Zhanqiang Ma

Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice.

The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and curcumin (50 mg/kg, 100 mg/kg, 200 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM). Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid. Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells. The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance. Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4(+)CD25(+)Foxp3+ regulatory T cells in ovalbumin-sensitized mice.

ETHNOPHARMACOLOGICAL RELEVANCE Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra), and has been found to be associated with multiple therapeutic properties. AIM OF THE STUDY In this study, we investigated immunoregulatory effects of glycyrrhizic acid on anti-asthmatic effects and underlying mechanisms. MATERIALS AND METHODS Asthma model was established by ovalbumin-induced. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg) and GA (10 mg/kg, 20 mg/kg, 40 mg/kg). Airway resistance (Raw) were measured by the forced oscillation technique, histological studies were evaluated by The hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was evaluated by Flow Cytometry (FCM), the forkhead/winged helix transcription factor (Foxp3) was evaluated by western blotting. RESULTS Our study demonstrated that, compared with model group, GA inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that GA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue compared with model group. Flow cytometry studies demonstrated that GA substantially enhanced Tregs compared with model group. CONCLUSION These findings suggest that GA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Effects of perillaldehyde on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration.

Perillaldehyde (PAH), a major component of essential oil of Perilla Frutescens, has antidepressant-like effects and anti-inflammatory effects. The present study was designed to determine whether PAH is effective in treating lipopolysaccharide (LPS)-induced depression-like behavior in mice and to explore the possible mechanism between its antidepressant-like effect and anti-inflammatory activity. PAH (60 and 120 mg/kg) and fluoxetine (20mg/kg) were administered intragastrically once daily for 7 consecutive days. In the 7th day, LPS (0.5mg/kg) was injected intraperitoneally 30 min after drug administration. Blood samples were collected 90 min after LPS injection to evaluate serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay (ELISA). Behavioral tests were measured 24h after LPS injection. After the behavioral tests the prefrontal cortex was rapidly dissected from the brain of the sacrificed mice, then the 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels in prefrontal cortex were determined by HPLC-MS, and IL-6 and TNF-α mRNA expression was measured using quantitative real-time PCR. Our results showed that a single administration of LPS significantly increased the levels of TNF-α and IL-6 in both the serum and the prefrontal cortex and decreased 5-HT and NE levels in the prefrontal cortex in mice. Pretreatment with fluoxetine (20mg/kg) or PAH (60 and 120 mg/kg) could effectively reverse the alterations in the concentrations of 5-HT and NE, and attenuate LPS-induced increases in TNF-α and IL-6 levels. Besides, LPS administration increased the immobility time in tail suspension test (TST) and forced swimming test (FST) without affecting spontaneous locomotor activity. Fluoxetine (20mg/kg) or PAH (60 and 120 mg/kg) significantly shortened LPS-induced increases of immobility time in both TST and FST. In conclusion, PAH exhibited significant antidepressant-like effects in mice with LPS-induced depression. The antidepressant activity of PAH might be related to the alteration of monoaminergic responses and the anti-inflammatory effects.

Formononetin Inhibited the Inflammation of LPS-Induced Acute Lung Injury in Mice Associated with Induction of PPAR Gamma Expression

Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice.

Asiaticoside attenuates memory impairment induced by transient cerebral ischemia-reperfusion in mice through anti-inflammatory mechanism.

Asiaticoside (AS) is isolated from Centella asiatica (L.) which has been using for a long time as a memory enhancing drug in India. This study was to investigate the effects of AS on memory impairment and inflammatory cytokines expression induced by transient cerebral ischemia and reperfusion in mice, as well as the potential signaling pathway. Transient bilateral common carotid artery occlusion (tBCCAO) induced severe memory deficits in mice according to the Morris water maze task and the step-down passive avoidance test. Meanwhile the microglial activation and the gene expression of inflammatory cytokines including interleukin (IL)-1β, interleukin (IL)-6 and tumor necrosis factor (TNF)-α were increased in the hippocampus of the mice with cerebral ischemia and reperfusion. Oral administration of AS (40 and 60 mg/kg, once per day, started the day after surgery and lasted for 7 days) significantly ameliorated the memory impairment and the inflammation. Moreover, AS (20, 40 and 60 mg/kg) markedly reduced the microglial overactivation and the phosphorylation of p38 MAPK in hippocampus compared with the transient cerebral ischemia and reperfusion group. These results suggested that AS showed the neuroprotective effect against transient cerebral ischemia and reperfusion in mice, and this effect might be associated with the anti-inflammation effect of AS via inhibiting overactivation of p38 MAPK pathway.

L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression.

Geraniol produces antidepressant-like effects in a chronic unpredictable mild stress mice model.

Geraniol (GE), which has neuroprotection and anti-inflammation activities, is mostly abundant in the essential oils of rose, ginger, lemon, orange, lavender etc. However, its antidepressant-like effect has not been reported before. The present study was designed to investigate whether GE confers an antidepressant effect in mice exposed to a chronic unpredictable mild stress (CUMS) model of depression and to explore its possible mechanisms. The results showed that GE treatments for 3 weeks significantly alleviated the depression-related behaviors of CUMS-exposed mice, as indicated by restored decreased sucrose preference and shortened immobile time in both the forced swimming tests (FST) and tail suspension tests (TST). And these ameliorative effects of GE treatment were involved with regulating CUMS-induced pro-inflammatory cytokine interleukin-1 beta (IL-1β) related neuro-inflammation. We further found that GE treatment reversed CUMS-induced IL-1β elevation, possibly by inhibiting nuclear factor kappa B (NF-κB) pathway activation and regulating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome expression. Taken together, our findings suggested that GE exerted a potential antidepressant-like effect in CUMS mice model of depression, which may provide an insight into the potential of GE in therapeutic implications for depression.

Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats

Salidroside (SA) is the primary bioactive marker compound in the standardized extracts from Rhodiola rosea. Although it has potential antidepressant activity in a rat behavioral despair model, the mechanisms of antidepressant effect for SA remain unclear. The objective of this study was to evaluate the antidepressant effects of SA and to discuss the potential mechanisms in olfactory bulbectomized (OBX) rats. SA of 20, 40 mg/kg (p.o.) for 2 weeks notably alleviated OBX-induced hyperactivity in open field test, decreased immobility time in TST and FST. Chronic treatment with SA could remarkably reduce TNF-α and IL-1β levels in hippocampus. Western blot showed that SA could markedly increase glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Besides, SA could also attenuate corticotropin-releasing hormone (CRH) expression in hypothalamus, as well as reducing significantly the levels of serum corticosterone. In conclusion, this study demonstrated that OBX rats treated with SA could significantly improve the depressive-like behaviors. The antidepressant mechanisms of SA might be associated with its anti-inflammatory effects and the regulation of HPA axis activity. Reversal of abnormalities of GR may be partly responsible for those effects. These findings suggested that SA might become a beneficial agent to prevent and treat the depression.

Metabonomic Study on the Antidepressant-Like Effects of Banxia Houpu Decoction and Its Action Mechanism

The aim of this study was to establish an experimental model for metabonomic profiles of the rats brain and then to investigate the antidepressant effect of Banxia Houpu decoction (BHD) and its possible mechanisms. Behavioral research and metabonomics method based on UPLC-MS were used to assess the efficacy of different fractions of BHD on chronic unpredictable mild stress (CUMS) model of depression. There was a significant difference between the BHD group and the model group. Eight endogenous metabolites, which are contributing to the separation of the model group and control group, were detected, while BHD group regulated the perturbed metabolites showing that there is a tendency of recovery compared to control group. Therefore, we think that those potential metabolite biomarkers have some relationship with BHDs antidepression effect. This work appraised the antidepressant effect of Banxia Houpu decoction as well as revealing a metabonomics method, a valuable parameter in the TCM research.

Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced rats by attenuating neuronal apoptosis via regulating ROCK/Akt pathway.

HighlightsUmbelliferone ameliorates CUMS‐induced depressive‐like behavior.Umbelliferone protects neurons by preventing neuronal apoptosis.The antidepressant‐like effects of umbelliferone are achieved by regulating ROCK/Akt pathway. ABSTRACT There is increasing evidence that major depressive disorder (MDD) is also a progressive neurodegeneration disorder and neuronal damage is the major pathology of MDD. Umbelliferone, a coumarin derivative, was found in a range of plants with proved anti‐oxidative, anti‐inflammatory and neuroprotective effects. The primary purpose of this investigation was to evaluate whether umbelliferone could confer an antidepressant‐like effect on the depressive model in rats developed by chronic unpredictable mild stress (CUMS) and explore the possible mechanism involved in its neuroprotective effects. We found that treatments with umbelliferone (15 mg/kg, 30 mg/kg) significantly ameliorated CUMS‐induced depressive‐like behaviors, such as decreased sucrose consumption, reduced locomotor activity and prolonged immobility time. Rats under CUMS stimulation treated with umbelliferone (15 mg/kg, 30 mg/kg) showed reduced neuronal apoptosis, as well as inhibited inflammatory cytokines levels by down‐regulating Rho‐associated protein kinase (ROCK) signaling and up‐regulating protein kinase B (Akt) signaling. In conclusion, umbelliferone showed neuroprotective effects on CUMS‐induced model of depression, which was associated with the inhibition of neuronal apoptosis modulated by ROCK/Akt pathway.