Jul 2026· Archives of Biochemistry and Biophysics· Vol 784, pp.
110948
· 0 citations· 41 references
Medicine
TL;DR
ADMET analysis indicates that orientin has promising pharmaceutical properties and provides a basis for future research focusing on structural optimization, metabolic transformation, and in vivo evaluation.
Abstract
Xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine. It further oxidizes xanthine to uric acid, making it an important target for treating hyperuricemia. This study focused on orientin as a model flavonoid for xanthine oxidase inhibition. We examined whether the C-glycosyl group changes its inhibitory potency, binding pattern, and predicted ADMET profile. In vitro enzyme activity was determined to be 364.79 ± 8.21 μM for the half-inhibitory concentration (IC50) of orientin. Kinetic analysis suggested a mixed-type inhibition pattern. Intrinsic fluorescence quenching further supported the interaction between orientin and XO. Molecular docking and molecular dynamics simulations provided structural insight into the binding mode and stability of the orientin-XO complex. ADMET analysis indicates that orientin has promising pharmaceutical properties. These findings provide a basis for future research focusing on structural optimization, metabolic transformation, and in vivo evaluation.
Hyperuricemia (HUA), a prevalent metabolic disorder, needs new xanthine oxidase (XOD) inhibitor studies to reduce severe side effects. In this study, the inhibitory activities of 20 dietary flavonoids against XOD were determined in vitro, and a structure-activity relationship (SAR) model was subsequently developed. Diosmetin and quercetin emerged as the most potent inhibitors, both of which displayed mixed-type inhibition. SWISS-MODEL-based docking revealed that the key binding sites for diosmetin are Asn768 (active site) and Phe1009 (allosteric site), whereas those for quercetin are Lys771 (active site) and Phe914 (allosteric site). In hyperuricemic mice, diosmetin and quercetin reduced serum uric acid levels, suppressed XOD activity, and improved renal damage. Analysis by 16S rRNA sequencing revealed that both diosmetin and quercetin supplementation increased the abundance of beneficial bacteria, such as Lactobacillus johnsonii, and reduced the abundance of harmful bacteria, such as Desulfovibrio fairfieldensis. Notably, diosmetin shows lower potential hepatotoxicity than quercetin, as evidenced by the restoration of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HUA-induced liver injury and a higher binding docking score with the p38MAPK protein. These findings provide a robust scientific basis for developing natural therapeutics with enhanced efficacy and safety.
Pingping Guo, Xing-Xing Liu, Feng-Ying Dong et al.· Food Science and Human Welln...· 0 citations
Xanthine oxidase (XO) represents a key therapeutic target for the treatment of hyperuricemia. Although dietary anthocyanins are known to ameliorate hyperuricemia, their structure-activity relationship (SAR) concerning XO inhibition has not been fully elucidated. This study systematically evaluated the inhibitory effects of anthocyanin extracts derived from various dietary sources-including fruits, vegetables, cereals, and edible flowers-on XO activity, uric acid (UA) levels, and hyperuricemia-associated biomarkers. Using inhibition kinetics, spectroscopic techniques, and molecular simulations, we confirmed the direct binding of anthocyanins to XO and identified delphinidin-3-O-sambubioside (D3S) as the most potent inhibitor. In vivo experiments showed that anthocyanin extract from kale significantly suppressed XO activity and improved renal function in hyperuricemic mice. Transcriptomic and qPCR analyses further revealed that anthocyanins modulate the PI3K-Akt signaling pathway, specifically through downregulation of PIK3R5. These findings highlight the potential of specific anthocyanin structures, particularly D3S, as effective natural XO inhibitors for the management of hyperuricemia.
Simeng Li, Mingkun Zhao, Yue Li et al.· Food & Function· 0 citations
Assessment of the anti-PPO activity of protocatechualdehyde (PCA) offers some valuable insights into the development of PPO inhibitor and anti-browning agent, and provides a theoretical foundation for the potential application of PCA in the area of food preservation.
Yan-Ping Lin, Dong-Yan Zhou, Shang-Guang Du et al.· International Journal of Bio...· 0 citations
In this study, the effects of roasting on the xanthine oxidase (XO) inhibitory activity of green tea were investigated based on chemical analysis. It was found that XO inhibitory activity increased with roasting temperature, reaching a maximum of 91% inhibition at 200 °C, before declining at higher temperatures. High-performance liquid chromatography (HPLC) analysis revealed that major tea catechins, such as epigallocatechin gallate (EGCG), were eliminated upon roasting at 200 °C, while flavonols (myricetin, quercetin, and kaempferol) formed and exhibited strong XO inhibitory activity. A newly defined activity-contributing value (ACV) analysis indicated that these flavonols became the primary contributors to XO inhibition in roasted tea among the compounds identified by HPLC. Additionally, pyrogallol, likely generated from EGCG during roasting, was identified as another potent inhibitor with a high ACV. These results demonstrate that controlled roasting at approximately 200 °C enhances the XO inhibitory activity of green tea through the formation of flavonols and pyrogallol.
Aiko Kano, Kazumi Kameda, A. Masuda et al.· ACS Food Science & Techn...· 0 citations
Abstract Tyrosinase is a key enzyme in melanogenesis and food enzymatic browning. This study systematically investigated tyrosinase inhibition effects and binding interactions of two tea catechins epigallocatechin (EGC) and gallocatechin (GC), and their practical efficacy. In vitro enzymatic assays showed that EGC and GC both reversibly inhibited tyrosinase in a mixed-type manner, with IC50 values of 0.059 ± 0.002 mg/ml (192.02 ± 7.19 µM) and 0.036 ± 0.001 mg/ml (118.77 ± 4.11 µM), respectively. Fluorescence quenching, synchronous fluorescence, CD spectra, ANS-binding assay, and molecular docking results revealed the binding between EGC or GC and tyrosinase, changed enzyme conformation and microenvironment, subsequently leading to a decrease in enzyme activity. Cellular studies demonstrated that EGC and GC obviously inhibited intracellular tyrosinase activity and melanin synthesis in B16 melanoma cells. These findings provide comprehensive mechanistic insights into the anti-tyrosinase activity of EGC and GC and support their potential application as natural inhibitors.
Jianjun Zhang, Zheng Shi, Jiang Li et al.· Journal of Enzyme Inhibition...· 0 citations
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