龍眼花萃取物對氧嗪酸鉀與次黃嘌呤誘導之高尿酸血症大鼠之影響

龍眼花萃取物具有改善肥胖及糖尿病的效果，高尿酸血症 (hyperuricemia, HUA) 亦屬於盛行率逐漸攀升的代謝性疾病，並與許多慢性疾病的發展密切相關。高尿酸血症成因複雜，近年來天然植物萃取物被廣泛研究做為輔助療法改善高尿酸血症之方式，本研究利用氧嗪酸鉀 (potassium oxonate, PO) 合併次黃嘌呤 (hypoxanthine, HX) 誘導大鼠HUA模式，探討龍眼花萃取物對改善HUA之功效性及分子機轉。本實驗將35隻7週齡Sprague–Dawley (SD) 大鼠隨機分成正常控制組 (control, C) 與高尿酸控制組 (hyperuricemia control, HC)，控制組每日腹腔注射 (intraperitoneal injection, IP) 0.5%CMC-Na水溶液，高尿酸組每日以腹腔注射方式給予PO (300 mg/kg rat) 並合併口服給予HX (100 mg/kg rat) 連續4週，誘導大鼠產生高尿酸血症，於誘導期間口服餵食樣品，其分組如下 (每組7隻)：(1) 正常控制組：SD大鼠給予正常飲食、(2) 高尿酸控制組：SD大鼠給予PO + HX、(3) 高尿酸給予低劑量之龍眼花萃取物組：[HC + longan flower extract-low dose (100 mg/kg rat), HC + LFE-L]、(4) 高尿酸給予高劑量之龍眼花萃取物組：[HC + longan flower extract-high dose (200 mg/kg rat) , HC + LFE-H] 及 (5) 高尿酸給予沒食子酸組：[HC + gallic acid (50 mg/kg rat), HC + GA]。實驗期間紀錄大鼠生理參數與前肢握力，後續分析血清及尿液尿酸含量、肝臟黃嘌呤氧化酶活性、臟器重量、血清生化參數、組織病理學切片、相關基因之表現、糞便中短鏈脂肪酸含量、腸道菌相組成和代謝體組成。研究結果顯示，高尿酸血症大鼠在給予龍眼花萃取物後，可以顯著降低血清尿酸濃度且增加尿液尿酸濃度，進而改善因高尿酸血症而導致的尿量增多、血清肌酸肝濃度上升、腎損傷與腎臟腫大。另一方面，龍眼花萃取物的介入也可顯著減少腎臟葡萄糖轉運蛋白9 (glucose transporter 9, GLUT9) 與迴腸腫瘤壞死因子-α (tumor necrosis factor alpha, TNF-α) 的基因表現，並顯著降低Erysipelotrichacea、Muribaculaceae PAC000186_g、Turicibacter、Muribaculaceae PAC001112_g、Clostridium及Blautia的菌群豐富度。由代謝體學分析結果顯示，高尿酸血症誘導與龍眼花萃取物的介入導致血清之丙胺酸、甘胺酸、胍基乙酸、纈胺酸和白胺酸，及尿液之膽鹼、苯甲酸、二甲胺、甘胺酸、乳酸、琥珀酸鹽、牛磺酸、葫蘆巴鹼及尿素發生顯著差異，影響麩胱甘肽代謝路徑；甘油磷脂代謝；甘胺酸、絲胺酸與蘇胺酸代謝；乙醛酸和二羧酸代謝；硫辛酸代謝；葉酸介導的單碳代謝及初級膽酸生合成之代謝路徑。綜上所述，龍眼花萃取物可透過抑制尿酸的再吸收、減輕發炎反應、調控腸道菌群與代謝變化，而具有抗HUA之潛力，未來可用以開發為輔助治療HUA的保健食品。

Longan flower extract (LFE) has beneficial effects on obesity and diabetes mellitus. Hyperuricemia (HUA) is a metabolic disease with an increasing prevalence that is closely related to the progression of several chronic diseases. The causes of hyperuricemia are complex, natural plant extracts have been widely investigated to as complementary therapies to improve HUA in recent years. The present study investigated the efficacy and molecular mechanisms of LFE on hyperuricemia using potassium oxonate (PO) and hypoxanthine (HX) -induced rats. Thirty-five 7-week-old Sprague–Dawley (SD) rats were randomly divided into control (C) and hyperuricemia control (HC) groups. The control group received daily intraperitoneal injection of 0.5% CMC-Na solution, while the HC group received intraperitoneal (IP) injection of PO (300 mg/kg) and orally administered HX (100 mg/kg) once a day for four weeks to induce hyperuricemia, and the samples were fed orally during the intervention. The rats were divided into the following groups (n = 7/group): (1) C group: rats received normal diet, (2) HC group: SD rats received PO + HX, (3) HC + LFE-L group: hyperuricemic rats receiving low dosed longan flower extract (100 mg/kg), (4) HC + LFE-H group: hyperuricemic rats receiving high dosed longan flower extract (200 mg/kg), and (5) HC + GA group: hyperuricemia rats receiving gallic acid (50 mg/kg). Physiological parameters, grip strength, serum and urine uric acid levels, hepatic xanthine oxidase activity, organ weights, serum biochemical parameters, tissue histopathological analysis, gene regulation, fecal short chain fatty acid content, gut microbiota composition, and metabolomic analysis were analyzed. The findings revealed that LFE significantly reduced serum uric acid and increased urinary uric acid levels, thereby ameliorated polyuria, elevated serum creatinine, renal injury, and kidney enlargement associated with HUA. LFE intervention significantly downregulated the expression of glucose transporter 9 (GLUT9) levels in renal uric acid reabsorption transporter and tumor necrosis factor alpha (TNF-α) levels in the ileal inflammaton. Gut microbiota analysis revealed that LFE significantly decreased the relative abundance of Erysipelotrichacea, Muribaculaceae PAC000186_g, Turicibacter, Muribaculaceae PAC001112_g, Clostridium, and Blautia. Metabolomic analysis identified significant alterations in serum alanine, glycine, guanidoacetate, leucine ,and valine, and urine choline, benzonate, dimethylamine, glycine, lactate, succinate, taurine, trigonelline, and urea. These changes impacted metabolic pathways such as glutathione metabolism, glycerophospholipid metabolism, gycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, lipoic acid metabolism, one carbon pool by folate, and primary bile acid biosynthesis after LFE intervention. In conclusion, LFE exhibits anti-hyperuricemic potential by inhibiting urate reabsorption, attenuating inflammation, and regulating gut microbiota composition and metabolite profiles. These findings suggest its potential as a nutraceutical for managing HUA.