Zicao, a traditional Chinese herbal medicine documented since the Shennong Ben Cao Jing (Classic of the Divine Husbandman's Materia Medica) in the Eastern Han Dynasty, exhibits significant anti-inflammatory, antitumor, and antibacterial activities. Modern pharmacological research confirms its efficacy in these areas. Commercially available Zicao is derived from multiple species—primarily Arnebia euchroma , Lithospermum erythrorhizon , and Onosma paniculatum —resulting in substantial quality variations. Among these, A. euchroma is recognized as the superior medicinal source. However, its supply is severely constrained by scarce wild resources and challenges in artificial cultivation, leading to frequent substitution with inferior varieties. This review elucidates critical distinctions between A. euchroma and other Zicao species in native habitats, chemical composition, emphasizing A. euchroma possesses unique chemical advantages, characterized by high concentrations of bioactive naphthoquinones (notably β, β-dimethylacrylalkannin, β-hydroxyisovalerylalkannin, and β-acetoxyisovalerylalkannin), polysaccharides, and phenolic acids. These constituents underpin its enhanced anti-inflammatory, antitumor, antioxidant, antimicrobial, neuroprotective, and dermatological activities compared to alternative Zicao sources. By integrating traditional knowledge with modern research, this review provides a scientific foundation for prioritizing A. euchroma in clinical and pharmaceutical applications of Zicao.

Ceramides constitute approximately 50% of the lipid mass in the stratum corneum and are essential for epidermal permeability barrier function. In acne vulgaris, barrier disruption is accompanied by altered ceramide composition, yet the molecular mechanisms that connect acne-associated signals to specific changes in ceramide metabolism remain incompletely understood. This review integrates evidence from lipidomic profiling, enzymatic pathway characterization, and inflammatory signaling studies to examine how ceramide biosynthesis and turnover are modulated in acne-prone skin. Particular attention is directed to the elongation of very-long-chain fatty acids (VLCFAs) and their incorporation into ceramides by ceramide synthase 3 (CerS3). In cultured keratinocytes, Cutibacterium acnes (C. acnes)-derived short-chain fatty acids (SCFAs) have been reported to suppress CerS3 and 3-ketodihydrosphingosine reductase (KDSR) through peroxisome proliferator-activated receptor α (PPARα), limiting ultra-long-chain fatty acid (ULCFA) supply. We propose a working model in which SCFAs act via PPARα to upregulate ELOVL-family elongases while suppressing CerS3 and KDSR, reducing ULCFA-ceramides and compromising barrier integrity. The CerS3–KDSR node is a candidate regulatory point coupling microbial metabolites to barrier impairment and inflammation. However, this model rests largely on in vitro evidence and requires in vivo validation. Clarifying these regulatory relationships may inform the development of barrier-restorative strategies as adjuncts to conventional acne therapy.