Psoriasis is an inflammatory skin disease mediated by the immune system and characterized by an inflammatory ring, also known as an epithelial immune microenvironment (EIME). The interaction between the epithelial tissue of the skin and the immune system has a crucial role in the immune cycle of psoriasis. Although the formation of new blood vessels in skin lesions provides energy support for the proliferation of epidermal keratinocytes, the role of angiogenesis in psoriasis has not been extensively studied. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis that has an important role in the development of psoriasis. VEGFA promotes angiogenesis and directly stimulates epidermal keratinocytes and infiltrating immune cells, thus contributing to the progression of psoriasis. Measuring VEGFA levels to identify angiogenic characteristics in psoriasis patients may be a predictive biomarker for disease severity and response to anti-angiogenic therapy. Clinical data have shown that anti-angiogenic therapy can improve skin lesions in psoriasis patients. Therefore, this study aimed to uncover the underestimated role of blood vessels in psoriasis, explore the relationship between VEGFA and keratinocytes in the EIME, and inspire innovative drug therapies for the treatment of psoriasis.

Silymarin, a polyphenolic flavonolignan complex extracted from Silybum marianum (milk thistle), has long been recognized for its hepatoprotective, antioxidant, anti-inflammatory, and anticancer properties. Among its constituents, silybin is the most pharmacologically active and has been extensively studied in both preclinical and clinical settings. However, the clinical application of silymarin-based therapies remains limited by poor aqueous solubility, low oral bioavailability, rapid metabolism, and physicochemical instability. This review systematically outlines the pharmacokinetic challenges of silymarin and highlights recent advancements in formulation strategies designed to overcome these barriers. Key innovations include nanotechnology-enabled delivery systems, lipid-based carriers, water-soluble derivatives, bioavailability enhancers, parenteral and transdermal formulations, as well as controlled and synchronous release technologies. These approaches significantly improve tissue targeting, intracellular uptake, and pharmacological efficacy. Additionally, this review evaluates currently marketed silymarin formulations and recent clinical/preclinical evidence, revealing a persistent gap between laboratory advances and commercially available products. By synthesizing the mechanistic, regulatory, and manufacturability barriers that hinder translation, we delineate the key challenges that must be addressed to enable clinically deployable next-generation silymarin products. Collectively, these insights illustrate a paradigm shift in the modernization of phytomedicine, positioning silymarin as a model compound for the transformation of traditional herbal remedies into precision therapeutics through interdisciplinary drug delivery innovations.