Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Institute of Urology, Anhui Medical University, Hefei, China.
J Cell Mol Med. 2024 Oct;28(20):e70180. doi: 10.1111/jcmm.70180.
Puerarin(PUE), an isoflavonoid extracted from Pueraria root, has anti-apoptotic effects. The objective of this research is to examine the impact of PUE on renal apoptosis and inflammation resulting from renal calculi and to elucidate its mechanism. The approach of network pharmacology and molecular docking was employed to discover potential targets and pathways of PUE. An animal model of calcium oxalate crystal deposition by intraperitoneal injection of glyoxylate and a model of COM-induced human renal tubular epithelial cells (HK2) were used to investigate the pharmacological mechanisms of PUE against apoptosis and inflammation. We used haematoxylin-eosin (H&E) and Periodic Acid-Schiff staining (PAS) to assess the effect of PUE on crystal deposition and damage. The mechanism of PUE was elucidated and validated using Western blotting, histology and immunohistochemical staining. Network pharmacology findings indicated that the PI3K/AKT pathway plays a crucial role in PUE. We experimentally demonstrate that PUE alleviated COM-induced changes in apoptotic proteins, increased inflammatory indicators and changes in oxidative stress-related indicators in HK2 cells by activating the PI3K/AKT pathway, reduced serum creatinine and urea nitrogen levels in mice caused by CaOx, alleviated crystal deposition and damage, and alleviated apoptosis, oxidative stress and inflammation. Puerarin attenuates renal apoptosis and inflammation caused by kidney stones through the PI3K/AKT pathway.
葛根素(PUE)是从葛根中提取的一种异黄酮,具有抗细胞凋亡作用。本研究旨在探讨 PUE 对肾结石引起的肾细胞凋亡和炎症的影响,并阐明其机制。采用网络药理学和分子对接的方法,发现 PUE 的潜在靶点和通路。通过腹腔注射乙醛酸诱导大鼠草酸钙晶体沉积模型和 COM 诱导人肾小管上皮细胞(HK2)模型,研究 PUE 抗凋亡和抗炎的药理机制。采用苏木精-伊红(H&E)和过碘酸希夫(PAS)染色评估 PUE 对晶体沉积和损伤的影响。采用 Western blot、组织学和免疫组织化学染色等方法阐明和验证 PUE 的作用机制。网络药理学研究结果表明,PI3K/AKT 通路在 PUE 中起关键作用。我们的实验表明,PUE 通过激活 PI3K/AKT 通路,减轻 COM 诱导的 HK2 细胞凋亡蛋白、炎症指标和氧化应激相关指标的变化,降低 CaOx 引起的小鼠血清肌酐和尿素氮水平,减轻晶体沉积和损伤,减轻细胞凋亡、氧化应激和炎症。葛根素通过 PI3K/AKT 通路减轻肾结石引起的肾细胞凋亡和炎症。