PMID- 38426932 OWN - NLM STAT- MEDLINE DCOM- 20240304 LR - 20240304 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 28 IP - 6 DP - 2024 Mar TI - Rhizoma Paridis saponins attenuate Gram-negative bacteria-induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways. PG - e18146 LID - 10.1111/jcmm.18146 [doi] LID - e18146 AB - Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1beta and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-kappaB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic. CI - (c) 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Yang, Yang AU - Yang Y AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. FAU - Wang, Chaofan AU - Wang C AD - State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China. FAU - Wang, Juan AU - Wang J AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China. FAU - Yang, Lingli AU - Yang L AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. FAU - Lv, Zheng AU - Lv Z AD - State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China. FAU - An, Quan AU - An Q AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. FAU - Wang, Yiming AU - Wang Y AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. FAU - Shao, Xue AU - Shao X AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. FAU - Wang, Fei AU - Wang F AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. FAU - Huo, Tong AU - Huo T AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. FAU - Liu, Jiali AU - Liu J AD - State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China. FAU - Luo, Haoshu AU - Luo H AD - State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China. FAU - Quan, Qianghua AU - Quan Q AUID- ORCID: 0000-0002-4051-3359 AD - R&D Department, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, Yunnan, China. AD - R&D Department, East Asia Skin Health Research Center, Beijing, China. AD - R&D Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, China. LA - eng GR - 2018ZF005/Yunnan Science and technology project/ PT - Journal Article PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (Lipopolysaccharides) RN - 0 (Saponins) RN - 0 (Anti-Inflammatory Agents) RN - 0 (NF-kappa B) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - 0 (KEAP1 protein, human) SB - IM MH - Humans MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-E2-Related Factor 2/genetics/metabolism MH - Kelch-Like ECH-Associated Protein 1/genetics/metabolism MH - Lipopolysaccharides/adverse effects MH - *Saponins/pharmacology/therapeutic use MH - Molecular Docking Simulation MH - Anti-Inflammatory Agents/therapeutic use MH - NF-kappa B/metabolism MH - Gram-Negative Bacteria/metabolism MH - *Acne Vulgaris/drug therapy MH - Heme Oxygenase-1/genetics/metabolism MH - Inflammation/metabolism PMC - PMC10906378 OTO - NOTNLM OT - Gram-negative bacteria OT - Rhizoma Paridis OT - acne vulgaris OT - anti-inflammation OT - kelch-like ECH-associated protein 1 OT - mitogen-activated protein kinase OT - polyphyllin H COIS- Yang Yang, Lingli Yang, Yiming Wang, Xue Shao, Fei Wang, Tong Huo, and Quan An are employed by Yunnan Baiyao Group Health Products Co., Ltd. Juan Wangs was employed by Yunnan Baiyao Group Health Products Co., Ltd. EDAT- 2024/03/01 12:44 MHDA- 2024/03/04 06:47 PMCR- 2024/03/01 CRDT- 2024/03/01 10:23 PHST- 2023/09/30 00:00 [revised] PHST- 2023/05/21 00:00 [received] PHST- 2024/01/16 00:00 [accepted] PHST- 2024/03/04 06:47 [medline] PHST- 2024/03/01 12:44 [pubmed] PHST- 2024/03/01 10:23 [entrez] PHST- 2024/03/01 00:00 [pmc-release] AID - JCMM18146 [pii] AID - 10.1111/jcmm.18146 [doi] PST - ppublish SO - J Cell Mol Med. 2024 Mar;28(6):e18146. doi: 10.1111/jcmm.18146.