Anti-Psoriatic Effects and IL-22 Targeting Mechanism of Indirubin by Suppressing Keratinocyte Inflammation and Proliferation

• Published in: Applied sciences Vol. 11; no. 24; p. 11599
• Main Authors: Nguyen, Ly Thi Huong, Oh, Tae-Woo, Choi, Min-Jin, Yang, In-Jun, Shin, Heung-Mook
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.12.2021
• Subjects: Cell cycle; Cyclin D1; Cytokines; Hyperplasia; Immunohistochemistry; indirubin; Intercellular adhesion molecule 1; Interleukin 22; Interleukin 6; Interleukin 8; Oxidative stress; Phosphorylation; proliferation; Psoriasis; Reagents; S phase; Skin diseases; Stat3 protein; Stress analysis; Tumor necrosis factor-α; St Louis Missouri; United States > US
• ISSN: 2076-3417; 2076-3417
• DOI: 10.3390/app112411599

Indigo naturalis, which is extracted from the leaves and branches of Baphicacanthus cusia (Nees) Bremek, has traditionally been used to treat psoriasis. The current study aimed to examine a new mechanism of the components of indigo naturalis, including indirubin, indigo, and tryptanthrin. The anti-psoriatic effects were assessed by the proliferation biomarkers (Ki67, K16), cell cycle progression, ROS production, and interleukin profiling (ICAM-1, TNF-α, IL-6, and IL-8) in IL-22-treated HaCaT cells. Among the components, indirubin significantly decreased intracellular ROS production and lowered the production of ICAM-1, TNF-α, and IL-6 in IL-22-treated HaCaT cells. Indirubin, indigo, and tryptanthrin could decrease the proportion of Ki67-positive cells, but only indirubin decreased the proportion of cells entering the S phase and suppressed the expression of cyclin D1 and cyclin E1 in IL-22-treated HaCaT cells. Indirubin significantly suppressed the phosphorylation of STAT3 and ERK. In vivo, IL-22 was intradermally injected into mouse ears for six days and topically treated with 0.1% or 1% indirubin. In the IL-22-injected mice, treatment with indirubin inhibited epidermal hyperplasia. Immunohistochemistry and western blot analysis demonstrated the downregulation of K16 expression in psoriatic lesions. These results suggest that indirubin, which is a major component of indigo naturalis, may have therapeutic potential in an IL-22-induced psoriasis model.