Preventive effects of inotodiol on polyinosinic–polycytidylic acid-induced inflammation in human dermal fibroblasts
Gun-Woo Won,
Seung Hoon Lee,
Mahesh Prakash Bhatta,
Seung-Hyeon Choi,
Cheong-Hae Oh,
Jong-Tae Park,
Jong-Il Park
Affiliations
Gun-Woo Won
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea; BK 21 FOUR, Chungnam National University Department of Medical Science, Daejeon, Republic of Korea
Seung Hoon Lee
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
Mahesh Prakash Bhatta
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
Seung-Hyeon Choi
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
Cheong-Hae Oh
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea
Jong-Tae Park
Department of Food Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea; CARBOEXPERT Inc., Daejeon, 34134, Republic of Korea; Corresponding author99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
Jong-Il Park
Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea; Translational Immunology Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea; BK 21 FOUR, Chungnam National University Department of Medical Science, Daejeon, Republic of Korea; Corresponding author282 Munhwa-ro, Jung-gu, Daejeon, 35015, Republic of Korea
Double-strand RNA(dsRNA), which can induce inflammation, can be generated by necrotic keratinocytes in the skin environment. As an analog of dsRNA, polyinosinic–polycytidylic acid (poly(I:C)) is used to induce inflammation via the Toll-like Receptor 3 (TLR3) signaling pathway. Inotodiol, isolated from Inonotus obliquus, known as Chaga mushroom, is a natural lanostane-type triterpenoid with significant pharmacological activity and notable anti-inflammatory effects. However, the functions of inotodiol on dsRNA-induced inflammation in human dermal fibroblast (HDFs) remains unclear. In this study, we evaluated the anti-inflammatory effects of inotodiol inflammation induced on by poly(I:C) in HDFs. After pre-treatment with inotodiol, poly (I:C) was used to induce inflammation. Subsequently, mRNA expression and protein secretion of inflammatory cytokines, as well as TLR3 signaling protein levels were assessed. Inflammatory cytokines IL-1β, IL-6, and TNF-α′s increased mRNA expression by poly(I:C) in HDFs was significantly suppressed in the inotodiol pre-treatment group in a dose-dependent manner. A similar pattern was evaluated in the protein levels of these three cytokines. The inflammatory signals of TLR3 via p-IKK, p-p38, and NF-κB was reduced by inotodiol pre-treatment. Taken together, inotodiol possesses strong anti-inflammatory activity against poly(I:C)-induced inflammation in HDFs. Therefore, our findings support potential application of inotodiol as an effective anti-inflammatory agent in cosmetics.
