Ye Jiamin, Yao Jiangyu, Xu Shaojing, Xiao Guyu, Jia Yuwei, Xie Ningjun, Yan Jizhong, Ying Xuhui, Zhang Hui
College of Pharmaceutical Science, Zhejiang University of Technology, No. 18, Chaowang Road, Hangzhou, 310014, China.
Research Institute of Chiatai Qingchunbao Pharmaceutical Co., Ltd., Hangzhou, 310030, China.
J Ethnopharmacol. 2024 Oct 28;333:118410. doi: 10.1016/j.jep.2024.118410. Epub 2024 Jun 5.
Fufang Qiling granules (FQG), derived from the traditional Qiling Decoction with a longstanding clinical history, is utilized for the treatment of hyperuricemia (HUA). FQG is formulated with a combination of seven Chinese herbs based on the principles of traditional Chinese medicine (TCM) theories. Clinical evidence indicates that FQG exhibits favorable therapeutic effects in reducing uric acid (UA) levels and attenuating renal damage.
To elucidate the potential active components and pharmacological mechanism of FQG in the treatment of HUA, and to provide an experimental basis for the development of efficient and low-toxicity TCM for HUA treatment.
A HUA rat model induced by potassium oxonate and adenine was established to initially evaluate the hypouricemic effects of FQG. Chemical analyses were conducted using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to investigate the active components and mechanism of FQG in the treatment of HUA. Potential Xanthine oxidase (XOD) inhibitors were screened from FQG based on ultrafiltration liquid chromatography and mass spectrometry (UF-LC-MS). Molecular docking, surface plasmon resonance (SPR) and circular dichroism (CD) spectroscopy were applied to validate the interactions between the active components and XOD.
In comparison to the model group, treatment with FQG significantly decreased serum UA, serum creatinine (CREA), serum blood urea nitrogen (BUN), and liver XOD activity. Additionally, the FQG administration notably ameliorated HUA-induced renal injury in rats. Through the pharmacodynamics of the HUA rat models and network pharmacology, it was found that XOD was a key pathway enzyme in UA metabolism. 18 XOD inhibitors were screened from FQG by UF-LC-MS, and 11 compounds with strong affinity were verified by SPR, molecular docking and CD spectroscopy.
In summary, flavonoids, organic acids and saponins may be the active components in FQG that alleviate HUA. The primary mechanism of FQG involves inhibiting XOD enzyme activity in the plasma to reduce UA production, alleviating renal tubular epithelial cell necrosis, tubulointerstitial injury, fibrosis, and urate deposition, ultimately exerting a therapeutic effect on HUA.
复方芪苓颗粒（FQG）源自具有悠久临床历史的传统芪苓汤，用于治疗高尿酸血症（HUA）。FQG根据中医理论原则，由七种中药组合而成。临床证据表明，FQG在降低尿酸（UA）水平和减轻肾损伤方面具有良好的治疗效果。
阐明FQG治疗HUA的潜在活性成分和药理机制，为开发高效低毒的治疗HUA的中药提供实验依据。
建立氧嗪酸钾和腺嘌呤诱导的HUA大鼠模型，初步评价FQG的降尿酸作用。采用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）进行化学分析。运用网络药理学研究FQG治疗HUA的活性成分和作用机制。基于超滤液相色谱和质谱（UF-LC-MS）从FQG中筛选潜在的黄嘌呤氧化酶（XOD）抑制剂。应用分子对接、表面等离子体共振（SPR）和圆二色光谱（CD）对活性成分与XOD之间的相互作用进行验证。
与模型组相比，FQG治疗显著降低了血清UA、血清肌酐（CREA）、血清尿素氮（BUN）和肝脏XOD活性。此外，FQG给药显著改善了HUA诱导的大鼠肾损伤。通过HUA大鼠模型的药效学和网络药理学研究发现，XOD是UA代谢中的关键途径酶。通过UF-LC-MS从FQG中筛选出18种XOD抑制剂，并通过SPR、分子对接和CD光谱验证了11种具有强亲和力的化合物。
综上所述，黄酮类、有机酸和皂苷可能是FQG中减轻HUA的活性成分。FQG的主要作用机制是抑制血浆中XOD酶的活性以减少UA生成，减轻肾小管上皮细胞坏死、肾小管间质损伤、纤维化和尿酸盐沉积，最终对HUA发挥治疗作用。
