Rediscovering Sandalwood: Fatty Acid for Anti-aging, Anti-inflammatory Action

Fatty acids are long-chain biomolecules found in nature that make up cell membrane structures. Plant-derived fatty acids are mainly found in the seeds, although they also are found in limited concentrations in other plant parts. While fatty acids are present in animal fats such as tallow and lard, consumer demand has diminished for animal-derived ingredients due in part to the rising veganism trend.

The most common fatty acids, e.g., stearic, palmitic and lauric, are used for the production of soaps and various emollient and emulsifier derivatives for beauty and personal care.¹ Interestingly, the seeds belonging to some plant families also contain rare fatty acids² with structures and functional groups affording them defensive properties against environmental stress.

One such molecule is ximenynic acid (XA), also known as santalbic acid. This eighteen-carbon acetylenic fatty acid has a triple bond in the ninth position and a double bond at the eleventh (see Figure 1). The presence of triple bond makes this molecule reactive and studies have shown that it inhibits certain enzymes involved in prostaglandin synthesis and fatty acid metabolism.³

Figure 1. Chemical structure of ximenynic acid and its ester

It is abundant in the seeds of plants belonging to the Santalaceae family, which includes nearly 25 species. The oil is obtained from the seed kernels through solvent or supercritical extraction methods, then purified from the oil. Despite its unique properties, however, the use of XA in cosmetics has generally been limited, as a brief Google search suggests.

Anti-inflammation, Anti-aging and Under-eye Care

Fatty acids are not new to skin care. Conventionally, they have been used as emulsifiers and sensory enhancers to help modulate aesthetics and textures in cosmetic products. The acetylenic fatty acid obtained from Santalaceae is different in that its anti-inflammatory action can be used to treat rashes and itching. Indeed, studies have proven that XA inhibits inflammation trigger factors such as leukotrienes and prostaglandins that promote the release of arachidonic acid.⁴

XA is additionally known to impart anti-aging benefits by strengthening the skin’s collagen and elastin via the inhibition of collagenase – in turn keeping the skin firm and delaying skin sagging. It also has been proven non-irritating and safe for cosmetics for the delicate and thin eye area⁵ – an area that is readily vulnerable to irritation and inflammation.

In fact, swollen eyes and under-eye bags can occur due to fluid accumulation, poor sleep and hormonal variations, or as post-operative eye oedema after blepharoplasty and rhinoplasty. In response, XA was found, by Belcaro, et al., to act as a decongestant and to improve blood circulation in periorbital regions.⁶

In independent studies, the regular use of face oils containing XA has been reported to improve aesthetics of the under-eye area and to reduce dryness.^{7, 8} In one case, the effects of ethyl ximenynate, an oily ester derivative of ximenynic acid^a, was compared in a randomized study of 57 subjects for eight weeks with the effects of a combination of ethyl ximenynate-, escin- and ruscogenin-loaded liposomes and 0.2% escin cream against a no-active vehicle control.

The test product, an eye cream with 0.5% oily XA ester along with other anti-inflammatory actives (escin and ruscogenin) significantl¬y reduced eye puffiness after four weeks. The product also increased blood microcirculation that reduced the appearance of curved lines under the eyes.

Belcaro, et al., also showed the synergistic anti-inflammatory and venotonic effects of ethyl ximenynate with other actives, compared with escin alone, proving the former to be an improved option to treat under-eye bags and eye oedema.⁶

In another double-blinded, half-face trial conducted for four weeks on 22 volunteers, a 3% blend^b of ethyl ximenynate, potassium lauroyl wheat amino acids, palm glycerides and capryloyl glycine showed anti-aging effects in the under-eye area. No study volunteers showed any irritation or sensitivity.⁹

The same ingredient blend also has been found in vivo to reduce dark circles, eye bags and skin roughness, and to improve eye contour and vascular tone under the eyes, without any eye or skin irritation.¹⁰ Furthermore, encapsulated ethyl ximenynate^c has shown vaso-active effects in vivo without any eye or skin irritation.¹¹

Anti-cellulite

Cellulite is a common skin concern characterized by “orange peel” textured skin on the thighs and hips. It is caused by genetics, hormonal factors, poor diet and lack of blood flow to the skin. XA has been found to reduce cellulitis by increasing the microcirculation of blood beneath the skin.¹¹ In relation, ethyl ximenynate has been reported to cause microvascular constriction and has been proposed for the management of cellulitis and varicose veins.¹¹

One XA ingredient^d was shown to increase blood perfusion in the cellulitic areas by 50% within 60 min of application as an emulsion. This increased circulation lasted higher than the initial value even after three hours. The subjects also showed no skin irritation during the study.¹²

Scalp Care

Androgenetic alopecia is the most common cause of baldness and has many treatment options, such as minoxidil, finasteride, dutasteride, platelet-rich plasma and laser therapy. However, a noninvasive topical formulation based on natural ingredients is often preferred in anticipation of lesser side effects and ease of use.

XA has been shown address hair loss by acting on deeper levels, as it stimulates the production of eicosanoids that increase blood circulation in the scalp.¹³ In a 90-day randomized double-blind vehicle-controlled study conducted in 40 androgenic alopecia subjects, a hair loss lotion containing 0.5% XA, 1% esculin and 0.2% lauric acid increased cutaneous blood circulation in the frontal and occipital areas. Hair pluck tests and microscopic evaluations and trichograms revealed a significant increase in hair’s anagen to telogen ratio (A:T ratio).

Treated subjects also reported an increase in hair volume and easier combing and setting, with no adverse reactions on the scalp.¹³ In a recent report, it was ascertained that this combination (ximenynic acid, esculin and lauric acid) improves A:T ratio with more than 75% reduction in hair fall and 44% increase in hair strength. The results were also visible 30 days after discontinuing the serum application, making it an effective anti-hair loss active.¹⁴

Conclusion

XA has proven to be a non-toxic, plant-derived fatty acid with excellent anti-inflammatory, venotonic and lipid metabolism regulatory properties, making it suitable for topical and systemic delivery. This review summarizes the available data on topical applications of XA and its derivatives. While extensive studies and clinical trials are lacking, the limited information available suggests multiple and unique benefits of this material. Extensive research must be carried out to determine the complete potential of this molecule.

^a Ximilene (INCI: Ethyl Ximenynate), Givaudan/Indena
^b Eyedren (INCI: Ethyl Ximenynate (and) Potassium Lauroyl Wheat Amino Acids (and) Palm Glycerides (and) Capryloyl Glycine) and
^c X-Solve (INCI: Ethyl Ximenynate (and) Lecithin (and) Caprylic/Capric Triglyceride (and) Glycerin), Sinerga Corp.
^d Ximenoil (INCI: Xymenynic Acid), Givaudan/Indena

References

1. Liebert, M. (1987). Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid and stearic acid. J Am Coll Toxicol, 6(3) 321-401.

2. Aitzetmuller, K. (2012, Nov). Santalbic acid in the plant kingdom. Plant Syst Evol, 298(9) 1609-17.

3. Cai, F., Liu, Y., Hettiarachichi, D.S., Wang, F., Li, J., Sunderland, B. and Li, D. (2020). Ximenynic acid regulation of n-3 PUFA content in liver and brain. Lifestyle Genom, 13(2) 64-73.

4. Croft, K.D., Beilin, L.J. and Ford, G.L. (1987). Differential inhibition of thromboxane B and leukotriene B4 biosynthesis by two naturally occurring acetylenic fatty acids. Biochim Biophys Acta, 921 621-4.

5. Shivatare, R.S., Musale, R., ... Ganu, G., et al. (2020). Isolation, identification and characterization of ximenynic acid with anti-aging activity from Santalum album. Int J Res Pharm Sci, 11(2) 1394-9.

6. Belcaro, G., Dugall, M., Maramaldi, G., Togni, S. and Giacomelli, L. (2016). Evaluation of the efficacy of a new escin-based, multi-component formulation in reducing eyelid edema. Minerva Oftalmol, 58(4) 65-9.

7. Living Earth Beauty. (Accessed 2024, Apr 1). Living Libations sandalwood nut oil. Available at https://www.livingearthbeauty.com/products/sandalwood-nut-oil

8. Esse. (Accessed 2024, Apr 1). Esse Protect Oil. Available at https://www.esseskincare.com/product/protect-oil/

9. Sparavigna, A., Tenconi, B., De Ponti, I. and Guglielmini, G. (2014, Jun). Evaluation of the activity and tolerability of a cosmetic treatment for the periocular area on the aging face: Controlled clinical and instrumental evaluation vs. placebo. Cosmetics, 1(2) 105-16.

10. Sinerga. (Accessed 2024, Apr 1). Eyedren. Available at: https://www.sinerga.it/en/raw-materials/products/active-ingredients/eyedren

11. Sinerga. (Accessed 2024, Apr 1). X-Solve. Available at https://www.sinerga.it/en/raw-materials/products/active-ingredients/xsolve/description

12. Indena. (Accessed 2023, Nov 29). Ximenoil. Available at https://www.ulprospector.com/en/asia/PersonalCare/Detail/3155/90648/Ximenoil?doc =987011&st=20

13. Maramaldi, G., Giacomelli, L., Meneghin, M., Eggenhoffner, R. and Togni, S. (2016). Effectiveness of a multi-component lotion in the control of hair loss. Dermatol Exp, 18(2) 70-5.

14. Kohli, M., Ganjoo, A., Sharma, A., Patil, C.Y., Sethi, S. and Patel, B. (2023, May 8). Prospective efficacy and safety study of an innovative Kerascalp hair growth serum in mild-to-moderate alopecia in India: Regrowth study. Cureus, 15(5) 1-11.