OBJECTIVE: To compare the metabolite profile of Chrysanthemum morifolium flower fraction with that of its detannified fraction in relation to XO inhibitory activity using a rapid and effective metabolomics approach.
METHODS: Proton nuclear magnetic resonance (1 H-NMR)-based metabolomics approach coupled with multivariate data analysis was utilised to characterise the XO inhibitors related to the antioxidant properties, total phenolic, and total flavonoid contents of the C. morifolium dried flowers.
RESULTS: The highest XO inhibitory activity, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, total phenolic and flavonoid content with strong positive correlation between them were observed in the ethyl acetate (EtOAc) fraction. Detannified EtOAc showed higher XO inhibitory activity than non-detannified EtOAc fraction. A total of 17 metabolites were tentatively identified, of which three namely kaempferol, 4-hydroxybenzoic acid and apigenin, could be suggested to be responsible for the strong XO inhibitory activity. Additive interaction between 4-hydroxybenzoic acid and apigenin (or kaempferol) in XO inhibition was demonstrated in the interaction assay conducted.
CONCLUSION: Chrysanthemum morifolium dried flower-part could be further explored as a natural XO inhibitor for its anti-hyperuricemic potential. Metabolomics approach served as an effective classification of plant metabolites responsible for XO inhibitory activity, and demonstrated that multiple active compounds can work additively in giving combined inhibitory effects.
METHOD: Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques.
RESULTS: The most active dichloromethane extract of M. pumilum var. pumila leaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50 value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL).
CONCLUSION: This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.
Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.
Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.
Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.