Red Ginseng Water Extract Aggravates Inflammation in Sebocytes and Outer Root Sheath Cells after Treatment with Lipopolysaccharide and Mice with Cutibacterium acnesinduced Inflammatory Nodules

Background: Ginseng, a well-known health-supportive herbal medicine in Korea, has various forms, including red ginseng (RG) produced through steaming and drying white ginseng. RG has been associated with numerous protective functions in various diseases. Objective: The objective of this study was to investigate whether RG water extract exacerbates inflammation in human sebocytes and outer root sheath (ORS) cells following treatment with lipopolysaccharide (LPS) and Cutibacterium acnes strain (ATCC 1182)-induced inflammatory nodules in mice. Methods: Sebocytes and ORS cells were isolated and cultured from the human scalp. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure the expression of inflammatory cytokine and sebum-related genes after treatment with RG and LPS. Mice with Cutibacterium acnesinduced inflammatory nodules were orally administered RG in water for two weeks, and immunofluorescence staining was performed to assess the inflammatory nodules. Results: RG enhanced LPS-mediated inflammation by increasing the mRNA and protein expression of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α in sebocytes and ORS cells. RG also upregulated the expression of p-nuclear factor-kappa B (p-NFκB), p-c-Jun, and c-Jun N-terminal kinase (p-JNK) in LPS-treated sebocytes and ORS cells. Moreover, RG promoted LPS-induced sebum production in sebocytes. Additionally, RG hindered the improvement of inflammatory nodules in mice and increased the expression of inflammatory biomarkers, such as neutrophil, myeloperoxidase, and IL-1β, as well as tissue remodeling biomarkers, such as myeloperoxidase (MMP)-2, MMP-3, and MMP-9 in the inflammatory nodules. Conclusion: Our findings strongly suggest that RG exacerbates acne vulgaris. It is advisable to avoid using RG in patients with inflammatory acne.