The plant flavonoid, fisetin alleviates cigarette smoke‐induced oxidative stress, and inflammation in Wistar rat lungs

Abstract

In the present study, we tested the antioxidant and anti‐inflammatory potential of the plant flavonoid, fisetin against cigarette smoke‐induced oxidative stress, and inflammation in rat lungs. Male Wistar rats were chronically exposed to cigarette smoke (CS) with or without administration of fisetin. Fisetin administration to CS‐exposed rats resulted in a significant reduction in neutrophils and macrophages in bronchoalveolar lavage fluid as well as malondialdehyde, 3‐nitrotyrosine, 8‐isoprostane, tumor necrosis factor‐alpha, interleukin‐1beta, granulocyte macrophage‐colony stimulating factor, interleukin‐4, and interleukin‐10 levels in lung tissues compared to those in CS‐exposed rats not treated with fisetin. Fisetin also significantly augmented lung hemoxinase‐1, glutathione peroxidase‐2, reduced glutathione, superoxide dismutase, nitric oxide, and nuclear factor erythroid 2‐related factor (Nrf2) levels in CS‐exposed rats. In addition, a marked reversal in CS‐induced histopathological changes was noted in fisetin‐treated rats. Collectively, these data demonstrate the potential of fisetin to blunt CS‐induced oxidative stress and inflammation in the lung and to prevent tissue damage via the Nrf2‐mediated upregulation of antioxidant gene expression. Practical applications In the present study, we found that the plant flavonoid, fisetin significantly abrogated the oxidative stress, inflammation, and tissue damage induced by cigarette smoke, a powerful pro‐oxidant in rat lungs. Additionally, fisetin markedly reversed cigarette smoke‐induced increases in neutrophil and macrophage cell populations in bronchoalveolar lavage fluid. These findings are particularly significant considering the association of cigarette smoking with increased oxidative stress and inflammation, which are central to the pathologies of a wide variety of chronic diseases including chronic obstructive pulmonary disease, cancer, and cardiovascular diseases. Therefore, the present work underscores the beneficial effects of the regular consumption of plant‐based foods with medicinal properties for the effective prevention of these chronic diseases.

Advances in Pharmacological Actions and Mechanisms of Flavonoids from Traditional Chinese Medicine in Treating Chronic Obstructive Pulmonary Disease

“…Fisetin, a plant flavonoid present in Gleditsiae spina , has been shown to be effective in lowering inflammation and oxidative stress associated with different disease conditions. Fisetin (25 or 50 mg) demonstrated a significant decrease in inflammatory mediators such as TNF- α , granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-1 β , IL-4, and IL-10 [ 44 ]. The anti-inflammatory mechanism of fisetin was related to suppressing the TNF- α -activated NF- κ B cascade via targeting protein kinase C [ 33 ].…”

Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence

“…Fisetin (FIS), a natural non-toxic flavonoid, is present in various plants, fruits and vegetables. Previous researches have demonstrated that FIS has anti-inflammatory (Huang et al, 2018), anti-fibrosis, anti-oxidant (Hussain et al, 2019) and anti-aging properties (Yousefzadeh et al, 2018). FIS supplementation can prevent or alleviate hepatic and myocardial fibrosis by inhibiting the expression of fibrosisrelated genes and inactivating TGF-β1/Smad3 signaling (Liu et al, 2019;Choi et al, 2020;Hu et al, 2020).…”

Chinese Herbs and Repurposing Old Drugs as Therapeutic Agents in the Regulation of Oxidative Stress and Inflammation in Pulmonary Diseases

“…Below we will discuss the protective mechanisms of HO-1/CO in respiratory inflammatory diseases. We particularly focus on herbal medicines with the potential to induce HO-1 expression, including salvianolic acid A, 87 asiatic acid, 41 celastrol, 88 fisetin, 89 galangin, 90,91 kaempferol, [92][93][94][95] luteolin, 96 madecassoside, 97,98 oleanolic acid, 99,100 saikosaponin A, 101 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), 102 and pristimerin. 49,103 In the following sections, the detailed pharmacological mechanisms of these herb ingredients will be further discussed.…”

“…255 Conversely, Hussain et al revealed that in lungs exposed to CS, fisetin attenuated inflammation and oxidative stress to protect the lung from CS-mediated injury via the Nrf2dependent expression of antioxidative genes (HO-1, glutathione peroxidase-2, reduced GSH, SOD) to reduce the infiltration of inflammatory cells and cytokine expression. 89 Galangin Galangin (3,5,7-trihydroxyflavone) is found in Alpinia officinarum and honey in high concentrations and is submit your manuscript | www.dovepress.com…”