Background:: A capsaicin cream was formulated by optimizing the rheological stability, the release behavior of the drug, and the pharmacological effect. Objectives:: This study aimed to: (a) apply the Design of Experiment approach to study the rheological stability and release behaviors of a drug (capsaicin) from a formulated oil-in-water cream and (b) investigate the skin irritation and anti-inflammatory and analgesic effects of the optimized cream. Methods:: The cream prepared by the emulsification method was optimized using the central composite design, and then the pharmacological effect in experimental animals was determined using Complete Freund's adjuvant (CFA). Results:: The effects of a permeation enhancer (X1), Vaseline (X2), and surfactants (X3) on the fluctuation of the ratio of the viscous modulus (G ') to elastic modulus (G') (tan δ) after three cycles of cooling-heating (10-40°C), flux, and skin deposition of capsaicin after 8 h on mouse skin were statistically analyzed and optimized. The final obtained CAP-cream did not cause irritation in the rabbit model and produced comparable anti-inflammatory and analgesic effects to the reference product (Voltaren® emulgel). Conclusions:: This study successfully integrated the DoE approach, rheological science, and pharmacological studies to develop a stable and highly effective semi-solid product containing capsaicin.

An ethnobotanical survey in the northern mountainous region of Vietnam identified four Elsholtzia species, E. blanda, E. ciliata, E. communis, and E. penduliflora, growing naturally above 1500 m and traditionally used by local ethnic communities to treat skin-related ailments. This study investigates their essential oil possible chemotypes, antimicrobial properties, and potential mechanisms of action through molecular docking. Essential oils obtained by steam distillation were analyzed using GC–MS. E. blanda (yield 1.17%) was characterized by high levels of 1,8-cineole (29.0%) and camphor (17.0%). E. ciliata (1.02%) represented a possible limonene-dominant chemotype (71.0%). E. communis (1.91%) contained an exceptionally high proportion of rosefuran oxide (86.2%), whereas E. penduliflora (0.91%) exhibited a pronounced 1,8-cineole chemotype (92.1%). All essential oils showed antimicrobial activity against Staphylococcus aureus (MSSA and MRSA), Escherichia coli, and Candida albicans, with MIC values ranging from 0.4% to 3.2%. Except for E. ciliata against C. albicans, MBC/MIC and MFC/MIC ratios ≤ 4 indicated predominantly bactericidal or fungicidal effects. Molecular docking further identified nine of twenty-eight detected constituents as strong binders to microbial target proteins. These findings expand current knowledge on possible chemotypic diversity within the genus, particularly the discovery of a high-altitude limonene chemotype in E. ciliata and the identification of E. penduliflora as a rich natural source of 1,8-cineole. The convergence of chemical, biological, and in silico evidence supports the ethnomedicinal relevance of Elsholtzia species and highlights their potential as candidates for developing natural antimicrobial agents.

Elsholtzia ciliata (Thunb.) Hyl., a plant from the Lamiaceae family, is an aromatic plant used in both culinary and traditional medicine in Vietnam and other Asian countries. The aim of this study is to classify chemotypes of E. ciliata from various ecological regions in Vietnam based on the essential oil compositions. A total of 11 accessions, including both cultivated and wild-grown plants, were collected. Their essential oil compositions were analyzed by using GC-MS. The results identified 61 compounds, with 15 major components of the essential oils. Hierarchical cluster analysis (HCA) based on 15 major components revealed two distinct chemotypes: citral and limonene. The cultivated accessions were primarily classified as the citral chemotype, characterized by high contents of (α+β)-citral. These compounds are commonly found in culinary herbs. On the other hand, the wild-grown accessions were classified as the limonene chemotype, dominated by limonene. This study contributes to the understanding of Elsholtzia ciliata (Thunb.) Hyl. chemotypes in Vietnam, suggesting potential applications based on chemotype classification