Effective treatment for sensitive skin: 4-t-butylcyclohexanol and licochalcone A

J Eur Acad Dermatol Venereol. 2016 Feb;30 Suppl 1:9-17. doi: 10.1111/jdv.13529.


Background: More than 50% of adults report to suffer from sensitive skin. This common condition is characterized by subjective sensations such as prickling, burning, skin tightness or pruritus, and is often accompanied by objective symptoms like inflammation and erythema.

Objective: The objective of this study was to develop an active ingredient concept for the treatment of sensitive skin. We tested compounds regarding their potential to (i) decrease the release of proinflammatory mediators, which among others induce erythema and (ii) counteract the hyperresponsiveness of nerve fibres and, thus, exert effects on cutaneous neurosensory dysfunction.

Methods: 4-t-butylcyclohexanol, licochalcone A and acetyl dipeptide-1 cetyl ester were analysed in vitro regarding their potential to (i) decrease the release of PGE2 and activation of NFκB and to (ii) inhibit TRPV1 activation or the release of neuronal CGRP. To assess subjective and objective symptoms of skin sensitivity in vivo, two controlled, single-blind, randomized studies were conducted with 4-t-butylcyclohexanol and the combination with licochalcone A.

Results: In vitro, 4-t-butylcyclohexanol significantly reduced TRPV1 activation, while acetyl dipeptide-1 cetyl ester had no effect on receptor activation. Licochalcone A significantly decreased NFκB signalling and PGE2 secretion, at lower concentrations than acetyl dipeptide-1 cetyl ester. A formulation containing 4-t-butylcyclohexanol showed a significant immediate anti-stinging/anti-burning effect in vivo, and a cream base containing a combination of 4-t-butylcyclohexanol and a licochalcone A-rich licorice extract reduced shaving-induced erythema.

Conclusion: In vitro and in vivo data indicate that the combination of the TRPV1 antagonist 4-t-butylcyclohexanol and the potent anti-inflammatory licochalcone A provide an effective active ingredient concept for the treatment of sensitive skin, as the topical application resulted in an immediate relief from symptoms such as erythema and stinging.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Calcitonin Gene-Related Peptide / metabolism
  • Capsaicin / pharmacology
  • Cell Line
  • Chalcones / pharmacology
  • Chalcones / therapeutic use*
  • Cyclohexanols / pharmacology
  • Cyclohexanols / therapeutic use*
  • Dinoprostone / metabolism
  • Dipeptides / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Erythema / chemically induced
  • Erythema / drug therapy
  • Facial Dermatoses / chemically induced
  • Facial Dermatoses / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Pain / chemically induced
  • Pain / drug therapy*
  • Sensation Disorders / chemically induced
  • Sensation Disorders / drug therapy*
  • Signal Transduction / drug effects
  • Single-Blind Method
  • Skin Cream / therapeutic use
  • Swine
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / metabolism
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Chalcones
  • Cyclohexanols
  • Dipeptides
  • Drug Combinations
  • NF-kappa B
  • TRPV Cation Channels
  • acetyltyrosyl-arginine cetyl ester
  • Calcitonin Gene-Related Peptide
  • licochalcone A
  • 4-tert-butylcyclohexanol
  • Dinoprostone
  • Capsaicin