Modulation of PPAR-γ, SREBP-1c and inflammatory mediators by luteolin ameliorates β-cell dysfunction and renal damage in a rat model of type-2 diabetes mellitus.

Abstract

BACKGROUND:

Natural products have been recommended as a complementary therapy for type 2 diabetes mellitus (T2DM) due to constraints of safety and tolerability of existing anti-diabetic agents. Luteolin exhibits anti-diabetic and anti-inflammatory effects. Hence, the impact of luteolin on glucose homoeostasis and organ damage was investigated in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM in rats.

METHODS AND RESULTS:

Male Wistar rats were maintained on HFD (provided 55% energy as fat) for 10 days. Subsequently, a single dose of 40 mg/kg STZ was injected intraperitoneally on the 11th day. Seventy-two hours after STZ administration, diabetic rats with established hyperglycemia (fasting serum glucose > 200 mg/dL) were randomized into different groups having six rats each and orally administered either 0.5% hydroxy propyl cellulose or pioglitazone (10 mg/kg) or luteolin (50 mg/kg or 100 mg/kg) once daily for 28 days, while continuing HFD for respective groups. Luteolin significantly reduced hyperglycaemia, homoeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) levels, and improved hypoinsulinemia and HOMA of b-cell function (HOMA-B) in a dose-dependent manner. Increased TNF-α, IL-6 and NFκB levels in diabetic rats were significantly regulated. Additionally, luteolin significantly augmented PPAR-γ expression while attenuating sterol regulatory element binding protein-1c (SREBP-1c) expression. Histopathological scrutiny validated that luteolin effectively attenuated HFD-STZ-induced injury in pancreatic β-cells and kidneys to near normalcy.

CONCLUSION:

Our study showed that luteolin ameliorated hyperglycemia and improved hypoinsulinemia, β-cell dysfunction, and renal impairment in HFD-STZ-induced diabetic rats by attenuating inflammation and dysregulated cytokine secretion through modulation of PPAR-γ, TNF-α, IL-6 and NF-kB expression and down-regulation of SREBP-1c.

• Authors: Syed Ilyas Shehnaz, Anitha Roy, Rajagopalan Vijayaraghavan, Senthilkumar Sivanesan, Natesan Pazhanivel
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 50 Issue 11 Pg. 9129-9142 (Nov 2023) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 37749346 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• PPAR gamma
• Sterol Regulatory Element Binding Protein 1
• Luteolin
• Insulin
• Tumor Necrosis Factor-alpha
• Interleukin-6
• Blood Glucose
• Glucose
• NF-kappa B
• Streptozocin

Topics

• Rats
• Male
• Animals
• Diabetes Mellitus, Type 2 (drug therapy)
• PPAR gamma (metabolism)
• Sterol Regulatory Element Binding Protein 1 (metabolism)
• Luteolin (pharmacology)
• Diabetes Mellitus, Experimental (metabolism)
• Insulin
• Tumor Necrosis Factor-alpha
• Interleukin-6
• Rats, Wistar
• Blood Glucose (metabolism)
• Glucose
• Hyperglycemia (complications, drug therapy, metabolism)
• NF-kappa B (metabolism)
• Kidney (metabolism)
• Streptozocin (adverse effects)