Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes

Abstract

Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with 1α, 25-dihydroxyvitamin D3 (VD3) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by VD3 were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea. (Ann Dermatol 30(6) 653∼661, 2018

The Effect of Capsaicin on Neuroinflammatory Mediators of Rosacea

“…TRPV1 is expressed on neuronal or non-neuronal cells (e.g., keratinocytes) and play an important role in nociception and neurogenic inflammation 10 11 12 . Therefore, TRPV1 is closely associated with manifestations of rosacea 12 .…”

“…VEGF has been reported to enhance angiogenesis and lymphangiogenesis in rosacea skin, which is also associated with neurovascular dysfunction 15 16 . Moreover, excessive production of LL37 and KLK-5 has also been reported to play a role in the rosacea pathophysiology 11 17 . Rosacea patients have an increased baseline on expression of KLK-5 and LL37, resulting in vasodilatation and leukocyte chemotaxis 11 14 17 18 .…”

“…Moreover, excessive production of LL37 and KLK-5 has also been reported to play a role in the rosacea pathophysiology 11 17 . Rosacea patients have an increased baseline on expression of KLK-5 and LL37, resulting in vasodilatation and leukocyte chemotaxis 11 14 17 18 . This study found that both TRPV1 and LL37 were expressed more strongly in almost the same area in the entire epidermis of the rosacea patients compared to that in normal skin.…”

“…During neurogenic inflammation, PAR2 is activated by rosacea-associated microorganism-derived proteases, resulting in the induction of the release of pro-inflammatory agents such as TNF-α, IL-1 and finally enhanced expression of LL37 3 18 . Likewise, these mediators are upregulated in rosacea patients, resulting in neurogenic dysregulation associated with rosacea symptoms such as persistent erythema and inflammation 11 18 . There have been few reports on how these factors, including TRPV1, are related to the pathogenesis of rosacea.…”

Recent Advances in the Management of Rosacea through Natural Compounds

“…In a study developed in 2018 (Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes), it was demonstrated that citron essential oils have a suppressive effect on LL-37, KLK5, and other pro-inflammatory mediators involved in the pathophysiology of rosacea [ 99 ]. Due to this study, it can now be concluded that citron essential oils may actually normalize the innate immune system response in rosacea patients, and help improve the symptoms in this skin condition.…”