天然产物抑制角质形成细胞增殖抗银屑病研究进展
Research Progress on Natural Products in Treating Psoriasis by Inhibiting Keratinocyte Proliferatione
DOI: 10.12677/pi.2026.154039, PDF,   
作者: 卢嘉琪, 夏玉凤*：中国药科大学中药学院，江苏 南京
关键词: 天然产物；银屑病；角质形成细胞；增殖；Natural Products； Psoriasis； Keratinocytes； Proliferation
摘要: 银屑病是一种慢性自身免疫性疾病，角质形成细胞在银屑病发病过程中占有重要地位，其异常增殖是银屑病最主要的病理特征之一，因此抑制角质形成细胞增殖是治疗银屑病的有效策略。银屑病当前难以被彻底治愈，患者需要长期用药，当前银屑病常用疗法存在不同局限性和副作用，仍需继续开发新的银屑病治疗药物。天然产物具有多靶点协同、副作用相对较小的优点，长期使用安全性更高，因此更适合开发为银屑病治疗长期药物。本文系统综述了天然产物通过多靶点抑制角质形成细胞异常增殖的研究进展，并指出未来需结合更精准的人源化模型与多组学技术，以推动其临床转化。
Abstract: Psoriasis is a chronic autoimmune disease in which keratinocytes play a pivotal role; their abnormal proliferation represents one of the disease’s core pathological features, making the inhibition of keratinocyte hyperproliferation an effective therapeutic strategy. As psoriasis remains incurable, patients require long-term medication; however, current therapies have various limitations and side effects, underscoring the need for novel drug development. Natural products offer multi-target synergistic effects with relatively low toxicity, providing higher long-term safety and making them particularly suitable for developing sustained psoriasis treatments. This review systematically summarizes recent advances in natural products that suppress keratinocyte hyperproliferation through multi-target mechanisms, and highlights the necessity of integrating more precise humanized models and multi-omics technologies to accelerate their clinical translation.
文章引用：卢嘉琪, 夏玉凤. 天然产物抑制角质形成细胞增殖抗银屑病研究进展[J]. 药物资讯, 2026, 15(4): 366-374. https://doi.org/10.12677/pi.2026.154039

参考文献

[1] Langley, R.G.B., Krueger, G.G. and Griffiths, C.E.M. (2005) Psoriasis: Epidemiology, Clinical Features, and Quality of Life. Annals of the Rheumatic Diseases, 64, ii18-ii23. [Google Scholar] [CrossRef] [PubMed]
[2] Michalek, I.M., Loring, B. and John, S.M. (2017) A Systematic Review of Worldwide Epidemiology of Psoriasis. Journal of the European Academy of Dermatology and Venereology, 31, 205-212. [Google Scholar] [CrossRef] [PubMed]
[3] Guo, J., Zhang, H., Lin, W., Lu, L., Su, J. and Chen, X. (2023) Signaling Pathways and Targeted Therapies for Psoriasis. Signal Transduction and Targeted Therapy, 8, Article No. 437. [Google Scholar] [CrossRef] [PubMed]
[4] Nestle, F.O., Kaplan, D.H. and Barker, J. (2009) Psoriasis. New England Journal of Medicine, 361, 496-509. [Google Scholar] [CrossRef] [PubMed]
[5] Zhou, X., Chen, Y., Cui, L., Shi, Y. and Guo, C. (2022) Advances in the Pathogenesis of Psoriasis: From Keratinocyte Perspective. Cell Death & Disease, 13, Article No. 81. [Google Scholar] [CrossRef] [PubMed]
[6] Sandoval, A.G.W., Mahajan, A. and Buzney, E. (2024) Phototherapy for Psoriasis in the Age of Biologics. Dermatologic Clinics, 42, 399-404. [Google Scholar] [CrossRef] [PubMed]
[7] Min, S., Wang, D., Xia, J., Lin, X. and Jiang, G. (2023) The Economic Burden and Quality of Life of Patients with Psoriasis Treated with Biologics in China. Journal of Dermatological Treatment, 34, Article ID: 2247106. [Google Scholar] [CrossRef] [PubMed]
[8] Leaviss, J., Carroll, C., Essat, M., van der Windt, D., Grainge, M.J., Card, T., et al. (2024) Prognostic Factors for Liver, Blood and Kidney Adverse Events from Glucocorticoid Sparing Immune-Suppressing Drugs in Immune-Mediated Inflammatory Diseases: A Prognostic Systematic Review. RMD Open, 10, e003588. [Google Scholar] [CrossRef] [PubMed]
[9] Potestio, L., Tommasino, N., Lauletta, G., Feo, F., Ruggiero, A., Martora, F., et al. (2024) Efficacy and Safety of Deucravacitinib for the Management of Psoriasis: A Drug Safety Evaluation. Expert Opinion on Drug Safety, 23, 677-685. [Google Scholar] [CrossRef] [PubMed]
[10] Sun, S., Zhang, X., Xu, M., Zhang, F., Tian, F., Cui, J., et al. (2019) Berberine Downregulates CDC6 and Inhibits Proliferation via Targeting JAK-STAT3 Signaling in Keratinocytes. Cell Death & Disease, 10, Article No. 274. [Google Scholar] [CrossRef] [PubMed]
[11] Lee, J., Song, K., Hiebert, P., Werner, S., Kim, T. and Kim, Y.S. (2020) Tussilagonone Ameliorates Psoriatic Features in Keratinocytes and Imiquimod-Induced Psoriasis-Like Lesions in Mice via NRF2 Activation. Journal of Investigative Dermatology, 140, 1223-1232.e4. [Google Scholar] [CrossRef] [PubMed]
[12] Palombo, R., Savini, I., Avigliano, L., Madonna, S., Cavani, A., Albanesi, C., et al. (2016) Luteolin-7-Glucoside Inhibits IL-22/STAT3 Pathway, Reducing Proliferation, Acanthosis, and Inflammation in Keratinocytes and in Mouse Psoriatic Model. Cell Death & Disease, 7, e2344. [Google Scholar] [CrossRef] [PubMed]
[13] Yu, Y.J., Xu, Y.Y., Lan, X.O., Liu, X.Y., Zhang, X.L., Gao, X.H. and Geng, L. (2019) Shikonin Induces Apoptosis and Suppresses Growth in Keratinocytes via CEBP-δ Upregulation. International Immunopharmacology, 72, 511-521. [Google Scholar] [CrossRef] [PubMed]
[14] Thatikonda, S., Pooladanda, V., Sigalapalli, D.K. and Godugu, C. (2020) Piperlongumine Regulates Epigenetic Modulation and Alleviates Psoriasis-Like Skin Inflammation via Inhibition of Hyperproliferation and Inflammation. Cell Death & Disease, 11, Article No. 21. [Google Scholar] [CrossRef] [PubMed]
[15] Chamcheu, J.C., Esnault, S., Adhami, V.M., Noll, A.L., Banang-Mbeumi, S., Roy, T., et al. (2019) Fisetin, a 3,7,3’,4’-Tetrahydroxyflavone Inhibits the PI3K/Akt/mTOR and MAPK Pathways and Ameliorates Psoriasis Pathology in 2D and 3D Organotypic Human Inflammatory Skin Models. Cells, 8, Article No. 1089. [Google Scholar] [CrossRef] [PubMed]
[16] Li, T., Wei, Z., Sun, Y., Wang, Q. and Kuang, H. (2019) Withanolides, Extracted from Datura metel L. Inhibit Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis via the STAT3/P38/ERK1/2 Pathway. Molecules, 24, Article No. 2596. [Google Scholar] [CrossRef] [PubMed]
[17] Yalamarthi, S.S., Puppala, E.R., Abubakar, M., Saha, P., Challa, V.S., NP, S., et al. (2022) Perillyl Alcohol Inhibits Keratinocyte Proliferation and Attenuates Imiquimod-Induced Psoriasis Like Skin-Inflammation by Modulating NF-κB and STAT3 Signaling Pathways. International Immunopharmacology, 103, Article ID: 108436. [Google Scholar] [CrossRef] [PubMed]
[18] Li, X., Xie, X., Zhang, L., Meng, Y., Li, N., Wang, M., et al. (2019) Hesperidin Inhibits Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis via the IRS-1/ERK1/2 Pathway. Life Sciences, 219, 311-321. [Google Scholar] [CrossRef] [PubMed]
[19] Zhao, Z.Z., Liang, X.B., He, H.J., Xue, G.M., Sun, Y.J., Chen, H., et al. (2024) Diterpenoids with Potent Anti-Psoriasis Activity from Euphorbia helioscopia L. Molecules, 29, Article No. 4104. [Google Scholar] [CrossRef] [PubMed]
[20] Zheng, Y., Zhang, X., Gu, X., Li, Y., Li, Q., Zhu, Y., et al. (2025) Undulanoids A-D: Unexpected Sesterterpenoids as Potent S100A8/A9 Complex Inhibitors for Psoriasis Treatment. Acta Pharmaceutica Sinica B, 15, 6495-6509. [Google Scholar] [CrossRef] 
[21] Tian, X., Peng, F., xiong, x., Xu, X., Zan, Y., Wang, X., et al. (2025) Artemisinin Analogues Are Effective in the Treatment of Psoriasis by Targeting RORγt. Molecular Immunology, 180, 11-22. [Google Scholar] [CrossRef] [PubMed]
[22] Bu, T., Gong, Z., Ma, Y., Dai, L., Ma, Y., Yu, X., et al. (2026) Synthesis, Biological Evaluation and Structure-Activity Relationship of Juglone Derived Naphthoquinones as Potential Antipsoriatic Agents. Biomolecules, 16, Article No. 802. [Google Scholar] [CrossRef] 
[23] Wang, W., Zhang, J., Jiang, S., Rao, Z., Liu, H., Wang, L., et al. (2026) Dictamnine Inhibited Keratinocyte Hyperproliferation and Alleviated Psoriasis-Like Dermatitis via Blocking HIF1A-Mediated Ferroptotic Pathway. Journal of Ethnopharmacology, 355, Article ID: 120607. [Google Scholar] [CrossRef] 
[24] Liu, L., Zhao, S., Wu, Y., Zhao, Y., Lu, C. and Zhao, R. (2025) Guben-Qushi-Huayu Formula and Calycosin Improve Epidermal Barrier Function in Psoriasis by Inhibiting Small Proline-Rich Protein 1A. Phytomedicine, 148, Article ID: 157395. [Google Scholar] [CrossRef] 
[25] Xiang, L., Shen, Y., Liu, S., Fan, B., Zhan, J., Zhou, Y., et al. (2025) Guggulsterone Ameliorates Psoriasis by Inhibiting Keratinocyte Proliferation and Inflammation through Induction of miR-17 Directly Targeting JAK1 and STAT3. Biochemical Pharmacology, 233, Article ID: 116745. [Google Scholar] [CrossRef] [PubMed]
[26] Li, M., Li, D., Zhang, Y., Wang, J., Wang, S., Zhao, H., et al. (2025) Cannabidiol-Loaded Hydrogel Microneedle Patches Inhibit TRIM14/TRAF3/NF-κB Axis for the Treatment of Psoriasis. International Journal of Biological Macromolecules, 304, Article ID: 140825. [Google Scholar] [CrossRef] [PubMed]
[27] Ma, J., Ji, C., Sun, Y., Liu, D., Pan, K. and Wei, Y. (2024) Wogonin Ameliorates the Proliferation, Inflammatory Response, and Pyroptosis in Keratinocytes via NOD‐Like Receptor Family Pyrin Domain Containing 3/Caspase‐1/Gasdermin‐D Pathway. Immunity, Inflammation and Disease, 12, e1303. [Google Scholar] [CrossRef] [PubMed]
[28] Zhou, X., Ning, J., Wu, D., Liu, Q., Jiang, W., Liu, J., et al. (2025) Paris Saponin VII Attenuates Psoriasiform Inflammation by Regulating STAT3/NF-κB Signaling Pathway and Caspase-1-Induced Pyroptosis. Molecular Medicine, 31, Article No. 200. [Google Scholar] [CrossRef] [PubMed]
[29] Zhou, X., Chen, Q., Chen, Z., Song, B., Li, J. and Ning, J. (2026) Polyphyllin I Mitigates Psoriasiform Inflammation and Prevents Relapse by Modulating CLEC7A and Inhibiting Pyroptosis. Phytomedicine, 150, Article ID: 157658. [Google Scholar] [CrossRef] 
[30] Li, J., Qiu, H., Li, S., Han, S., He, Y., He, J., et al. (2024) Pulsatilla Saponin Inhibits the Proliferation of Keratinocytes and Ameliorates Imiquimod-Induced Psoriasis through the NF-κB and STAT3 Signaling Pathways. Journal of Traditional and Complementary Medicine, 15, 356-368. [Google Scholar] [CrossRef] [PubMed]
[31] Xu, X., Zhang, H., Chang, A., Peng, H., Li, S., Zhang, K., et al. (2025) Astilbin Alleviates IL-17-Induced Hyperproliferation and Inflammation in HaCaT Cells via Inhibiting Ferroptosis through the cGAS-STING Pathway. International Journal of Molecular Sciences, 26, Article No. 5075. [Google Scholar] [CrossRef] [PubMed]
[32] Chen, B.L., Zhang, W.M., Dong, X.W., Liu, J.Y. and Bai, Y.P. (2025) Quercetin Induces Keratinocytes Apoptosis via Triple Inhibition of Notch, PI3K/AKT Signaling and Glut1 in the Treatment of Psoriasis. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1871, Article ID: 167879. [Google Scholar] [CrossRef] [PubMed]
[33] Sood, A. and Tikoo, K. (2025) Topical Delivery of Pterostilbene Nanoemulgel Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice. Nanomedicine, 20, 791-802. [Google Scholar] [CrossRef] [PubMed]
[34] Liu, T., He, Y. and Liao, Y. (2024) Gypenosides Alleviates HaCaT Keratinocyte Hyperproliferation and Ameliorates Imiquimod-Induced Psoriasis in Mice. Allergologia et Immunopathologia, 52, 22-32. [Google Scholar] [CrossRef] [PubMed]
[35] Lv, Y., Yang, L., Mao, Z., Zhou, M., Zhu, B., Chen, Y., et al. (2024) Tetrastigma hemsleyanum Polysaccharides Alleviate Imiquimod-Induced Psoriasis-Like Skin Lesions in Mice by Modulating the JAK/STAT3 Signaling Pathway. Phytomedicine, 133, Article ID: 155917. [Google Scholar] [CrossRef] [PubMed]
[36] Chen, E., Wang, L., Wang, Q., Cai, Y., Dou, Y., Qu, H., et al. (2025) Triptolide Alleviates Psoriasis through Inhibiting the Wnt5a/β-Catenin Signaling Pathway. Frontiers in Pharmacology, 16, Article ID: 1534118. [Google Scholar] [CrossRef] [PubMed]
[37] Xu, H.T., Zheng, Q., Tai, Z.G., Jiang, W.C., Xie, S.Q., Luo, Y., Fei, X.Y., et al. (2024) Formononetin Attenuates Psoriasiform Inflammation by Regulating Interferon Signaling Pathway. Phytomedicine, 128, Article ID: 155412. [Google Scholar] [CrossRef] [PubMed]
[38] Li, H., Xu, J., Liu, J., Li, J., Xu, M., Ma, P., et al. (2024) Sappanone a Ameliorated Imiquimod-Induced Psoriasis-Like Dermatitis in BALB/c Mice via Suppressing Mmp8 Expression and IL-17 Signaling Pathway. European Journal of Pharmacology, 978, Article ID: 176746. [Google Scholar] [CrossRef] [PubMed]
[39] Wang, Q., Luo, X., Su, Y., Jin, Y., Kuang, Q., Li, S., et al. (2025) Tanshinone I Ameliorates Psoriasis-Like Dermatitis by Suppressing Inflammation and Regulating Keratinocyte Differentiation. Drug Design, Development and Therapy, 19, 539-552. [Google Scholar] [CrossRef] [PubMed]
[40] Yang, D., Peng, M., Fu, F., Zhao, W. and Zhang, B. (2024) Diosmetin Ameliorates Psoriasis-Associated Inflammation and Keratinocyte Hyperproliferation by Modulation of PGC-1α/YAP Signaling Pathway. International Immunopharmacology, 134, Article ID: 112248. [Google Scholar] [CrossRef] [PubMed]
[41] Liu, J., Tan, C., Shi, J., Shi, Y., Zhang, Q., Wei, Y., et al. (2025) Exploring the Mechanism of Notopterygii rhizoma Et Radix in the Treatment of Psoriasis Using a Network Pharmacology Approach and Experimental Validation. Scientific Reports, 15, Article No. 40422. [Google Scholar] [CrossRef] 
[42] Ahn, J.Y., Lim, D.W., Kim, J.H., Park, S.Y., Park, S.D. and Lee, J.H. (2025) Sinhyotaklisan as a Potential Therapeutic for Psoriasis: Network Pharmacology and Experimental Validation. International Journal of Molecular Sciences, 26, Article No. 5082. [Google Scholar] [CrossRef] [PubMed]
[43] Zhao, Q., Bai, J., Chen, Y., Liu, X., Zhao, S., Ling, G., et al. (2022) An Optimized Herbal Combination for the Treatment of Liver Fibrosis: Hub Genes, Bioactive Ingredients, and Molecular Mechanisms. Journal of Ethnopharmacology, 297, Article ID: 115567. [Google Scholar] [CrossRef] [PubMed]
[44] van der Fits, L., Mourits, S., Voerman, J.S.A., Kant, M., Boon, L., Laman, J.D., et al. (2009) Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis. The Journal of Immunology, 182, 5836-5845. [Google Scholar] [CrossRef] [PubMed]
[45] Boehncke, W.H. and Schön, M.P. (2015) Psoriasis. The Lancet, 386, 983-994. [Google Scholar] [CrossRef] [PubMed]
[46] Gangwar, R.S., Gudjonsson, J.E. and Ward, N.L. (2022) Mouse Models of Psoriasis: A Comprehensive Review. Journal of Investigative Dermatology, 142, 884-897. [Google Scholar] [CrossRef] [PubMed]
[47] Alimujiang, A., Kang, Y., Wei, W., Zhang, Z., Bai, Y., Zhu, Y., et al. (2025) Apigenin Suppresses Keratinocyte Hyperproliferation and Inflammation in Psoriasis by Inhibiting CDK2/E2F2 Pathway. Phytomedicine, 144, Article ID: 156486. [Google Scholar] [CrossRef] [PubMed]
[48] Tian, T., Wei, M., Guan, Y., Rao, L., Luo, T., Han, C., et al. (2025) Paeoniflorin-6’-o-benzene Sulfonate Inhibits Keratinocyte Proliferation by Restoring GRK2-JAK1 Colocalization in Mouse Model of Psoriasis. Cellular Signalling, 131, Article ID: 111706. [Google Scholar] [CrossRef] [PubMed]