The protective effect of natural medicines against excessive inflammation and oxidative stress in acute lung injury by regulating the Nrf2 signaling pathway

Abstract

Acute lung injury (ALI) is a common critical disease of the respiratory system that progresses into acute respiratory distress syndrome (ARDS), with high mortality, mainly related to pulmonary oxidative stress imbalance and severe inflammation. However, there are no clear and effective treatment strategies at present. Nuclear factor erythroid 2-related factor 2(Nrf2) is a transcription factor that interacts with multiple signaling pathways and regulates the activity of multiple oxidases (NOX, NOS, XO, CYP) related to inflammation and apoptosis, and exhibits antioxidant and anti-inflammatory roles in ALI. Recently, several studies have reported that the active ingredients of natural medicines show protective effects on ALI via the Nrf2 signaling pathway. In addition, they are cheap, naturally available, and possess minimal toxicity, thereby having good clinical research and application value. Herein, we summarized various studies on the protective effects of natural pharmaceutical components such as polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides on ALI through the Nrf2 signaling pathway and demonstrated existing gaps as well as future perspectives.

Hesperidin Attenuates Hypothyroidism-Induced Lung Damage in Adult Albino Rats by Modulating Oxidative Stress, Nuclear Factor Kappa-B Pathway, Proliferating Cell Nuclear Antigen and Inflammatory Cytokines

“…Flavonoids are compounds that have the capacity to disrupt the NF-κB signaling pathway engaged in regulating the inflammatory enzymes and cytokines involving interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) [ 29 ]. Recent works have shown that natural medicine such as flavonoid active ingredients can decrease inflammatory and oxidative stress and have protective effects against lung injury through the erythroid 2 related factor 2 (Nrf2) signaling pathway [ 30 , 31 ]. Activated Nrf2 is an intracellular antioxidant protective signal distributed in several organs, including the lungs, where antioxidation and detoxification cascades are routinely processed [ 32 ].…”

Dimethyl fumarate alleviates allergic asthma by strengthening the Nrf2 signaling pathway in regulatory T cells

“…It is known that the nuclear translocation of Nrf2 is pivotal to responding to chemical or oxidative stress through its interaction with ARE ( 49 ). Ample investigations have shown that genetic ablation of Nrf2 worsens the inflammation and increases the oxidative stress in numerous disease models, including pulmonary fibrosis ( 50 ), sepsis ( 51 ), acute lung injury ( 52 ), COPD exacerbations ( 53 ), and emphysema ( 54 ). Pharmacological or genetic activation of Nrf2 decreases oxidative stress and inflammation ( 55 ).…”

Alismol Purified from the Tuber of Alisma orientale Relieves Acute Lung Injury in Mice via Nrf2 Activation

“…As shown in Figure 7A and 7B, as low as 10 −7 M of alismol could activate Nrf2. To confirm that alismol activated Nrf2, we examined whether alismol suppressed the ubiquitination of Nrf2 to activate Nrf2, given that Nrf2 became inactivated by ubiquitination [15]. HEK 293 cells were transfected with plasmids encoding V5-tagged Nrf2, Flag-tagged Keap1, and HA-tagged ubiquitin.…”

“…As a countermeasure to the deleterious ROS, cells can activate nuclear factor-E2-related factor 2 (Nrf2) [10], a transcription factor that regulates the expression of NAD(P)H: quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), and glutamyl cysteine ligase catalytic units (GCLC) [11], which are involved in removing and guarding against the harmful effects of ROS. Since studies with Nrf2 knock-out mice have shown a critical role of Nrf2 in protecting mice from ALI [12,13], Nrf2 can be another therapeutic target for treating ALI [14,15].…”