Combination Therapy of Acarbose and Cyclosporine a Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Molecules. 2020 Apr 16;25(8):1822. doi: 10.3390/molecules25081822.

Abstract

Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients' lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4+ T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.

Keywords: acarbose; combination therapy; cyclosporine; imiquimod; psoriasis.

MeSH terms

  • Acarbose / adverse effects*
  • Acarbose / pharmacology
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Cyclosporine / adverse effects*
  • Cyclosporine / pharmacology
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Gene Expression Regulation / drug effects
  • Humans
  • Imiquimod / adverse effects*
  • Male
  • Mice
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • Cyclosporine
  • Imiquimod
  • Acarbose