Amentoflavone Ameliorates Carrageenan-Induced Pleurisy and Lung Injury by Inhibiting the NF-κB/STAT3 Pathways via Nrf2 Activation

Abstract

Many natural flavonoids can activate nuclear factor erythroid 2-related factor 2 (Nrf2), which is pivotal for alleviating various diseases related to inflammation and oxidative stress, including pleurisy. Amentoflavone (AMF), a biflavonoid extracted from many plants, has some beneficial bioactivities, especially anti-inflammatory and antioxidative activities. We aimed to investigate whether AMF protects against pleurisy and lung injury induced by carrageenan (Car) by activating Nrf2. Pleurisy was induced in wild-type (WT) and Nrf2-deficient (Nrf2-/-) mice. Then, pleural exudate and lung tissue were collected for biochemical analysis, H&E staining, immunocytochemistry and western blotting. Our results indicated that AMF protected against Car-induced pleurisy and lung injury. The Wright-Giemsa and H&E staining results showed that AMF alleviated inflammatory effusion and pathological injury. In addition, AMF decreased SOD and GSH depletion and MDA and MPO generation in the lung tissue of mice. AMF activated Nrf2 through keap-1 dissociation and subsequently increased heme oxygenase-1 (HO-1), NAD(P)H-quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine ligase (GCL) levels. Furthermore, AMF suppressed IL-1β and TNF-α levels and increased IL-10 levels in pleural exudate by blocking the proinflammatory NF-κB, signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) pathways induced by Car. However, these antioxidative and anti-inflammatory effects were weakened in Nrf2-/- mice. Moreover, AMF failed to suppress the NF-κB and STAT3 pathways in Nrf2-/- mice. Our results demonstrated that AMF exerted anti-inflammatory and antioxidative effects in Car-induced lung injury and pleurisy in a Nrf2-dependent manner.

Renieramycin T Inhibits Melanoma B16F10 Cell Metastasis and Invasion via Regulating Nrf2 and STAT3 Signaling Pathways

“…Persistently activated STAT3 is associated with the proliferation, survival, and invasiveness of tumor cells, including those of breast, lung, pancreatic, and head and neck origin. Recent studies suggested the possibility of the interplay or cross talk between Nrf2 and STAT3 [40,41]. In our studies, RT restrained the phosphorylation of STAT3 and decreased Nrf2 in protein levels, suggesting that the STAT3/Nrf-2 signaling axis might be involved in the mechanism of RT repressing migration and invasion.…”

Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis

“…Interestingly, these characteristic effects of SIRT1 inhibition by CPA were dose-dependently mitigated in the present work with the administration of AMV. These favorable effects may be attributed to the ability of AMV to increase the genetic expression of SIRT1 with a subsequent increase in Nrf2 content in the pulmonary tissues, which restores the prooxidant/antioxidant balance to normal values [16,42]. In addition, the enhancement of the histone deacetylase activity of SIRT1 mediated by AMV may underlie the mitigating effects of AMV detected in the present study on the inflammatory cascade [16,43].…”

A Review on Bioactive Phytochemical Constituents and Pharmacological Activities of Aegiceras corniculatum: A Pharmaceutically Important Mangrove Plant

“…By combining diferent in vivo and in vitro models (Tables 2 and 3), a study indicates that extracts obtained from A. corniculatum, specifcally methanol and ethyl acetate extracts, exhibit notable inhibitory efects on the chronic infammatory phase and these efects are observed through the suppression of mononuclear cell infltration, fbroblast proliferation, collagen fber production, and connective tissue formation, all of which contribute to the development of granuloma [45]. Carrageenan-induced pleurisy is a very common method used to test anti-infammatory therapeutics [49]. Methanol and ethyl acetate extract of A. corniculatum protects against acute lung infammation by lowering nitrate/nitrite concentrations and MPO enzyme levels and also decreases neutrophils and mononuclear infltration at a higher dose (100 mg/kg) in a mice model of pleurisy [47] (Table 3).…”