Renoprotective effects of Tilianin in diabetic rats through modulation of oxidative stress via Nrf2-Keap1 pathway and inflammation via TLR4/MAPK/NF-κB pathways

Ruibin Zhang; Min Lu; Shan Zhang; Jinyan Liu

doi:10.1016/j.intimp.2020.106967

Renoprotective effects of Tilianin in diabetic rats through modulation of oxidative stress via Nrf2-Keap1 pathway and inflammation via TLR4/MAPK/NF-κB pathways

Int Immunopharmacol. 2020 Nov:88:106967. doi: 10.1016/j.intimp.2020.106967. Epub 2020 Sep 22.

Authors

Ruibin Zhang¹, Min Lu¹, Shan Zhang¹, Jinyan Liu²

Affiliations

¹ Department of Nephrology, Central Hospital Affiliated to Shandong First Medical University, Jinan City 250013, China.
² Department of Nephrology, Jining First People's Hospital, Jining 272000, China. Electronic address: [email protected].

PMID: 33182074
DOI: 10.1016/j.intimp.2020.106967

Abstract

The present study was undertaken to assess the protective effects of Tilianin (TN) on type-2 diabetes-induced renal dysfunction in experimental rats. Diabetes was induced by injecting Nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg) by i.p. and then the rats were treated with TN (10 and 20 mg/kg) daily by oral gavage for 28 days. TN treatment significantly decreases the BUN, creatinine, 24-hour urinary protein, urea, uric acid, and albumin protein levels. The protein of expression of Nrf2, NQO1, and HO-1 was augmented while the expression of Keap-1 decreased significantly. TN also reduces the oxidative/nitrosative status by lowering MDA content, NO, and MPO levels. TN exerted anti-inflammatory effects by suppressing TLR4/NF-κB/MAPK signaling cascades and inhibiting MyD88, TRAF6, IκBα, p38MAPK, JNK, and ERK2 in the diabetic rats. Histopathological findings supported the biochemical and molecular results. The results showed that TN modulated Nrf2-Keap1 and TLR4/MAPK/NF-κB signaling pathways and provided significant protection against diabetes-induced renal dysfunction.

Keywords: Antioxidants; Diabetes; Kidney dysfunction; Oxidative stress; Tilianin.

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use*
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / metabolism
Diabetes Mellitus, Experimental / pathology
Diabetes Mellitus, Experimental / physiopathology
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / pathology
Diabetes Mellitus, Type 2 / physiopathology
Flavonoids / pharmacology
Flavonoids / therapeutic use*
Glycosides / pharmacology
Glycosides / therapeutic use*
Heme Oxygenase (Decyclizing) / genetics
Heme Oxygenase (Decyclizing) / metabolism
Kelch-Like ECH-Associated Protein 1 / genetics
Kelch-Like ECH-Associated Protein 1 / metabolism
Kidney / drug effects*
Kidney / pathology
Kidney / physiology
Male
Mitogen-Activated Protein Kinases / genetics
Mitogen-Activated Protein Kinases / metabolism
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism
NF-kappa B / metabolism
Oxidative Stress / drug effects
Protective Agents / pharmacology
Protective Agents / therapeutic use*
Rats, Sprague-Dawley
Signal Transduction / drug effects
Toll-Like Receptor 4 / metabolism

Substances

Anti-Inflammatory Agents
Flavonoids
Glycosides
KEAP1 protein, rat
Kelch-Like ECH-Associated Protein 1
NF-E2-Related Factor 2
NF-kappa B
Nfe2l2 protein, rat
Protective Agents
Tlr4 protein, rat
Toll-Like Receptor 4
tilianin
Heme Oxygenase (Decyclizing)
Hmox1 protein, rat
Mitogen-Activated Protein Kinases