A novel salviadione derivative, compound 15a, attenuates diabetes-induced renal injury by inhibiting NF-kappa B-mediated inflammatory responses

doi:10.1016/j.taap.2020.115322

	A novel salviadione derivative, compound 15a, attenuates diabetes-induced renal injury by inhibiting NF-kappa B-mediated inflammatory responses
	Li, Li 1,2; Ding, Chunyong 3; Zou, Chunpeng 4; Xiong, Zhi 5,6; Zhu, Weiwei 1; Qian, Jianchang 1; Xu, Mingjiang 1; Zhang, Ao 3,5; Liang, Guang 1
刊名	TOXICOLOGY AND APPLIED PHARMACOLOGY
	2020-12-15
卷号	409 页码:11
关键词	Salviadione derivative 15a Diabetic nephropathy Inflammation Macrophage infiltration Fibrosis Nuclear factor-kappa B Cytokines
ISSN号	0041-008X
DOI	10.1016/j.taap.2020.115322
通讯作者	Zhang, Ao(ao6919zhang@sjtu.edu.cn) ; Liang, Guang(wzmcliangguang@163.com)
英文摘要	Diabetic nephropathy is the leading cause of renal failure worldwide. Elevated inflammatory signaling has been shown to lead to deterioration of renal function in human and experimental diabetes. We recently developed a salviadione derivative (compound 15a) that prevented microbial lipopolysaccharide-induced inflammatory responses, which are largely driven by nuclear factor-kappa B (NF-kappa B). In the present study, we have tested the hypothesis that 15a will protect kidneys from diabetes-induced dysfunction by suppressing NF-kappa B activation and inflammatory signaling. Treatment of diabetic mice with 15a inhibited diabetes-induced renal fibrosis, NF-kappa B activation, and upregulation of proinflammatory cytokines. Histologically, kidney specimens from diabetic mice treated with 15a were indistinguishable from non-diabetic controls. We confirmed our findings in cultured renal tubular epithelial cells exposed to high levels of glucose. In these cultured cells, 15a pretreatment prevented high glucose-induced NF-kappa B activation and expression of inflammatory cytokines. These protective effects were also reflected in reduced levels of proteins involved in matrix expansion. Overall, our studies show that a salviadione derivative, 15a, is effective in suppressing diabetes-induced NF-kappa B activation and inflammatory signaling.
资助项目	National Key Research Project[2017YFA0506000] ; National Natural Science Foundation of China[21961142009] ; National Natural Science Foundation of China[81803600] ; National Natural Science Foundation of China[81970323] ; Zhejiang Provincial Key Scientific Project[2018C03068] ; Wenzhou Key Scientific Project[2018ZY009]
WOS关键词	OXIDATIVE STRESS ; IN-VIVO ; NEPHROPATHY ; ACTIVATION ; MILTIORRHIZA ; MACROPHAGES ; PROGRESSION ; EXPRESSION ; MOLECULE-1 ; APOPTOSIS
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000599506300006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296263]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Ao; Liang, Guang
作者单位	1.Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China 2.Zhejiang Univ, Affiliated Hosp 4, Sch Med, Dept Anesthesiol, Yiwu, Zhejiang, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai, Peoples R China 4.Wenzhou Med Univ, Affiliated Hosp 2, Dept Ultrasonog, Wenzhou, Zhejiang, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 6.Nanchang Univ, Sch Pharm, Nanchang 330031, Jiangxi, Peoples R China
推荐引用方式 GB/T 7714	Li, Li,Ding, Chunyong,Zou, Chunpeng,et al. A novel salviadione derivative, compound 15a, attenuates diabetes-induced renal injury by inhibiting NF-kappa B-mediated inflammatory responses[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2020,409:11.
APA	Li, Li.,Ding, Chunyong.,Zou, Chunpeng.,Xiong, Zhi.,Zhu, Weiwei.,...&Liang, Guang.(2020).A novel salviadione derivative, compound 15a, attenuates diabetes-induced renal injury by inhibiting NF-kappa B-mediated inflammatory responses.TOXICOLOGY AND APPLIED PHARMACOLOGY,409,11.
MLA	Li, Li,et al."A novel salviadione derivative, compound 15a, attenuates diabetes-induced renal injury by inhibiting NF-kappa B-mediated inflammatory responses".TOXICOLOGY AND APPLIED PHARMACOLOGY 409(2020):11.