Therapy For Rosacea Research Articles

Effect of combined probiotics and doxycycline therapy on the gut-skin axis in rosacea.

This research elucidates rosacea management with novel insights into probiotic use alongside doxycycline, showing dual benefits in symptom relief and inflammation reduction in patients. The study maps probiotic-induced shifts in gut and skin microbiota, underscoring microbial shifts correlating with skin health improvements. Crucially, it deciphers the gut-skin axis modulation by probiotics, proposing a method to curb antibiotic resistance in rosacea therapies. This study furnishes robust evidence for probiotics in rosacea, advancing our grasp of the gut-skin relationship.

Signaling pathways and targeted therapy for rosacea.

Rosacea is a chronic skin inflammatory disease with a global prevalence ranging from 1% to 20%. It is characterized by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Its pathogenesis involves a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors. Recent studies have advanced our understanding of its molecular basis, focusing on toll-like receptor (TLR) 2 pathways, LL37 expression, mammalian target of rapamycin (mTOR) activation, interleukin (IL)-17 signaling, transient receptor potential vanilloid (TRPV) functions, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. LL37-associated signaling pathways, particularly involving TLR2 and mTORC1, are critical in the pathogenesis of rosacea. LL37 interacts with signaling molecules such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear factor kappa B (NF-κB), inflammasomes, C-X-C motif chemokine ligand 8 (CXCL8), mas-related G-protein-coupled receptor X2 (MRGPRX2)-TRPV4, and vascular endothelial growth factor (VEGF). This interaction activates macrophages, neutrophils, mast cells, and vascular endothelial cells, leading to cytokine release including tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, C motif chemokine ligand (CCL) 5, CXCL9, and CXCL10. These processes contribute to immune response modulation, inflammation, and angiogenesis in rosacea pathophysiology. The IL-17 signaling pathway also plays a crucial role in rosacea, affecting angiogenesis and the production of inflammatory cytokines. In addition, recent insights into the JAK/STAT pathways have revealed their integral role in inflammatory and angiogenic mechanisms associated with rosacea. Rosacea treatment currently focuses on symptom management, with emerging insights into these molecular pathways providing more targeted and effective therapies. Biological agents targeting specific cytokines, IL-17 inhibitors, JAK inhibitors, and VEGF antagonists are promising for future rosacea therapy, aiming for enhanced efficacy and fewer side effects. This review provides a comprehensive overview of the current knowledge regarding signaling pathways in rosacea and potential targeted therapeutic strategies.

The treatment of Tofacitinib for rosacea through the inhibition of the JAK/STAT signaling pathway.

Rosacea is a chronic inflammatory skin disease characterized by facial erythema and telangiectasia. Despite ongoing research, the pathogenesis of rosacea remains incompletely understood, and current therapies are not entirely satisfactory. The JAK/STAT signaling pathway plays an essential role in immunoregulation, inflammation, and neurovascular regulation. Inhibition of the JAK/STAT pathway appears to hold promise as a potential therapy for rosacea. This study aimed to investigate the effects of the JAK inhibitor tofacitinib on rosacea and to preliminarily explore its therapeutic mechanism. To this end, a rosacea-like mouse model was induced using LL37 and treated with a 2% tofacitinib emulsion. The results demonstrated that topical application of tofacitinib significantly ameliorated rosacea-like phenotype, reduced the infiltration of CD4+ T cells and mast cells, and suppressed dermal angiogenesis. RT-qPCR analysis revealed a reduction in mRNA expression levels of STAT1, STAT4, and STAT5a in skin lesions following topical tofacitinib treatment. Additionally, three patients diagnosed with erythematotelangiectatic rosacea (ETR) were included in the study and treated with oral tofacitinib, leading to a significant improvement in erythema and flushing symptoms. These findings collectively suggest that tofacitinib alleviates LL37-induced rosacea-like skin inflammation in mice and rosacea skin lesions by inhibiting the JAK/STAT signaling pathway.

Cutaneous angiosarcoma arising over rhinophyma: an unusual variant of lymphoedema-associated angiosarcoma?

Cutaneous angiosarcoma is a rare tumour with poor prognosis. When arising on phymatous nose its diagnosis can be very deceptive and lead to delayed treatment as well as metastatic dissemination. Our case report highlights that some red flag as oedema, ulceration, unresponsiveness to conventional rosacea therapies or bluish vascular structures at dermoscopy should prompt biopsy to rule out malignancy.

Formulation and evaluation of ivermectin-loaded dissolving microarray patches for rosacea disease

PurposeThis investigation aims to develop and characterise dissolving microarray patches (MAPs) loaded with ivermectin (IVM) for rosacea therapy.MethodsTween® 80 and Soluplus® were evaluated to enhance the water solubility of IVM powder. Three dissolving MAPs were fabricated using a two-layer casting method, pure IVM-loaded (F1), IVM-Tween® 80 (F2), and IVM-Soluplus® (F3) loaded patches. Formulations were evaluated for drug content, in vitro and ex vivo mechanical performances, ex vivo skin dissolution time, dermatokinetics, in vitro biocompatibility and activity against rosacea.ResultsIVM solubility in water was improved with surfactants, reaching 1206.42 ± 53.78 and 130.78 ± 12.78 µg/mL in Tween® 80 and Soluplus® solutions, respectively. The MAPs, featuring bubble-free, perfectly shaped pyramidal needles of approximately 800 μm, exhibited considerably higher IVM content in F2 and F3 than in F1 (2.31 ± 0.26 mg for F1, 3.58 ± 0.15 mg for F2, and 3.19 ± 0.22 mg for F3). All formulations demonstrated mechanical robustness and penetrated the skin to a depth of 650 μm. The highest IVM deposition in the skin at 24 h was achieved by F2, selected as the lead formulation (F1 = 1456.35 ± 266.90 µg; F2 = 2165.24 ± 130.13 µg; F3 = 1684.74 ± 212.09 µg). Furthermore, F2 and F3 provided faster IVM deposition, most likely due to the quicker dissolution rate of microneedles in the skin. F2 proved biocompatible to skin cells in vitro and effectively inhibited the inflammatory cascade associated with rosacea diseases.ConclusionThis study encourages further investigation into IVM-loaded dissolving MAPs formulated with Tween® 80 for rosacea therapy.

Enhancing Tranexamic Acid Penetration through AQP-3 Protein Triggering via ZIF-8 Encapsulation for Melasma and Rosacea Therapy.

The systemic use of tranexamic acid (TA) as an oral drug can bring adverse reactions, while intradermal injection leads to pain and a risk of infection. Moreover, it is difficult for highly hydrophilic TA to penetrate the skin barrier that contains lots of hydrophobic lipid compounds, which poses enormous restrictions on its topical application. Current transdermal TA delivery strategies are suffering from low drug load rates, plus their synthesis complexity, time-consumption, etc. adding to the difficulty of TA topical application in clinical therapeutics. To increase the penetration of TA, a novel approach using TA-loaded ZIF-8 (TA@ZIF-8) is developed. The encapsulation efficiency of TA@ZIF-8 reaches ≈25% through physical adsorption and chemical bonding of TA indicates by theoretical simulation and the improved TA penetration is elevated through activating the aquaporin-3 (AQP-3) protein. Additionally, in vivo and in vitro experiments demonstrate the preponderance of TA@ZIF-8 for penetration ability and the advantages in intracellular uptake, minor cytotoxicity, and inhibition of melanogenesis and inflammatory factors. Moreover, clinical trials demonstrate the safety and efficacy of TA@ZIF-8 in the treatment of melasma and rosacea. This work presents a potential topical application of TA, free from the safety concerns associated with systemic drug administration.

Methods of rosacea treatment to achieve stable remission in a megalopolis

The review article is devoted to the aspects of rosacea therapy in a megalopolis, where a dermatological service is widely developed and it is possible to provide modern diagnostic, therapeutic and preventive measures. Rosacea negatively affects the emotional state of patients, and low awareness of chronic dermatoses often leads to self-medication and skin deterioration. The pathogenetic mechanisms of the disease have not been fully studied. Both genetic predisposition and environmental factors contribute to the occurrence of rosacea. A number of studies confirm that the triggers can be ultraviolet radiation, stress, intense physical activity, temperature changes, dietary characteristics, imbalance of the intestinal microbiota, alcohol consumption. Every day, residents of megalopolises face a combination of these factors, which combined with genetically determined features of the epidermal barrier and immune function, makes them more susceptible to rosacea and other skin diseases. The multifactorial nature of rosacea causes a variety of treatment methods that must be individualized in accordance with the clinical picture of the disease. With mild to moderate rosacea, monotherapy with external drugs is effective – azelaic acid, brimonidine tartrate, ivermectin, metronidazole. For the treatment of severe forms of rosacea, it is advisable to prescribe systemic therapy from groups of retinoids and antibiotics. The results of numerous studies are presented that physiotherapy methods which are available in large cities increase the effectiveness of treatment by reducing erythema and telangiectasia, enhancing repair and microcirculation in the epidermis. The accumulated experience of Russian dermatologists and foreign colleagues allows to determine the most effective combinations of treatment methods to achieve stable remission in patients.

Dendrobium polysaccharide (DOP) ameliorates the LL-37-induced rosacea by inhibiting NF-κB activation in a mouse model.

Rosacea, a common chronic inflammatory skin disease worldwide, is currently incurable with complex pathogenesis. Dendrobium polysaccharide (DOP) may exert therapeutic effects on rosacea via acting on the NF-κB-related inflammatory and oxidative processes. In this study, an LL-37-induced rosacea-like mouse model was established. HE staining was used to assess the skin lesions, erythema severity scores, pathological symptoms, and inflammatory cell numbers of mice in each group. The inflammation level was quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of TLR4 and p-NF-κB were finally detected. DOP improved skin pathological symptoms of rosacea mice. DOP also alleviated the inflammation of rosacea mice. Moreover, the TLR4/NF-κB pathway was observed to be inhibited in the skin of mice after DOP application. These findings evidenced the anti-inflammatory effects of DOP on the LL-37-induced rosacea mouse model. DOP could inhibit NF-κB activation, suppress neutrophil infiltration, and reduce pro-inflammatory cytokines production, which may be the reason for DOP protecting against rosacea. This study may propose an active candidate with great potential for rosacea drug development and lay a solid experimental foundation for promoting DOP application in rosacea therapy.

Pathogenetic therapy of rosacea with systemic tetracyclines

The article presents modern data on the pathophysiology of rosacea and diagnostic criteria for dermatosis. The historical aspects of the introduction of systemic tetracyclines into the therapy of rosacea are outlined. The effect of doxycycline and minocycline on the mechanisms of rosacea development is covered in detail, taking into account modern ideas about the pathogenesis of the disease. At the same time, the advantage of minocycline, compared with doxycycline, is noted, which is manifested by a more pronounced anti-inflammatory effect, as well as a higher antibacterial efficacy, which allows the use of low dosages of minocycline and thereby reduces the risk of adverse events, especially from the gastrointestinal tract. The data of various studies are presented, indicating the expediency of prescribing subantimicrobial doses, as well as the results of evaluating the effectiveness and safety of domestic minocycline minoleksin.
 It has been proven that the effectiveness of tetracyclines is associated with a pathogenetic effect on innate immunity reactions, with a pronounced anti-inflammatory effect, especially minocycline, suppression of a number of microorganisms, which, apparently, are not a key link in the pathogenesis of rosacea, but can be a trigger factor and initiate inflammation. In addition, minocycline most effectively inhibits the activity of metalloproteinases and increases epidermal hydration

Case Series: Infrared Energy Device for the Treatment of Erythematotelangiectatic Rosacea

Rosacea is a common chronic dermatosis which occurs mainly in middle-aged patients. The etiology of the disease remains unknown but immune and vascular factors are seen to play a crucial role. Diagnosis is established based on clinical manifestation. We present four case reports of rosacea therapy using a medical device emitting near-infrared light.

Pathogenetic substantiation of combination therapy for rosacea (review)

Rosacea is a chronic inflammatory dermatosis predominantly damage to the skin of the face, which has a significant negative impact on the quality patients' lives. The main goal of treatment is to achieve the most complete remission. However, due to the fact that the pathogenesis of the disease is not fully understood, the search for new methods of treatment is especially relevant. Combined use pulsed dye laser and ivermectin drug is presented as alternative pathogenetically substantiated method of therapy.

Retracted: Analysis of the Effect of DPL Combined with Clarithromycin in the Therapy and Improvement of Rosacea.

[This retracts the article DOI: 10.1155/2022/9437697.].

The role of dermatocosmetics in the management of rosacea

Rosacea is a chronic inflammatory disease that affects the facial skin. This pathology is characterized by hyperaemia, erythema, telangiectasia and other manifestations. It is also accompanied by a group of unpleasant symptoms, such as burning sensations, itching, and skin tightness. The pathogenesis of the disease has not been sufficiently studied. But it is generally accepted that it is based on abnormalities in the immune system. In addition, excessive Demodex colonization and exposure to ultraviolet radiation may play a role in the development of rosacea. The incidence rate of rosacea worldwide reaches 5%. It is emphasized that some ethnicities face a greater risk of this disease than others. It is a very difficult task to treat rosacea for a specialist. The therapeutic approach differs in different forms of the disease. There is a wide range of treatments available for papulopustular rosacea, including systemic and topical medications and even physiotherapy. However, the therapy of erythematous rosacea mainly centres around the use of dermatocosmetic care. For patients with rosacea, it is important to choose products that, first of all, can effectively reduce skin redness and discomfort and will be well tolerated. A dermo-cosmetic composition has to have an anti-inflammatory effect and the ability to repair damaged skin. This article presents our own experience of using such drug in the monotherapy of erythematous rosacea and in the complex treatment of papulopustular disease. A significant effect had been achieved at 3–4 weeks of complex therapy in patients with papulopustular rosacea. We present a clinical case report of a 46-year-old patient N. as an example of the effectiveness of therapy.

A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea

Introduction: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases. Methods: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test. Results: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated. Conclusion: CAP is a promising new treatment of rosacea, especially for PPR.

Demonstration of a clinical case based on the phenotypic approach of rosacea therapy

Rosacea is a chronic inflammatory disease of the skin mainly of the central facial region, having gender and age correlations. Currently, more and more data is accumulating on the analysis of rosacea phenotypes, scientific discussions are underway on the feasibility of switching from subtype classification to phenotypic classification to justify individualized approaches to therapy. The phenotypic classification is based on the manifestations of rosacea and distinguishes diagnostic signs from the main and secondary symptoms. Thus, phymatous changes and persistent central facial erythema are the only diagnostic signs (criteria) of rosacea, and erythema, telangiectasia and inflammatory papules/pustules are the main symptoms and only in combination can indicate the diagnosis of rosacea. Secondary signs of rosacea are hot flashes, burning, pain, swelling and a feeling of dryness. The symptoms of rosacea are based on various pathophysiological mechanisms, so therapy in most cases will consist of a combination of topical agents with systemic drugs or physiotherapy. The article presents a clinical case of rosacea based on a phenotypic approach to therapy.

New approaches to the treatment of rosacea on the basis pathogenesis factors and clinical forms

Uncovering the molecular mechanisms of the rosacea pathogenesis and treatment are still of great importance. The review encompasses the modern knowledge of rosacea classification, characterization of the severity of the course of the subtypes, and pathogenesis features. Recent methods of rosacea treatment are presented, including the use of botulinum neuroprotein for the correction of the erythematous-telangiectatic subtype of the dermatosis.
 The relevance of this problem is due to the chronic course of the disease and the peculiarity of the localization of rosacea manifestations that leads to a traumatic effect and often causes social exclusion of patients.
 The rise of the rosacea incidences, along with other reasons like characteristics of the course of dermatosis, accompanied by frequent long-term relapses, is due to the resistance to generally accepted methods of drug therapy, often resulting in shortened clinical remission. All the factors lead to decreasing of patients life quality that require the search for effective therapy approaches. Among modern rosacea therapy, the application of botulinum neuroprotein is widely used; however, the clinical studies confirming the effectiveness of this technique are not presented enough.

Development of a Specific Variant of Patient Benefit Index (PBI) Assessing Patient Needs, Goals and Benefits in Rosacea Treatment.

Evaluation of patient-reported outcomes including health-related quality of life (HRQoL) and perceived benefits from treatment has become a fundamental component of medical decision-making. Standardized evaluation of treatment benefits in rosacea based on patient preferences is still lacking. Development and validation of an instrument for recording patient-defined benefits in rosacea therapy based on the Patient Benefit Index (PBI) methodology. In an open survey of n = 50 patients, potential benefits of therapy from the patient's perspective were examined. The generated item pool was combined with pre-existing PBI items for other skin conditions and reviewed by an expert panel of dermatologists, psychologists and patients. Items were condensed to n = 25 and converted into a Likert-scaled questionnaire. The validity and feasibility of the resulting Patient Benefit Index for rosacea (PBI-RO) were tested on individuals with rosacea recruited from a German rosacea patient organization. N = 446 patients with rosacea completed the PBI-RO. The internal consistencies measured by Cronbach's alpha were high (Patient Needs Questionnaire [PNQ] 0.94). Mean PBI-RO was 1.9 ± 1.2 (scale from 0 = no benefit to 4 = maximum benefit), 23.5% of the patients experienced a PBI-RO < 1 (no clinically relevant benefit). The PBI-RO correlated with HRQoL, health state, current extent of rosacea lesions and treatment satisfaction. The highest correlation was found between PBI-RO and satisfaction with previous treatment (r = -0.59, p < 0.001); correlation with the extent of rosacea lesions was low (r = 0.16, p < 0.001). The PBI-RO shows satisfying internal consistency and construct validity. It offers the option of a patient-weighted evaluation of the therapeutic benefit of rosacea therapy and may add to more stringent goal orientation in therapy.

648 Sequential therapy for erythematotelangiectatic rosacea: Alpha-hydroxy acid (AHA) 30% chemical peels in combination with intense pulsed light (IPL) could be an alternative to carvedilol

648 Sequential therapy for erythematotelangiectatic rosacea: Alpha-hydroxy acid (AHA) 30% chemical peels in combination with intense pulsed light (IPL) could be an alternative to carvedilol

Efficacy and tolerance of Oral minocycline combined with photobiomodulation therapy for rosacea: An evaluator-blinded randomized, controlled clinical trial.

Photodermatology, Photoimmunology & PhotomedicineAccepted Articles LETTER TO THE EDITOR Efficacy and Tolerance of Oral Minocycline Combined with Photobiomodulation Therapy for Rosacea: An Evaluator-blinded Randomized, Controlled Clinical Trial Yaoxi Su, Yaoxi Su Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China Yaoxi Su and Shuwei Wu should be considered joint first author.Search for more papers by this authorShuwei Wu, Shuwei Wu Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China Yaoxi Su and Shuwei Wu should be considered joint first author.Search for more papers by this authorLian Wang, Lian Wang Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorBensen Sun, Bensen Sun Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorXian Jiang, Corresponding Author Xian Jiang [email protected] Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China Correspondence Xian Jiang, PhD, Department of Dermatology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu City, Sichuan Province, PR China, 610041, Email: [email protected]Search for more papers by this author Yaoxi Su, Yaoxi Su Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China Yaoxi Su and Shuwei Wu should be considered joint first author.Search for more papers by this authorShuwei Wu, Shuwei Wu Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China Yaoxi Su and Shuwei Wu should be considered joint first author.Search for more papers by this authorLian Wang, Lian Wang Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorBensen Sun, Bensen Sun Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaSearch for more papers by this authorXian Jiang, Corresponding Author Xian Jiang [email protected] Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China Correspondence Xian Jiang, PhD, Department of Dermatology, West China Hospital, Sichuan University, No.37 Guoxue Alley, Wuhou District, Chengdu City, Sichuan Province, PR China, 610041, Email: [email protected]Search for more papers by this author First published: 24 February 2023 https://doi.org/10.1111/phpp.12869 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/phpp.12869. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

EGCG identified as an autophagy inducer for rosacea therapy.

Background: Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited. Methods: Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. In vivo and in vitro experiments were conducted to verify its therapeutic role. Drug-target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets. Results: WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the in vivo experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed in vivo and in vitro. Finally, drug-target prediction and molecular docking revealed that AKT1/MAPK1/MMP9 could be the pharmacological targets of EGCG in rosacea. Conclusion: Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation via inducing autophagy in keratinocytes.