Apigenin Ameliorates Hyperuricemia and Renal Injury through Regulation of Uric Acid Metabolism and JAK2/STAT3 Signaling Pathway

Abstract

Hyperuricemia (HUA) is a kind of metabolic disease with high incidence that still needs new countermeasures. Apigenin has uric-lowering and kidney-protective activities, but how apigenin attenuates HUA and renal injury remains largely unexploited. To this end, an acute HUA mouse model was established by intraperitoneal injection of potassium oxazinate and oral administration with hypoxanthine for 7 consecutive days. Apigenin intervention decreased serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin-18 (IL-18), liver xanthine oxidase (XOD), and urine protein levels, and increased serum interleukin-10 (IL-10) and urine UA and CRE levels in HUA mice. Moreover, administration of apigenin to HUA mice prevented renal injury, decreased renal glucose transporter 9 (GLUT9) and urate anion transporter 1 (URAT1) levels, and increased renal organic anion transporter 1 (OAT1). These alterations were associated with an inhibition of IL-6, phospho-janus kinase 2 (P-JAK2), phospho-signal transducer, and activator of transcription 3 (P-STAT3), and suppression of cytokine signaling 3 (SOCS3) expression in the kidneys. Additionally, the molecular docking results showed that apigenin had strong binding capacity with UA transporters and JAK2 proteins. In summary, apigenin could improve UA metabolism and attenuate renal injury through inhibiting UA production, promoting excretion, and suppressing the JAK2/STAT3 signaling pathway in HUA mice. The results suggest that apigenin may be a suitable drug candidate for management of HUA and its associated renal injury.

Dispelling Dampness, Relieving Turbidity and Dredging Collaterals Decoction, Attenuates Potassium Oxonate-Induced Hyperuricemia in Rat Models

“…Hyperuricemia was induced in rats by potassium oxazinate (PO) intragastric administration. 16 The model method was as follows: except for the control group, which was given the same amount of normal saline by intragastric administration, the other groups were given 750 mg/kg/d PO by intragastric administration once a day for 14 consecutive days. 16 All male rats were divided into six groups: control group (control, n=8), hyperuricemia model group (HU, n=8), low-dose group (DED-L, n=8), medium-dose group (DED-M, n=8), high-dose group (DED-H, n=8) and benzbromarone (BBR, n=8) group.…”

“… 16 The model method was as follows: except for the control group, which was given the same amount of normal saline by intragastric administration, the other groups were given 750 mg/kg/d PO by intragastric administration once a day for 14 consecutive days. 16 All male rats were divided into six groups: control group (control, n=8), hyperuricemia model group (HU, n=8), low-dose group (DED-L, n=8), medium-dose group (DED-M, n=8), high-dose group (DED-H, n=8) and benzbromarone (BBR, n=8) group. The drug volume of the treatment group was 10 mL/kg, and the dose was 9.48 g/kg/d in the high-dose group, 4.74 g/kg/d in the medium-dose group, and 2.37 g/kg/d in the low-dose group.…”

TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter

“…It exhibits a robust affinity for JAK2 proteins and, UA transporters effectively enhancing UA metabolism and mitigating renal damage ( Liu et al, 2017b ). This is accomplished by curtailing UA production, enhancing excretion, and dampening the activity of the JAK2/STAT3 signaling pathway in hyperuricemia mice ( Liu et al, 2022a ). Lagotis brachystachya Maxim., primarily employed for treating yellow water disease (gouty arthritis) and hepatitis, is capable of reducing the expression of phospho-JAK2 and phospho-STAT3.…”

Correction: Liu et al. Apigenin Ameliorates Hyperuricemia and Renal Injury through Regulation of Uric Acid Metabolism and JAK2/STAT3 Signaling Pathway. Pharmaceuticals 2022, 15, 1442

“…In the original publication [ 1 ], there were mistakes in Figures 5 and 9 as published. In Figure 5C, the molecular weight of URAT1 protein was labeled incorrectly.…”