Esculetin as bioactive marker: towards a rational scientific approach for the treatment of hyperuricemia using Traditional Chinese Medicine

Zuo, Jieyu; Zhang, Wugang; Jian, Hui; Bou‐Chacra, Nádia Araci; Löbenberg, Raimar

doi:10.1590/s2175-97902019000417827

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…Phytochemical constituents such as phenolics, flavonoids, coumarins, lignans, triterpenoids, and alkaloids have been reported to inhibit xanthine oxidase [ 27 , 34 – 36 ]. Esculetin, a hydroxycoumarin derivative, displayed strong xanthine oxidase inhibitory activity [ 37 ] and was proposed as an appropriate bioactive quality control marker for a traditional Chinese medicine formula used in the treatment of hyperuricemia [ 38 ]. The extract of M. pumilum was reported to alleviate hyperuricemia in vivo [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

Aladdin

Husain

Jalil

et al. 2020

BMC Complement Med Ther

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Background In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds. 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.

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Section: Introductionmentioning

confidence: 99%

Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

Aladdin

Husain

Jalil

et al. 2020

BMC Complement Med Ther

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Xanthine Oxidase Inhibitory Activity of Euphorbia peplus L. Phenolics

Kamel

Ahmed

El-Bassuony

et al. 2022

CCHTS

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Background: Various phenolics show inhibitory activity towards xanthine oxidase (XO), an enzyme that generates reactive oxygen species which cause oxidative damage. Objective: This study investigated the XO inhibitory activity of Euphorbia peplus phenolics. Methods: The dried powdered aerial parts of E. peplus were extracted, fractioned and phenolics were isolated and identified. The XO inhibitory activity of E. peplus extract (EPE) and the isolated phenolics was investigated in vitro and in vivo. Results: Three phenolics were isolated from the ethyl acetate fraction of E. peplus. All isolated compounds and the EPE showed inhibitory activity towards XO in vitro. In hyperuricemic rats, EPE and the isolated phenolics decreased uric acid and XO activity. Molecular docking showed the binding modes of isolated phenolics with XO, depicting significant interactions with the active site amino acid residues. Molecular dynamics simulation trajectories confirmed the interaction of isolated phenolics with XO by forming hydrogen bonds with the active site residues. Also, the root mean square (RMS) deviations of XO and phenolics-XO complexes achieved equilibrium and fluctuated during the 10 ns MD simulations. The radius of gyration and solvent accessible surface area investigations showed that different systems were stabilized at ≈ 2500 ps. The RMS fluctuations profile depicted that the drug binding site exhibited a rigidity behavior during the simulation. Conclusion: In vitro, in vivo and computational investigations showed the XO inhibitory activity of E. peplus phenolics. These phenolics might represent promising candidates for the development of XO inhibitors.

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The Efficacy and Mechanism of Chinese Herbal Medicines in Lowering Serum Uric Acid Levels: A Systematic Review

et al. 2021

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Background. Chinese herbal medicines are widely used to lower serum uric acid levels. However, no systemic review summarizes and evaluates their efficacies and the underlying mechanisms of action. Objectives. To evaluate the clinical and experimental evidences for the effectiveness and the potential mechanism of Chinese herbal medicines in lowering serum uric acid levels. Methods. Four electronic databases PubMed, Wed of Science, the Cochrane Library and Embase were used to search for Chinese herbal medicines for their effects in lowering serum uric acid levels, dated from 1 January 2009 to 19 August 2020. For clinical trials, randomized controlled trials (RCTs) were included; and for experimental studies, original articles were included. The methodological quality of RCTs was assessed according to the Cochrane criteria. For clinical trials, a meta-analysis of continuous variables was used to obtain pooled effects. For experimental studies, lists were used to summarize and integrate the mechanisms involved. Results. A total of 10 clinical trials and 184 experimental studies were included. Current data showed that Chinese herbal medicines have promising clinical efficacies in patients with elevated serum uric acid levels (SMD: −1.65, 95% CI: −3.09 to −0.22; p = 0.024). There was no significant difference in serum uric acid levels between Chinese herbal medicine treatments and Western medicine treatments (SMD: −0.13, 95% CI: −0.99 to 0.74; p = 0.772). Experimental studies revealed that the mechanistic signaling pathways involved in the serum uric acid lowering effects include uric acid synthesis, uric acid transport, inflammation, renal fibrosis and oxidative stress. Conclusions. The clinical studies indicate that Chinese herbal medicines lower serum uric acid levels. Further studies with sophisticated research design can further demonstrate the efficacy and safety of these Chinese herbal medicines in lowering serum uric acid levels and reveal a comprehensive picture of the underlying mechanisms of action.

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Esculetin as bioactive marker: towards a rational scientific approach for the treatment of hyperuricemia using Traditional Chinese Medicine

Cited by 3 publications

References 23 publications

Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

Xanthine Oxidase Inhibitory Activity of Euphorbia peplus L. Phenolics

The Efficacy and Mechanism of Chinese Herbal Medicines in Lowering Serum Uric Acid Levels: A Systematic Review

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