Nepetoidin B from Salvia plebeia R. Br. Inhibits Inflammation by Modulating the NF-κB and Nrf2/HO-1 Signaling Pathways in Macrophage Cells

• Published in: Antioxidants 2021-07, Vol.10 (8), p.1208
• Main Authors: Kim, Mina, Kim, Ji Yeong, Yang, Hee Sun, Choe, Jeong-Sook, Hwang, In Guk
• Format: Article
• Language: English
• Subjects: anti-inflammatory effects; Antioxidants; Bronchitis; Catalase; Cell culture; Chromatography; Cytokines; Enzymes; Heme; IL-1β; Immune response; Inflammation; Inflammatory diseases; Laboratories; Lipopolysaccharides; luteolin; Macrophages; Magnetic resonance spectroscopy; nepetoidin B; NF-κB protein; Nitric oxide; NMR; Nrf-2; Nuclear magnetic resonance; Oxidative stress; Oxygenase; Pathogenesis; Prostaglandin E2; Protoporphyrin; Reactive oxygen species; ROS; Salvia plebeia; Scientific imaging; Signal transduction; Superoxide dismutase; Tin protoporphyrin; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox10081208

Salvia plebeia has been used to treat a variety of inflammatory diseases, as well as colds and bronchitis. Macrophages have antioxidant defense mechanisms to cope with the intracellular reactive oxygen species (ROS) produced as part of the immune response. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathway in inflamed macrophages is an appealing target due to its protective effect against ROS-induced cell damage. In this study, nepetoidin B (NeB) was first isolated from S. plebeia and identified by nuclear magnetic resonance spectroscopy. NeB reduced pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β) in LPS-activated RAW 264.7 cells by inhibiting the NF-κB signaling pathway. In the NeB-treated group, catalase and superoxide dismutase levels were significantly higher, and ROS expression decreased. By activating Nrf2 signaling, NeB enhanced HO-1 expression. Furthermore, when the cells were pretreated with tin protoporphyrin (an HO-1 inhibitor), the anti-inflammatory effects of NeB were reduced. Therefore, NeB may activate the Nrf2/ HO-1 pathway. These results reveal the NeB isolated from S. plebeia exerts anti-inflammatory effects by modulating NF-κB signaling and activating the Nrf2/HO-1 pathway in LPS-stimulated RAW 264.7 cells.