A Comprehensive Bibliographic Review Concerning the Efficacy of Organic Acids for Chemical Peels Treating Acne Vulgaris.

Acne vulgaris stands out as the most prevalent skin disorder among teenagers and young adults, causing physical discomfort and considerable economic and psychological burdens on individuals and society. A wide range of topical and systemic therapies are available in acne treatment. Chemical peeling is a skin resurfacing technique designed to rebuild healthy skin using exfoliating substances, a simple and affordable process with various dermatological uses. Chemical peels, classified as superficial, medium, and deep, have been utilized for acne vulgaris and multiple other skin issues. In these chemical peels, a diverse range of chemical substances is employed, each with its unique mode of action. Among these, α-hydroxy and ß-hydroxy acids have gathered attention for their efficacy in reducing acne lesions and enhancing overall skin appearance. Acids, such as salicylic acid, glycolic acid, or lactic acid, are commonly used in chemical peels due to their exfoliating and sebum-regulating properties. Despite the widespread use of these acids, there exists a lack of consensus regarding the most effective acid type and concentration for treating acne-prone skin. This review aims to bridge this knowledge gap by evaluating the effectiveness and safety of various organic acids used in chemical peels specifically for acne-prone skin. The findings of this comprehensive bibliographic review indicate that organic acid-based chemical peels represent effective and safe treatment options for individuals with acne-prone skin. Their adaptability sets these treatments apart; the choice of organic acid can be tailored to meet individual patient needs and tolerability levels. This personalized approach ensures that patients receive optimal care while minimizing the risks associated with the treatment. As research in this field progresses, it is anticipated that a more nuanced understanding of the ideal acid type and concentration will emerge, further enhancing the efficacy and safety of chemical peels for acne-prone skin.

Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing.

Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1α, TNF-α, IL-6, and IL22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDMHSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-α and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.

Repurposing Acitretin as an Antipseudomonal Agent Targeting the Pseudomonas aeruginosa Iron-Regulated Heme Oxygenase.

Iron is an essential micronutrient for the survival and virulence of the bacterial pathogen Pseudomonas aeruginosa. To overcome iron withholding and successfully colonize a host, P. aeruginosa uses a variety of mechanisms to acquire iron, including the secretion of high-affinity iron chelators (siderophores) or the uptake and utilization of heme. P. aeruginosa heme oxygenase (HemO) plays pivotal roles in heme sensing, uptake, and utilization and has emerged as a therapeutic target for the development of antipseudomonal agents. Using a high-throughput fluorescence quenching assay combined with minimum inhibitory concentration measurements, we screened the Selleck Bioactive collection of 2100 compounds and identified acitretin, a Food and Drug Administration-approved oral retinoid, as a potent and selective inhibitor of HemO. Acitretin binds to HemO with a KD value of 0.10 ± 0.02 µM and inhibits the growth of P. aeruginosa PAO1 with an IC50 of 70 ± 18 µg/mL. In addition, acitretin showed good selectivity for HemO, which uniquely generates BVIXß/δ, over human heme oxygenase (hHO1) and other BVIXα-producing homologues such as the heme oxygenases from Neisseria meningitidis (nmHO) and Acinetobacter baumannii (abHO). The binding of acitretin within the HemO active site was confirmed by 1H-15N heteronuclear single-quantum coherence nuclear magnetic resonance, and molecular modeling provided further insight into potential interactions of acitretin with residues specific for orienting heme in the ß/δ selective HemO. Moreover, at 20 µM, acitretin inhibited the enzymatic activity of HemO in P. aeruginosa cells by >60% and effectively blocked the ability of P. aeruginosa to sense and acquire heme as demonstrated in the ß-galactosidase transcriptional reporter assay.

Myeloid-derived suppressor cells exert immunosuppressive function on the T helper 2 in mice infected with Echinococcus granulosus.

Cystic echinococcosis (CE) is a worldwide hazardous zoonotic parasitosis caused by Echinococcus granulosus. CE development involves complex immunological mechanisms, including participation of multiple immune cells and effector molecules. Myeloid-derived suppressor cells (MDSCs) are known to be involved in chronic and acute inflammatory conditions. In this study, we aimed to characterize the immune function of MDSCs in CE to improve the understanding, prevention and treatment of CE. Our results indicated that MDSCs overexpressing Ly6C and Ly6G inhibit the formation and activity of T helper 2 cells in a NO-dependent manner during E. granulosus infection.

Retinoic Acid Organizes the Zebrafish Vagus Motor Topographic Map via Spatiotemporal Coordination of Hgf/Met Signaling.

Information flow through neural circuits often requires their organization into topographic maps in which the positions of cell bodies and synaptic targets correspond. To understand how topographic map development is controlled, we examine the mechanism underlying targeting of vagus motor axons to the pharyngeal arches in zebrafish. We reveal that retinoic acid organizes topography by specifying anterior-posterior identity in vagus motor neurons. We then show that chemoattractant signaling between Hgf and Met is required for vagus innervation of the pharyngeal arches. Finally, we find that retinoic acid controls the spatiotemporal dynamics of Hgf/Met signaling to coordinate axon targeting with the developmental progression of the pharyngeal arches and show that experimentally altering the timing of Hgf/Met signaling is sufficient to redirect axon targeting and disrupt the topographic map. These findings establish a mechanism of topographic map development in which the regulation of chemoattractant signaling in space and time guides axon targeting.

Exploring the potential of minoxidil tretinoin liposomal based hydrogel for topical delivery in the treatment of androgenic alopecia.

Purpose: Androgenic alopecia (AGA) is a condition of progressive hair loss and involves follicular miniaturization triggered mainly due to varying levels of androgen besides environmental and genetic factors, which may also play some role. Minoxidil (MXD) has been considered as most effective therapeutic moiety to treat this disorder. Another drug Tretinoin (TRET) is known for its comedolytic activity and is reported to enhance percutaneous absorption of MXD. Presently both these drugs are being utilized for treatment of androgenic alopecia (AGA) in solution form which poses several problems in terms of poor solubility of drug, frequency of application and side effects.Materials and methods: Current work investigates liposomal hydrogel system for simultaneous delivery of MXD and TRET to overcome the limitations of existing formulation. Successful development of liposomes was commenced by thin film hydration method and various parameters affecting desired characteristics like size, morphology, entrapment efficiency; stability and ex vivo permeation were optimized. The formulated liposomes were further characterized for various physicochemical properties and evaluated for in vivo irritancy study in animals.Results and discussion: Results suggested prepared liposomes to be stable, homogenous and capable to hold both the drugs within. Association with hydrogel enhanced the permeation of MXD through skin ex vivo but TRET retained on the skin. Liposome loaded hydrogel was found to be non-irritant to skin.Conclusion: Overall developed system showed potential for effective and simultaneous delivery of both the drugs.

NF-κB Signaling Negatively Regulates Osteoblast Dedifferentiation during Zebrafish Bone Regeneration.

Dedifferentiation of mature cells is an intriguing cellular process associated with regeneration of several organs. During zebrafish fin regeneration, osteoblasts dedifferentiate to osteogenic progenitors that provide source cells for bone restoration. We performed a high-content in vivo chemical screen for regulators of osteoblast dedifferentiation and fin regenerative growth. NF-κB signaling emerged as a specific regulator of dedifferentiation. The pathway is active in mature osteoblasts and downregulated prior to dedifferentiation. Pathway activation blocked osteoblast dedifferentiation, while NF-κB signaling inhibition enhanced dedifferentiation. Conditional Cre-lox-mediated NF-κB signaling manipulation specifically in osteoblasts showed that the pathway acts cell autonomously to interfere with osteoblast dedifferentiation. NF-κB signaling acts upstream of retinoic acid (RA) signaling, which also needs to be downregulated for dedifferentiation to occur, via suppression of the RA-degrading enzyme cyp26b1. Our findings shed light on the molecular regulation of regenerative cellular plasticity.

Chemical peeling for acne and melasma: current knowledge and innovations.

The skin is a dynamic organ that continuously eliminates an infinite number of keratinized cells through physiological mechanism. Chemical peeling is a widely used cosmetic procedure in medical practice. This technique consists of the application of one or more chemical ablative agents to the skin's surface in order to induce keratolysis or keratocoagulation. Exfoliation is followed by skin and epidermal regeneration from the adjacent epithelium and skin adnexa. Moreover, through an inflammatory reaction and the activation of the inflammation mediators, an increase in fibroblastic synthesis and in the production of new collagen and glycosaminoglycan fibers is induced. After the first treatment session, the appearance and the texture of the skin are significantly improved. Peeling agents may be divided into superficial (epidermis-papillary dermis), medium-depth (papillary to upper reticular dermis) and deep subtypes based on the depth of their penetration (mid-reticular dermis). Superficial peel is mainly used for dyschromia, acne, post-inflammatory hyperpigmentation, melasma and actinic keratosis. Medium depth peel mainly treats solar keratosis or lentigines, pigmentary disorders and superficial scars. Skin photo-ageing, deep scars or wrinkles and precancerous skin lesions require a deep chemical peeling. The aim of this article is to review recent advances in chemical peel of melasma and acne.

All­trans­retinoic acid modulates TGF­ß­induced apoptosis, proliferation, migration and extracellular matrix synthesis of conjunctival fibroblasts by inhibiting PI3K/AKT signaling.

Conjunctival fiber generation is implicated in a wide spectrum of ocular diseases. Conjunctival wound healing is characterized by inflammation followed by re­epithelialization, synthesis of new extracellular matrix (ECM), wound contraction and subconjunctival scar formation. The primary cause for the failure of glaucoma filtration surgery results from the excessive scarring of the filtering bleb. All­trans­retinoic acid (ATRA), a derivative of vitamin A, is a potent regulator of ECM synthesis, growth and differentiation. Following a previous study, which revealed that ATRA could inhibit transforming growth factor­ß­induced human conjunctival fibroblast (HConF)­mediated collagen gel contraction, the present study aimed to investigate the effects of ATRA on HConF migration, apoptosis, proliferation and ECM synthesis. To achieve this, the present study used Transwell migration, wound healing and Cell Counting Kit­8 assays, flow cytometry and western blot analysis. In addition, the present study aimed to elucidate the mechanism of ATRA in mediating resistance to conjunctival scar formation. ATRA treatment resulted in an increased level of HConF apoptosis, reduced proliferation and migration, decreased collagen I and fibronectin expression, and decreased phosphorylation of PI3K and AKT. Thus, the present study showed a role for ATRA in inhibiting HConF migration, proliferation and ECM synthesis, and in promoting HConF apoptosis through the inhibition of the PI3K/AKT signaling pathway.

UV fluorescence excitation spectroscopy as a noninvasive predictor of epidermal proliferation and clinical performance of cosmetic formulations.

BACKGROUND: The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). Thinning of the epidermis and decreased proliferation of its cells are associated with aging related changes in skin, including wrinkling and laxity. Fluorescence excitation spectroscopy is a noninvasive method of monitoring characteristic excitation-emission peaks in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in epidermal thickness, proliferation, and skin aging. AIM: The goal of this study is to correlate changes in the F295 signal with proliferation of cells and thickening of the epidermis induced by cosmetic formulations. We hypothesize that two commonly used cosmetic ingredients, retinol and glycolic acid, will increase these markers that have been implicated in skin anti-aging. METHODS: In a placebo-controlled study subjects' forearms were treated with formulations containing retinol or glycolic acid under occlusive patch for a period of 21 days. Skin fluorescence was measured at baseline and after treatment, and biopsies were taken following treatment for histological analysis of epidermal thickness and cell proliferation. RESULTS: After 21 days of treatment retinol and glycolic acid formulas significantly increased F295 (by 265.1±33.5% and 162.2±18.7% respectively), whereas the placebo control formula did not induce a change from baseline. Furthermore, retinol and glycolic acid treatments significantly increased epidermal thickness (by 63.1% and 7.8% respectively) and keratinocyte proliferation (by 236.9% and 62.8% respectively) versus placebo control. CONCLUSION: Increases in F295 were found to correlate with epidermal renewal, but more so with increased cell proliferation than epidermal thickness. We conclude that the F295 signal is a fast and reliable early indicator of epidermal remodeling in skin that can be used to distinguish between formulations with different cosmetic ingredients.

Long-term safety and drug survival of acitretin in psoriasis: a retrospective observational study.

BACKGROUND: This retrospective observational study aimed to investigate the long-term safety, drug survival, and factors associated with the survival of acitretin in a real-world setting. METHODS: Data of adult patients with psoriasis who attended Siriraj Hospital between 2012 and 2017 and were treated with acitretin were reviewed. Demographic data and clinical courses were recorded. The Kaplan-Meier curve and Cox regression were used to calculate drug survival and the factors associated with drug survival, respectively. RESULTS: Of 104 patients, 56 and 48 were male and female, respectively, with a mean treatment duration of 3.2 years. The mean cumulative dose per patient was 19.28 ± 7.84 mg/day. Acitretin was administered to 73, 39, 24, and six patients for more than 1, 3, 5, and 10 years, respectively. Most side effects were mild and tolerable; only nine patients withdrew acitretin due to side effects. No patients developed clinical features of cirrhosis or uncontrolled hyperlipidemia. The drug survival rates were 79%, 69.5%, 61.2%, 57.6%, and 53.5% at 1, 2, 3, 4, and 5 years, respectively, higher than those of previous studies. Patients without obesity, metabolic syndrome, and dyslipidemia did not have a significantly longer acitretin survival compared to patients with these comorbidities. CONCLUSIONS: Long-term, low-dose acitretin in patients with psoriasis is unlikely to cause significant liver or lipid problems. In countries with difficulty accessing biological agents for psoriasis, acitretin may have a high drug survival rate due to its long-term safety. This study has several limitations: its retrospective nature, single-center study design, and small sample size.

Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.

Acitretin is widely used to treat psoriasis, but the efficacy varies significantly among individuals. To explore the association between polymorphisms and acitretin efficacy, we enrolled 46 and 105 Chinese Han psoriasis vulgaris patients for discovery and validation phases, respectively. The patients were treated with acitretin (30 mg/day) and calcipotriol ointment for at least 8 weeks, and their genotypes were detected. The wild-type genes and variants were transfected into HEK293 cells, which were then incubated with acitretin. The cellular acitretin concentration was measured by liquid chromatography-mass spectrometry. We found that the polymorphisms rs4149056 in the SLCO1B1 gene and rs2282143 in the SLC22A1 gene were associated with efficacy, both in the discovery (P = 0.013 and P = 0.002) and validation phases (P = 0.028 and P = 0.014), based on a 50% reduction from before to after treatment of the psoriasis area severity index (PASI50). When the PASI75 was used as an efficacy cutoff, a similar conclusion was drawn. The uptake of acitretin was lower with the rs4149056C (P = 0.002) and rs2282143T alleles (P = 0.038) than the wild-type alleles. Our results imply that the rs4149056C and rs2282143T variants decrease the acitretin uptake, and significantly associated with clinical effective responsiveness.

Identification of Retinoic Acid Receptor Agonists as Potent Hepatitis B Virus Inhibitors via a Drug Repurposing Screen.

Currently available therapies for chronic hepatitis B virus (HBV) infection can efficiently reduce viremia but induce hepatitis B surface antigen (HBsAg) loss in very few patients; also, these therapies do not greatly affect the viral covalently closed circular DNA (cccDNA). To discover new agents with complementary anti-HBV effects, we performed a drug repurposing screen of 1,018 Food and Drug Administration (FDA)-approved compounds using HBV-infected primary human hepatocytes (PHH). Several compounds belonging to the family of retinoic acid receptor (RAR) agonists were identified that reduced HBsAg levels in a dose-dependent manner without significant cytotoxicity. Among them, tazarotene exhibited the most potent anti-HBV effect, with a half-maximal inhibitory concentration (IC50) for HBsAg of less than 30 nM in PHH. The inhibitory effect was also observed in HBV-infected differentiated HepaRG (dHepaRG) models, but not in HepG2.215 cells, and HBV genotypes A to D were similarly inhibited. Tazarotene was further demonstrated to repress HBV cccDNA transcription, as determined by the levels of HBV cccDNA and RNAs and the activation of HBV promoters. Moreover, RNA sequence analysis showed that tazarotene did not induce an interferon response but altered the expression of a number of genes associated with RAR and metabolic pathways. Inhibition of RARß, but not RARα, by a specific antagonist significantly attenuated the anti-HBV activity of tazarotene, suggesting that tazarotene inhibits HBV in part through RARß. Finally, a synergistic effect of tazarotene and entecavir on HBV DNA levels was observed. Therefore, RAR agonists as represented by tazarotene were identified as potential novel anti-HBV agents.

Understanding the Mechanism of Action of the Anti-Dandruff Agent Zinc Pyrithione against Malassezia restricta.

Dandruff is known to be associated with Malassezia restricta. Zinc pyrithione (ZPT) has been used as an ingredient in anti-dandruff treatments. The mechanism of ZPT has been investigated in several studies; however, a non-pathogenic model yeast, such as Saccharomyces cerevisiae was most often used. The aim of the present study was to understand how ZPT inhibits the growth of M. restricta. We analyzed the cellular metal content and transcriptome profile of ZPT-treated M. restricta cells and found that ZPT treatment dramatically increased cellular zinc levels, along with a small increase in cellular copper levels. Moreover, our transcriptome analysis showed that ZPT inhibits Fe-S cluster synthesis in M. restricta. We also observed that ZPT treatment significantly reduced the expression of lipases, whose activities contribute to the survival and virulence of M. restricta on human skin. Therefore, the results of our study suggest that at least three inhibitory mechanisms are associated with the action of ZPT against M. restricta: (i) an increase in cellular zinc levels, (ii) inhibition of mitochondrial function, and (iii) a decrease in lipase expression.

Antiaging efficacy of a retinaldehyde-based cream compared with glycolic acid peel sessions: A randomized controlled study.

BACKGROUND: Glycolic acid (GA) chemical peels are a popular treatment for photoaged skin rejuvenation, but retinaldehyde (RAL)-based cosmetic creams have also demonstrated efficacy in improving photoaging, and are potentially better tolerated than chemical peels. AIMS: To compare the efficacy and safety of an antiaging cream containing 0.1% RAL associated with Glycylglycine Oleamide (GGO, Relastide® ) and Pre-tocopheryl® , to GA peels sessions in the treatment of photoaging. PATIENTS AND METHODS: Fifty-five women with photoaging were randomized in 2 treatment groups: (1) Daily application of the antiaging cream for 8 weeks or (2) Three sequential GA peels (20%, 50%, and 70%), 2-3 weeks apart. Skin surface texture, length of wrinkles, complexion radiance, and evenness of pigmentation and texture were assessed by profilometry using skin replicas, computer image analysis, and self-assessment. RESULTS: Efficacy of both treatments was similar in reducing crow's feet wrinkles depth (STm -7.61%, P = .0007 vs -4.34%, P = .0348; P = .3049 intergroup) and volume, crow's feet and periorbital wrinkle length, and number of fine lines and wrinkles at end of treatments. The efficacy of the cream in refining skin texture was superior to the peels (contrast: -5.61%, P = .0025 vs +3.54, P = .08; P intergroup = .0252). The 8-week treatment with the antiaging cream was well tolerated; adverse events were fewer and of milder intensity than with the peels, (12-fold lower incidence of physical signs). CONCLUSION: A dermocosmetic cream containing 0.1% RAL, GGO (Relastide® ) and Pre-tocopheryl® is as effective as 3 sequential GA peels, better tolerated, and is an alternative in the management of photoaged skin.

[Changes in autophagy during maturation and differentiation of Hepa1-6 cells induced by all-trans retinoic acid].

OBJECTIVE: To investigate the effects of different concentrations of all-trans retinoic acid (ATRA) on the maturation, differentiation and autophagy of Hepa1-6 cells. MONTHOD: Hepa1-6 cells were treated with 0.1, 1, and 10 µmol/L ATRA, and the changes in the expressions of hepatic specific markers were detected using real-time PCR and Western blotting. Indocyanine green (ICG) and periodic acid-schiff (PAS) staining was used to assess the functional maturation of Hepa1-6 cells, and the cell-cell junction and autophagy were observed under transmission electron microscopy to determine the optimal concentration of ATRA for treatment. The expressions of autophagy-related markers in the cells were detected using Western blotting, and confocal microscopy was used to observe the autophagic flow in the cells transfected with ptfLC3 plasmid. RESULTS: Compared with the control cells, the hepatocytes treated with ATRA showed a concentration-dependent decrease in AFP expression and increase in the expressions of ALB, CK18, TAT and ApoB. ICG and PAS staining revealed significantly increased number of positive cells after ATRA treatment. Following ATRA treatment, the cells exhibited obviously increased tight junctions, cytoskeleton and number of autophagosomes under transmission electron microscopy. ATRA treatment resulted in significantly increased the expressions of autophagy-related markers LC3-II, Beclin-1, RAB7 and P62 and also an increased ratio of LC3-II/LC3-I(P<0.05). Confocal microscopy revealed obviously increased green and red spots in the cells after ATRA treatment. CONCLUSION: ATRA can induce the maturation and differentiation and enhance the level of autophagy in Hepa1-6 cells.

Long-term safety and efficacy of continuous acitretin monotherapy for three children with different severe hyperkeratotic disorders in China.

Long-term systemic treatment with acitretin for severe hyperkeratotic disorders is needed to maintain quality of life of afflicted patients, but treatment has been limited owing to its potential side-effects including skeletal malformations, particularly for children during their growth and development. A retrospective investigation was conducted with three children afflicted with a severe hyperkeratotic disorder, namely Darier's disease, bullous ichthyosiform erythroderma or lamellar ichthyosis, who were continuously maintained on 0.2-0.3 mg/kg per day acitretin for more than 12 years after an initial period at a larger acitretin dose to bring each disease under control. The patients had good responses to acitretin treatment, which was assessed for safety, skeletal abnormalities, growth retardation and other potential side-effects. Acitretin monotherapy was an effective treatment for these children, and maintenance doses were well tolerated with no skeletal or other observable side-effects during the course of the study.

Comparative instrumental evaluation of efficacy and safety between a binary and a ternary system in chemexfoliation.

OBJECTIVE: To instrumentally evaluate the efficacy and the safety of a new ternary system chemo exfoliating formulation (water-dimethyl isosorbide-acid) vs traditional binary systems (water and acid) where the acid is maintained in both the systems at the same concentration. METHODS: Different peelings (binary system pyruvic acid and trichloroacetic acid-TCA, and ternary system pyruvic acid and TCA) were tested on the volar forearm of 20 volunteers of both sexes between 28 and 50 years old. The outcomes were evaluated at the baseline, 10 minutes, 24 hours, and 1 week after the peeling by means of noninvasive skin diagnosis techniques. In vivo reflectance confocal microscopy was used for stratum corneum evaluation, transepidermal waterloss, and Corneometry for skin barrier and hydration, Laser Doppler velocimetry in association with colorimetry for irritation and erythema analysis. RESULTS: The instrumental data obtained showed that the efficacy and safety of the new ternary system peel compounds were significantly higher compared with the binary system formulations tested. The new formulation peels improved chemexfoliation and reduced complications such as irritation, redness, and postinflammatory pigmentation compared to the traditional aqueous solutions. CONCLUSION: The study showed that ternary system chemexfoliation, using a controlled delivery technology, was able to provide the same clinical effects in term of stratum corneum reduction with a significantly reduced barrier alteration, water loss, and irritation/erythema compared to traditional binary system peels.

The essential oil from Citrus limetta Risso peels alleviates skin inflammation: In-vitro and in-vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruit peels are traditionally used in folk medicine for the treatment of skin disorders but it lacks proper pharmacological intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit crops used by juice processing industries in all continents. Ethnopharmacological validation of an essential oil isolated from its peels may play a key role in converting the fruit waste materials into therapeutic value added products. AIM OF THE STUDY: To evaluate the chemical and pharmacological (in-vitro and in-vivo) profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin inflammation for its ethnopharmacological validation. MATERIALS AND METHODS: Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprint of Clp-EO revealed the presence of monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp-EO to the macrophages was able to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in LPS-induced inflammation as well as the production of reactive oxygen species (ROS) in H2O2-induced oxidative stress. In in-vivo study, topical application of Clp-EO was also able to reduce the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid peroxidation, pro-inflammatory cytokines production and ameliorate the histological damage in the ear tissue. In-vitro and in-vivo toxicity study indicate that it is safe for topical application on skin. CONCLUSION: These findings suggested the preventive potential of Clp-EO for the treatment of inflammation linked skin diseases.