Suppression of Lipopolysaccharide‐stimulated Cytokine/Chemokine Production in Skin Cells by Sandalwood Oils and Purified α‐santalol and β‐santalol

Abstract

Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme-linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co-cultured human dermal fibroblasts and neo-epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α-santalol and β-santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α-santalol and β-santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α-santalol and β-santalol also suppressed lipopolysaccharide-induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co-cultures. The ability of SOs to mimic ibuprofen non-steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects.

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

“…At 0.002% EISO suppressed ENA-78 by 45%, IL-6 by 75%, IL-8 by 83%, MCP-1 by 65%, GM-CSF by 80%, and IL-1β by 56%. The robust suppression of pro-inflammatory cytokine production suggests that the ability of EISO to revert the psoriatic phenotype might be due to the previously reported ability of EISO to effectively suppress epidermal inflammatory cytokine production (Sharma et al, 2014). …”

“…Both santalol isoforms are biologically active, and are being explored for possible chemo-preventative, and anti-viral activites (Kaur et al, 2005; Ochi et al, 2005; Dwivedi et al, 2006; Kim et al, 2006). Although EISO’s mechanisms of action are not completely elucidated, santalols derived from EISO have been shown to have anti-proliferative properties (Lee et al, 2015) as well as significant anti-inflammatory properties in skin models that are linked to suppression of prostaglandin and thromboxane production and cytokine/chemokine expression (Sharma et al, 2014). We hypothesized that the ability of EISO to suppress pro-inflammatory events by keratinocytes and dermal fibroblasts, as well as its antiproliferative properties, would make EISO useful as a potential treatment of a variety of pathophysiologic inflammatory and autoimmune skin ailments, including psoriasis.…”

“…The treatment regimen was well tolerated and notable reductions in lesion counts were observed in patients with more severe or inflamed lesions. Another demonstrated that EISO, and its primary constituents, α- and β-santalols can suppress LPS-mediated pro-inflammatory responses and documented its impact on cyclooxygenase activity and cytokine/chemokine expression in skin models (Sharma et al, 2014). We hypothesized that the ability of EISO and its santalol constituents to suppress dermal proinflammatory cytokine production would be of use to treat various inflammation and autoimmune-mediated skin conditions, including psoriasis.…”

A phase II, proof-of-concept pilot clinical study of a mouth rinse containing sandalwood album oil (SAO) for the prevention of oral and oropharyngeal mucositis associated with (Chemo-) radiation therapy in head and neck cancer patients

“…Sandalwood album oil (SAO; also known as East Indian sandalwood oil (EISO)) is an essential oil that has previously been shown to be anti-inflammatory [14,15] and active against a variety of pathogens, including Candida [16][17][18].…”

A novel chemopreventive mechanism for a traditional medicine: East Indian sandalwood oil induces autophagy and cell death in proliferating keratinocytes

“…In fact, purified α-santalol, as well as sandalwood oil, has previously been demonstrated to prevent skin tumor development in mice [2-7]. Cell-based studies have found that α-santalol activates proapoptotic caspases, induces G 2 /M cell cycle arrest and blocks inflammation, which may be responsible for the prevention of tumor development after UV exposure [8, 9]. Although these studies identified some of the chemopreventive properties of α-santalol, little is known about the essential oil from which it was extracted and its potential value in preventing UV-induced skin cancer.…”