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Punicalagin alleviates the hyperproliferation of keratinocytes in psoriasis through inhibiting SKP2 expression.
Tang, Lipeng; Zhang, Bowen; Li, Guanzhuo; Zhu, Ying; Feng, Bing; Su, Zuqing; Han, Wenhui; Huang, Huilin; Li, Qiuping; Wang, Maojie; Chen, Yuchao; Liu, Huazhen; Dai, Zhenhua; Wu, Dinghong; Li, Hongxia; Yang, Laijun; Lu, Yanjing; Ye, Zeting; Zheng, Guangjuan.
Afiliação
  • Tang L; State Key Laboratory of Dampness, Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510000, China.
  • Zhang B; Guangdong-Hong Kong-Macau Joint Lab On Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Li G; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Zhu Y; State Key Laboratory of Dampness, Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510000, China.
  • Feng B; Guangdong-Hong Kong-Macau Joint Lab On Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Su Z; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Han W; State Key Laboratory of Dampness, Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510000, China.
  • Huang H; Guangdong-Hong Kong-Macau Joint Lab On Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Li Q; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Wang M; Guangdong-Hong Kong-Macau Joint Lab On Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Chen Y; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Liu H; Guangdong-Hong Kong-Macau Joint Lab On Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Dai Z; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Wu D; Guangdong-Hong Kong-Macau Joint Lab On Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Li H; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Yang L; School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
  • Lu Y; School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510000, China.
  • Ye Z; School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510000, China.
  • Zheng G; Department of Rheumatology Clinical and Basic Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
J Nat Med ; 77(4): 712-720, 2023 Sep.
Article em En | MEDLINE | ID: mdl-37306932
Psoriasis is a chronic inflammatory skin disorder characterized by abnormal keratinocytes proliferation and multiple immune cells infiltration in the dermis and epidermis. Although most psoriasis-related researches have been concentrated on the interleukin-23 (IL-23)/interleukin-17 (IL-17) axis, new data suggest that keratinocytes also play a pivotal role in psoriasis. Previously, we found that punicalagin (PUN), a bioactive ellagitannin extracted from Pericarpium Granati (the pericarpium of Punica granatum L.), exerts a therapeutic effect on psoriasis. However, the underlying mechanism, especially its potential modulatory effect on keratinocytes, remains obscure. Our study aims to reveal the potential regulatory effect and its underlying cellular mechanism of PUN on the hyperproliferation of keratinocytes. We used tumor necrosis factor α (TNF-α), IL-17A and interleukin-6 (IL-6) to induce abnormal proliferation of HaCaT cells (Human Keratinocytes Cells) in vitro. Then, we evaluated the effects of PUN through MTT assay, EdU staining and cell cycle detection. Finally, we explored the underlying cellular mechanisms of PUN via RNA-sequencing, WB in vitro and in vivo. Here, we found that PUN can directly and dose-dependently decrease TNF-α, IL-17A and IL-6-induced abnormal proliferation of HaCaT cells in vitro. Mechanically, PUN suppresses the hyperproliferation of keratinocytes through repressing S-phase kinase-associated protein 2 (SKP2) expression in vitro and in vivo. Moreover, overexpression of SKP2 can partly abolish PUN-mediated inhibition of aberrantly proliferative keratinocytes. These results illustrate that PUN can reduce the severity of psoriasis through directly repressing SKP2-mediated abnormal proliferation of keratinocytes, which gives new insight into the therapeutic mechanism of PUN on psoriasis. Moreover, these findings imply that PUN might be a promising drug candidate for the treatment of psoriasis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Taninos Hidrolisáveis Idioma: En Revista: J Nat Med Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Psoríase / Taninos Hidrolisáveis Idioma: En Revista: J Nat Med Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China