East Indian Sandalwood Oil (EISO) Alleviates Inflammatory and Proliferative Pathologies of Psoriasis.

Manju Sharma,Corey Levenson,Paul Castella,Ian Clements,Kurt Gebauer,Michael E Cox

doi:10.3389/fphar.2017.00125

Abstract

Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2–3% of the world’s population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1β. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized in vitro psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies.

Highlights

Psoriasis is a chronic T-cell-mediated autoimmune inflammatory skin disease marked by hyperproliferation and aberrant keratinocyte differentiation affecting 2–3% of the world’s population (Gisondi et al, 2011)
Treatment of the psoriatic tissue model with East Indian Sandalwood oil (EISO) exhibited equivalent dose dependent suppression of 6 tested cytokines/chemokines, in some cases to levels indistinguishable from that seen in the normal skin model samples (Figure 9)
An examination of a panel of psoriasis indicator proinflammatory cytokine levels in the reconstituted skin models demonstrated very low levels in the normal skin model and profoundly higher levels in the psoriatic skin model, and that EISO treatment suppressed cytokine/chemokine production, in some cases to levels indistinguishable from that seen in the normal skin model samples

Summary

Introduction

Psoriasis is a chronic T-cell-mediated autoimmune inflammatory skin disease marked by hyperproliferation and aberrant keratinocyte differentiation affecting 2–3% of the world’s population (Gisondi et al, 2011). The acquired and innate immune systems interact, resulting in the production of growth factors, cytokines and chemokines Such triggers as injury, infections, stress, and drugs initiate the inflammatory process resulting in keratinocyte hyperproliferation (Papp et al, 2012; Schafer, 2012; Dubois Declercq and Pouliot, 2013; Mease and Armstrong, 2014). It is thought that in susceptible individuals, a variety of insults activate release of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) from skin cells. This activates antigen presenting cells in the skin that migrate to regional lymph nodes to activate T cells (Dubois Declercq and Pouliot, 2013; Garcia-Perez et al, 2013). These CD4+, CD8+, and Th17 T cells return to the skin, where, through the release of interferon (INF)-γ, TNF-α, IL-6, IL-22, perforin, and granzyme B, activate macrophages, neutrophils, dendiritic cells and promote proliferation of keratinocytes

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