Mangiferin Ameliorates Hyperuricemic Nephropathy Which Is Associated With Downregulation of AQP2 and Increased Urinary Uric Acid Excretion

Figures

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  Figure 1. Effects of mangiferin on uric acid level and renal injury. Serum uric acid was measured (A). Kidney injury was evaluated by calculated kidney index (B), level of serum creatinine (C), and BUN (D). Kidney sections were applied to H&E staining (200×) (E). n = 4-6. #P < 0.05, ##P < 0.01, ###P < 0.001 vs. Con; *P < 0.01 vs. HN; △△P < 0.01, △△△P < 0.001 vs. Con+Mang.

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  Figure 2. Protective effect of mangiferin on renal inflammation. F4/80 staining was applied to present macrophage infiltration in kidney (200×) (A). The positive brown-stained area was calculated (B). Expression of NLRP3, p-JNK and JNK was determined by western blot (C) and quantifications (D). ##P < 0.01, ###P < 0.001 vs. Con; *P < 0.05, **P < 0.01, ***P < 0.001 vs. HN.

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  Figure 3. Protective effect of mangiferin on renal fibrosis. Kidney sections were applied to Masson’s trichrome stain (200×) (left) and α-SMA staining (200×) (right) (A). Expression of fibronectin, α-SMA, p-PKCβ, and PKC-β was determined by western blot (B) and quantifications (C–E). ##P < 0.01, ###P < 0.001 vs. Con; *P < 0.05, ***P < 0.001 vs. HN; △△△P < 0.001 vs. Con+Mang.

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  Figure 4. Effect of mangiferin on urinary uric acid excretion. The 24-hour urine output (A) and urine uric acid level was determined (B) from collected 24-hour urine. The 24-hour urine excretion was calculated (C). Urine uric acid normalized by urine creatinine (uUA/uScr) was calculated (D). Data was presented as normalized ratio comparing to control group. n = 3-6. #P < 0.05 vs. Con; ##P < 0.01 vs. Con; *P < 0.05, **P < 0.01 vs. HN; △△P < 0.01 vs. Con+Mang; △△△P < 0.001 vs. Con+Mang.

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  Figure 5. Effect of mangiferin on uric acid excretion-related transporters. Expression of AQP1, AQP2, URAT1, Glut9, and OAT1 was determined by western blot (A) and quantifications (B–F). #P < 0.05, ##P < 0.01, ###P < 0.001 vs. Con; ***P < 0.001 vs. HN; △P < 0.05, △△△P < 0.001 vs. Con+Mang.

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  Figure 6. Effect of mangiferin on XOD activity and level of SOD. Serum XO (A) and SOD (B) activity was measured. n = 3-6. #P < 0.05, ###P < 0.001 vs. Con; *P < 0.05, **P < 0.01 vs. HN.

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  Figure 7. Multitarget role of mangiferin in protecting from HN. Mangiferin decreased uric acid level by inhibiting XO-mediated uric acid synthesis and promoting AQP2-related uric acid excretion. The decreasing level of uric acid or mangiferin or both contributed to anti-oxidative, anti-inflammatory and anti-fibrotic effect and prevented from HN.