Chronic inflammatory skin disorders such as psoriasis (PS) and atopic dermatitis (AD) can cause pain and irritation and significantly impact patients’ quality of life. Environmental and genetic factors contribute to PS and AD. Although they are 2 distinct disorders, differentiating them during the acute phase is difficult, as both are caused by overproduction of inflammatory cytokines. Symptomatic relief for patients with PS and AD is provided by therapies that target cytokine and chemokine signaling pathways; however, some topical and systemic medications can cause adverse effects. East Indian sandalwood (Santalum album, Santalaceae) oil (EISO) is known to have anti-inflammatory, antiseptic, and astringent activities. These authors report the results of a single-center, open-label, proof-of-concept, phase 2 trial using topical EISO formulations containing 0.1% colloidal oat (Avena sativa, Poaceae) meal (Santalis Pharmaceuticals, Inc.; San Antonio, Texas) to treat AD in pediatric patients. Additionally, the authors conducted in vitro studies to determine if EISO suppresses proinflammatory responses by inhibiting cyclic adenosine monophosphate (cAMP)-degrading phosphodiesterases (PDEs) and promoting cAMP-mediated nuclear factor kappa B (NF-ĸB) activation.
Of the 25 pediatric patients with mild, moderate, or severe AD who were enrolled in the phase 2 study,1 22 completed the treatment regimen, which combined bubble bath gel, EISO cream, and daily cleanser for 60 days. Outcome measures included changes in AD severity, as assessed by using the Eczema Area and Severity Index (EASI), with a 25% reduction in scores being the primary endpoint.
The authors report that AD improved in all but 1 patient (who had an allergic reaction to carpet cleaning solution before the final visit). EASI scores decreased by 25% in 87.5% of patients. The average reduction in overall scores was 67.8%, with reductions > 50% seen in 75% of patients. In 18.8% of patients, complete remission of symptoms was reported. No adverse effects or safety issues were reported.
For in vitro studies, human dermal fibroblast (DF), BEAS-2B immortalized human bronchial epithelial cells, A549 cells (an alveolar type II epithelium-like cell line from lung adenocarcinoma), and THP-1 human acute monocytic leukemia cells were used. Total cAMP PDE activity was assessed from cell lysates at 2 and 4 hours after stimulation with lipopolysaccharide (LPS) (1 μg/mL) and EISO (0.001% to 0.002%), or the reagents 3-isobutyl-1-methylxanthine or rolipram (10 μM) (concentrations earlier reported to saturate for PDE inhibition). Enzyme-linked immunosorbent assays for tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin (IL)-6, IL-8, and the CXCL5 chemokine were conducted on LPS-stimulated DF, BEAS-2B, A549, and THP-1 cells, with and without EISO treatment.
The authors report that “EISO directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-ĸB) activation, and pro-inflammatory cytokines/chemokine production.” These results are consistent with EISO’s anti-inflammatory properties, they write.
The preliminary clinical trial results suggest EISO for management of AD. The in vitro results provide mechanistic support in EISO’s ability to decrease NF-ĸB activation by suppressing proinflammatory stimulation of PDE transcription and directly suppressing PDE enzymatic activity. This “provides a strong rationale for the continued study of EISO as a potential new therapeutic for the treatment of inflammatory skin conditions such as PS and AD,” conclude the authors.
Santalis Pharmaceuticals, Inc., provided EISO for experimental use and designed and sponsored the clinical trial. Laboratory studies were supported by a research agreement between author M.E. Cox and Santalis Pharmaceuticals, Inc. Authors C. Levenson, I. Clements, and P. Castella are employees of Santalis Pharmaceuticals, Inc.
Browning JC, Rock J, Levenson C, Becker EM. Safety, tolerability, and efficacy of a novel regimen containing 0.1% colloidal oatmeal and East Indian sandalwood oil (EISO) for the treatment of mild, moderate and severe pediatric eczema (atopic dermatitis) – results of a single-center, open-label study. Poster presented at Orlando Dermatology Aesthetic and Clinical Conference; January 13-16, 2017; Doral, FL.
Sharma M, Levenson C, Browning JC, et al. East Indian sandalwood oil is a phosphodiesterase inhibitor: a new therapeutic option in the treatment of inflammatory skin disease. Front Pharmacol. 2018;9:200. doi: 10.3389/fphar.2018.00200.