Chen Na, Li Hua, Meng Jing, Yang Yi-Fei, Yang Bin
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):148-159. doi: 10.19540/j.cnki.cjcmm.20220928.401.
A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg(-1)) and ethambutol(250 mg·kg(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.
建立腺嘌呤和乙胺丁醇诱导的高尿酸血症大鼠模型，以研究藏红花花生物残渣中黄酮类提取物的抗高尿酸血症活性及其作用机制。将67只SD大鼠随机分为对照组、模型组、阳性对照组和黄酮类提取物组（3个剂量组），每组11或12只大鼠。通过连续7天口服腺嘌呤（100 mg·kg⁻¹）和乙胺丁醇（250 mg·kg⁻¹）建立高尿酸血症模型。同时，阳性对照组给予别嘌醇（每天20 mg·kg⁻¹），黄酮类提取物组分别给予剂量为340、170和85 mg·kg⁻¹的黄酮类提取物。第8天，采集大鼠血清、肝脏、肾脏和肠道组织，检测血清和组织中的尿酸水平、血清和肝脏中的黄嘌呤氧化酶活性及抗氧化活性，并进行肾脏组织病理学检查。此外，进行了非靶向血清代谢组学研究。结果表明，黄酮类提取物能有效降低高尿酸血症大鼠血清、肾脏和回肠中的尿酸水平，抑制黄嘌呤氧化酶活性，提高血清和肝脏的抗氧化活性。同时，降低肾脏炎症因子水平，保护肾功能。此外，筛选出高尿酸血症大鼠的68种差异代谢物，其中大部分为脂质和氨基酸。黄酮类提取物显著恢复了高尿酸血症大鼠差异代谢物的水平，如SM（d18:1/20:0）、PC[18:0/18:2(9Z,12Z)]、棕榈酸和瓜氨酸，可能通过精氨酸生物合成、甘氨酸、丝氨酸和苏氨酸代谢以及组氨酸代谢这三条途径。综上所述，藏红花花生物残渣中的黄酮类提取物降低了高尿酸血症大鼠的尿酸水平，提高了抗氧化活性，减轻了炎症症状，这可能与其抑制黄嘌呤氧化酶活性以及调节血清脂质和氨基酸代谢有关。
