Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-12, Vol.26 (24), p.7642
• Main Authors: Ko, Wonmin, Liu, Zhiming, Kim, Kwan-Woo, Dong, Linsha, Lee, Hwan, Kim, Na Young, Lee, Dong-Sung, Woo, Eun-Rhan
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; anti-inflammatory effects; Bark; BV2; Carbon monoxide; Chemical compounds; Cyclooxygenase-2; Cytokines; Cytotoxicity; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Heme; Heme Oxygenase-1 - metabolism; Homeostasis; Inflammation; Inflammatory diseases; Interleukin 6; kuwanon T; Lipopolysaccharides; Macrophages; Membrane Proteins - metabolism; Mice; Microglia; Morus - chemistry; Morus alba; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Oxygenase; Pharmacology; Pretreatment; Prostaglandin E2; RAW 264.7 Cells; RAW264.7 cells; sanggenon A; Signal transduction; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26247642

We previously investigated the methanolic extract of bark and characterized 11 compounds from the extract: kuwanon G ( ), kuwanon E ( ), kuwanon T ( ), sanggenon A ( ), sanggenon M ( ), sanggenol A ( ), mulberofuran B ( ), mulberofuran G ( ), moracin M ( ), moracin O ( ), and norartocarpanone ( ). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them, and markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with and inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with and , suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together, and are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.