Foeniculum vulgare Mill.inhibits lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in mice.Methods:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA assay.The antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western blotting.For in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic neuroinflammation.Cognitive and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced mice.Results:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(P<0.05).Moreover,LPS-induced oxidative stress and reduced antioxidative enzyme levels were significantly improved by Foeniculum vulgare extract(P<0.05).The extract also regulated the NF-κB/MAPK signaling in BV-2 cells.In an in vivo study,Foeniculum vulgare extract(50,100,and 200 mg/kg)markedly mitigated the LPS-induced cognitive and locomotor impairments in mice.The fingerprinting analysis showed distinctive peaks with rutin,kaempferol-3-O-glucoside,and anethole as identifiable compounds.Conclusions:Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

Alleviatory effect of isoquercetin on benign prostatic hyperplasia via IGF-1/PI3K/Akt/mTOR pathway

We evaluated the effect of isoquercetin(quercetin-O-3-glucoside-quercetin,IQ)as a functional component of Abeliophyllum disistichum Nakai ethanol extract(ADLE)on prostate cell proliferation and apoptosis and its effects on the IGF-1/PI3K/Akt/mTOR pathway in benign prostatic hyperplasia(BPH).Metabolites in ADLE were analyzed using UHPLC-qTOF-MS and HPLC.IQ was orally administered(1 or 10 mg/kg)to a testosterone propionate-induced BPH rat model,and its effects on the prostate weight were evaluated.The effect of IQ on androgen receptor(AR)signaling was analyzed in LNCaP cells.Whether IGF-1 and IQ affect the IGF-1/PI3K/Akt/mTOR pathway in BPH-1 cells was also examined.The metabolites in ADLE were identified and quantified,which confirmed that ADLE contained abundant IQ(20.88 mg/g).IQ significantly reduced the prostate size in a concentration-dependent manner in a BPH rat model,and significantly decreased the expression of AR signaling factors in the rat prostate tissue and LNCaP cells in a concentration-dependent manner.IQ also inhibited the PI3K/AKT/mTOR pathway activated by IGF-1 treatment in BPH-1 cells.In BPH-1 cells,IQ led to G0/G1 arrest and suppressed the expression of proliferation factors while inducing apoptosis.Thus,IQ shows potential for use as a pharmaceutical and nutraceutical for BPH.

Chrysanthemum indicum ethanol extract attenuates hepatic stellate cell activation in vitro and thioacetamide-induced hepatofibrosis in rats

Objective:To investigate the antifibrotic effects of Chrysanthemum indicum ethanol extract(CIEE)against activated hepatic stellate cells(HSC)and thioacetamide(TAA)-induced hepatofibrosis in rats.Methods:Cell viability and proliferation of HSC-T6 cells were measured using MTT assay.Primary HSCs were used to study morphology.TAA(200 mg/kg)was used to induced hepatic fibrosis in rats.CIEE(100 and 500 mg/kg)and silymarin(50 mg/kg)were administered orally.Liver functions including alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels were measured using commercial kits.Liver sections and fibrotic biomarker expression were measured using hematoxylin and eosin staining and real-time polymerase chain reaction.Results:In vitro study revealed that CIEE(0.1,0.25,and 0.5 mg/mL)inhibited the proliferation of activated HSCs exposed to transforming growth factor(TGF)-β and restored the activated primary HSC morphology.In in vivo studies,TAA-induced increase in liver/body weight ratio(5.46±0.26)was significantly reduced(4.13±0.22)by CIEE(P<0.05 at 500 mg/kg).CIEE(100 and 500 mg/kg)improved the liver functions by significantly attenuating changes in alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels(P<0.05).Further,CIEE(100 and 500 mg/kg)ameliorated the histological changes in liver tissue and TGF-β expression significantly(P<0.05)in TAA-induced rats.Conclusions:CIEE significantly protects against TAA-induced liver damage in rats and can be used in the treatment of liver fibrosis.

Attenuation of lipopolysaccharide-induced neuroinflammatory events in BV-2 microglial cells by Moringa oleifera leaf extract

Objective: To determine the anti-neuroinflammatory activity of Moringa oleifera leaf extract(MLE) under lipopolysaccharide stimulation of mouse murine microglia BV2 cells in vitro. Methods: The cytotoxicity effect of MLE was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. The inflammatory response of BV-2 cells were induced with lipopolysaccharide. The generation of nitric oxide levels was determined by using Griess assay and the level of pro-inflammatory cytokines(IL-1β, IL-6 and TNF-α) was evaluated by ELISA kit. The expression of iNOS, COX-2 as well as IκB-ααwas carried out by immunoblot analysis. Results: MLE reduced the nitric oxide production in concentration-dependent manner, and maintained the viability of BV-2 microglial cells which indicated absence of toxicity. In addition, MLE repressed the activation of nuclear factor kappa B by arresting the deterioration of IκB-α, consequently resulted in suppression of cytokines expression such as COX-2 and iNOS. Conclusions: MLE inhibitory activities are associated with the inhibition of nuclear factor kappa B transcriptional activity in BV2 microglial cells. Thus MLE may offer a substantial treatment for neuroinflammatory diseases.