{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:09:45Z","timestamp":1789474185813,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570069"],"award-info":[{"award-number":["82570069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: This article employs both in vivo and in vitro experiments. Methods: The core targets and key pathways of Paeoniflorin were predicted using a PPI network analysis, GO analysis, and KEGG analysis. Subsequently, molecular docking analysis and molecular simulation dynamics were performed on the core effector. In vitro experiments employed a UVB-irradiated B16F10 cell model. The effects of Paeoniflorin on melanin content and tyrosinase activity were evaluated. Apoptosis and inflammatory cytokine levels were also assessed in vitro. In vivo experiments used a model combining progesterone injection with UV irradiation. Histopathological skin changes and melanin granule distribution were examined using HE staining. Skin melanin content, tyrosinase activity, and expression levels of related proteins were measured. Additionally, ELISA assays measured serum IL-6 and TNF-\u03b1 inflammatory cytokines in mice. Results: Rese screening identified 69 targets involved in Paeoniflorin\u2019s effects on melanogenesis, including TNF-\u03b1, IL-6, TP53, MAPK3, HIF1A and BCL2. Molecular docking and molecular dynamics simulations indicate that Paeoniflorin exhibits strong affinity for tumor necrosis factor-\u03b1. In in vitro experiments, Paeoniflorin significantly reduced UVB-induced melanin content and tyrosinase activity in B16F10 cells. It also promoted melanocyte apoptosis and a dose-dependent decrease in IL-6 and TNF-\u03b1 levels. In vivo, Paeoniflorin significantly reduced epidermal and dermal thickness and inhibited inflammatory infiltration. It decreased melanin granules, melanin content, tyrosinase activity, and IL-6 and TNF-\u03b1 levels in mouse skin tissue. Conclusions: This research indicates that Paeoniflorin can significantly suppress UVB-induced cellular inflammatory responses by inhibiting the TNF signaling pathway, thereby reducing hyperpigmentation.<\/jats:p>","DOI":"10.3390\/ph19030443","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:49:42Z","timestamp":1773071382000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Study on the Mechanism of Paeoniflorin, an Active Component of Paeonia lactiflora Pall., in Improving Skin Pigmentation by Inhibiting the TNF-\u03b1 Signaling Pathway"],"prefix":"10.3390","volume":"19","author":[{"given":"Kela","family":"Yin","sequence":"first","affiliation":[{"name":"School of Pharmacy, Bengbu Medical University, Bengbu 233030, China"},{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bengbu Medical University, Bengbu 233030, China"},{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"},{"name":"Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, E-32004 Ourense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan M. A.","family":"Rashed","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghui","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Uygur Medicine, Xinjiang Institute of Materia Medica, Urumqi 830010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0914-0080","authenticated-orcid":false,"given":"Mengxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-4332","authenticated-orcid":false,"given":"Kefeng","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bengbu Medical University, Bengbu 233030, China"},{"name":"School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou 234000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121612","DOI":"10.1016\/j.indcrop.2025.121612","article-title":"Functional peptides from the Thai medicinal plant Curcuma wanenlueanga suppress tyrosinase activity and melanin production","volume":"234","author":"Boonchai","year":"2025","journal-title":"Ind. Crops Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155565","DOI":"10.1016\/j.phymed.2024.155565","article-title":"Exploring the anti-skin inflammation substances and mechanism of Paeonia lactiflora Pall. Flower via network pharmacology-HPLC integration","volume":"129","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114607","DOI":"10.1016\/j.jep.2021.114607","article-title":"A novel high-resolution monophenolase\/diphenolase\/radical scavenging profiling for the rapid screening of natural whitening candidates from Peaonia lactiflora root and their mechanism study with molecular docking","volume":"282","author":"Chu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1096\/fj.06-6649rev","article-title":"Human skin pigmentation: Melanocytes modulate skin color in response to stress","volume":"21","author":"Costin","year":"2007","journal-title":"FASEB J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s11658-024-00631-4","article-title":"Paeoniflorin protects hepatocytes from APAP-Induced damage through launching autophagy via the MAPK\/mTOR signaling pathway","volume":"29","author":"Deng","year":"2024","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1007\/s11030-024-11019-z","article-title":"Investigating the molecular mechanism of epimedium herb in treating rheumatoid arthritis through network pharmacology, molecular docking, and experimental validation","volume":"29","author":"Ding","year":"2025","journal-title":"Mol. Divers."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11110","DOI":"10.7150\/thno.47413","article-title":"Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin","volume":"10","author":"Ding","year":"2020","journal-title":"Theranostics"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Duo, X., Wang, J., Wu, C., Deng, J., Huang, Y., Yu, M., Ri, K., Wang, G., and Wang, J. (2025). Extracts from Dark Tea with Dual Effects of Anti-Melanogenesis and Prevention of Post-Inflammatory Hyperpigmentation. Cosmetics, 12.","DOI":"10.3390\/cosmetics12050210"},{"key":"ref_9","first-page":"1421","article-title":"Roles of inflammation factors in melanogenesis","volume":"21","author":"Fu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1021\/acscentsci.6b00230","article-title":"Mimicking melanosomes: Polydopamine nanoparticles as artificial microparasols","volume":"3","author":"Huang","year":"2017","journal-title":"ACS Cent. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jiang, W., Zhang, S., Sun, X., Wang, S., Zhu, J., Liu, Z., Zhang, W., Guo, H., Li, H., and Xie, H. (2025). Glycyrrhetinic acid augments lipid catabolism via immune-neural modulation in adipose tissue. J. Adv. Res., in press.","DOI":"10.1016\/j.jare.2025.11.019"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1034\/j.1600-0749.2000.130403.x","article-title":"Assembly, target-signaling and intracellular transport of tyrosinase gene family proteins in the initial stage of melanosome biogenesis","volume":"13","author":"Jimbow","year":"2000","journal-title":"Pigment. Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Konstantinou, E., Longange, E., and Kaya, G. (2024). Mechanisms of senescence and Anti-Senescence strategies in the skin. Biology, 13.","DOI":"10.3390\/biology13090647"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, A., He, H., Chen, Y., Liao, F., Tang, J., Li, L., Fan, Y., Li, L., and Xiong, L. (2023). Effects of donkey milk on UVB-induced skin barrier damage and melanin pigmentation: A network pharmacology and experimental validation study. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1121498"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e02436","DOI":"10.1002\/advs.202502436","article-title":"Regenerative Hair Pigmentation via Skin Organoids: Adaptive Patterning Mediated by Collagen VI and Semaphorin 3C","volume":"12","author":"Li","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102108","DOI":"10.1016\/j.mtbio.2025.102108","article-title":"Topical application of Tea leaf-derived nanovesicles reduce melanogenesis by modulating the miR-828b\/MYB4 axis: Better permeability and therapeutic efficacy than conventional tea extracts","volume":"34","author":"Lin","year":"2025","journal-title":"Mater. Today Bio."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nature05660","article-title":"Melanocyte biology and skin pigmentation","volume":"445","author":"Lin","year":"2007","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22988","DOI":"10.1021\/acsnano.5c02767","article-title":"Engineering Liposomes with Cell Membrane Proteins to Disrupt Melanosome Transfer between Cells","volume":"19","author":"Liu","year":"2025","journal-title":"ACS Nano"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.hpj.2022.06.001","article-title":"Composition and antioxidant activity of Paeonia lactiflora petal flavonoid extract and underlying mechanisms of the protective effect on H2O2-induced oxidative damage in BRL3A cells","volume":"9","author":"Liu","year":"2023","journal-title":"Hortic. Plant J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jphs.2016.08.004","article-title":"Protective and therapeutic effects of fucoxanthin against sunburn caused by UV irradiation","volume":"132","author":"Matsui","year":"2016","journal-title":"J. Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111701","DOI":"10.1016\/j.scienta.2022.111701","article-title":"PlMAPK1 facilitates growth and photosynthesis of herbaceous peony (Paeonia lactiflora Pall.) under high-temperature stress","volume":"310","author":"Qian","year":"2023","journal-title":"Sci. Hortic."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23957","DOI":"10.1021\/acs.jafc.4c05392","article-title":"Ethanolic Extract of Bergenia purpurascens Exhibits Antimelanogenic Effects in B16F10 Cells through Multiple Mechanisms That Suppress Tyrosinase","volume":"72","author":"Seo","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/ics.12466","article-title":"Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation","volume":"40","author":"Serre","year":"2018","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_24","first-page":"7","article-title":"Identification and functional verification of PlFT gene associated with flowering in herbaceous peony based on transcriptome analysis","volume":"1","author":"Sun","year":"2021","journal-title":"Ornam. Plant Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110403","DOI":"10.1016\/j.plaphy.2025.110403","article-title":"Modulation of senescence-related genes by the transcription factor PlPLATZ5 prolongs the lifespan of Paeonia lactiflora petals","volume":"229","author":"Sun","year":"2025","journal-title":"Plant. Physiol. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/plphys\/kiac507","article-title":"The herbaceous peony transcription factor WRKY41a promotes secondary cell wall thickening to enhance stem strength","volume":"191","author":"Tang","year":"2023","journal-title":"Plant Physiol."},{"key":"ref_27","first-page":"e020","article-title":"Integrative transcriptome and metabolome evaluation of melanin biosynthesis in Phyllostachys nigra during low-temperature growth","volume":"5","author":"Wang","year":"2025","journal-title":"For. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"uhae344","DOI":"10.1093\/hr\/uhae344","article-title":"Advances in the study of senescence mechanisms in the genus Paeonia","volume":"12","author":"Wang","year":"2025","journal-title":"Hortic. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106309","DOI":"10.1016\/j.phrs.2022.106309","article-title":"Paeoniflorin prevents aberrant proliferation and differentiation of intestinal stem cells by controlling C1q release from macrophages in chronic colitis","volume":"182","author":"Wang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1111\/jocd.15789","article-title":"Paeoniflorin found in Paeonia lactiflora root extract inhibits melanogenesis by regulating melanin-related signal transduction in B16F10 cells","volume":"22","author":"Wen","year":"2023","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"176137","DOI":"10.1016\/j.ejphar.2023.176137","article-title":"Promoting reverse cholesterol transport contributes to the amelioration of atherosclerosis by paeoniflorin","volume":"961","author":"Wu","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","first-page":"337","article-title":"Anti-inflammatory mechanism of paeoniflorin in treating non-alcoholic fatty liver disease based on network pharmacology, molecular docking and experimental validation","volume":"37","author":"Liu","year":"2025","journal-title":"Nat. Prod. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e150","DOI":"10.1002\/efd2.150","article-title":"Flavonoid profiling of Plumula nelumbinis and evaluation of their anti-inflammatory effects on lipopolysaccharide-induced RAW 264.7 macrophages","volume":"5","author":"Li","year":"2024","journal-title":"Efood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"119726","DOI":"10.1016\/j.jep.2025.119726","article-title":"Revealing the molecular mechanism of Buzhong Yiqi Decoction for tendon bone healing on the basis of network pharmacology, molecular docking and experimental validation","volume":"347","author":"Xu","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e128","DOI":"10.1002\/efd2.128","article-title":"GLGPGVG derived from bovine elastin repairs UV-induced photoaging in human foreskin fibroblasts and its potential bioavailability","volume":"5","author":"Sun","year":"2024","journal-title":"Efood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e17093","DOI":"10.1002\/advs.202417093","article-title":"Role of SLC16A10 in Psoriasis Through the Regulation of Arachidonic Acid Metabolism in Keratinocytes","volume":"12","author":"Yang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jid.2024.07.034","article-title":"The Pigmentation of Blue Light Is Mediated by Both Melanogenesis Activation and Autophagy Inhibition through OPN3\u2013TRPV1","volume":"145","author":"Yu","year":"2025","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"109126","DOI":"10.1016\/j.plaphy.2024.109126","article-title":"Analysis of flower color diversity revealed the co-regulation of cyanidin and peonidin in the red petals coloration of Rosa rugosa","volume":"216","author":"Zan","year":"2024","journal-title":"Plant Physiol. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"116422","DOI":"10.1016\/j.jep.2023.116422","article-title":"Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-protein interaction","volume":"310","author":"Zhang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"uhaf141","DOI":"10.1093\/hr\/uhaf141","article-title":"The PlMYB73-PlMYB70-PlMYB108 complex regulates PlTPS1 to promote geraniol biosynthesis in Paeonia lactiflora","volume":"12","author":"Zhao","year":"2025","journal-title":"Hortic. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110505","DOI":"10.1016\/j.biopha.2020.110505","article-title":"A review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effects","volume":"130","author":"Zhou","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/fft2.360","article-title":"An evaluation of animal models for using bioactive compounds in the treatment of inflammatory bowel disease","volume":"5","author":"Tie","year":"2024","journal-title":"Food Front."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/fft2.441","article-title":"Functions of immunologically active peptides and their roles in intestinal inflammation","volume":"6","author":"Wang","year":"2025","journal-title":"Food Front."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:57:56Z","timestamp":1773071876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030443"],"URL":"https:\/\/doi.org\/10.3390\/ph19030443","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}