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Inhibitory Effects on the Polyol Pathway in Type 2 Diabetic Rats by Chickpea Flavonoid Extract
Jingteng Wang1, Ting Yang1, Jintian Guo1
1College of Smart Agriculture (Research Institute), Xinjiang University, Urumqi 830017, China.
Chickpea flavonoid extract (CFE) effectively lowers blood glucose and insulin resistance in type 2 diabetes models. CFE also inhibits the polyol pathway and reduces oxidative stress, showing promise for diabetes prevention.
Area of Science:
- Biochemistry
- Metabolism
- Nutritional Science
Background:
- Chickpea flavonoids possess known hypoglycemic activity.
- Type 2 diabetes mellitus (T2DM) involves complex metabolic dysregulation.
- The polyol pathway is implicated in glucose metabolism and diabetic complications.
Purpose of the Study:
- To investigate the effects of chickpea flavonoid extract (CFE) on the polyol pathway in a rat model of T2DM.
- To evaluate CFE's impact on glucose control, insulin resistance, oxidative stress, and related metabolic pathways.
Main Methods:
- A male Sprague-Dawley (SD) rat model of T2DM was induced using a high-fat, high-sugar diet and streptozotocin (STZ).
- The study assessed fasting blood glucose (FBG), insulin sensitivity (HOMA-IS), insulin resistance (HOMA-IR), oxidative stress markers (H2O2, MDA, carbonylated proteins, GSH-Px activity), and polyol pathway enzymes (AR, SDH).
- Metabolomic analysis identified changes in metabolites and modulated pathways, including NAD+/NADH ratio and related enzymes (PARP, Sirt3).
Main Results:
- CFE significantly reduced FBG and improved insulin sensitivity (increased HOMA-IS, decreased HOMA-IR).
- CFE alleviated oxidative stress by decreasing harmful markers and increasing antioxidant enzyme activity (GSH-Px).
- CFE inhibited the polyol pathway (downregulated AR and SDH, reduced sorbitol and fructose) and enhanced antioxidant defense (increased GR activity, GSH; decreased GSSG).
- CFE mitigated reductive stress by increasing NAD+ content and the NAD+/NADH ratio, suppressing PARP, and upregulating Sirt3.
- CFE modulated key metabolites and seven metabolic pathways linked to diabetes improvement, with ten differential metabolites reversing and correlating with polyol pathway and oxidative stress markers.
Conclusions:
- Chickpea flavonoid extract (CFE) demonstrates significant hypoglycemic activity in a T2DM rat model.
- CFE effectively inhibits the polyol pathway and ameliorates oxidative and reductive stress.
- CFE shows potential as a natural product for the prevention and management of type 2 diabetes.
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