PMID- 38367463 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20240325 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 130 DP - 2024 Mar 30 TI - Punicalagin from pomegranate ameliorates TNF-alpha/IFN-gamma-induced inflammatory responses in HaCaT cells via regulation of SIRT1/STAT3 axis and Nrf2/HO-1 signaling pathway. PG - 111665 LID - S1567-5769(24)00183-8 [pii] LID - 10.1016/j.intimp.2024.111665 [doi] AB - Punicalagin (PUN) was isolated from the peel of pomegranate (Punica granatum L.), is a polyphenol with anti-inflammatory, hepatoprotective, and antioxidant activities. However, it remains unclear whether PUN alleviates the inflammation and anti-inflammatory mechanisms in pro-inflammatory cytokines-induced human keratinocyte HaCaT cells. Here, we investigated that tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mixture-stimulated HaCaT cells were treated with various concentrations of PUN, followed by analyzed the expression of inflammation-related mediators and evaluate anti-inflammatory-related pathways. Our results demonstrated that PUN /= 3 muM was sufficient to decrease interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 5 (CCL5), CCL17 and CCL20 concentrations. We found that PUN >/= 10 muM and >/= 3 muM significantly increased sirtuin 1 (SIRT1) expression and inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. PUN downregulated inflammation-related proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), enhanced nuclear factor erythroid-2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, PUN decreased intercellular adhesion molecule-1 (ICAM-1) expression and inhibited monocyte adhesion to inflamed HaCaT cells. PUN also suppressed inflammatory-related pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) signaling pathways in TNF-alpha/IFN-gamma- stimulated HaCat cells. Collectively, there is significant evidence that PUN has effective protective defenses against TNF-alpha/IFN-gamma-induced skin inflammation by enhancing SIRT1 to mediate STAT3 and Nrf2/HO-1 signaling pathway. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Huang, Wen-Chung AU - Huang WC AD - Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City 33303, Taiwan, ROC; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan, ROC. FAU - Liou, Chian-Jiun AU - Liou CJ AD - Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taoyuan City 33303, Taiwan, ROC; Department of Nursing, Division of Basic Medical Sciences, Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan City 33303, Taiwan, ROC. FAU - Shen, Szu-Chuan AU - Shen SC AD - Graduate Program of Nutrition Science, National Taiwan Normal University, 88 Ting-Chow Rd, Sec 4, Taipei 11677, Taiwan, ROC. FAU - Hu, Sindy AU - Hu S AD - Department of Cosmetic Science, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan, ROC; Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, ROC. FAU - Chao, Jane C-J AU - Chao JC AD - School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan, ROC. FAU - Huang, Chun-Hsun AU - Huang CH AD - Department of Cosmetic Science, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan, ROC; Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, ROC. FAU - Wu, Shu-Ju AU - Wu SJ AD - Department of Dermatology, Aesthetic Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, ROC; Department of Nutrition and Health Sciences, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan, ROC. Electronic address: sjwu@mail.cgust.edu.tw. LA - eng PT - Journal Article DEP - 20240216 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.5.1.- (Sirtuin 1) RN - 82115-62-6 (Interferon-gamma) RN - 65995-63-3 (punicalagin) RN - 0 (NF-E2-Related Factor 2) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - 0 (STAT3 Transcription Factor) RN - 0 (NF-kappa B) RN - 0 (Anti-Inflammatory Agents) RN - EC 3.5.1.- (SIRT1 protein, human) RN - 0 (STAT3 protein, human) RN - 0 (Hydrolyzable Tannins) SB - IM MH - Humans MH - *Tumor Necrosis Factor-alpha/metabolism MH - Sirtuin 1/metabolism MH - Interferon-gamma/metabolism MH - *Pomegranate/metabolism MH - NF-E2-Related Factor 2/metabolism MH - Heme Oxygenase-1/metabolism MH - HaCaT Cells MH - STAT3 Transcription Factor/metabolism MH - Signal Transduction MH - NF-kappa B/metabolism MH - Anti-Inflammatory Agents/therapeutic use MH - Inflammation/metabolism MH - *Hydrolyzable Tannins OTO - NOTNLM OT - HaCaT cells OT - MAPKs OT - NF-kappaB OT - Nrf2/HO-1 OT - Punicalagin OT - SIRT1/STAT3 axis COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/18 00:42 MHDA- 2024/03/25 06:43 CRDT- 2024/02/17 18:09 PHST- 2023/10/24 00:00 [received] PHST- 2024/01/29 00:00 [revised] PHST- 2024/02/05 00:00 [accepted] PHST- 2024/03/25 06:43 [medline] PHST- 2024/02/18 00:42 [pubmed] PHST- 2024/02/17 18:09 [entrez] AID - S1567-5769(24)00183-8 [pii] AID - 10.1016/j.intimp.2024.111665 [doi] PST - ppublish SO - Int Immunopharmacol. 2024 Mar 30;130:111665. doi: 10.1016/j.intimp.2024.111665. Epub 2024 Feb 16.