20年前, 私たちは, 皮膚において温度や化粧品による刺激感覚が同じ分子によって感知されているとは想像もしていなかった。1997年, TRPV1というイオンチャネルが, 熱だけでなくカプサイシンに反応することが発見され, 皮膚感覚の理解が一変した。われわれは, 2003年に発見されたTRPA1が, さまざまな成分による刺激感覚と関係していることを明らかにしてきた。今回, 化粧品への応用例も含めて紹介する。

加齢に伴いさまざまな組織でL-アスパラギン酸 (L-Asp) の異性体を含むタンパク質の蓄積が確認されている。L-Asp残基の異性化はタンパク質の立体構造を変化させ, 異常凝集の引き金となる。皮膚においても, 加齢に伴い特に露光部の真皮中層で異性化したAsp残基を含むタンパク質の蓄積が確認されている。生体内にはタンパク質中のL-イソアスパラギン酸 (L-isoAsp) およびD-アスパラギン酸 (D-Asp) 残基にメチル基を導入し, L-Asp残基への修復を促進する酵素Protein L-isoaspartyl／D-aspartyl O-methyltransferase (PIMT) が存在するが, 皮膚でのPIMTの存在や作用についてはほとんど報告がない。本研究では, PIMTが皮膚線維芽細胞に発現しているが, 加齢やUVB曝露によりPIMT量が低下することを明らかにした。またPIMT量の低下はL-isoAsp残基を含むタンパク質の蓄積を引き起こした。UVB曝露によるPIMT量の低下に対して, 赤ワイン抽出物およびシラカバ樹皮抽出物が抑制あるいは回復する作用を有することを確認した。以上から, 皮膚においてPIMTはL-isoAsp残基を含む変性タンパク質の蓄積を抑制する作用を有することが考えられた。また, 赤ワイン抽出物およびシラカバ樹皮抽出物はPIMT量を維持することで皮膚の老化症状の抑制に有効だと示唆された。

In the past, skincare products have only focused on the function of caring for the skin. In practical use, however, base makeup products such as foundations are applied on dried cosmetic films of skincare products. Generally speaking, in order to obtain a natural finish, the foundations should be applied evenly. Hence, we aimed to develop new formulations of skincare products which have excellent compatibility with makeup foundations. Silicone surfactants provide a lower surface tension than hydrocarbon surfactants. Due to this low surface tension, excellent spreading capacity and skin compatibility are thought to be obtainable. We reported a novel silicone surfactant, 3-(10-carboxydecyl)-1,1,1,3,5,5,5-heptamethyl trisiloxane (CDTS) and found an α-form hydrated crystalline phase (often referred to as “α-gel,” especially in the cosmetics field), composed of CDTS, polyoxyethylen (e 5 mol) glyceryl monostearate (GMS-5), fatty alcohol, and water. In this study, we first investigated the fundamental physical properties of CDTS. The water solubility of CDTS is quite low (ca. 17 μmol/L) and its approximate pK_a is 5.7 at 20 ºC. Titration curves also indicated that CDTS is a weak acid. We observed a microemulsion (ME) phase containing CDTS, GMS-5, fatty alcohol, dimethicone, and hydrogenated polydecene. A novel fine nanoemulsion, whose diameter was less than 100 nm, was obtained by the dilution of the microemulsion phase with the water phase. The obtained fine emulsion was applied for tribology tests. Tribological characteristics indicated that the fine emulsion containing the CDTS α-form hydrated crystal is superior to conventional fine emulsions composed of polyoxyethylene 60 mol hydrogenated castor oil, from the viewpoint of low friction at application. Moreover, powder foundation could be applied evenly on the dried cosmetic film of fine emulsions containing CDTS.

In order to prevent photoaging and to provide a younger impression of appearance, the composite powder was examined for its year-round UV-A protection effect and for improvement of skin color by its make-up effect. However, in recent years, many limitations have been imposed on the use of powders, including fine titanium dioxide and zinc oxide, in consideration of issues such as nanoparticles, dissolution into water and scattering into air. In addition, organic UV protection agents also have restrictions on their use due to their irritation and environmental risks. From the above background, iron oxides and titanium dioxide were fixed on the sericite surface by combining the original pulverizing and dispersion processes with bead mill and the spray-drying process. As a coated particle, titanium dioxide could be used as a UV-B protective material, and the pulverized iron oxides could be used as UV-A protective materials. The obtained composite powder was capable of protecting against ultraviolet rays in a wide range from UV-A to UV-B. In addition, it was confirmed that this composite powder had a reddish high chroma tone, and the powder foundation containing this composite powder gave a healthy impression of appearance. Therefore, the prepared composite powder that possesses these functions is thought to be a useful material with defensive and improvement effects on senior skin.

Human skin is influenced by ultraviolet-B (UV-B) irradiation. UV-B induces DNA damage and mitochondrial damage in epidermal keratinocytes； then accumulation of excessive DNA damage and damaged mitochondria finally leads to apoptosis. Recently, we investigated effective means to repair or to eliminate fatal damage leading to excessive apoptosis in UV-B-exposed normal human epidermal keratinocytes (NHEKs) . Concerning repair of DNA damage, we previously established a method for measuring activity of cellular DNA polymerase (pol) which synthesizes DNA strands in the repair system in NHEKs, and found that Rhodomyrtus tomentosa fruit extract, which has properties to protect epidermal keratinocytes from UV-B-induced apoptosis, enhanced activity of pol in UV-B-irradiated NHEKs. With regard to repair and elimination of mitochondrial damage, we focused on mitophagy, which is the cellular function to remove dysfunctional mitochondria by autophagy. In the present study, we detected mitophagy and evaluated mitochondrial reductase activity providing an indication of cell viability in UV-B-irradiated NHEKs. As a result of evaluating the influence of UV-B irradiation on mitophagy in NHEKs, we observed that mitophagy became weak after irradiation with 40 mJ/cm² UV-B. In addition, mitochondrial reductase activity also decreased at 24 h after irradiation. Following these results, we also found that Rhodomyrtus tomentosa fruit extract suppressed the UV-B-induced decrease in mitophagy and in mitochondrial reductase activity. Furthermore, we investigated influence of UV-B irradiation and effect of the extract on mitochondrial membrane potential in NHEKs to elucidate the mechanisms of modulating mitophagy. The results showed that the extract retained normal function of mitophagy by decreasing mitochondrial membrane potential in advance. In conclusion, it was suggested that the enhancement of inherent cellular DNA repair properties and the efficient elimination of the mitochondrial damage are essential for protecting the epidermal keratinocytes from UV-B-induced excessive apoptosis.

われわれはこれまでに年齢とともに増加しやすい肌のくすみがカリクレイン (KLK)-5の活性を促す製剤の使用で軽減することを明らかにしてきた。今回, KLK-5と類似した表皮剥離作用を示すKLK-7に着目, その活性増加を介して肌くすみを軽減させることが可能か否か, 植物抽出物を活用して見出すことを目的として検討した。まず, 培養表皮角化細胞のKLK-7遺伝子発現量, 細胞増殖作用を指標として有効な植物抽出物を探索, その結果, ローズマリー抽出物による有意な増加がそれぞれ認められた。次に, 同抽出物配合化粧水を用いたヒト連用試験の結果, ヒト角層KLK-7活性の増加傾向, 角層細胞面積の有意な減少が認められ, 被験者が感じる肌くすみ, ごわつきは減少, 特に女性被験者でより減少した。以上より, ローズマリー抽出物は表皮細胞の増殖に加えて角層剥離を緩やかに促すことで表皮ターンオーバーを維持しつつ肌くすみを軽減させる可能性が示唆された。

糖類は生命活動において不可欠な栄養素であるが, 糖化反応によって生体内のタンパク質が架橋形成されると立体構造が変化し, その活性や物性に多大な影響を及ぼすことがしられている。皮膚ではコラーゲンやエラスチンなどの半減期が長いタンパク質が糖化による影響を受けやすく, 褐変化して糖化最終生成物 (advanced glycation end products; AGEs) が蓄積し, シワやクスミの増加, 弾力の低下や乾燥などの老化現象が引き起こされる。本研究では, 糖化が表皮機能に及ぼす影響に着目し検討したところ, 糖化したコラーゲンあるいは基底膜抽出物上で培養した表皮角化細胞ではATP 産生量の減少, 表皮機能の維持に重要なフィラグリン, セリンパルミトイルトランスフェラーゼ2 およびトランスグルタミナーゼ1 の発現低下が認められ, ワイルドタイムエキスに, これらの表皮機能低下を防御する作用が認められたので報告する。