Cissus quadrangularis extract attenuates diabetic nephropathy by altering SIRT1/DNMT1 axis

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Diabetic nephropathy (DN) is a major complication of diabetes, characterized by hyperglycemia, oxidative stress, and inflammation.
• Sirtuin 1 (SIRT1), DNA methyltransferase 1 (DNMT1), and superoxide dismutases (SODs) are implicated in DN pathogenesis.
• Cissus quadrangularis (CQ) possesses antioxidant and hypoglycemic properties, but its protective role in DN is not well-established.

Purpose of the Study:

• To investigate the protective effects of ethanolic extract of Cissus quadrangularis (EECQ) on high-fat diet/streptozotocin (HFD/STZ)-induced diabetic nephropathy in rats.
• To elucidate the underlying mechanisms involving SIRT1, DNMT1, SODs, oxidative stress, and renal fibrosis markers.

Main Methods:

• Rats were fed a high-fat diet (HFD) and administered a single low dose of streptozotocin (STZ) to induce diabetic nephropathy.
• The treatment group received oral administration of EECQ (200 mg/kg) for six weeks.
• Biochemical parameters, renal function markers, oxidative stress indicators, and gene/protein expression (SIRT1, DNMT1, SODs, TGFβ, Smad2/3, col1/3) were assessed.

Main Results:

• EECQ treatment significantly improved insulin resistance, lipid profile, and creatinine levels.
• EECQ restored albuminuria, glomerular filtration rate, and creatinine clearance.
• EECQ administration normalized SIRT1 and DNMT1 expression, increased SOD 1 and 3 levels, reduced oxidative damage and renal inflammation, and attenuated renal fibrosis by downregulating TGFβ, Smad2/3, and col1/3.

Conclusions:

• Ethanolic extract of Cissus quadrangularis (EECQ) demonstrates significant protective effects against diabetic nephropathy.
• EECQ mitigates hyperglycemia-induced kidney damage by combating oxidative stress, inflammation, and fibrosis.
• These findings support the therapeutic potential of Cissus quadrangularis in managing diabetic nephropathy.