Sandalwood Album Oil as a Botanical Therapeutic in Dermatology


by Ronald L. Moy, MD, and Corey Levenson, PhD

Dr. Moy is from Facial Cosmetic Surgery in Beverly Hills, California, and Dr. Levenson is an employee of Santalis Pharmaceuticals, San Antonio, Texas.

Funding: No funding was provided.

Disclosures: Dr. Moy has no financial conflicts relevant to the content of this article. Dr. Levenson is an employee of

Santalis Pharmaceuticals, which holds several Investigational New Drug Applications (INDs) for clinical investigations on sandalwood oil, the topic of this review.

Abstract: Many skin conditions and diseases are characterized by inflammation, infection, and hyperplasia. Safe and effective topical treatment options that can be used long-term are needed. Traditional botanical medicines, which are often complex mixtures that exert their biological activities via multiple mechanisms of action, are being studied as potential new active ingredients in dermatology. Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is an essential oil distilled from the Santalum album tree and has demonstrated biological activity as an anti-inflammatory, anti-microbial, and anti-proliferative agent. Sandalwood album oil has also shown promise in clinical trials for treatment of acne, psoriasis, eczema, common warts, and molluscum contagiosum. The favorable safety profile, ease of topical use, and recent availability of pharmaceutical-grade sandalwood album oil support its broader use as the basis of novel therapies in dermatology.

Keywords: Santalum album oil, East Indian sandalwood oil, sandalwood oil, botanical drugs, anti-inflammatory, antimicrobial, antiproliferative, acne, psoriasis, Molluscum contagiosum, atopic dermatitis, eczema

J Clin Aesthet Dermatol. 2017;10(10):34–39

Sandalwood album oil (SAO) has been utilized topically for centuries in both Ayurvedic and traditional Chinese medicine. The oil is distilled from the heartwood of the Santalum album tree and contains over 125 structurally related compounds, with fewer than a dozen components present in concentrations greater than 1% by weight.1 Because SAO is a significant item of commerce, used in many personal care products and perfumes, there is an international specification for the oil (ISO 3518:2002). SAO is listed in the United States Food and Drug Administration (FDA) Food Chemicals Codex as a natural flavoring ingredient, and the Australian Therapeutic Goods Administration (TGA) has classified the oil as a Listed Medicine, available as an active ingredient in many non-prescription products.

Worldwide, there are more than a dozen species of sandalwood, most of which have served as sources of essential oil. However, the International Organization for Standardization (ISO) has issued standards for only two species: Santalum album and Santalum spicatum (West Australian sandalwood). Of the two species, S. album produces oil with much higher concentrations of alpha- and beta-santalol. SAO was previously produced from wild-grown trees in India, but over-harvesting and poaching has led to Santalum album trees being pushed to the brink of extinction in their native habitats. Since 1998, the trees have been listed as Vulnerable by the International Union for the Conservation of Nature, and the harvesting and export of wild-grown Indian trees is highly restricted. The trees that are currently being used to produce sandalwood album oil for pharmaceutical applications are sustainably cultivated by Quintis, Ltd. (formerly TFS Corp. Ltd.) on Australian plantations.

The FDA has issued guidelines for the development of traditional medicines derived from plants.2 Such botanicals are often mixtures of numerous active compounds acting via multiple mechanisms of action. In general, if the mixture’s composition is under tight control and there are no known safety issues, botanical drugs can be studied in clinical trials as mixtures and can receive marketing approval as long as they are shown to be safe and effective. Veragen®, a green tea (Camellia senensis) extract for treatment of genital warts, and Fulyzac®, an anti-diarrheal extract from Croton lechleri, were the first two botanical drugs approved for sale in the United States under the FDA guidelines.

Anti-inflammatory, anti-oxidant, and related properties of sandalwood album oil. SAO is known to mediate its anti-inflammatory properties in vitro through multiple mechanisms. The oil inhibits the oxidative enzyme 5-lipoxygenase and has DPPH radical scavenging activity and, in vivo, SAO was able to protect mouse livers from damage resulting from oxidative stress and the formation of reactive oxygen species.3-7

In co-cultures of dermal fibroblasts and keratinocytes, the oil suppressed the production of numerous pro-inflammatory chemokines and cytokines produced in response to stimulation by lipopolysaccharide (LPS). Production of PGE2 was also suppressed, suggesting that SAO might be acting, at least in part, through inhibition of cyclooxygenase.8 Additional anti-inflammatory activity in skin was reported to rely on the activation of the enzyme 11b-HSD1, which plays a role in cortisol synthesis by keratinocytes. The oil also suppressed the expression of the pro-inflammatory cytokine, IL-1b, in keratinocytes and reduced irritant dermatitis in mouse skin stimulated with haptens.9

Recent interest in inflammatory-specific targets for the treatment of skin conditions such as psoriasis and atopic dermatitis has led to the development of a number of drugs and drug candidates that reduce levels of IL-17 and the activity of PDE4.10-13 SAO has been shown to specifically inhibit both of these targets in various in-vitro models,14-16 suggesting a mechanism for the activity seen in clinical studies of the oil in the treatment of these skin conditions.

Alpha-santalol was found to be an inhibitor of tyrosinase, a key enzyme in the biosynthetic pathway for the skin pigment melanin.17 This intriguing finding suggests that SAO may potentially act as an inhibitor of abnormal pigmentation associated with aging and exposure to ultraviolet light.

Anti-microbial properties of album oil. The use of essential oils fell out of favor in the 1900s with the advent of sulfa drugs and other antibiotics, but interest in essential oils, such as SAO, has been re-vitalized in recent years due to their activity against antibiotic-resistant strains of bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA).18,19

Album oil has been found to be broadly active against many gram-positive strains of bacteria, including Staphylococcus (including antibiotic-resistant strains MRSA and VRSA), Streptococcus, and some gram-negative bacteria.20–23

SAO has demonstrated potent activity against many fungal dermatophytes and yeasts including Trichophyton, Microsporum and Candida.4, 24–29 Album oil is active against Herpes simplex viruses-1 and -2.30,31 Beta-santalol, one of the principal components of SAO, was found to inhibit the replication of influenza virus A/HK (H3N2) in vitro at 100µg/mL.32

The anti-microbial mechanism(s) of action of album oil have not been thoroughly elucidated but the effects seen might be partly due to the disruption of membrane integrity, a phenomenon that has been demonstrated for other essential oils.33-35

Anti-proliferative and anti-cancer properties of sandalwood album oil.
The ability of SAO to prevent the formation of tumors in mouse skin as a result of exposure to chemical carcinogens and ultraviolet light has been extensively studied in vitro and in vivo by the Dwivedi group.36 The anti-cancer effects of album oil and its major components have also been demonstrated in bladder cancer cells and oral cancer cells.37,38 In two papers published in 2013, Saraswati reported that alpha-santalol, the primary component of SAO, is anti-angiogenic and inhibits the growth of hepatocellular carcinoma and prostate tumors in vitro and in vivo.39,40 A common mechanistic feature in these studies seems to be the ability of the oil to cause cell cycle arrest at G2/M and to induce apoptosis and subsequent cell death. SAO was also shown to induce autophagy and cell death in proliferating keratinocytes, suggesting that album oil may be able to prevent the progression of pre-cancerous conditions, such as actinic keratosis, to skin cancers.41

When SAO was screened against the National Cancer Institute’s NCI-60 panel of 60 human tumor cell lines, the oil inhibited the growth of all cells lines with IC50s ranging from 7 to 126?m (unpublished data, 2010, Southern Research Institute, Birmingham Alabama). Interestingly, this cytotoxicity was generally not seen when album oil was applied to non-cancerous cells.

A recently published study examined the effects of essential oil from Santalum austrocalidonicum trees on human breast cancer cell lines (MCF-7) and non-tumorigenic epithelial breast cells (MCF-10A).42 The authors demonstrated that the oil induced deoxyribonucleic acid (DNA) strand breaks in both cell lines. Unlike the MCF-10A cells, the MCF-7 cells were not able to repair the damage, and therefore, the essential oil showed a selective cytotoxicity toward the MCF-7 breast cancer cell line. It should be noted that the spectrum of components in Santalum austrocalidonicum oil differs from that seen in SAO but the general phenomenon observed might explain, in part, why sandalwood oil seems to be preferentially cytotoxic towards cancerous cell lines.

A recent publication presented data showing that, in cultured keratinocytes, SAO enhanced expression of transcription factors (snail, twist) and mesenchymal factor (vimentin), all of which are related to the epithelial-mesenchymal transition (EMT). Album oil also promoted epidermal wound healing in vivo compared to vehicle control.43

The olfactory receptor, OR2AT4, is expressed in keratinocytes and has been shown to bind to sandalwood odorants resulting in elevation of intracellular calcium levels and phosphorylation of extracellular kinases (Erk1/2) and p38 mitogen-activated kinases, promoting keratinocyte proliferation and wound healing in human skin ex vivo.44 The relationship between OR2AT4 (or other sandalwood component receptors) and chemopreventive mechanisms in skin is speculative at this time, but these initial, intriguing findings are likely to stimulate further studies exploring the role of dermal sandalwood receptors in cellular proliferation.45

Safety profile of sandalwood album oil. SAO has a long history of topical use as a traditional medicine and in personal care products. The dermal LD50 in rats is in excess of 5gm/kg of body weight.46 When applied to human subjects in patch testing, neither neat sandalwood oil, nor a 10% SAO ointment, produced irritation or sensitization (unpublished data, 2013, Santalis Healthcare Corporation, San Antonio, Texas). In routine testing, a small percentage (0.1–2.4%) of people have been found to be allergic to album oil.1 However, in many of these studies, the provenance, purity, and source of the sandalwood is not clear. For example, other species of sandalwood, such as Western Australian (Santalum spicatum) or Hawaiian sandalwood (Santalum paniculatum), contain significant percentages of farnesol, an irritant, that is not found in oil from S. album.

SAO contains no known carcinogens and was not genotoxic in the Bacillus subtilis rec-assay.47 The safety profile of album oil was reviewed by Burdock in 2008 and, more recently, by Tisserand and Young.48,49

Little is known about the metabolism of SAO and its components by humans. However, in rabbits, alpha-santalol is oxidized to various diols; in dogs, it is oxidized to a carboxylic acid.50

Human clinical trials of SAO. Pediatric clinical studies looking at SAO in the treatment of human papillomavirus (HPV) warts or Molluscum contagiosum led to the issuance of three United States patents related to the use of sandalwood album oil for the treatment of these skin conditions.51–53 Since those early studies, a number of additional studies in the field of dermatology have been initiated in the United States and Australia.

Several on-going and completed clinical trials studying SAO are listed on in a variety of indications, including Verruca vulgaris (common warts), Molluscum contagiosum, genital warts, psoriasis, oral mucositis, and atopic dermatitis.54

In an open-label study of 50 patients undergoing high-dose radiation therapy for head and neck cancer, a cream containing SAO and turmeric was compared to baby oil for its ability to reduce the severity of radiodermatitis.55 The SAO/turmeric group had reduced incidence of Grade 3 radiodermatitis, and a comparison between the two groups for the degree of radiodermatitis showed that the cohorts using the SAO/turmeric cream had delayed appearance and reduced levels of dermatitis at all time points. The drawbacks of the study included lack of blinding and the fact that the beneficial effects could not be attributed to the album oil, the turmeric, or a combination of the two.

A randomized, double-blind, placebo-controlled dose range finding trial of SAO ointment (10%, 20%, and 30% strengths) was studied in subjects with common warts (Verruca vulgaris) caused by HPV (NCT01286441). The primary endpoints of the trial were efficacy, safety, and tolerability. All three treatment arms were deemed to be safe and well tolerated. There were no serious adverse events considered to be related to the study medication, and only four adverse events (3 in the 30% arm and 1 in the 10% arm) were deemed to be related to the study medication; notably, all were mild, reversible irritation at the site of application. All three treatment arms showed greater rates of wart clearance and reduction in wart area than did those in the placebo arm (unpublished results, 2016, Santalis Healthcare Corporation, San Antonio, Texas).

In addition to the on-going and completed studies looking at SAO being conducted under multiple investigational new drug (IND) applications in the United States, several small proof-of-concept studies have been conducted examining SAO in combination with various over-the-counter monograph drugs for the treatment of acne, common warts, and atopic dermatitis.

A single-center, open-label pilot study of a novel over-the-counter topical blend of 0.5% salicylic acid and up to 2% SAO was conducted in adolescent and adult subjects with mild to moderate facial acne. Over the course of the eight-week treatment period, approximately 89 percent of participants experienced an improvement in their disease when compared with baseline. No adverse events were observed that would limit use of the regimen.56 The four-component treatment regimen employed in the Moy acne study56 subsequently became commercially available in the United States as an over-the-counter acne product line sold by Galderma (Fort Worth, Texas) under the Benzac® name.

Atopic dermatitis was treated in a pediatric population with a novel three-product regimen containing 0.1% colloidal oatmeal and SAO in a single-center, open-label confirmatory study. Overall, the treatment regimen was very well-tolerated, safe, and seemed to be effective at reducing the severity of atopic dermatitis in the target patient population.57

For the treatment of common warts, a proprietary topical blend of 17% salicylic acid and approximately 2% alpha-santalol was used in two open-label studies in children and adolescents with common warts. For the two studies, 44 percent (11/25) and 30 percent (10/33) of patients who completed treatment and follow-up met the primary endpoint. A total of 16 percent (4/25) and 21 percent (7/33) of patients experienced complete resolution of treated warts. The treatment was well tolerated with 10 to 30 percent of patients experiencing mild-to-moderate itching, burning, dryness, and stinging.58


Botanical therapies have been used for centuries by many cultures as traditional medicines to treat a wide variety of skin and other conditions. The use of botanical remedies, such as green tea and tea tree oil, in modern dermatology clinical trials has been reviewed.59–61 More recent reviews have focused on the use of botanical therapies for specific skin conditions such as rosacea and psoriasis.62,63 Botanicals and phytochemicals have shown promise in the treatment of skin disorders, and this class of drugs is generally well-received by patients who tend to perceive botanical remedies as being “natural.”

SAO has been, and continues to be, extensively used as an herbal medicine, particularly in Asia. It is also widely used as an ingredient in many personal care products and fragrances, but at very low concentrations. Its safety profile has been well-characterized and, although a small percentage of the general population is allergic to SAO, it has been shown through extensive Human Repeat Insult Patch Test (HRPIT) testing to be non-irritating and non-sensitizing as a pure oil or when formulated for topical use. In preclinical models, the oil has been shown to have broad anti-inflammatory, anti-infective, and anti-proliferative properties. These properties are likely due to multiple mechanisms of action resulting from the interaction of the many components in the oil with multiple biological targets. The various mechanisms of action of SAO are depicted in Figure 1.

Data from initial proof-of-concept clinical studies in acne, warts, Molluscum contagiosum, atopic dermatitis, and psoriasis indicate that SAO is safe, well-tolerated, and has potential for broader use as a novel botanical therapeutic. SAO is now being produced in compliance with Current Good Manufacturing Practices (cGMPs) from sustainably grown cultivated trees and is available for use in commercial drug development programs. Larger, confirmatory clinical trials are underway and, if successful, might pave the way for the introduction of SAO-containing topical drugs for treatment of a variety of skin conditions.


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