. ECH has protective effects on the MPTP subacute model mice, its mechanism may be through inhibiting activation of microglia and astrocytes, reducing inflammatory reaction and promoting the secretion of neurotrophic factors, and eventually resulting in the reduction of the DA neurons apoptosis.

It has been reported that Banxia‐houpo decoction (BXHPD) serves as the anti‐depressant treatment for a mild and severe depressive disease with limited side effects. The present study was performed to evaluate the protective effect of BXHPD on chronic unpredicted mild stress (CUMS)‐induced depression and explore its effect on TrkA/Akt‐mediated microglia polarization. The CUMS procedure was carried out, and the mice were intragastrically treated with BXHPD once daily. The selective TrkA inhibitor GW441756 was applied to further investigate the role of TrkA in BXHPD‐mediated microglia polarization. The behaviour test including open field test (OFT), sucrose preference test (SPT), novelty‐suppressed feeding test (NSFT), tail suspension test (TST) and forced swim test (FST) was performed. The concentrations of pro‐inflammatory cytokines IL‐6, TNF‐α, IL‐1β, IL‐12 and anti‐inflammatory cytokines IL‐4, IL‐10 were determined using Enzyme‐linked immunosorbent assay. The population of Iba1+ cells and the length of microglia processes were observed under the fluorescence microscope. The mRNA expressions of Arg1, Ym1 and Fizzl1 were measured by PCR. The protein expressions of TrkA, p‐Tyr490‐TrkA, p‐Ser473‐Akt, p‐Ser473‐Akt1, p‐Ser474‐Akt2, p‐CREB and Jmjd3 were detected by western blot. Our results showed that BXHPD attenuated CUMS‐induced depressive‐like behaviour, promoted anti‐inflammatory cytokines, inhibited pro‐inflammatory cytokines, suppressed microglia activation, promoted M2 phenotype‐specific indices and upregulated the expressions of TrkA, p‐Tyr490‐TrkA, p‐Ser473‐Akt, p‐Ser473‐Akt1, p‐Ser474‐Akt2, p‐CREB and Jmjd3. The above beneficial effect of BXHPD can be blocked by TrkA inhibitor GW441756. This work demonstrated that BXHPD exerted an anti‐depressant effect by promoting M2 phenotype microglia polarization via TrkA/Akt pathway.

This study aimed to explore the protective effects of Wenshen-Yanggan decoction on dopaminergic (DA) neuron injury in a rotenone‐induced mouse model with chronic Parkinson’s disease (PD) and explore its mechanism of action. Ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) was used to measure the content of six main components in the Wenshen-Yanggan decoction. The chronic PD mouse model was established by treating 10‐month‐old healthy wild C57BL/6 male mice with rotenone 30 mg/kg/day for 28 days in succession. The pole test and rotarod test were applied to detect the rescue effect of Wenshen-Yanggan decoction in high, medium, and low dosages, respectively, on PD‐like behaviors in mice with chronic PD. The protective effect of Wenshen-Yanggan decoction on the mesencephalic nigrostriatal DA neuron injury was determined employing tyrosine hydroxylase (TH) immunofluorescence staining. Enzyme‐linked immunosorbent assay (ELISA) was adopted to measure the inflammatory cytokines in serum, including TNF‐α (tumor necrosis factor‐alpha), IFN‐γ (interferon gamma), NF‐κB (nuclear factor kappa‐B), and IL‐1β (interleukin‐1 beta). Western blotting was performed to quantify the expression of phosphorylated c‐Jun N‐terminal kinase (p‐JNK), cleaved caspase‐3, B‐cell lymphoma‐2 (Bcl‐2), and NF‐κB in the brain. Our results showed that the Wenshen-Yanggan decoction in high, medium, and low dosages reduced the turning time of mice (P < 0.01, P < 0.01, and P < 0.05). The high and medium dosages shortened the total climbing time of PD mice in the pole test (P < 0.01 and P < 0.05). Meanwhile, the high, medium, and low dosages increased the rod‐standing time of PD mice in the rotarod test (P < 0.01, P < 0.05, and P < 0.05). Besides, the decoction reversed the decrease in TH‐positive neurons induced by rotenone, upregulated TH protein expression, and downregulated the α‐syn expression in the PD model. Moreover, the decoction in high dosage significantly inhibited the expression of p‐JNK, cleaved caspase‐3, and NF‐κB in the midbrain of PD mice (P < 0.05, P < 0.05, and P < 0.01), upregulated the expression of Bcl‐2 (P < 0.05), and decreased the content of TNF‐α, IFN‐γ, NF‐κB, and IL‐1β in the serum (P < 0.001, P < 0.001, P < 0.001, and P < 0.001). Taken together, the Wenshen-Yanggan decoction could protect mice from rotenone‐induced chronic PD, which might be related to the reduction of the DA neuron apoptosis via suppressing the inflammatory reaction and the neuronal apoptosis pathway.

To investigate the effect of RNA interference mediated angiopoietin-2 (ANG-2) gene silencing on human endometrial carcinoma cell line Ishikawa. Short hairpin RNA (shRNA) targeting ANG-2 gene was designed and transfected into Ishikawa cells with Lipofectamine 2000. The mRNA and protein expression level of ANG-2, proliferation, morphological changes, apoptosis, cell cycle and invasive ability of the cells after transfection were analyzed. The shRNA targeting the human ANG-2 gene effectively decreased the expression of ANG-2 on both mRNA and protein level, the proliferation inhibition rate of the Ishikawa cells was 63.11%, cell apoptosis was induced, and the cell cycle was arrested in G1 phase. The apoptotic rate of the Ishikawa cells in the transfected group was significantly higher, and the invasive ability was decreased markedly, than that of control groups. The shRNA targeting human ANG-2 gene could reduce ANG-2 expression, inhibit cellular growth and invasion in Ishikawa cells in vitro.