Artocarpus altilis heartwood extract protects skin against UVB in vitro and in vivo

J Ethnopharmacol. 2015 Dec 4:175:153-62. doi: 10.1016/j.jep.2015.09.023. Epub 2015 Sep 18.

Abstract

Ethnopharmacological relevance: Artocarpus altilis (Moreceae) has been widely used as a traditional folk medicine in Southeast Asia for the treatment of many diseases, including skin disorders, such as ulcers and dermatitis.

Aim of the study: The present study aimed to investigate the ability of an artocarpin-enriched extract to prevent ultraviolet radiation B-induced photodamage.

Materials and methods: The content of artocarpin in the extract was determined by high performance liquid chromatography (HPLC). A DPPH assay was used to evaluate the free radical scavenging activity of the extract, which was compared with those of l-ascorbic acid and α-tocopherol. Cytotoxicity and proliferation of cells treated with the extract were determined using XTT and BrdU assays, respectively. Human skin fibroblasts and keratinocytes were pretreated with the extract for 24h and later irradiated with ultraviolet radiation B at 128 J/cm(2). The levels of TNF-α and IL-6 released from ultraviolet radiation B-irradiated keratinocytes and, MMP-1 and type-I procollagen produced by ultraviolet radiation B-irradiated fibroblasts were measured by ELISA and/or western blotting. The hairless skin of male mice (outbred ICR) was treated with the extract or l-ascorbic acid solution prior to exposure to ultraviolet radiation B irradiation. The dose of ultraviolet B irradiation was consecutively increased to 18, 36, 54, and 72 J/cm(2) at weeks 1-4, 4-7, 7-10, and 10-12, respectively. The epidermal thickness and collagen content in the skin of ultraviolet radiation B-irradiated mice were evaluated.

Results: The extract concentration of 50 µg/mL was not toxic and did not inhibit the proliferation of fibroblasts. The pretreatment of fibroblasts with 50 µg/mL extract prior to ultraviolet radiation B irradiation attenuated MMP-1 production but did not affect type-I procollagen production. The extract also decreased the ultraviolet radiation B-induced production of TNF-α and IL-6 in keratinocytes. Moreover, the topical administration of the extract suppressed epidermal thickening and collagen loss in chronically ultraviolet radiation B-exposed skin in mice.

Conclusions: The experimental study revealed that A. altilis extract suppresses structural alterations in skin damaged by ultraviolet radiation B irradiation. This suppression was, at least partially, mediated by decrease in MMP-1 production in fibroblasts and TNF-α and IL-6 productions in keratinocytes.

Keywords: Artocarpin (PubChem CID: 5458461); Artocarpin-enriched extract; Artocarpus altilis; Matrix metalloproteinase-1 (MMP-1); Pro-inflammatory cytokine; Ultraviolet radiation B (UVB).

MeSH terms

  • Animals
  • Artocarpus*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Collagen / metabolism
  • Dermatologic Agents / pharmacology*
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Humans
  • Interleukin-6 / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • Matrix Metalloproteinase 1 / metabolism
  • Mice, Inbred ICR
  • Middle Aged
  • Plant Extracts / pharmacology*
  • Skin / cytology
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / radiation effects*
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultraviolet Rays / adverse effects*
  • Wood

Substances

  • Dermatologic Agents
  • Interleukin-6
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Matrix Metalloproteinase 1