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1.
Am J Transl Res ; 9(9): 4206-4216, 2017.
Article in English | MEDLINE | ID: mdl-28979694

ABSTRACT

This study sought to investigate the anti-inflammatory effect of Polyene Phosphatidylcholine (PPC), a clinical drug that is used to treat hepatopathy, on lipopolysaccharide (LPS)-stimulated macrophages and on bovine collagen II-induced arthritis (CIA) rats. In stimulated primary and Raw264.7 macrophages by LPS, PPC significantly down-regulated the relative expression of mRNA such as IL-6, TNF-α, TLR-2, TLR-4, MyD88, and NF-κB while up-regulated IL-10 and TGF-ß expression. Moreover, the concentration of IL-6, TNF-α, IL-10, and TGF-ß in the cultured supernatants showed the similar tendency with their mRNA alterations. In addition, PPC could significantly inhibit the LPS-induced expression of MyD88 and NF-κB p65 in both mRNA and protein levels. These results suggest that PPC could down-regulate the LPS-stimulated inflammation in macrophages through TLR-2/TLR-4/MyD88/NF-κB pathway in vitro. Furthermore, to explore its effects in vivo, PPC was administrated to CIA rats. In comparison to CIA group, PPC-treated rats showed decreased arthritis score and osteopenia. Besides, PPC exhibited its ability to alleviate the degree of synovial hyperplasia, inflammatory cell infiltration, and destruction of cartilage and bone, thus remarkably improving the condition of CIA rats. In short, this study demonstrated that PPC had the potential to be an anti-inflammatory drug to treat inflammatory disorders such as rheumatoid arthritis.

2.
Molecules ; 22(8)2017 Aug 08.
Article in English | MEDLINE | ID: mdl-28786950

ABSTRACT

Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, exhibits beneficial effects on metabolic syndrome. Sustained inflammation plays a crucial role in the pathogenesis of metabolic syndrome. Here we explored the effects of PSPC on high-fat diet (HFD)-induced hepatic inflammation and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + PSPC group, and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. Nicotinamide riboside (NR) was used to increase NAD⁺ levels. Our results showed that PSPC effectively ameliorated obesity and liver injuries in HFD-fed mice. Moreover, PSPC notably blocked hepatic oxidative stress in HFD-treated mice. Furthermore, PSPC dramatically restored NAD⁺ level to abate endoplasmic reticulum stress (ER stress) in HFD-treated mouse livers, which was confirmed by NR treatment. Consequently, PSPC remarkably suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and nucleotide oligomerization domain protein1/2 (NOD1/2) signaling in HFD-treated mouse livers. Thereby, PSPC markedly diminished the NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation, ultimately lowering the expressions of inflammation-related genes in HFD-treated mouse livers. In summary, PSPC protected against HFD-induced hepatic inflammation by boosting NAD⁺ level to inhibit NLRP3 inflammasome activation.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Hepatitis, Animal/drug therapy , Hepatitis, Animal/metabolism , Inflammasomes/metabolism , Ipomoea batatas/chemistry , NAD/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pigments, Biological/pharmacology , Plant Extracts/pharmacology , Animals , Anthocyanins/chemistry , Anthocyanins/pharmacology , Anti-Inflammatory Agents/chemistry , Diet, High-Fat , Endoplasmic Reticulum Stress , Gene Expression Regulation/drug effects , Hepatitis, Animal/pathology , Liver/drug effects , Liver/metabolism , Liver/pathology , Mice , NF-kappa B/metabolism , Nod Signaling Adaptor Proteins/genetics , Nod Signaling Adaptor Proteins/metabolism , Obesity/drug therapy , Obesity/metabolism , Obesity/pathology , Oxidative Stress/drug effects , Pigments, Biological/chemistry , Plant Extracts/chemistry , Protein Transport
3.
Appl Physiol Nutr Metab ; 42(10): 1082-1091, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28636830

ABSTRACT

Our previous work showed that purple sweet potato colour (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat-diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into 4 groups: control group, HFD group, HFD+PSPC group, and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/(kg·day)-1). Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice. Moreover, PSPC dramatically attenuated hepatic steatosis in HFD-treated mice. PSPC markedly prevented oxidative stress-mediated Src activation in HFD-treated mouse livers. Furthermore, PSPC feeding remarkably suppressed mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) signalling and consequent CCAAT/enhancer binding protein ß (C/EBPß) activation and restored AMPK activation in HFD-treated mouse livers, which was confirmed by U0126 treatment. Ultimately, PSPC feeding dramatically reduced protein expression of FAS and CD36 and the activation of ACC, and increased the protein expression of CPT1A in the livers of HFD-treated mice, indicating decreased lipogenesis and fatty acid uptake and enhanced fatty acid oxidation. In conclusion, PSPC exhibited beneficial effects on hepatic steatosis, which were associated with blocking Src and C/EBPß activation.


Subject(s)
Anthocyanins/pharmacology , CCAAT-Enhancer-Binding Protein-beta/metabolism , Diet, High-Fat , Extracellular Signal-Regulated MAP Kinases/metabolism , Ipomoea batatas , Liver/drug effects , Non-alcoholic Fatty Liver Disease/prevention & control , Pigments, Biological/pharmacology , src-Family Kinases/metabolism , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Animals , Anthocyanins/isolation & purification , CD36 Antigens/metabolism , Disease Models, Animal , Energy Metabolism/drug effects , Enzyme Activation , Ipomoea batatas/chemistry , Liver/enzymology , Liver/pathology , Male , Mice, Inbred ICR , Non-alcoholic Fatty Liver Disease/enzymology , Non-alcoholic Fatty Liver Disease/pathology , Obesity/enzymology , Obesity/pathology , Obesity/prevention & control , Oxidative Stress/drug effects , Phytotherapy , Pigments, Biological/isolation & purification , Plants, Medicinal , Signal Transduction/drug effects , Time Factors , fas Receptor/metabolism
4.
Asian Pac J Trop Med ; 10(5): 524-527, 2017 May.
Article in English | MEDLINE | ID: mdl-28647192

ABSTRACT

OBJECTIVE: To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus (E. granulosus). METHODS: We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1 (DNASTAR Inc., Madison, WI), and the phylogenetic analysis was performed by using MEGA5.1 (CEMI, Tempe, AZ, USA). In addition, linear and conformational epitopes were analysed, including secondary structure, NXT/S glycosylation, fibronectin type III (FnIII) domain and glycosylphosphatidylinositol anchor signal (GPI-anchor). The secondary structure was predicted by PSIPRED method. RESULTS: Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence, X90928. However, EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates, respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine, X90928, and they belonged to Subgroup 1. However, in comparison to X90928, several amino acid mutations occurred in most isolates besides oncosphere, which potentially altered the immunodominant linear epitopes, glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. CONCLUSIONS: This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates, and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

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