Tier 3 — preclinical

Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats

Prasath GS, Subramanian SP
European Journal of Pharmacology 2011 668(3):492-6

Bibliography

PubMed
PMID 21816145
DOI
10.1016/j.ejphar.2011.07.021
Funding
Not explicitly stated in the reviewed abstract; conducted at the Department of Biochemistry, University of Madras.
Competing interests
Not stated in the reviewed abstract.

Study snapshot

DesignStreptozotocin-induced diabetic rat model, oral fisetin (10 mg/kg/day, 30 days), assaying key carbohydrate-metabolism enzymes in liver and kidney tissue.
ModelMale Wistar rats, streptozotocin-induced experimental diabetes.
SampleNot stated in the reviewed abstract beyond group-level design.
InterventionFisetin 10 mg/kg body weight, oral, once daily for 30 days.
Duration30 days.
EndpointsHepatic and renal hexokinase activity; Pyruvate kinase activity; Lactate dehydrogenase activity; Glucose-6-phosphatase activity; Fructose-1,6-bisphosphatase activity; Glucose-6-phosphate dehydrogenase activity; Glycogen synthase activity; Glycogen phosphorylase activity

What the study showed, in plain terms

Diabetes doesn't just raise blood sugar, it disrupts the enzymes the liver and kidneys use to store and release sugar. This study, from the same University of Madras group behind the earlier fisetin-diabetes papers, tested which of those enzymes fisetin actually corrects.

Researchers gave streptozotocin-diabetic rats oral fisetin for 30 days and measured eight carbohydrate-metabolism enzymes across liver and kidney tissue.

Fisetin significantly reverted the activity of all eight enzymes toward normal levels in both tissues, broadening the mechanistic case beyond the single-enzyme findings of the companion 2013 and 2014 papers from the same group.

Bottom line: further rodent mechanistic support for fisetin's blood-sugar-lowering effect, this time across a broader enzyme panel and two organs — still rat data, not human evidence.

Key findings

Oral fisetin (10 mg/kg/day, 30 days) significantly reverted the activity of eight key carbohydrate-metabolism enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase, glycogen phosphorylase) toward normal in liver and kidney tissue of streptozotocin-diabetic rats.

What this study can and cannot tell us

Streptozotocin rat model of diabetes, not a model of human type 2 diabetes with insulin resistance. Single dose tested; no dose-response curve. No human pharmacokinetic or efficacy data. Enzyme-activity assays only, no gene expression data in this particular paper.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology