Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1

Cell Physiol Biochem. 2016;39(2):531-43. doi: 10.1159/000445645. Epub 2016 Jul 7.

Abstract

Background/aims: Psoriasis is one of the most common inflammatory skin disorders, affecting 3% of the general population. Terminalia chebulanin (TC) is a polyphenolic compound that possesses antioxidant and anti-inflammatory activities. The current study was designed to investigate the effect of TC on psoriatic lesions.

Methods: We examined the protective effect of TC against psoriatic lesions in mice and keratinocyte proliferation in HaCaT cells.

Results: We found that TC exhibited potent anti-psoriatic activities, as evidenced by improvement of erythema and scaling scores, decrease of epidermal, ear and skinfold thickening, decrease of tumor necrosis factor α (TNFα), interleukin (IL)-17A, IL-23 and matrix metalloproteinase (MMP)-9 expression, and decrease of TBARS content and increase of GSH content in IMQ-treated mice, and decrease of keratinocyte proliferation, TNFα, IL-17A and IL-23 expression, and ROS level in M5-treated cells. All those effects induced by TC were inhibited by zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase (HO)-1, indicating that HO-1 was responsible the anti-psoriatic effect of TC. Moreover, TC inhibited the upregulation of p65 NF-x03BA;B under in vitro psoriatic condition. ZnPP suppressed TC-induced inhibition of p65 NF-x03BA;B expression. Overexpression of p65 NF-x03BA;B significantly suppressed TC-induced decrease of TNFα, IL-17A and IL-23 expression and keratinocyte proliferation, indicating that HO-1-mediated downregulation of NF-x03BA;B was involved in the anti-psoriatic effect of TC.

Conclusions: The data demonstrate that TC may serve as a potential therapeutic option for psoriatic patients.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Enzyme Inhibitors / pharmacology
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Hydrolyzable Tannins / pharmacology*
  • Interleukin-17 / metabolism
  • Interleukin-23 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, Inbred BALB C
  • Phytotherapy
  • Protoporphyrins / pharmacology
  • Psoriasis / genetics
  • Psoriasis / metabolism
  • Psoriasis / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Terminalia / chemistry*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cyclin E
  • Enzyme Inhibitors
  • Hydrolyzable Tannins
  • Interleukin-17
  • Interleukin-23
  • Protoporphyrins
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • chebulanin
  • Cyclin D1
  • zinc protoporphyrin
  • Heme Oxygenase-1
  • Matrix Metalloproteinase 9