Huang Zhichao, Zhang Wugang, An Qiong, Lang Yifan, Liu Ye, Fan Huifang, Chen Haifang
Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang, 330004, China.
State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, China.
Chin Med. 2023 Feb 16;18(1):17. doi: 10.1186/s13020-023-00716-w.
TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed to investigate the anti-hyperuricemia mechanism using metabolomics and confirm the active CF fraction.
The hyperuricemia model was established through intraperitoneal injection containing 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. We used serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, interleukin-6 (IL-6) and interleukin-1β (IL-1β) as indicators to evaluate the efficacy of CF and the four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF was considered through non-targeted metabolomics depending on the UPLC-Q-TOF-MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) helped explore the potential biomarkers in hyperuricemia. Moreover, the differential metabolites and metabolic pathways regulated by CF and four fractions were also assessed.
CF revealed a significant anti-hyperuricemia effect by down-regulating the level of sUA, sCRE, sIL-1β, and XOD. SX, CF30, CF60, and CF90 differed in the anti-hyperuricemia effect. Only CF60 significantly lowered the sUA level among the four fractions, and it could be the main efficacy fraction of TFTS. Forty-three differential metabolites were identified in hyperuricemia rats from plasma and kidney. Pathway analysis demonstrated that seven pathways were disrupted among hyperuricemia rats. CF reversed 19 metabolites in hyperuricemia rats and exerted an anti-hyperuricemia effect by regulating purine metabolism. CF60 was the main active fraction of TFTS and exerted a similar effect of CF by regulating purine metabolism.
CF and CF60 could exert an anti-hyperuricemia effect by regulating the abnormal purine metabolism because of hyperuricemia while improving intestinal and renal function. CF60 could be the main active fraction of TFTS.
痛风汤散（TFTS）是一种常用的治疗痛风的藏药方剂。此前，已证实痛风汤散（CF）具有显著的降尿酸作用。然而，其抗高尿酸血症的机制及主要活性成分仍不清楚。本研究旨在运用代谢组学方法探究其抗高尿酸血症机制，并确定CF的活性成分。
通过腹腔注射100mg/kg氧嗪酸钾和灌胃150mg/kg次黄嘌呤建立高尿酸血症模型。我们以血清尿酸（sUA）、肌酐（CRE）、血尿素氮（BUN）、黄嘌呤氧化酶（XOD）活性、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）作为指标，评估CF及四个组分（SX、CF30、CF60和CF90）的疗效。基于超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）技术，通过非靶向代谢组学研究CF抗高尿酸血症的机制。主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）有助于探索高尿酸血症中的潜在生物标志物。此外，还评估了CF及四个组分调节的差异代谢物和代谢途径。
CF通过下调sUA、sCRE、sIL-1β和XOD水平显示出显著的抗高尿酸血症作用。SX、CF30、CF60和CF90在抗高尿酸血症作用方面存在差异。四个组分中只有CF60显著降低了sUA水平，它可能是痛风汤散的主要有效组分。在高尿酸血症大鼠的血浆和肾脏中鉴定出43种差异代谢物。通路分析表明，高尿酸血症大鼠中有7条代谢通路受到干扰。CF使高尿酸血症大鼠中的19种代谢物发生逆转，并通过调节嘌呤代谢发挥抗高尿酸血症作用。CF60是痛风汤散的主要活性组分，通过调节嘌呤代谢发挥与CF相似的作用。
CF和CF60可通过调节高尿酸血症所致的异常嘌呤代谢，同时改善肠道和肾功能，发挥抗高尿酸血症作用。CF60可能是痛风汤散的主要活性组分。
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