Ingredient research cosmetics "Tvert"'s joint research receives Excellent Presentation Award at the 26th Annual Meeting of the Japanese Society of Anti-Aging Medicine

Tvert (Headquarters: Minoh City, Osaka Prefecture / Representative: Yu Komatsu), a cosmetics manufacturer dedicated to ingredient research, is pleased to announce that its joint research with Professor Genji Imokawa, specially appointed professor at the Utsunomiya University Center for Education and Research in Bioscience, has received the "Excellent Presentation Award" at the 26th Annual Meeting of the Japanese Society of Anti-Aging Medicine (June 26-28, 2026 / Pacifico Yokohama North). This research revealed that "nobiletin," a polyphenol abundant in citrus fruits, suppresses the intracellular "signals" that increase the enzyme "neprilysin (NPL)," which is implicated in wrinkle formation, thereby preventing the increase of NPL itself. Nobiletin's characteristic is not to directly target the enzyme, but to cut off the "increase switch" upstream, demonstrating the potential for a new anti-wrinkle approach through topical application to the skin.

Award Summary

Society: The 26th Annual Meeting of the Japanese Society of Anti-Aging Medicine

Dates: June 26 (Fri) - 28 (Sun), 2026

Venue: Pacifico Yokohama North (Yokohama City, Kanagawa Prefecture)

Award: Excellent Presentation Award

Presentation Title: Nobiletin Suppresses Intracellular Signal Transduction Involved in the Upregulation of Wrinkle Formation Enzyme Neprilysin Expression in Dermal Fibroblasts

Presenters: Mariko Takada1, Naomi Asano1, Shinichi Hirano2, Yu Komatsu2, Genji Imokawa1 (First Presenter: Mariko Takada) Affiliations: 1 Utsunomiya University Center for Education and Research in Bioscience, 2 Tvert Co., Ltd.

Background of the Research | Why Do Wrinkles Form?

Skin elasticity is supported by spring-like fibers called "elastin" in the dermis. However, when exposed to ultraviolet (UVB) rays, the mechanism that supports this elasticity is gradually broken down. Specifically, epidermal cells exposed to UV rays release an inflammatory substance called "IL-1α (Interleukin-1α)." When this reaches "fibroblast cells" in the dermis, the enzyme "neprilysin (NPL)," which breaks down elastin, increases. It is thought that NPL cleaves elastin, leading to a loss of elasticity and the formation of wrinkles. The research group has previously revealed that NPL is deeply involved in wrinkle formation and that the main trigger for increasing NPL is IL-1α. This study investigated whether a component could be found to suppress this "increase mechanism."

Mechanism of Wrinkle Formation

This Discovery | Nobiletin Suppresses the "Switch that Increases Wrinkle Enzyme"

Through a series of experiments using human dermal fibroblast cells, this research has clarified the following:

Identified the pathway that increases NPL: The increase in NPL by IL-1α was suppressed by inhibiting two signaling pathways, the "ERK pathway" and the "JNK pathway," and by blocking the action of "c-Fos." This reconfirmed the flow from IL-1α → ERK/JNK → c-Jun/c-Fos → AP-1 → increase in NPL.

Nobiletin blocks this pathway: "Nobiletin," a polyphenol derived from citrus fruits, significantly suppressed the activation (phosphorylation) of JNK, ERK, and c-Jun induced by IL-1α stimulation, and consequently significantly suppressed the increase in NPL expression and activity.

"Cutting off the signal" rather than "directly targeting" the enzyme: On the other hand, nobiletin showed no direct inhibitory effect on the enzyme NPL itself. In other words, nobiletin is thought to work by cutting off the "signal" that increases NPL, rather than directly inhibiting NPL.

This mechanism of suppressing the signal upstream is a new concept that rationally approaches the root cause of wrinkles and shows potential as an anti-wrinkle strategy through topical application to the skin.

Mechanism by which Nobiletin Blocks the Signal

Significance of the Research | A New Concept for Anti-Wrinkle Care with Citrus-Derived Ingredients

Nobiletin is a familiar plant-derived polyphenol found abundantly in the peel of citrus fruits such as mandarins. This finding, that the component suppresses the "entry signal" that increases enzymes involved in wrinkles, adds a new perspective to material research for wrinkle countermeasures. Tvert will continue to engage in research and development of ingredients and formulations based on the "mechanisms" of skin concerns, drawing on such basic research findings.

*This research is a basic study that investigated the mechanism of wrinkle formation and the action of components involved in its control. It represents findings at the research stage and does not guarantee or claim the efficacy of any specific product.

Glossary

Nobiletin: A flavonoid (a type of polyphenol) found abundantly in the peel of citrus fruits such as mandarins.

Neprilysin (NPL): An enzyme (a type of elastase) that breaks down elastin, located on the surface of dermal fibroblast cell membranes.

Elastin: A rubber-like, elastic fiber that supports skin elasticity.

Fibroblast cells: Cells in the dermis that produce elastin and collagen.

IL-1α: An inflammatory substance (cytokine) released by epidermal cells exposed to UV rays.

ERK pathway / JNK pathway: Representative signaling pathways (MAP kinases) that transmit information within cells. "Phosphorylation" is a reaction that serves as a marker when these pathways are activated.

c-Fos / c-Jun / AP-1: c-Fos and c-Jun bind to form the transcription factor AP-1, which acts as a switch to turn on gene expression.

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