Santalum Album: efficacy studies in an anti-hair loss protocol

INTRODUCTION
Hair life cycle involves the alternation of three phases: anagen (growth), catagen (rest), and telogen (fall). The average duration of this cycle varies from 2 to 7 years.
Baldness or androgenetic alopecia (AGA) is defined as a slow transformation of large scalp terminal hair follicles to shorter and thinner hair with a much shorter anagen phase (hair miniaturization) (1, 2).
AGA hits 50% of men and up to 40% of women at some stage in their lives: men typically present it with recession of the hairline at the temples and hair loss at the vertex, while women normally have diffused thinning across the entire upper part of the scalp (3).
Besides genetic factors and age, the main aspects that adversely affect hair growth are hormone imbalance (high testosterone, high cortisol, unbalanced thyroid hormone), stress and exogenous factors causing inflammation (pollution, sun exposure, excessive use of hair bleaching or dyeing products) (4, 7). Prolonged follicular inflammation contributes to the onset of alopecia (8).
The subsequent steps of AGA occur in the bulbs of the frontal and vertex region. Anagen phase time decreases, and consequently the telogen phase begins earlier. The resulting stem will be thinner and shorter (vellus). Over a period of many months or years, earlier bulbs death leads to the definitive disappearance of hair.
This process does not occur uniformly and is described in the ‘stages’ of the Hamilton Scale (9 ) and the Norwood Scale (10).
Generally, in men the hair-loss process starts in the frontal region, where 5α-reductase, the enzyme responsible for converting testosterone into DHT, is more active, so more DHT is concentrated there : DHT is the androgenetic hormone held responsible for the miniaturization of hair follicles in AGA (11). Later the same happens in the vertex; finally, baldness affects the entire upper part of the head.
The mechanisms just described add up to the fact that the nourishment of the bulbs is a critical factor. Indeed, the most peripheral area of blood circulation is the scalp, and in this part of the body is the most prone to vessel atrophy.
Reduced blood flow to hair follicles may be related to the pathogenesis of premature male pattern baldness (12).
Ideal treatment for hair loss is a combination of 5α-reductase inhibitors with hair growth promoter substances and substances capable of inhibiting micro-inflammation of the hair follicles of the scalp (13).
Anti-androgen mechanisms are generally categorized into three actions: either inhibit or trap DHT or inhibit 5α-reductase or blocking androgen receptors (14).
From the literature it is possible to identify another target in the treatment of hair loss: olfactory receptors.
In human body, olfactory receptors are not only expressed by the nasal epithelium, but also by different cell types.
Specifically, the epithelium of human hair follicles, particularly the outer root sheath, prominently expresses the olfactory receptor OR2AT4 in situ, namely in basal keratinocytes layer (15).
The specific stimulation of OR2AT4 by a synthetic sandalwood odorant called Sandalore promotes proliferation and migration of keratinocytes and prolongs human hair growth ex vivo (organ-cultured human scalp hair follicles); in particular, decreasing apoptosis and increasing production of the anagen-prolonging growth factor IGF-1 are observed (16). Concurrently, silencing of OR2AT4 inhibits hair growth.
This supports that human hair follicle diseases treatments with selected odorants may be possible, since olfactory recep-tors-mediated signaling regulates human hair follicles and keratinocytes biology in situ and OR2AT4 stimulation by endogenous ligands is required to down-regulate keratinocytes apoptosis and, consequently, the catagen phase (17).
Currently, the anti-hair loss efficacy of sandalwood essential oil is not supported by a great amount of data in the scientific literature; in particular, the sandalwood essential oil is the object of a patent in which it is used in mixture with other plant extracts for the preparation, defined as Chinese medicine, and tested for its potential use as anti-hair loss product (18).

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