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

J Pharm Pharmacol. 2021 Oct 7;73(11):1442-1450. doi: 10.1093/jpp/rgab078.


Objectives: Hyperglycemia-induced SIRT1, DNMT1, SODs, as well as oxidative stress, play a pivotal role in the progression of diabetic nephropathy. Cissus quadrangularis, holds antioxidant and hypoglycemic activity; however, a direct link between its activity and prevention of diabetic nephropathy has not been ascertained yet. Accordingly, we aimed to delineate the protective effect of ethanolic extract of Cissus quadrangularis (EECQ) against high-fat diet/streptozotocin (HFD/STZ) induced diabetic nephropathy rats.

Methods: The control group was fed with a normal chow diet. Rats kept on an HFD for 12 weeks with a single low dose of STZ manifested the features of diabetic nephropathy. The treatment was done by the oral administration of EECQ (200 mg/kg) for six weeks (six rats in each group).

Key findings: Treatment with EECQ demonstrated substantial attenuation of elevated insulin resistance, lipid profile and creatinine level. Additionally, EECQ restored albuminuria, glomerular filtration rate and creatinine clearance in diabetic nephropathy rats. Furthermore, HFD consumption in rats culminated in reduced SIRT1 and enhanced DNMT1 expression, nonetheless, rescued by EECQ. Moreover, EECQ augmented the SOD 1 and 3 levels, thereby safeguarded from oxidative damage and renal inflammation. Besides, treatment protected from renal fibrosis by downregulating TGFβ, Smad2/3 and col1/3 expression in diseased rats.

Conclusions: Thus, based on the above findings, we conclude that EECQ shows a protective effect against diabetic nephropathy.

Keywords: Cissus quadrangularis; DNMT1; SIRT1; SOD; diabetic nephropathy; oxidative stress.

MeSH terms

  • Albuminuria
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Cissus*
  • Creatinine / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / prevention & control
  • Diet, High-Fat
  • Glomerular Filtration Rate
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Inflammation
  • Insulin Resistance
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipids / blood
  • Male
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins / metabolism*
  • Sirtuin 1 / metabolism*
  • Smad Proteins, Receptor-Regulated / metabolism
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta / metabolism


  • Antioxidants
  • Hypoglycemic Agents
  • Lipids
  • Plant Extracts
  • Repressor Proteins
  • Smad Proteins, Receptor-Regulated
  • Transforming Growth Factor beta
  • Creatinine
  • Superoxide Dismutase
  • Sirt1 protein, rat
  • Sirtuin 1