Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

被引：108

作者：

Huang, Xiaozhong ^{[1
,2
]}

Shi, Yujuan ^{[3
]}

Chen, Hongjin ^{[4
]}

Le, Rongrong ^{[5
,6
]}

Gong, Xiaohua ^{[7
]}

Xu, Ke ^{[7
]}

Zhu, Qihan ^{[7
]}

Shen, Feixia ^{[7
]}

Chen, Zimiao ^{[7
]}

Gu, Xuemei ^{[7
]}

Chen, Xiaojun ^{[7
]}

Chen, Xiong ^{[7
]}

机构：

[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Pediat Surg, Wenzhou, Peoples R China

[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China

[3] Jiangshan Peoples Hosp, Dept Endocrinol, Jiangshan, Zhejiang, Peoples R China

[4] Nanjing Med Univ, Sch Basic Med Sci, Dept Pathol, Nanjing, Peoples R China

[5] Wenzhou Med Univ, Eye Hosp, Wenzhou, Zhejiang, Peoples R China

[6] Wenzhou Med Univ, Sch Ophthalmol & Optometry, Wenzhou, Zhejiang, Peoples R China

[7] Wenzhou Med Univ, Affiliated Hosp 1, Dept Endocrinol, Wenzhou, Zhejiang, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 12期

基金：

中国国家自然科学基金;

关键词：

DIABETIC-NEPHROPATHY; SIRT1; ACTIVATION; P38; KINASE; IMPAIRMENT; PROTECTS; FIBROSIS; PATHWAY; DAMAGE;

D O I：

10.1038/s41419-020-03260-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.

引用

页数：14

共 46 条

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