Perillaldehyde Attenuates Diabetic Nephropathy through Modulation of the Nrf2/Keap1 and NF-κB Signalling Pathways

Area of Science:

• Nephrology
• Pharmacology
• Biochemistry

Background:

• Diabetic nephropathy (DN) is a major diabetes complication.
• DN involves oxidative stress, inflammation, and renal dysfunction.
• Nuclear factor kappa B (NF-κB) activation is implicated in DN pathogenesis.

Purpose of the Study:

• To evaluate the renoprotective effects of perillaldehyde (PA) in diabetic nephropathy.
• To investigate PA's mechanisms in vitro and in vivo models.
• To assess PA's impact on oxidative stress and inflammatory pathways.

Main Methods:

• In vitro: NRK-52E cells exposed to high glucose, treated with PA.
• In vivo: Streptozotocin-induced diabetic rats treated with PA (35 and 70 mg/kg).
• Assessed reactive oxygen species, antioxidant enzymes (Nrf2, Keap1, HO-1), inflammatory markers (NF-κB), renal function (creatinine, BUN), and kidney histology.

Main Results:

• PA reduced reactive oxygen species and lipid peroxidation in vitro and in vivo.
• PA upregulated Nrf2/Keap1/HO-1 pathway and inhibited NF-κB signaling.
• PA improved renal function parameters and attenuated kidney structural damage in diabetic rats.
• PA enhanced antioxidant status (GSH) and lowered MDA levels.

Conclusions:

• Perillaldehyde demonstrates significant renoprotective effects against diabetic nephropathy.
• PA acts by coordinating the regulation of oxidative stress and inflammation.
• PA's mechanism involves modulation of the Nrf2/Keap1/HO-1 and NF-κB pathways.