Effects of Gancao Nourish Yin Decoration on Liver Metabolic Profiles in hTNF-α Transgenic Arthritic Mouse Model

BackgroundGancao Nurish Yin (GCNY) decoction has been applied to clinical rheumatoid arthritis (RA) patients and it had shown effectiveness not only in disease activity controlling but also on improving patients’ physical status. However, its mechanism of function has not been investigated. Metabolic perturbations have been associated with RA and targeting the metabolic profile is one of the ways to manage the disease. The aim of this study was to observe the effect of GCNY on metabolic changes of human tumor necrosis factor alpha (hTNF-α) transgenic arthritic mouse model. MethodshTNF-α transgenic arthritic model mice were divided into control and GCNY groups with 6 mice in each group. After 8 weeks of treatment, liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry (LC/MS) analysis. Significantly regulated metabolites by GCNY treatment were first identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analysis.ResultsOf the 126 metabolites detected in the liver, 17 metabolites were with significantly altered between control group mice and mice treated with GCNY. Specifically, thiamine, gamma-L-Glutamyl-L-valine, pantothenic acid, pyridoxal (Vitamin B6), succinic acid, uridine 5'-diphospho-glucuronic acid (UDP-D-Glucuronate), uridine, allantoic acid, N-Acetyl-D-glucosamine, nicotinamide ribotide and N2,N2-Dimethylguanosine were down-regulated by GCNY treatment whereas isobutyrylglycine, N-Acetylcadaverine, N-Carbamoyl-L-aspartic acid, L-Anserine, creatinine and cis-4-Hydroxy-D-proline were up-regulated. Six metabolic pathways were significantly altered including the alanine, aspartate and glutamate metabolism, pyrimidine metabolism, thiamine metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and CoA biosynthesis and citrate cycle (TCA cycle). Integrative metabolic network analysis suggested the possibility of GCNY having both positive and negative effects on RA through the suppression of angiogenesis and promotion of leukocyte extravasation into the synovium, respectively. ConclusionsGCNY can induce a change in the metabolic profiles of hTNF-α transgenic arthritic mouse model. Further optimization of this decoction may lead to better therapeutic effects on RA patients.

INVESTIGATING THE ANTI-INFLAMMATORY ACTIVITY OF AN ETHANOLIC EXTRACT FROM ARTOCARPUS TONKINENSIS LEAVES USING A COLLAGEN ANTIBODY-INDUCED ARTHRITIC MOUSE MODEL

The obtained results here demonstrate that the 70% ethanolic leaf extract of A. tonkinensis (AT2), traditionally used in Vietnamese folk medicine for treating arthritic symtoms, has beneficial effects on pro-inflammatory cytokine inhibition and in an experimental arthritic mouse model. LPS-stimulated RAW 264.7 macrophages treated with AT2 showed a significant decrease in the production of IL-6 and TNFa at concentrations of 12.5, 25 and 50 µg/mL (P<0.05), indicating its potential anti-inflammatory properties. Treatment of CAIA mice with AT2 also led to diminish the incidence of arthritis at doses of 200 and 300 mg/kg body weight.