Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages

Jiang, Cheng; Zhang, Jiechun; Xie, Hui; Guan, Huiting; Li, Rui; Chen, Caixia; Dong, Hua; Zhou, You; Zhang, Wei

doi:10.1016/j.biopha.2021.112408

Cited by 24 publications

(12 citation statements)

References 47 publications

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“…Studies have demonstrated that QJHTD has an obvious effect in the treatment of ALI (Zhang, 2021). Major components of QJHTD such as baicalin (Ding et al, 2016), baicalein (Jiang et al, 2022), wogonin (Takagi et al, 2014), wogonoside (Zhang et al, 2014), geniposide (Xiaofeng et al, 2012), glycyrrhizic acid (Zhao et al, 2016), and platycodin D (Tao et al, 2015) showed good therapeutic effects on ALI. Furthermore, baicalein has been found to inhibit neutrophil respiratory burst activity and its ROS production (Reina et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

et al. 2022

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Qing-Jin-Hua-Tan-Decoction (QJHTD), a classic famous Chinese ancient prescription, has been used for treatment of pulmonary diseases since Ming Dynasty. A total of 22 prototype compounds of QJHTD absorbed into rat blood were chosen as candidates for the pharmacological network analysis and molecular docking. The targets from the intersection of compound target and ALI disease targets were used for GO and KEGG enrichment analyses. Molecular docking was adopted to further verify the interactions between 22 components and the top 20 targets with higher degree values in the component–target–pathway network. In vitro experiments were performed to verify the results of network pharmacology using SPR experiments, Western blot experiments, and the PMA-induced neutrophils to produce neutrophil extracellular trap (NET) model. The compound–target–pathway network includes 176 targets and 20 signaling pathways in which the degree of MAPK14, CDK2, EGFR, F2, SRC, and AKT1 is higher than that of other targets and which may be potential disease targets. The biological processes in QJHTD for ALI mainly included protein phosphorylation, response to wounding, response to bacterium, regulation of inflammatory response, and so on. KEGG enrichment analyses revealed multiple signaling pathways, including lipid and atherosclerosis, HIF-1 signaling pathway, renin–angiotensin system, and neutrophil extracellular trap formation. The molecular docking results showed that baicalin, oroxylin A-7-glucuronide, hispidulin-7-O-β-D-glucuronide, wogonoside, baicalein, wogonin, tianshic acid, and mangiferin can be combined with most of the targets, which might be the core components of QJHTD in treatment of ALI. Direct binding ability of baicalein, wogonin, and baicalin to thrombin protein was all micromolar, and their KD values were 11.92 μM, 1.303 μM, and 1.146 μM, respectively, revealed by SPR experiments, and QJHTD could inhibit Src phosphorylation in LPS-activated neutrophils by Western blot experiments. The experimental results of PMA-induced neutrophils to produce NETs indicated that QJHTD could inhibit the production of NETs. This study revealed the active compounds, effective targets, and potential pharmacological mechanisms of QJHTD acting on ALI.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

et al. 2022

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“…Studies on acute lung injury described that the increased DRP1 damaged mitochondrial function, reduced the production of mitochondrial ATP, and increased ROS. DRP1 reduced the expression of inflammatory factors in macrophages by inhibiting the nuclear factor kappa B (NF‐κB) signalling pathway 54 . A similar phenomenon was observed in the airway epithelium stimulated by PM2.5, accompanied by a decrease in mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis 55 .…”

Section: Mitochondrial Dysfunction In Copd Is Related To Lipid Metabo...mentioning

confidence: 67%

The relationship between cholesterol metabolism and mitochondrial function in chronic obstructive pulmonary diseases

Wang

2022

Clinical and Translational Dis

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With the development of lipidomics, the significance of lipid metabolism in various lung diseases has been noticed recently. Among them, cholesterol metabolism plays a crucial role in the pathological process of chronic obstructive pulmonary diseases (COPD). Cholesterol accumulation could lead to mitochondrial dysfunction, such as impaired respiration, imbalanced dynamics and decreased adenosine triphosphate production, while mitochondrial dysfunction, especially altered mitochondrial dynamics, could also disrupt lipid homeostasis in cells. This review focuses on cholesterol metabolism and mitochondrial function in COPD and discusses the potential mechanisms of the steroidogenic acute regulatory-related lipid transfer domain family (STARD), especially STARD3. The review provides new insights for understanding the pathological process between STARD and mitochondria and new therapeutic targets in COPD.

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“…Baicalein is a flavonoid compound naturally found in the Chinese herb Scutellaria baicalensis . Baicalein possesses several pharmacological activities, including alleviation of inflammation ( Wang X. et al, 2021 ; Jiang et al, 2022 ) and oxidative stress ( Dai C. et al, 2021 ; Liu BY. et al, 2021 ).…”

Section: Phytochemicals For the Treatment Of Idd By Targeting Inflamm...mentioning

confidence: 99%

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

et al. 2022

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Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

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Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages

Cited by 24 publications

References 47 publications

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

The relationship between cholesterol metabolism and mitochondrial function in chronic obstructive pulmonary diseases

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

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