Anti-inflammatory activity in skin by biomimetic of Evodia rutaecarpa extract from traditional Chinese medicine

Summary 

Background

Wu-Zhu-Yu, is an extract prepared from the small berry fruit of Evodia rutaecarpa and is reported to have anti-inflammatory and anti-nociceptic activity. Methyl nicotinate (MN) is known to induce the release of PGD₂ resulting in localized erythema within 30min after topical application to human skin.

Objective

The purpose of this study was to determine if a defined biomimetic mixture of components of Evodia fruit extract inhibit inflammation in human cells and skin.

Methods

In order to control the potency of the test article, we prepared a defined biomimetic mixture of synthetic and natural forms of the active components of Evodia fruit extract, containing rutaecarpine, dehydroevodiamine, and evodin. This was tested for anti-inflammatory activity in UVB-irradiated cultured cells and in the MN model of micro-inflammation in human skin.

Results

This Evodia biomimetic mixture was a potent inhibitor of UVB-induced PGE₂ released by keratinocytes in culture. We found that MN also induces release of nitric oxide from cultured keratinocytes and microvascular endothelial cells. Twice daily application of 0.1–1% Evodia biomimetic mixture for 2 weeks significantly inhibited erythema after a MN challenge. A single application of 1% Evodia biomimetic mixture also significantly inhibited MN-induced erythema when applied at 60min before, or within 5min after MN exposure. The Evodia biomimetic mixture was significantly more effective at inhibiting erythema than bisabolol, the active component of chamomile.

Conclusions

These results demonstrate that compounds found in E. rutaecarpa (including the indole quinazoline alkaloids) have powerful anti-inflammatory activity when applied topically to human skin.

Abbreviations: BHT, butylated hydroxytoluene, COX-2, cyclooxygenase-2, HMVEC, human microvascular endothelial cells, MN, methyl nicotinate, NHEK, normal human epidermal keratinocytes, NO, nitric oxide, PGD₂, prostaglandin D₂, PGE₂, prostaglandin E₂, UVB, ultraviolet B

Keywords: Evodia rutaecarpa, Biomimetic, Methyl nicotinate, Prostaglandin, Nitric oxide, Inflammation, Skin