https://www.prime-journal.com/anti-inflammatory-and-skin-repair-treatments-with-d-limonene/
Anti-inflammatory and skin repair treatments with d-limonene:
The major source of d-limonene (enantiomeric excess higher than 98%2) is the oily substance contained in the peel of citrus fruits. However d-limonene is also present in numerous other botanical species such as Carum carvi (caraway oil) or Anethum graveolens (dill oil). d-Limonene represents more than 30% of the caraway oil, where it is accompanied by its oxygenated derivative (+)-carvone (48–65%)3, which has been shown to have anti-cancer activities4. d-Limonene and carvone are both also prominent in oil-based dill extracts, which demonstrate significant anti-inflammatory effects5. The most interesting source of d-limonene remains the cold-pressed oil obtained from the peel of citrus fruits, owing to their superior quality and properties since there is no thermal degradation of the components, as is sometimes observed in essential oils obtained by hydro-distillation.
d-Limonene is known for its capacity for high penetration particularly appreciable in the skin, which is why it is referred to as an ‘enhancer’. The enhancing power of d-limonene allows it to be used as a carrier for other molecules solely unable to cross epithelial barriers20. On its own, d-limonene has been shown to have impressing repair effects on skin and gut epithelia21–22. In general terms, epithelial barriers are major determinants of first line defense in innate immunity, preserving the integrity of environmental interfaces. These barriers include mucosal areas as well as the most exposed skin areas. In the epidermis and dermis, numerous mechanisms are employed for the elimination of pathogens and irritants, while containing inflammation. When these naturally active protections are overwhelmed (i.e. through infections and wounds), a rapid sequence of events aims at restoring integrity. Among terpenes, thymol was recently shown to accelerate wound healing23. d-Limonene, long known to inhibit tumor growth24 via a number of cellular mechanisms25,26 may contribute to this effect owing to its additional capacity of angiogenesis inhibition27. As neoangiogenesis is an inherent component of inflammation, d-limonene anti-inflammatory properties also lie, among other mechanisms, in this capacity. The authors’ group has been involved in thoroughly identifying the beneficial properties of monoterpenes in inflammation control and tissue repair28,29. It was shown that terpenes from essential oils are able to repress the production of tumor necrosis alpha (TNF) and interleukin-6 (IL-6), both being major pro-inflammatory cytokines29–31.
As for the effects of d-limonene on the skin, it seems that its metabolite POH is the key molecule helping to restore skin homeostasis and integrity22,32.
d-Limonene and skin ageing
Besides its medical properties, d-limonene, contained in OPE, has been shown to display remarkable rejuvenating properties28. In a series of studies by the authors, 21 women aged between 53 and 69 years old used OPE for 29 days as a mist. This specific preparation uses, as in the previously reported studies, d-limonene-rich OPE, which also contains minute amounts of a number of other terpenes present in orange peel. It is prepared using the patented Wpe/Ultradrops® (AR2I, Le Plessis Robinson, France) technology, providing a micellar emulsion with a rapid penetration of actives. s a whole, 84% of the subjects considered that the treatment had a positive effect on fine wrinkles (Figure 1 and 2).
In the same study, the regenerating effect of OPE was also measured. The Quantisquam® (Monaderm) technique was used, which measures the squamae and exfoliation index after stripping a 1 cm² area on the cheekbone. The desquamation index was significantly decreased on day 29 (p<0.0005) as well as the surface of desquamation (p<0.001). These particular results on the desquamation index, although obtained for a healthy population, sustain the notion that d-limonene is efficient in the treatment of psoriasis44.
Moreover, firmness, scored on a 4 level scale (from very relaxed to very firm), improved from a mean of 1.74 to 2.14 (p=0.004). The pores aspect was evaluated on a similar scale ranging from 0 (very dilated pores and irregular skin) to 3 (no visible pores; tightened, smooth skin) and improved from 0.98 to 1.29 (p=0.004). Finally, complexion radiance, evaluated from very dull (0) to very radiant (5), improved from 1.95 to 2.29 (p=0.002).
In another study performed on 10 healthy volunteers (aged between 42 and 68 years old, mean 59), the hydrating effect of OPE was tested with the Corneometer® CM 825 (Courage & Khazaka Electronics, Köln, Germany). The hydration index was measured on the upper side of the forearms. The corneometric index showed a significant improvement at 2 and 4 hours (p<0.0005 in both cases) on the OPE-treated forearm, while the control site was unchanged (p=0.5). Overall, the improvement of skin hydration on the OPE-treated forearms was 16.6% at 2 hours and 14.1% at 4 hours.
Clinical evidence of the tissue repair capacities of d-limonene in humans comes from such diseases as psoriasis and skin cancer, characterized by immune dysregulation or impairment35. The preclinical studies mentioned above confirmed the safety and efficacy of d-limonene. Dermatologists at the University La Sapienza, on the basis of AISA’s preclinical models, developed a pilot study in psoriatic patients with mild to moderate lesions35. Topical and/or oral administration of OPE was carried out for 45 days, with pre- and post-therapy scoring of the lesions and quality of life. A highly significant decrease of the VSCAPSI and PASI scores was observed in this pilot cohort. Both patients and clinicians reported subjectively to a satisfactory improvement of the lesions. Finally, quality of life indexes were also significantly improved.
Conclusion
The long-standing empirical usage of terpenes of vegetal origin has gained scientific support in recent years. The pleomorphic actions of these natural compounds can find applications in such diverse fields as wound repair, psoriasis treatment, and cancer cure or prevention. On a more daily basis, global skin care and toning can be improved and age-dependent skin sagging and stretch marks prevented. Moreover, the potent activity of d-limonene’s main metabolite, POH, as an anti-inflammatory and anti-angiogenic agent, supports its medical application to such inflammatory conditions as psoriasis or atopic dermatitis. In addition, the more complex composition of OPE, of which d-limonene is the major but not only component, carries the additional properties of providing an enhancer effect facilitating skin penetration and positively influencing the production of dopamine45 thereby acting as an anti-stress product and mood enhancer29,45.