Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage

Abstract

BackgroundAcute lung injury (ALI) is a life-threatening inflammatory disease without effective therapeutic regimen. Macrophage polarization plays a key role in the initiation and resolution of pulmonary inflammation. Therefore, modulating macrophage phenotype is a potentially effective way for acute lung injury. Cryptotanshinone (CTS) is a lipophilic bioactive compound extracted from the root of Salvia miltiorrhiza with a variety of pharmacological effects, especially the anti-inflammatory role. In this study, we investigated the therapeutic and immunomodulatory effects of CTS on ALI.Materials and methodsThe rat model of ALI was established by intratracheal instillation of LPS (5 mg/kg) to evaluate the lung protective effect of CTS in vivo and to explore the regulation of CTS on the phenotype of lung macrophage polarization. LPS (1 μg/mL) was used to stimulate RAW264.7 macrophages in vitro to further explore the effect of CTS on the polarization and metabolic reprogramming of RAW264.7 macrophages and to clarify the potential mechanism of CTS anti-ALI.ResultsCTS significantly improved lung function, reduced pulmonary edema, effectively inhibited pulmonary inflammatory infiltration, and alleviated ALI. Both in vivo and in vitro results revealed that CTS inhibited the differentiation of macrophage into the M1 phenotype and promoted polarization into M2 phenotype during ALI. Further in vitro studies indicated that CTS significantly suppressed LPS-induced metabolic transition from aerobic oxidation to glycolysis in macrophages. Mechanistically, CTS blocked LPS-induced metabolic transformation of macrophages by activating AMPK.ConclusionThese findings demonstrated that CTS regulates macrophage metabolism by activating AMPK, and then induced M1-type macrophages to transform into M2-type macrophages, thereby alleviating the inflammatory response of ALI, suggesting that CTS might be a potential anti-ALI agent.

Cryptotanshinone affects HFL-1 cells proliferation by inhibiting cytokines secretion in RAW264.7 cells and ameliorates inflammation and fibrosis in newborn rats with hyperoxia induced lung injury

“…However, effective therapeutic agents for BPD treatment are scarce ( Poets and Lorenz, 2018 ). Previous studies have shown that CTS plays an important role in lung injury ( Jiang et al, 2019 ; Ye et al, 2022 ), and the anti-inflammatory and anti-fibrotic effects of CTS are gradually being explored ( Li et al, 2021 ). Accordingly, this study aimed to explore the anti-inflammatory and anti-fibrotic effects of CTS in a BPD model.…”

“…Six fields of view were randomly selected for each stained section for observation under a light microscope (magnification, ×40). Ye et al (2022) assessed the degree of inflammatory damage in the lung using a score based on four parameters: the degree of interstitial oedema, inflammatory cell infiltration, alveolar septal thickness and alveolar congestion level. The score was graded as follows: Level 0 was normal; Level 1 was 25%; Level 2 was 25%–50%; Level 3 was 50%–75%; and Level 4 was ≥75%.…”

“…Cryptotanshinone (CTS) is a bioactive ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza , which possess the pharmacological activities such as anti-inflammatory ( Li et al, 2011 ; Nagappan et al, 2019 ), anti-tumour ( Dalil et al, 2022 ), anti-fibrotic ( Wang et al, 2022 ; Wei et al, 2023 ) and neuroprotective ( Mao et al, 2021 ) effects. Recently, it was reported that CTS showed potent anti-inflammatory properties by modulating macrophage polarization in vitro ( Ye et al, 2022 ) and attenuated lipopolysaccharide-induced acute lung injury in mice by inhibiting the TLR4-mediated NF-κB signaling pathway ( Tang et al, 2014 ). In a radiation-induced lung injury model in rats, CTS ameliorated lung injury by regulating TGF-β signaling as well as NOX4 expression ( Jiang et al, 2019 ).…”

Fibroblast Growth Factor 21 Relieves Lipopolysaccharide-Induced Acute Lung Injury by Suppressing JAK2/STAT3 Signaling Pathway

“…HE lung injury scores were calculated by light microscopic analysis of 4 parameters including alveolar septal thickness, interstitial edema, infiltration of inflammatory cells, and alveolar congestion/collapse. Each parameter was categorized into four grades: 0 = normal, 1 ≤ 25%, 2 = 25–50%, 3 = 50–75%, and 4 ≥ 75%, and the mean score of the four parameters was used to represent the overall lung injury [ 23 ].…”