PMID- 35008862 OWN - NLM STAT- MEDLINE DCOM- 20220203 LR - 20220203 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 1 DP - 2021 Dec 31 TI - Anti-Inflammatory, Antioxidant, Moisturizing, and Antimelanogenesis Effects of Quercetin 3-O-beta-D-Glucuronide in Human Keratinocytes and Melanoma Cells via Activation of NF-kappaB and AP-1 Pathways. LID - 10.3390/ijms23010433 [doi] LID - 433 AB - Quercetin 3-O-beta-D-glucuronide (Q-3-G), the glucuronide conjugate of quercetin, has been reported as having anti-inflammatory properties in the lipopolysaccharide-stimulated macrophages, as well as anticancer and antioxidant properties. Unlike quercetin, which has been extensively described to possess a wide range of pharmacological activities including skin protective effects, the pharmacological benefits and mechanisms Q-3-G in the skin remained to be elucidated. This study focused on characterizing the skin protective properties, including anti-inflammatory and antioxidant properties, of Q-3-G against UVB-induced or H(2)O(2)-induced oxidative stress, the hydration effects, and antimelanogenesis activities using human keratinocytes (HaCaT) and melanoma (B16F10) cells. Q-3-G down-regulated the expression of the pro-inflammatory gene and cytokine such as cyclooxygenase-2 (COX-2) and tumor necrosis factor (TNF)-alpha in H(2)O(2) or UVB-irradiated HaCaT cells. We also showed that Q-3-G exhibits an antioxidant effect using free radical scavenging assays, flow cytometry, and an increased expression of nuclear factor erythroid 2- related factor 2 (Nrf2). Q-3-G reduced melanin production in alpha-melanocyte-stimulating hormone (alpha-MSH)-induced B16F10 cells. The hydration effects and mechanisms of Q-3-G were examined by evaluating the moisturizing factor-related genes, such as transglutaminase-1 (TGM-1), filaggrin (FLG), and hyaluronic acid synthase (HAS)-1. In addition, Q-3-G increased the phosphorylation of c-Jun, Jun N-terminal kinase (JNK), Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and TAK1, involved in the MAPKs/AP-1 pathway, and the phosphorylation of IkappaBalpha, IkappaB kinase (IKK)-alpha, Akt, and Src, involved in the NF-kappaB pathway. Taken together, we have demonstrated that Q-3-G exerts anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis properties in human keratinocytes and melanoma cells through NF-kappaB and AP-1 pathways. FAU - Ha, Anh Thu AU - Ha AT AD - Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. FAU - Rahmawati, Laily AU - Rahmawati L AUID- ORCID: 0000-0002-7977-1814 AD - Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. FAU - You, Long AU - You L AUID- ORCID: 0000-0001-6978-0066 AD - Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. FAU - Hossain, Mohammad Amjad AU - Hossain MA AUID- ORCID: 0000-0001-8941-1065 AD - Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Korea. FAU - Kim, Jong-Hoon AU - Kim JH AD - Department of Veterinary Physiology, College of Medicine, Chonbuk National University, Iksan 54596, Korea. FAU - Cho, Jae Youl AU - Cho JY AUID- ORCID: 0000-0001-8141-9927 AD - Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea. AD - Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. LA - eng GR - 20008861/the Ministry of Trade, Industry, and Energy of Korea/ PT - Journal Article DEP - 20211231 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Melanins) RN - 0 (NF-kappa B) RN - 0 (Transcription Factor AP-1) RN - 0 (quercetin 3-O-glucuronide) RN - 9IKM0I5T1E (Quercetin) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/*pharmacology MH - HEK293 Cells MH - HaCaT Cells MH - Humans MH - Hydrogen Peroxide/toxicity MH - Keratinocytes/drug effects/*pathology/radiation effects MH - Melanins/*metabolism MH - Melanoma, Experimental/*pathology MH - Models, Biological MH - NF-kappa B/*metabolism MH - Quercetin/*analogs & derivatives/chemistry/pharmacology MH - Signal Transduction/drug effects/radiation effects MH - Transcription Factor AP-1/*metabolism MH - Transcriptional Activation/drug effects/genetics/radiation effects MH - Ultraviolet Rays PMC - PMC8745180 OTO - NOTNLM OT - AP-1 OT - NF-kappaB OT - UV protection OT - antimelanogenesis OT - moisturizing OT - quercetin 3-O-beta-D-glucuronide COIS- The authors declare no conflict of interest. EDAT- 2022/01/12 06:00 MHDA- 2022/02/04 06:00 PMCR- 2021/12/31 CRDT- 2022/01/11 01:04 PHST- 2021/12/16 00:00 [received] PHST- 2021/12/26 00:00 [revised] PHST- 2021/12/29 00:00 [accepted] PHST- 2022/01/11 01:04 [entrez] PHST- 2022/01/12 06:00 [pubmed] PHST- 2022/02/04 06:00 [medline] PHST- 2021/12/31 00:00 [pmc-release] AID - ijms23010433 [pii] AID - ijms-23-00433 [pii] AID - 10.3390/ijms23010433 [doi] PST - epublish SO - Int J Mol Sci. 2021 Dec 31;23(1):433. doi: 10.3390/ijms23010433.