December 1, 2010

Mandom discovers that suppressing inflammation caused byultraviolet (UV) rays using “Paeonia extract” helps to brighten
the skin- A new lightening mechanism that focuses on sunburns caused by UV rays -Mandom Corporation (Head Office: Osaka, President Executive Officer: Motonobu Nishimura, hereafter“Mandom”), together with the Institute of Biomedical Research and Innovation, have been engaging in researchand development of highly fast-acting, lightening ingredients. We determined that sunburn, the trigger for skinpigmentation caused by UV radiation, is a key inflammatory response in the study of fast-acting ingredients.
Therefore, we performed a detailed analysis of this phenomenon at the molecular level. From this study, we foundthat the inflammatory molecule, CXCR3, is key to the elucidation of this fast-acting effect. We also revealed thatsuppressing CXCR3 and UV-induced sunburns by Paeonia extract subsequently suppresses skin pigmentation.
Paeonia extract was demonstrated to exert its lightening effect using a different mechanism than the lightening
ingredient, Vitamin C, which suppresses skin pigmentation by inhibiting the production of melanin following
sunburns.
Mandom will continue to examine the effects and sensation caused by Paeonia extract from the consumer's
point of view and foster technologies to aid in customer satisfaction.
The results of this research was presented at the “Asian Societies of Cosmetic Scientists (ASCS) Conference”
held in Seoul in 2011.
*Sunburn: An inflammatory reaction due to UV radiation that results in erythema.

1. Sunburn is a red light towards skin pigmentation
Most lightening agents, to date, have been discovered in studies that aimed to restore skin pigmentation
caused by UV rays, to the original color. At Mandom, we referred to the rules set for lightening agents “Preventspots and freckles due to sunburn.” Instead of preventing skin pigmentation caused by UV rays, preventing UVinduced damage at a far earlier stage would allow the development of a lightening agent that is far more fast-acting
than past agents (Figure 1). We, therefore, focused on sunburns that occur at an earlier stage than does skinpigmentation. As the skin affected by sunburns has local inflammation, inflammatory substances that trigger skinpigmentation may be present in these inflammation sites.
2. “Paeonia extract” suppresses the generation of inflammatory substances due to UV exposure
Mandom has examined hundreds of substances to find an ingredient that suppresses sunburns caused by UV.
Based on the search, “Paeonia extract” was discovered to be highly effective in suppressing sunburns. To elucidate
the inflammatory substances that are involved in the sunburn-suppressing effect of “Paeonia extract”, we performed
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-1-analyses using DNA microarray; several tens of candidate genes related to inflammatory responses were discovered.
After detailed analysis of each gene, the inflammatory molecule, CXCR3 (chemokine (C-X-C motif) receptor 3),
was observed to increase with UV radiation and was suppressed by the Paeonia extract. We also found that
reducing the level of CXCR3 resulted in a reduced level of melanin, the origin of pigmentation (Figure 2).
*DNA microarrays can be used to perform comprehensive analysis of approximately 20,000 genes in skin cells
irradiated with UV rays.
3. Lightening effect of “Paeonia extract”
We surmised that applying “Paeonia extract”, which suppresses the increase in CXCR3, to skin, would
suppress sunburn from UV rays and subsequently suppress pigmentation. Therefore, we evaluated the effects
exhibited by “Paeonia extract” against UV rays on human skin. “Paeonia extract” was found to suppress sunburns
from UV rays and elevate blood flow associated with sunburn (Figure 3). In addition, this extract significantly
suppressed subsequent skin pigmentation (Figure 4).
<<Mandom’s ideaof lightening
agent

Conventional lightening agent

Figure1. Concept of Mandom’s new lightening agent.

-2-Melanin level(Decrease leads to lightening effect)

Figure3. Suppression of inflammation
by “Paeonia extract.

Figure2. Lightening effect bysuppressing CXCR3.

Figure4. Lightening effect of “Paeonia extract.

-3-