TY - JOUR
T1 - A standardized Terminalia chebula fruit extract alters the expression of genes associated with skin architecture and barrier formation
AU - Swindell, William R.
AU - Bojanowski, Krzysztof
AU - Chaudhuri, Ratan K.
N1 - Funding Information:
Acknowledgements: we thank Stephanie Ma, Pedro Corona, Jakub Smoczynski (Sunny Biodiscovery, Santa Paula, CA), Tony Chang and Marsha Sintara (International Chemistry Testing, Milford, MA) for excellent technical assistance in carrying out experiments. Financial support: these studies were funded by Sytheon Ltd (Boonton, NJ). Conflicts of interest: the standardized TC extract analyzed in this study (Synastol® TC) was developed and patented by Sytheon Ltd (Boonton, NJ). RKC is president and CEO of Sytheon with ownership interest. KB is chief executive officer of Sunny BioDiscovery, Inc. (Santa Paula, CA) and has received consulting reimbursement from Sytheon. WRS has received consulting reimbursement from Sytheon.
Publisher Copyright:
© 2020, JLE/Springer.
PY - 2020/9
Y1 - 2020/9
N2 - Background: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear. Objective: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (Synastol® TC). Materials and Methods: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures. Results: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes. Conclusion: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.
AB - Background: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear. Objective: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (Synastol® TC). Materials and Methods: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures. Results: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes. Conclusion: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.
KW - extracellular matrix
KW - keratinocyte
KW - skin aging
KW - Terminalia chebula
KW - wound healing
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U2 - 10.1684/ejd.2020.3882
DO - 10.1684/ejd.2020.3882
M3 - Article
C2 - 33021480
AN - SCOPUS:85096202901
SN - 1167-1122
VL - 30
SP - 469
EP - 492
JO - European Journal of Dermatology
JF - European Journal of Dermatology
IS - 5
ER -