Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice

Naunyn Schmiedebergs Arch Pharmacol. 2022 Feb;395(2):187-194. doi: 10.1007/s00210-021-02182-3. Epub 2022 Jan 7.


Purpose: Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity.

Methods: Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue.

Results: The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD, and GPx activities.

Conclusion: Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

Keywords: Berberine; Cyclophosphamide; Inflammation; Nephrotoxicity; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents, Alkylating / toxicity
  • Antioxidants / pharmacology*
  • Berberine / pharmacology*
  • Cyclophosphamide / toxicity*
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / metabolism
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • Inflammation Mediators
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Berberine
  • Cyclophosphamide