Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes
Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects hig...
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2025-07-01
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| author | Anna Arai Takahiro Oyama Toyoaki Nakajima Michiru Usui Ena Sato Takanori Kamiya Midori Oyama Takashi Tanikawa Tomoharu Takeuchi Takehiko Abe Tomomi Hatanaka |
| author_facet | Anna Arai Takahiro Oyama Toyoaki Nakajima Michiru Usui Ena Sato Takanori Kamiya Midori Oyama Takashi Tanikawa Tomoharu Takeuchi Takehiko Abe Tomomi Hatanaka |
| author_sort | Anna Arai |
| collection | DOAJ |
| description | Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects highlight the need for novel therapeutic agents. We previously observed that <i>Morus alba</i> extract (MAE) suppressed IL-17-induced <i>CCL20</i> mRNA expression in normal human epidermal keratinocytes (NHEKs). In this study, we focused on the IL-17 signaling pathway and investigated the effects of pentacyclic triterpenoids, betulinic acid (BA), and ursolic acid (UA), which are present in MAE, on NHEK cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that both BA and UA suppressed CCL20 expression, while only UA alone inhibited CCL20 release. ELISA using specific inhibitors demonstrated that both the p38 and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways were crucial for IL-17-induced CCL20 release in NHEK. UA effectively suppressed ERK1/2 nuclear localization and moderately affected p38 phosphorylation. These results indicated that UA is a potential seed compound for psoriasis treatment through its targeting of the IL-17 pathway. |
| format | Article |
| id | doaj-art-16e1e2e8c9144021be06b67494fb6cc5 |
| institution | Kabale University |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj-art-16e1e2e8c9144021be06b67494fb6cc52025-08-20T03:36:18ZengMDPI AGLife2075-17292025-07-01157107310.3390/life15071073Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal KeratinocytesAnna Arai0Takahiro Oyama1Toyoaki Nakajima2Michiru Usui3Ena Sato4Takanori Kamiya5Midori Oyama6Takashi Tanikawa7Tomoharu Takeuchi8Takehiko Abe9Tomomi Hatanaka10Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, JapanHinoki Shinyaku Co., Ltd., 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, JapanHinoki Shinyaku Co., Ltd., 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, JapanHinoki Shinyaku Co., Ltd., 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, JapanHinoki Shinyaku Co., Ltd., 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, JapanSchool of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Aichi, JapanHinoki Shinyaku Co., Ltd., 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, JapanPsoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects highlight the need for novel therapeutic agents. We previously observed that <i>Morus alba</i> extract (MAE) suppressed IL-17-induced <i>CCL20</i> mRNA expression in normal human epidermal keratinocytes (NHEKs). In this study, we focused on the IL-17 signaling pathway and investigated the effects of pentacyclic triterpenoids, betulinic acid (BA), and ursolic acid (UA), which are present in MAE, on NHEK cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that both BA and UA suppressed CCL20 expression, while only UA alone inhibited CCL20 release. ELISA using specific inhibitors demonstrated that both the p38 and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways were crucial for IL-17-induced CCL20 release in NHEK. UA effectively suppressed ERK1/2 nuclear localization and moderately affected p38 phosphorylation. These results indicated that UA is a potential seed compound for psoriasis treatment through its targeting of the IL-17 pathway.https://www.mdpi.com/2075-1729/15/7/1073psoriasisepidermal keratinocytebetulinic acidursolic acidinterleukin 17C-C motif chemokine ligand 20 |
| spellingShingle | Anna Arai Takahiro Oyama Toyoaki Nakajima Michiru Usui Ena Sato Takanori Kamiya Midori Oyama Takashi Tanikawa Tomoharu Takeuchi Takehiko Abe Tomomi Hatanaka Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes Life psoriasis epidermal keratinocyte betulinic acid ursolic acid interleukin 17 C-C motif chemokine ligand 20 |
| title | Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes |
| title_full | Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes |
| title_fullStr | Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes |
| title_full_unstemmed | Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes |
| title_short | Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes |
| title_sort | effects of betulinic acid and ursolic acid on il 17 induced ccl20 release in normal human epidermal keratinocytes |
| topic | psoriasis epidermal keratinocyte betulinic acid ursolic acid interleukin 17 C-C motif chemokine ligand 20 |
| url | https://www.mdpi.com/2075-1729/15/7/1073 |
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