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A combination of linalool and linalyl acetate synergistically alleviates imiquimod-induced psoriasis-like skin inflammation in BALB/c mice.

ABSTRACT: Introduction: Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and differentiation with increased immune cell infiltration. The anti-psoriatic effect of lavender oil has been reported. However, its phytoconstituents, linalool (L) and linalyl acetate (LA), showed a distinctive affinity with psoriasis targets. Objectives: This investigation was aimed to determine the combined effect of L and LA in ameliorating psoriasis-like skin inflammation and its safety in long-term topical uses. Methods: The combined effect of L and LA was compared with their individual effects. The anti-psoriatic activity was performed using imiquimod (IMQ)-induced psoriasis in BALB/c mice and evaluated to reduce PASI and CosCam scores and Th-1 and Th-17 cell-specific cytokine levels. The acute and repeated dose dermal toxicities were investigated as per the OECD guidelines. Results: L and LA combination (LLA) in the 1:1 w/w ratio at 2% concentration showed a synergistic effect. The combination showed 76.31% and 71.29% recovery in PASI and CosCam Scores; however, L2% and LA2% showed 64.28% and 47.61% recovery in PASI and 64.75 and 56.76% recovery in CosCam scores, respectively. It showed >90% and >100% recovery in Th-17 and Th-1 cell-specific cytokines, respectively, and restored epidermal hyperplasia and parakeratosis toward normal compared with psoriatic mice. A marked reduction in NF-κB, cck6, and the IL-17 expression was also observed in the LLA-treated group. This combination was safe in a therapeutically effective dose for 28 days as no significant changes were observed in organ and body weights, liver and kidney parameters, and differential leukocyte counts. Conclusion: This study proves the synergy between L and LA in a 1:1 w/w ratio at 2% in the treatment of psoriasis-like skin inflammation and provides strong scientific evidence for its safe topical use.

SUBMITTER: Rai VK

PROVIDER: S-EPMC9388787 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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A combination of linalool and linalyl acetate synergistically alleviates imiquimod-induced psoriasis-like skin inflammation in BALB/c mice.

Rai Vineet Kumar VK Chanda Debabrata D Chanotiya Chandan Singh CS Yadav Narayan Prasad NP

Frontiers in pharmacology 20220805

<b>Introduction:</b> Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and differentiation with increased immune cell infiltration. The anti-psoriatic effect of lavender oil has been reported. However, its phytoconstituents, linalool (L) and linalyl acetate (LA), showed a distinctive affinity with psoriasis targets. <b>Objectives:</b> This investigation was aimed to determine the combined effect of L and LA in ameliorating psoriasis-like skin infl ...[more]

PMID: 35991888

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Project description:BackgroundThe polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to down regulate NF-κB; an important contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the effects.MethodsThe study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting.ResultsImiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways. Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis.ConclusionsResveratrol ameliorates psoriasis, and changes expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner, which suggests resveratrol, might have a role in the treatment of psoriasis and should be explored further in a human setting.

Dataset Information

A combination of linalool and linalyl acetate synergistically alleviates imiquimod-induced psoriasis-like skin inflammation in BALB/c mice.

Publications

A combination of linalool and linalyl acetate synergistically alleviates imiquimod-induced psoriasis-like skin inflammation in BALB/c mice.

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