98 ANTI-AGEING
The inhibition of HDAC in cells can reduce inflammation.43,44
Intervention with HDAC
inhibitors (HDACi) has been shown to be anti- inflammatory for the skin and support beneficial outcomes in atopic dermatitis, psoriasis, vitiligo, and wound healing.45-48 The dual botanical extract is a multifaceted
HDACi in skin cells (Figure 6). The dual botanical extract inhibits HDAC activity dose-dependently (Figure 6B). Additionally, the dual botanical extract acts epigenetically to reduce the expression of HDAC genes by upregulating seven HDAC- targeting miRNAs in the skin (Figure 5B). Concurrently, the expression of 16 genes, including three genes with protective effects against oxidative and proteolytic stress, aryl hydrocarbon receptor (AHR), a superoxide dismutase (SOD2), and a metalloproteinase inhibitor (TIMP1) are elevated in model skin tissues treated with the dual botanical extract (Figure 6C). These findings further support the ability of the dual botanical extract to increase gene expression by maintaining beneficial histone acetylation.
Inflammation The exposome can exacerbate common inflammatory skin disorders, especially atopic dermatitis and psoriasis. Skin inflammation contributes to ageing through tissue damage and is a major component of senescence initiation and SASP. The dual botanical extract directly inhibits
the production of inflammatory factors in keratinocytes. Specifically, the dual botanical extract inhibits the production of a colony- stimulating factor (M-CSF), a macrophage inflammatory protein (MIP-1β), a monocyte chemoattract protein (MCP-1), and a chemokine (IP10) (Figure 7A). Remarkably, 0.001% of the dual botanical extract reduced each of these inflammatory cytokines by at least 50% compared to untreated controls. Furthermore, the dual botanical extract also
inhibits phospholipase 2 (PLA2), an enzyme responsible for pro-inflammatory eicosanoid production in the skin, in a dose-dependent manner.49
inflammatory factors are established SASP proteins,12,50
extract helps mitigate damage and the propagation of senescence in the skin.
Oxidative stress UV radiation in sunlight directly triggers the
A
100 75 50 25 0
** ** * ** **
Notably, all of the aforementioned suggesting that the dual botanical
A
B
100 75 50 25 0
Induction of histone deacetylation
(HDAC) with the dual botanical extract **p<0.01 **
** ** ** **
C
type VII collagen DCN
decorin fibronectin
FBN1 fibrillin FN1
Concentration of the dual botanical extract (%) 0.2
0.5 1.0 2.0
Trichostatin A + control
metalloproteinase 2
MMP2 matrix
metalloproteinase 9
MMP9 matrix
SERPINH1 serpin
peroxisome prolif. activated receptor
Hyaluronansynthase PPARG
versican HAS2
VCAN
aryl hydrocarbonreceptor SOD2
AHR
superoxide dismutase
MMP inhibitor 1 TIMP1
0% 200% 100%
Gene Expression 600% 800% 1000%
400% Figure 6: The dual botanical extract inhibits HDACs and elevates gene expression
oxidation of lipids in the skin, undermining the proper function of cellular membranes. In addition, the breakdown products of oxidized lipids are toxic, inflicting damage upon other cellular constituents, including proteins and DNA. The dual botanical extract helps to reduce
oxidative stress in the skin. Specifically, the dual botanical extract acts dose-dependently to inhibit UV-induced lipid oxidation, with a 0.50% use level demonstrating 99% antioxidant activity (Figure 7B). The dual botanical extract is also an effective scavenger of singlet oxygen (data not shown).
0.0001% ■ 0.001% ■ 0.01% ■
Induction of inflammatory cytokines with the dual botanical extract ***
*** ***
*p<0.05 **p<0.01
** B
100 75 50 25 0
M-CSF IP-10 MIP-1β MCP-1
0.05 Concentration of dual botanical extract (%)
0.10 Figure 7: The dual botanical extract combats exposome-induced inflammatory and oxidative stress PERSONAL CARE March 2024
www.personalcaremagazine.com 0.20 0.50
Conclusion Our expanding knowledge of how the exposome accelerates skin ageing through senescence, epigenetic dysfunction, and inflammatory and oxidative stresses supports the development of multifunctional anti- ageing skincare ingredients. As a demonstrated epigenetic modulator, DermalRx Acetygen offers exposomal protection and repair to maintain resilient, youthful skin.
References to this article are available at:
https://bit.ly/3OpzlvF
Inhibition of UV-induced lipid oxidation with the dual botanical extract
type IV collagen COL7A1
type III collagen COL4A2
type I collagen COL3A1
COL1A1
Regulation of gene expression with the dual botanical extract
PC
Inhibition (%)
Inhibition (%)
Antioxidant activity (%)
Protection
Hydration & plumping
ECM synthesis & support
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