Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy

The Journal of Nutritional Biochemistry
Veera Ganesh YerraAshutosh Kumar

Abstract

Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells. Diabetic rats and high glucose-exposed N2A cells showed reduction in SIRT1 expression with consequent decline in mitochondrial biogenesis and autophagy. ILQ (10 & 20 mg/kg, po) administration to diabetic rats for 2 weeks and exposure to glucose-insulted N2A cells resulted in significant SIRT1 activation with concurrent increase in mitochondrial biogenesis and autophagy. ILQ administration also enhanced NAD+/NADH ratio in peripheral sciatic nerves which explains its possible SIRT1 modulatory effect. Functional and behavioural studies show beneficial effect of ILQ as it alleviated nerve conduction and nerve blood flow deficits in diabetic rats along with impr...Continue Reading

Citations

May 9, 2018·Cardiovascular & Hematological Disorders Drug Targets·Karthika NellaiappanAshutosh Kumar
Jun 22, 2019·Lasers in Medical Science·Victória Regina da Silva OliveiraCamila Squarzoni Dale
Sep 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Seongtae JeongSoyeon Lim
Apr 29, 2020·American Journal of Physiology. Endocrinology and Metabolism·Shanling YiJianjun Zhou
Jul 24, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Sharifa AlzahraniNehal M Elsherbiny
Dec 22, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Ho-Sung LeeDae-Yeon Lee
Dec 12, 2020·Frontiers in Endocrinology·Teng MengBaohua Liu
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