Abstract：
Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.
摘要：
桑黄是一种重要的药用和食用菌，具有多种生物活性。本研究旨在研究天牛水提物(API)对高尿酸血症(HUA)及相关肾损害的治疗作用。测定了原料药的化学成分。在腺嘌呤/氧酸盐钾(PO)处理的小鼠中评估API对HUA和肾损伤的治疗效果。原料药的成分分析显示，多糖占主导地位(33.4%)，其次是总黄酮(9.1%)，和总三萜类化合物(3.5%)。与控制相比，腺嘌呤/PO治疗显著升高了血清尿酸(UA)水平,但API减轻了这种升高.在肝脏中，HUA增加黄嘌呤氧化酶（XOD）的表达和活性，而API减少。此外，发现API可增强HUA小鼠肾脏和肠道中UA转运体ABCG2的表达，提示UA排泄增加。此外,API改善HUA诱导的肾损伤，如血清BUN/肌酐水平降低所示，肾小球和肾小管损伤减少，降低纤维化水平。网络药理学分析预测天牛可能通过调节线粒体功能来改善HUA相关性肾损伤。然后通过API诱导的NAD/NADH比率上调证实了这一预测，ATP水平,SOD2活性，和SOD2/PCG-1α/PPARγ在HUA小鼠肾脏中的表达。我们的结果表明，API可以通过减少肝脏中的UA产生和增强肾脏和肠道中的UA排泄来有效改善HUA。它可能是HUA相关肾损伤的潜在治疗方法。
