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

Vineet Kumar Rai; Debabrata Chanda; Chandan Singh Chanotiya; Narayan Prasad Yadav

doi:10.3389/fphar.2022.913174

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

Front Pharmacol. 2022 Aug 5:13:913174. doi: 10.3389/fphar.2022.913174. eCollection 2022.

Authors

Vineet Kumar Rai¹, Debabrata Chanda¹, Chandan Singh Chanotiya², Narayan Prasad Yadav¹

Affiliations

¹ Bio-prospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U. P., India.
² Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U. P., India.

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.

Keywords: PASI; imiquimod; lavender oil; linalool; linalyl acetate; psoriasis; synergistic activity; topical.