<p>Inhibition Of JNK Phosphorylation By Curcumin Analog C66 Protects LPS-Induced Acute Lung Injury</p>

Abstract

BackgroundAcute lung injury (ALI) is characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Curcumin analog C66, having reported as an inhibitor of c-Jun N-terminal kinase (JNK), exhibits anti-inflammatory property both in vitro and in vivo. However, whether C66 is capable of reducing lipopolysaccharide (LPS)-induced ALI through the inhibition of inflammation by targeting JNK remains unknown.MethodsIntratracheal injection of LPS was employed to build a mouse ALI model. H&E staining, wet/dry ratio, immunofluorescence staining, inflammatory cell detection, and inflammatory gene expression were used to evaluate lung injury and lung inflammation. In vitro, LPS was used to induce the expression of inflammatory cytokines both in protein and gene levels.ResultsThe results of our studies showed that the pretreatment with C66 and JNK inhibitor SP600125 was capable of attenuating the LPS-induced ALI by detecting pulmonary edema, pathological changes, total protein concentration, and inflammatory cell number in bronchoalveolar lavage fluid (BALF). Besides, C66 and SP600125 also suppressed LPS-induced inflammatory cytokine expression in BALF, serum, and lung tissue. In vitro, LPS-induced production of TNF-α and IL-6 and gene expression of TNF-α, IL-6, IL-1β, and COX-2 could be inhibited by the pretreatment with C66 and SP600125. It was found that C66 and SP600125 could inhibit LPS-induced phosphorylation of JNK both in vitro and in vivo.ConclusionIn brief, our results suggested that C66 protects LPS-induced ALI through the inhibition of inflammation by targeting the JNK pathway. These findings further confirmed the pivotal role of JNK in ALI and implied that C66 is likely to serve as a potential therapeutic agent for ALI.

The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia

“…Inflammation plays a pivotal role in the pathogenesis of lung complications of viral infection, as manifested by lung edema, hemorrhage, neutrophil infiltration, and alveolar thickening. Studies indicate that curcumin and its analogs are capable of attenuating lung injury (Suresh et al, 2012;Avasarala et al, 2013;Zhang et al, 2015;Xiao et al, 2019). Polymorphonuclear neutrophils (PMNs) infiltration is associated with pulmonary edema and could release oxidants and proteases, which consequently damage the alveolar-capillary membrane, leading to leakage of plasma proteins out of blood vessels, thereby causing pulmonary edema (Matthay and Zimmerman, 2005).…”

“…It has been shown that curcumin can inhibit the infiltration of PMNs, including (GR1 + ), CD4 + , CD19 + B cells, NK cells, and CD8 + T cells, and promote the apoptosis of PMN by increasing the level of P-p38 (Avasarala et al, 2013). More recently, Xiao et al (2019) have reported that curcumin analog C66 protects lipopolysaccharide (LPS)induced ALI through suppression of the JNK pathway and subsequent inhibition of inflammatory cytokine expression. Similar protective effects of curcumin have been reported in the rodent model of ventilator-induced lung injury (Wang et al, 2018) and Staphylococcus S.aureus-induced ALI (Xu et al, 2015) as evidenced by attenuation of inflammatory cell infiltration, lung edema due to its anti-inflammatory and antioxidant effects.…”

“…Mechanistically, curcumin protects the lung by inhibiting inflammation and production of ROS through regulation of multiple signaling pathways engaging peroxisome proliferatoractivated receptor γ (PPARγ) (Cheng et al, 2018), JNK (Xiao et al, 2019), NF-κB (Suresh et al, 2012;Wang et al, 2018), and Nrf2 (Dai et al, 2018;Han et al, 2018). Notably, the role of curcumin in regulating Nrf2/HO-1 has been reported in IAV infection (Dai et al, 2018;Han et al, 2018).…”

Salvianolic acid B attenuated cisplatin-induced cardiac injury and oxidative stress via modulating Nrf2 signal pathway

“…Cisplatin purchased from MedChemExpress (Monmouth, NJ, USA) was dissolved in phosphate buffer and given intraperitoneally for 3 days. The dosage and treatment time of SalB were chosen according to previous published papers (Feng et al, 2015;Liu et al, 2016Liu et al, , 2018Xiao et al, 2019). Experiment 2: 18 male mice were randomly divided into 3 groups: saline group, cisplatin (10 mg/kg) group, and cisplatin (10 mg/kg/day) +SalB (10 mg/kg/day) group, with n = 6 in each group.…”

A Review on the Relevance of Curcuminoids in Corona Pandemic Situation

“…Studies show that curcumin and its analogues are able to ameliorate lung damage.Infiltration of polymorphonuclear neutrophils (PMNs) is associated with pulmonary edoema and may release oxidants and proteases that damage the alveolar-capillary membrane and cause plasma proteins to leak out of the blood vessels, thus causing pulmonary edoema [16]. More recently, Xiao et al [17]reported that curcumin analogue C66 prevents lipopolysaccharide (LPS)-induced ALI by suppressing the JNK pathway (Jun aminoterminal kinases) and subsequently inhibiting the expression of inflammatory cytokines. Cytokine storm is triggered by numerous causes that may emerge from autoimmune, inflammatory, iatrogenic, and infectious origins [18].…”