Isoorientin exerts a urate-lowering effect through inhibition of xanthine oxidase and regulation of the TLR4-NLRP3 infla
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ORIGINAL PAPER
Isoorientin exerts a urate‑lowering effect through inhibition of xanthine oxidase and regulation of the TLR4‑NLRP3 inflammasome signaling pathway Meng‑Fei An1,3 · Ming‑Yue Wang1,3 · Chang Shen1,3 · Ze‑Rui Sun1,3 · Yun‑Li Zhao1,2,4 · Xuan‑Jun Wang1,2,5 · Jun Sheng1,2,5 Received: 21 May 2020 / Accepted: 29 October 2020 © The Japanese Society of Pharmacognosy 2020
Abstract Isoorientin (ISO), a natural flavonoid compound, has been identified in several plants and its biological activity is determined and the study on lowering uric acid has not been reported. In view of the current status of treatment of hyperuricemia, we evaluated the hypouricemic effects of ISO in vivo and in vitro, and explored the underlying mechanisms. Yeast extractinduced hyperuricemia animal model as well as hypoxanthine and xanthine oxidase (XOD) co-induced high uric acid L-O2 cell model and enzymatic experiments in vitro were selected. The XOD activity and uric acid (UA) level were inhibited after the treatment of ISO in vitro and in vivo. Furthermore, serum creatinine (CRE) and blood urea nitrogen (BUN) levels were also significantly reduced and liver damage was recovered in pathological histology after the ISO administration in hyperuricemia animal model. The results of mechanism illustrated that protein expressions such as XOD, toll-like receptor 4 (TLR4), cathepsin B (CTSB), NLRP3, and its downstream caspase-1 as well as interleukin-18 (IL-18) were markedly downregulated by ISO intervention in vitro and in vivo. Our results suggest that ISO exerts a urate-lowering effect through inhibiting XOD activity and regulating TLR4-NLRP3 inflammasome signal pathway, thus representing a promising candidate therapeutic agent for hyperuricemia. Meng-Fei An and Ming-Yue Wang have contributed equally to this work. * Yun‑Li Zhao [email protected] * Xuan‑Jun Wang [email protected] * Jun Sheng [email protected] 1
Key Laboratory of Pu‑erh Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650224, People’s Republic of China
2
College of Science, Yunnan Agricultural University, Kunming 650224, People’s Republic of China
3
College of Food Science and Technology, Yunnan Agricultural University, Kunming 650224, People’s Republic of China
4
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China
5
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming 650224, People’s Republic of China
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Vol.:(0123456789)
Journal of Natural Medicines
Graphic abstract Both animal models and in vitro experiments suggested that ISO may effectively lower uric acid produce. The mechanism might be the inhibition of XOD activity and NLRP3 inflammasome of upregulation.
Keywords Isoorientin · Hyperuricemia · Xanthine oxidase · NLRP3 inflammasome · Uric acid Abbreviations ISO Isoorientin XOD Xanthine oxidase UA Uric acid
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