4-O-methylhonokiol ameliorates type 2 diabetes-induced nephropathy in mice likely by activation of AMPK-mediated fatty acid oxidation and Nrf2-mediated anti-oxidative stress.
Toxicol Appl Pharmacol
; 370: 93-105, 2019 05 01.
Article
in En
| MEDLINE
| ID: mdl-30876865
ABSTRACT
Diabetic nephropathy (DN) is one of the most serious long-term complications of type 2 diabetes (T2D). 4-O-methylhonokiol (MH) is one of the biologically active ingredients extracted from the Magnolia stem bark. In this study, we aim to elucidate whether treatment with MH can ameliorate or slow-down progression of DN in a T2D murine model and, if so, whether the protective response of MH correlates with AMPK-associated anti-oxidant and anti-inflammatory effects. To induce T2D, mice were fed normal diet (ND) or high fat diet (HFD) for 3â¯months to induce insulin resistance, followed by an intraperitoneal injection of STZ to induce hyperglycemia. Both T2D and control mice received gavage containing vehicle or MH once diabetes onset for 3â¯months. Once completing 3-month MH treatment, five mice from each group were sacrificed as 3â¯month time-point. The rest mice in each group were sacrificed 3â¯months later as 6â¯month time-point. In T2D mice, the typical DN symptoms were induced as expected, reflected by increased proteinuria, renal lipid accumulation and lipotoxic effects inducing oxidative stress, and inflammatory reactions, and final fibrosis. However, these typical DN changes were significantly prevented by MH treatment for 3â¯months and even at 3â¯months post-MH withdrawal. Mechanistically, MH renal-protection from DN may be related to lipid metabolic improvement and oxidative stress attenuation along with increases in AMPK/PGC-1α/CPT1B-mediated fatty acid oxidation and Nrf2/SOD2-mediated anti-oxidative stress. Results showed the preventive effect of MH on the renal oxidative stress and inflammation in DN.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Biphenyl Compounds
/
Lignans
/
Oxidative Stress
/
Diabetic Nephropathies
/
NF-E2-Related Factor 2
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AMP-Activated Protein Kinases
/
Fatty Acids
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Year:
2019
Type:
Article