PMID- 28052368
OWN - NLM
STAT- MEDLINE
DCOM- 20171013
LR  - 20181113
IS  - 1365-2230 (Electronic)
IS  - 0307-6938 (Print)
IS  - 0307-6938 (Linking)
VI  - 42
IP  - 3
DP  - 2017 Apr
TI  - Synthesis and activity of the salicylic acid ester of bakuchiol in 
      psoriasis-surrogate keratinocytes and skin substitutes.
PG  - 251-260
LID - 10.1111/ced.13024 [doi]
AB  - BACKGROUND: Topical retinoids are effective in retarding skin ageing and 
      restoring homeostasis in skin conditions such as psoriasis. However their adverse 
      effects (AEs), which include irritation (retinoid dermatitis), photosensitivity 
      and teratogenicity, limit their use and patient compliance. Development of 
      retinoid analogues with minimal AEs would allow a broader and more compliant use. 
      AIM: To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a 
      modulatory gene expression profile similar to retinoids, using as reference three 
      prescription retinoids: tretinoin, tazarotene and adapalene. METHODS: We 
      hypothesized that because bakuchiol salicylate has a structure entirely different 
      from existing retinoids, there would be at least a partial uncoupling of AEs from 
      the skin-normalizing activity of this retinoid. This hypothesis was tested at the 
      transcriptional level in psoriatic cytokine-treated cultures of keratinocytes and 
      organotypic skin substitutes, using DNA microarrays and custom PCR arrays. 
      RESULTS: Evaluation of the gene expression profile of bakuchiol salicylate 
      revealed elimination of several components of the retinoid-like proinflammatory 
      response and teratogenic signature, without a substantial loss of normalizing 
      potential. A possible mechanism of action, consisting of keratinocyte 
      desensitization to psoriatic cytokine signalling through inhibition of the signal 
      transducer and regulator of transcription (STAT)1/3/interferon inflammatory 
      signal transduction axis was also identified. CONCLUSION: Bipartite materials 
      obtained by merging two skin-active entities with specific, complementary 
      bioactivities, such as bakuchiol and salicylic acid, may yield a new class of 
      functional retinoids.
CI  - (c) 2017 British Association of Dermatologists.
FAU - Ma, S
AU  - Ma S
AD  - Sunny BioDiscovery, Inc., Santa Paula, CA, USA.
FAU - Gobis, K
AU  - Gobis K
AD  - Department of Organic Chemistry, Medical University of Gdansk, Gdansk, Poland.
FAU - Swindell, W R
AU  - Swindell WR
AD  - University of Ohio, Athens, OH, USA.
FAU - Chaudhuri, R
AU  - Chaudhuri R
AD  - Sytheon, Boonton, NJ, USA.
FAU - Bojanowski, R
AU  - Bojanowski R
AD  - Sunny BioDiscovery, Inc., Santa Paula, CA, USA.
AD  - Polish Academy of Sciences, Institute of Oceanology, Sopot, Poland.
FAU - Bojanowski, K
AU  - Bojanowski K
AD  - Sunny BioDiscovery, Inc., Santa Paula, CA, USA.
LA  - eng
GR  - R43 AR062935/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20170104
PL  - England
TA  - Clin Exp Dermatol
JT  - Clinical and experimental dermatology
JID - 7606847
RN  - 0 (Cytokines)
RN  - 0 (Phenols)
RN  - 0 (Retinoids)
RN  - 0 (Salicylates)
RN  - OT12HJU3AR (bakuchiol)
SB  - IM
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Humans
MH  - Keratinocytes/*drug effects/metabolism
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Phenols/chemical synthesis/*chemistry/pharmacology
MH  - Polymerase Chain Reaction/methods
MH  - Psoriasis/*drug therapy/genetics
MH  - Retinoids/adverse effects
MH  - Salicylates/chemical synthesis/*chemistry/pharmacology
MH  - Skin, Artificial
PMC - PMC5600152
MID - NIHMS828611
EDAT- 2017/01/05 06:00
MHDA- 2017/10/14 06:00
PMCR- 2018/04/01
CRDT- 2017/01/05 06:00
PHST- 2016/03/31 00:00 [accepted]
PHST- 2017/01/05 06:00 [pubmed]
PHST- 2017/10/14 06:00 [medline]
PHST- 2017/01/05 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - 10.1111/ced.13024 [doi]
PST - ppublish
SO  - Clin Exp Dermatol. 2017 Apr;42(3):251-260. doi: 10.1111/ced.13024. Epub 2017 Jan 
      4.