Ferulic acid alleviates lipopolysaccharide‐induced acute lung injury through inhibiting TLR4/NF‐κB signaling pathway

Abstract

Ferulic acid (FA) exhibits anti‐inflammatory, antidiabetic, antihyperlipidemic, antioxidant, neuroprotective, and antihypertensive effects. This study aimed to determine whether FA could ameliorate lipopolysaccharide (LPS)‐induced inflammatory responses and acute lung injury (ALI) in mice. Mice were challenged with LPS intratracheally to induce ALI 1 h after 3 days of FA (25, 50, and 100 mg/kg) or dexamethasone (DEX; 5 mg/kg) administration. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected 12 h after the LPS challenge. Pretreatment with FA or DEX could attenuate lung histopathological change, complement deposition, and lung wet‐to‐dry weight ratio of mice injured by LPS. Meanwhile, the influx of neutrophils and macrophages, as well as the production of proinflammatory cytokine (tumor necrosis factor‐alpha, interleukin 1 beta [IL‐1β], and IL‐6), in BALF of ALI mice was significantly decreased. Moreover, FA or DEX markedly reversed the LPS‐induced elevation of myeloperoxidase activity and monocyte chemoattractant protein‐1 level in lung tissues of ALI mice. In addition, the Western blot analysis demonstrated that FA or DEX effectively inhibited the LPS‐induced activation of the toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐κB) signaling pathway in lung tissues. The current study suggested that the alleviating effect of FA against LPS‐induced ALI might be partially due to the inhibition of the inflammatory response via inactivation of the TLR4/NF‐κB signaling pathway.

Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway

“…CMU2020088). Mice were randomly divided into six groups: Control, LPS, FA (Sigma, Saint Louis, MO, USA), FA + LPS, LPS + Rp-cGMP, and FA + LPS + Rp-cGMP group [ 19 ]. The mice were intratracheally instilled with 5 mg/kg LPS (LPS, FA + LPS LPS + Rp-cGMP, and FA + LPS + Rp-cGMP group) and 5 μg/kg Rp-cGMP (LPS + Rp-cGMP and FA + LPS + Rp-cGMP group), respectively.…”

“…FA has low toxicity and possesses many physiological functions (anti-inflammatory, antioxidant, antimicrobial activity, anticancer, and antidiabetic effect) [ 15 ], which has been proved to be effective in many disease models such as lung injury, diabetes, epilepsy, and hepatotoxicity [ 16 , 17 ]. Nevertheless, the research on the mechanism of FA in respiratory diseases is still limited, most of which stays at the level of inflammatory factors, free radicals and inflammatory cell infiltrations, and rarely involves the level of ion transport [ 18 , 19 ]. Although FA can attenuate LPS-induced lung injury through anti-inflammatory and anti-oxidant activities, there are no detailed studies about the regulation of FA on ENaC, which may also be relevant with the anti-inflammatory effects in LPS induced tracheal injury.…”

Therapeutic Effects and Molecular Mechanisms of Bioactive Compounds Against Respiratory Diseases: Traditional Chinese Medicine Theory and High-Frequency Use

“…Both processes are ameliorated by ferulic acid and hesperidin from Aster tataricus L.f. and Eriobotrya japonica (Thunb.) Lindl., which have antiinflammatory activities and protective effects against ALI by downregulating cytokines and chemokines (Ma et al, 2015;Wu et al, 2021). Furthermore, myeloid differentiation 2 (MD2) and high-mobility group box 1 (HMGB1) are the key targets of hesperidin, through which it can effectively inhibit inflammation during ALI (Liu et al, 2015;Ma et al, 2015).…”

Recent Advances in Biological Activity, New Formulations and Prodrugs of Ferulic Acid

“…The compound shows antithrombotic activity [ 20 ] and anti-inflammatory properties and has a protective function in eye diseases, such as retinal degeneration (observed after supplementation of mice diet with 50 mg/kg of FA) [ 21 ]. It also alleviates acute lung injury through inhibiting the TLR4/NF-κB signaling pathway [ 22 ]. Ferulic acid amide derivatives demonstrated in vivo antidiabetic and hypolipidemic effects [ 23 ].…”