Tong Rong, Ding Bonan, Chen Shiyun, Yang Wenli, Yi Yuhang, He Wenjiang, Zhou Runze, Wang Yixue, Li Wenzhi, Qin Si
Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, 410128, China.
College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, China.
J Ethnopharmacol. 2025 Aug 29;352:120185. doi: 10.1016/j.jep.2025.120185. Epub 2025 Jun 20.
Benincasae Exocarpium (BE) is the outer peel of the herbaceous plant Benincasa hispida Cogn., belonging to the Cucurbitaceae family. BE has a long-standing history in medicinal applications for its capabilities to relieve thirst, promote diuresis, eliminate dampness, and clear heart fire, which suggest its potential for the intervention of hyperuricemia (HUA).
This study aimed to clarify how BE exerts its anti-HUA effect in HUA rats, especially its protective function on liver and kidney damage.
UPLC-MS/MS analysis was employed to identify the components of BE, HUA rats were established by potassium oxonate and hypoxanthine, and the biochemical parameters and transcriptomics analyses of liver and kidney in BE-treated HUA rats were carried out with further verification by Western Blot.
BE mainly consisted of amino acids, flavonoids, alkaloids, and terpenoids with a moderate inhibitory effect on xanthine oxidase (XOD, IC = 720.6 μg/mL) in vitro and reduced serum levels of uric acid (UA), TC, TG, IL-1β, IL-6 and TNF-α, as well as lowered AST, CRE, and BUN levels in vivo, which supported the efficacy of BE in improving liver and kidney function in HUA rats. In addition, BE inhibited UA synthesis and facilitated UA excretion by regulating the expressions of XOD in liver and URAT1, GLUT9, ABCG2 and OAT1 in kidney. Moreover, BE regulated HUA-induced renal inflammation and glomerular swelling through TLR4/NF-κB/NLRP3 signaling pathway, as evidenced by validation experiments combining transcriptomics with Western Blot analysis. Notably, liver transcriptome analysis and further molecular data indicated that BE alleviated metabolic disorders caused by HUA through regulation of IRS2/FoxO1/AMPK/ACC signaling pathway.
Above results suggest that BE primarily promotes UA excretion and is effective in both reducing UA reabsorption and inhibiting UA production. Notably, BE exerts protective effect on liver and kidney of HUA rats by reducing glomerular swelling and alleviating hepatic metabolic disorders. Therefore, BE can act as a dietary supplement with anti-HUA property.
冬瓜皮（BE）是葫芦科草本植物冬瓜Benincasa hispida Cogn.的外层果皮。冬瓜皮在药用方面历史悠久，具有清热生津、利水、祛湿、清心火的功效，提示其在干预高尿酸血症（HUA）方面具有潜力。
本研究旨在阐明冬瓜皮如何对高尿酸血症大鼠发挥抗高尿酸血症作用，尤其是其对肝损伤和肾损伤的保护作用。
采用超高效液相色谱-串联质谱（UPLC-MS/MS）分析法鉴定冬瓜皮的成分，用氧嗪酸钾和次黄嘌呤建立高尿酸血症大鼠模型，并对经冬瓜皮处理的高尿酸血症大鼠的肝脏和肾脏进行生化参数及转录组学分析，进一步通过蛋白质免疫印迹法进行验证。
冬瓜皮主要含有氨基酸、黄酮类、生物碱和萜类化合物，在体外对黄嘌呤氧化酶（XOD，IC = 720.6 μg/mL）有中度抑制作用，在体内可降低血清尿酸（UA）、总胆固醇（TC）、甘油三酯（TG）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平，还可降低天冬氨酸转氨酶（AST）、肌酐（CRE）和尿素氮（BUN）水平，这支持了冬瓜皮对改善高尿酸血症大鼠肝肾功能的疗效。此外，冬瓜皮通过调节肝脏中XOD以及肾脏中尿酸转运蛋白1（URAT1）、葡萄糖转运蛋白9（GLUT9）、ATP结合盒转运体G2（ABCG2）和有机阴离子转运体1（OAT1）的表达来抑制尿酸合成并促进尿酸排泄。此外，结合转录组学和蛋白质免疫印迹分析的验证实验表明，冬瓜皮通过Toll样受体4（TLR4）/核因子κB（NF-κB）/NOD样受体蛋白3（NLRP3）信号通路调节高尿酸血症诱导的肾脏炎症和肾小球肿胀。值得注意的是，肝脏转录组分析及进一步的分子数据表明，冬瓜皮通过调节胰岛素受体底物2（IRS2）/叉头框蛋白O1（FoxO1）/腺苷酸活化蛋白激酶（AMPK）/乙酰辅酶A羧化酶（ACC）信号通路减轻高尿酸血症引起的代谢紊乱。
上述结果表明，冬瓜皮主要促进尿酸排泄，在减少尿酸重吸收和抑制尿酸生成方面均有效。值得注意的是，冬瓜皮通过减轻肾小球肿胀和缓解肝脏代谢紊乱，对高尿酸血症大鼠的肝脏和肾脏发挥保护作用。因此，冬瓜皮可作为具有抗高尿酸血症特性的膳食补充剂。
