School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
NERC for the Pharmaceutics of Traditional Chinese Medicines, Benxi 117004, PR China.
Food Funct. 2022 Jan 24;13(2):904-919. doi: 10.1039/d1fo03494d.
Chronic renal failure (CRF) is a result of the progression of chronic kidney diseases (CKD), a global health problem with a high cost of treatment and no ideal therapy. The aim of this study is to evaluate the pharmacological efficacy of the total flavonoids in Nakai (TFE), a dietary supplement, against CRF and to determine the mechanism of actions. An adenine-induced CRF rat model and a TGF-β1 induced human kidney proximal tubule epithelial (HK-2) cell based renal fibrosis model were established and used to evaluate TFE's efficacy. Renal hemodynamics, biochemical indexes, inflammatory cytokines, histopathology and the reactive oxygen species (ROS) levels were determined to evaluate the efficacy of TFE on CRF. NMR-based metabolomics, immunohistochemical (IHC) staining, immunofluorescence (IF) staining, quantitative real time-PCR (qRT-PCR) and western blotting were conducted to determine the mechanism. The results showed that TFE had a significant effect on CRF at 150 mg kg d and could significantly alleviate renal fibrosis in the animal model. Twelve potential biomarkers, which mainly involve energy metabolism pathways, for CRF were identified using the metabolomics approach. The mechanism study suggested that TFE regulated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and AMPK/silent information regulator 1 (SIRT1)/nuclear factor kappa-B (NF-κB) signaling pathways. Furthermore, the effect of TFE was inhibited by compound C in the experiment, which also confirmed the above conclusion.
慢性肾衰竭（CRF）是慢性肾脏病（CKD）进展的结果，是一个具有高治疗成本但尚无理想疗法的全球性健康问题。本研究旨在评估 Nakai（TFE）膳食补充剂总黄酮对 CRF 的药理功效，并确定其作用机制。建立了腺嘌呤诱导的 CRF 大鼠模型和 TGF-β1 诱导的人肾近端小管上皮（HK-2）细胞肾纤维化模型，用于评估 TFE 的功效。通过测定肾血流动力学、生化指标、炎症细胞因子、组织病理学和活性氧（ROS）水平来评估 TFE 对 CRF 的疗效。通过基于 NMR 的代谢组学、免疫组织化学（IHC）染色、免疫荧光（IF）染色、实时定量 PCR（qRT-PCR）和 Western blot 进行机制研究。结果表明，TFE 在 150 mg kg d 时对 CRF 有显著作用，并能显著缓解动物模型中的肾纤维化。通过代谢组学方法鉴定出了 12 种与 CRF 相关的潜在生物标志物，主要涉及能量代谢途径。机制研究表明，TFE 调节 AMP 激活蛋白激酶（AMPK）/乙酰辅酶 A 羧化酶（ACC）和 AMPK/沉默信息调节因子 1（SIRT1）/核因子 kappa-B（NF-κB）信号通路。此外，实验中用化合物 C 抑制了 TFE 的作用，这也证实了上述结论。
