Fermented dried Citrus unshiu peel extracts exert anti-inflammatory activities in LPS-induced RAW264.7 macrophages and improve skin moisturizing efficacy in immortalized human HaCaT keratinocytes

• Published in: Pharmaceutical biology Vol. 57; no. 1; pp. 392 - 402
• Main Authors: Kim, Chulwon, Ji, Jun, Ho Baek, Seung, Lee, Jong Hyun, Ha, In Jin, Lim, Soon Sung, Yoon, Hong Jae, Je Nam, Yun, Ahn, Kwang Seok
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-01-2019; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Bacillus subtilis; Bacillus subtilis - metabolism; Cell Line; Citrus - chemistry; Citrus - metabolism; Citrus - microbiology; Citrus unshiu; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; cytokine; Cytokines; Cytotoxicity; Diabetes; Diabetes mellitus; Dinoprostone - metabolism; Enzymes; Fermented food; Filaggrin; Flavonoids; Humans; Hyaluronic acid; Immunologic Factors - pharmacology; Inflammation; Interleukin 6; Keratin; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophage Activation - drug effects; Macrophages; Macrophages - drug effects; Medicine; Mice; moisturizing effect; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Plant extracts; Plant Extracts - pharmacology; Prostaglandin E2; Proteins; RAW 264.7 Cells; Skin; Skin Cream - pharmacology; Tumor necrosis factor-α; Viral infections; cytokine; nitric oxide; Inflammation; moisturizing effect; hyaluronic acid
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2019.1621353

Context: Citrus unshiu Markovich (Rutaceae) peel is known to contain high concentrations of flavonoids and exerts pharmacological effects on antioxidant, anti-inflammation, allergies, diabetes and viral infections.
Objective: Very little is known about potential activity of fermented dried Citrus unshiu peel extracts (FCU) using Bacillus subtilis, as well as its mechanism of action. We investigated the effects of FCU on the anti-inflammatory activities in murine macrophages and moisturizing effects in human keratinocytes.
Materials and methods: We isolated the Bacillus subtilis from Cheonggukjang and FCU using these Bacillus subtilis to prepare samples. The cells were pre-treated with various extracts for 2 h and then induced with LPS for 22 h. We determined the NO assay, TNF-α, IL-6 and PGE
2
in RAW 264.7 ells. The expression of SPT and Filaggrin by FCU treatment was measured in HaCaT cells.
Result: We found that two types of FCU highly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells (21.9 and 15.4% reduction). FCU inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNAs in a concentration-dependent manner. TNF-α (59 and 30.9% reduction), IL-6 (39.1 and 65.6% reduction), and PGE
2
secretion (78.6 and 82.5% reduction) were suppressed by FCU in LPS-stimulated macrophages. Furthermore, FCU can induce the production of hyaluronic acid (38 and 38.9% induction) and expression of Filaggrin and SPT in HaCaT keratinocyte cells.
Discussion and conclusion: FCU potentially inhibits inflammation, improves skin moisturizing efficacy, and it may be a therapeutic candidate for the treatment of inflammation and dry skin.