Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics.
Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics.
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基于UPLC-Q-TOF/MS的非靶向代谢组学探讨痛风糖散（TFTS）的抗高尿酸血症作用
DOI：
10.1186/s13020-023-00716-w
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发表时间：
2023-02-16
期刊：
影响因子：
4.9
通讯作者：
Chen, Haifang
中科院分区：
文献类型：
--
作者：
Huang, Zhichao;Zhang, Wugang;An, Qiong;Lang, Yifan;Liu, Ye;Fan, Huifang;Chen, Haifang
痛风糖散是治疗痛风的常用藏方。此前，TFTS（CF）被证实具有显著的降尿酸作用。然而，其抗高尿酸血症的机制和主要活性部位尚不清楚。本研究旨在通过代谢组学方法探讨其抗高尿酸血症的机制，并确定其活性部位。方法采用腹腔注射氧肟酸钾100 mg/kg和次黄嘌呤150 mg/kg建立高尿酸血症模型。以血尿酸（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）、白细胞介素-1 β（IL-1β）为指标，评价CF及其4个组分（SX、CF 30、CF 60、CF 90）的疗效。采用UPLC-Q-TOF-MS技术，从非靶向代谢组学角度探讨CF抗高尿酸血症的作用机制。主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）有助于探索高尿酸血症的潜在生物标志物。结果CF能显著降低血清sUA、sCRE、sIL-1β和XOD水平，具有明显的抗高尿酸血症作用。SX、CF 30、CF 60和CF 90的抗高尿酸血症作用不同。4个部位中，仅CF 60能显著降低sUA水平，可作为TFTS的主要药效部位。从高尿酸血症大鼠血浆和肾脏中鉴定出43种差异代谢产物。通路分析表明，高尿酸血症大鼠有7条通路被破坏。CF可逆转高尿酸血症大鼠的19种代谢产物，通过调节嘌呤代谢发挥抗高尿酸血症作用。CF 60是TFTS的主要活性部位，其作用机制与CF相似，主要通过调节嘌呤代谢发挥作用。结论CF和CF 60可通过调节高尿酸血症引起的嘌呤代谢异常发挥抗高尿酸血症的作用，同时改善肠、肾功能。CF 60可能是TFTS的主要活性部位。
BackgroundTongFengTangSan (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.MethodsThe 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.ResultsCF 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.ConclusionsCF 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.
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影响因子：
--
作者：
Han, Bin;Gong, Mengjuan;Zou, Zhongjie
通讯作者：
Zou, Zhongjie
乳酸菌通过 LPL 分泌 IL-22 诱导 STAT3 信号通路激活，加速 ISC 再生，保护肠粘膜完整性
影响因子：
12.4
作者：
Hou, Qihang;Ye, Lulu;Yu, Qinghua
通讯作者：
Yu, Qinghua
DOI：
10.1053/j.ajkd.2017.12.009
发表时间：
2018-06
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Johnson RJ;Bakris GL;Borghi C;Chonchol MB;Feldman D;Lanaspa MA;Merriman TR;Moe OW;Mount DB;Sanchez Lozada LG;Stahl E;Weiner DE;Chertow GM
通讯作者：
Chertow GM
影响因子：
4.1
作者：
KING, LJ;PARKE, DV;WILLIAMS, RT
通讯作者：
WILLIAMS, RT
影响因子：
5
作者：
Guo Y;Yu Y;Li H;Ding X;Li X;Jing X;Chen J;Liu G;Lin Y;Jiang C;Liu Z;He Y;Li C;Tian Z
通讯作者：
Tian Z