Li Dongdong, Han Yusheng, Zhou Jingjing, Chen Jing, Tey Hong Liang, Tan Timothy T Y
College of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
Front Pharmacol. 2025 Aug 22;16:1631977. doi: 10.3389/fphar.2025.1631977. eCollection 2025.
To provide a comprehensive narrative synthesis of recent advances in the pharmacological actions and therapeutic potential of natural flavonoids in atopic dermatitis (AD), with emphasis on their multi-target pharmacological effects across core pathological mechanisms. The review also addresses pharmacokinetic limitations, formulation challenges, delivery innovations, safety concerns, and emerging clinical evidence to inform translational research and therapeutic development.
This narrative review is based on a targeted literature search of PubMed, Web of Science, ScienceDirect, and SpringerLink, covering English-language, peer-reviewed articles published between 2010 and 2025. Search terms included natural flavonoid metabolites (e.g., quercetin, baicalin, epigallocatechin-3-gallate [EGCG]) combined using Boolean operators (e.g., AND, OR) with keywords related to atopic dermatitis, its underlying mechanisms, and therapeutic interventions. Studies focusing on , , or clinical evaluations of mechanistic pathways, therapeutic potential, or delivery strategies were included, while those addressing synthetic flavonoids, non-AD models, or lacking mechanistic relevance were excluded. This review does not follow a systematic review protocol.
Natural flavonoids exert multi-target effects in AD models by restoring skin barrier integrity, modulating immune and chemokine dysregulation, alleviating pruritus, regulating microbial homeostasis and programmed cell death, and attenuating oxidative stress. However, pharmacokinetic and physicochemical limitations such as poor solubility, low bioavailability, metabolic instability, and limited dermal targeting currently constrain clinical application. Potential safety concerns, including hepatotoxicity and endocrine disruption, also warrant careful evaluation. To address these challenges, advanced delivery platforms including microneedles, hydrogels, nanocarriers, microsponges, and liposomes have been explored to improve dermal delivery. Additionally, oral delivery systems developed in other inflammatory and oncological models provide valuable insights for guiding translational strategies in AD. Preliminary clinical evidence suggests potential benefits of flavonoid-based interventions; nevertheless, larger and well-controlled trials are necessary to substantiate their pharmacological effects and evaluate long-term safety.
Natural flavonoids exhibit multi-target effects in AD by modulating core pathological processes. Although challenges such as limited bioavailability and safety concerns continue to impede clinical translation, these limitations may be addressed through the optimization of delivery strategies, rigorous pharmacokinetic and toxicological assessments, mechanism-driven , , studies, and well-designed clinical trials.
全面叙述天然黄酮类化合物在特应性皮炎（AD）中的药理作用和治疗潜力的最新进展，重点关注其在核心病理机制中的多靶点药理作用。本综述还探讨了药代动力学限制、制剂挑战、给药创新、安全性问题以及新出现的临床证据，以为转化研究和治疗开发提供参考。
本叙述性综述基于对PubMed、Web of Science、ScienceDirect和SpringerLink的针对性文献检索，涵盖2010年至2025年发表的英文同行评审文章。检索词包括天然黄酮类代谢产物（如槲皮素、黄芩苷、表没食子儿茶素-3-没食子酸酯[EGCG]），使用布尔运算符（如AND、OR）与特应性皮炎及其潜在机制和治疗干预相关的关键词组合。纳入关注机制途径、治疗潜力或给药策略的研究，而排除涉及合成黄酮类化合物、非AD模型或缺乏机制相关性的研究。本综述未遵循系统综述方案。
天然黄酮类化合物在AD模型中发挥多靶点作用，可恢复皮肤屏障完整性、调节免疫和趋化因子失调、减轻瘙痒、调节微生物稳态和程序性细胞死亡以及减轻氧化应激。然而，药代动力学和物理化学限制，如溶解度差、生物利用度低、代谢不稳定和皮肤靶向性有限，目前限制了其临床应用。潜在的安全问题，包括肝毒性和内分泌干扰，也需要仔细评估。为应对这些挑战，已探索了包括微针、水凝胶、纳米载体、微海绵和脂质体在内的先进给药平台，以改善皮肤给药。此外，在其他炎症和肿瘤模型中开发的口服给药系统为指导AD的转化策略提供了有价值的见解。初步临床证据表明基于黄酮类化合物的干预措施具有潜在益处；然而，需要更大规模且严格对照的试验来证实其药理作用并评估长期安全性。
天然黄酮类化合物通过调节核心病理过程在AD中表现出多靶点作用。尽管生物利用度有限和安全性问题等挑战继续阻碍临床转化，但可通过优化给药策略、严格的药代动力学和毒理学评估、机制驱动的研究以及精心设计的临床试验来解决这些限制。
