Anti-inflammatory activity of Echinosophora koreensis nakai root extract in lipopolysaccharides-stimulated RAW 264.7 cells and carrageenan-induced mouse paw edema model

Inflammation is a spontaneous process of the immune system that plays an essential role in protective responses against harmful stimuli such as toxins, pathogens, and tissue injury (Ko et al., 2017, 2019). However, excessive inflammation generates hyperreactivity in the body, which can cause several diseases such as pulmonary fibrosis, atherosclerosis, rheumatoid arthritis, heart disease, neurodegenerative disorder, diabetes, cancer, and autoimmune disease (Ko et al., 2019; Serhan and Savill, 2005; Medzhitov and Janeway Jr, 1997; Zhang et al., 2020; Ginwala et al., 2019). Macrophages are immune cells that play essential roles in immune responses and protect the body from various pathogens through phagocytosis (Xu et al., 2017; Shi et al., 2009). Lipopolysaccharides (LPS), outer cell membrane molecules of gram-negative bacteria, are well-known endotoxins that can activate macrophages to generate many inflammatory factors (Lin et al., 2020; Wang et al., 2020). Macrophages activated by LPS express pro-inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which promote the generation of nitric oxide (NO) and prostaglandin E2 (PGE2) (Xu et al., 2017). This process activates nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling cascades (Eo et al., 2021). Therefore, NF-κB and MAPK are considered important targets for the treatment of inflammatory diseases.

Sophora flavescens Ait., S. japonica, and Echinosophora koreensis Nakai. belongs to the genus Sophora (Krishna et al., 2012; Ramekar et al., 2020). E. koreensis Nakai is an endemic plant species with limited distribution within the Korean province of Gangwon, including in the Yanggu-gun, Inje-gun, Cheorwon-gun, Chuncheon-si, and Hongchen-gun counties (Cheon et al., 2009; Yi et al., 2013; Kim et al., 2020). Kang reported that E. koreensis Nakai is used in traditional medicine to treat various disorders such as fever, skin diseases, diuresis, and neuralgia (Kang, 2008). It contains many active compounds, including isoflavonoids and isoflavanones (Iinuma et al., 1991; Choi et al., 2009; Iinuma et al., 1993; Iinuma et al., 1992). Compounds isolated from the roots of E. koreensis Nakai have a variety of biological activities. A previous study reported that sophoraisoflavanone A is a selective inhibitor of cyclooxygenase (COX)-1 (Chi et al., 2001) and has significant antibacterial and antifungal activity (Sohn et al., 2004). Moreover, kenusanone A suppressed 5-lipoxygenase (LOX) and 12-LOX (Chi et al., 2001). Sophoronol potentially prevents “hangovers” after alcohol intake by enhancing the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) (Choi et al., 2009). However, the effects of E. koreensis Nakai root extract (EKRE) on inflammatory responses have not yet been reported. Therefore, the present study seeks to elucidate the anti-inflammatory activity of E. koreensis Nakai root extract in LPS-induced inflammatory responses in RAW 264.7 cells and mouse models with carrageenan-induced paw edema.

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