Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases

Wang, Jiahui; Liu, Yongjian; Guo, Yushi; Liu, Cen; Yang, Yuping; Fan, Xiaoxiao; Yang, Hongliu; Liu, Yonggang; Ma, Tao

doi:10.1016/j.bcp.2023.115973

Cited by 16 publications

(2 citation statements)

References 190 publications

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“…The MAPK family, encompassing extracellular signalregulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase, is activated by the MAPK-like protein, MAPK kinase, and the MAPK signaling cascade system. It has been reported that the MAPK pathway regulates the orchestration of inflammatory cascades (Wang et al, 2024). Numerous studies have highlighted the multifaceted connections between MAPK pathway and lipid metabolism (Wu et al, 2022).…”

Section: Gapdh Aacgaccccttcattgac Tccacgacatactcagcacmentioning

confidence: 99%

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

Chen,

Feng

et al. 2024

Biomedical Chromatography

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Qingxuan Zhike granules (QXZKG), a traditional Chinese patent medication, has shown therapeutic potential against acute lung injury (ALI). However, the precise mechanism underlying its lung‐protective effects requires further investigation. In this study, integrated network pharmacology, molecular docking, and lipidomics were used to elucidate QXZKG's regulatory effect on lipid metabolism in lipopolysaccharide‐induced ALI. Animal experiments were conducted to substantiate the efficacy of QXZKG in reducing pro‐inflammatory cytokines and mitigating pulmonary pathology. Network pharmacology analysis identified 145 active compounds that directly targeted 119 primary targets of QXZKG against ALI. Gene Ontology function analysis emphasized the roles of lipid metabolism and mitogen‐activated protein kinase (MAPK) cascade as crucial biological processes. The MAPK1 protein exhibited promising affinities for naringenin, luteolin, and kaempferol. Lipidomic analysis revealed that 12 lipids showed significant restoration following QXZKG treatment (p < 0.05, FC >1.2 or <0.83). Specifically, DG 38:4, DG 40:7, PC O‐40:8, TG 18:1_18:3_22:6, PI 18:2_20:4, FA 16:3, FA 20:3, FA 20:4, FA 22:5, and FA 24:5 were downregulated, while Cer 18:0;2O/24:0 and SM 36:1;2O/34:5 were upregulated in the QXZKG versus model groups. This study enhances our understanding of the active compounds and targets of QXZKG, as well as the potential of lipid metabolism in the treatment of ALI.

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Section: Gapdh Aacgaccccttcattgac Tccacgacatactcagcacmentioning

confidence: 99%

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

Chen,

Feng

et al. 2024

Biomedical Chromatography

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“…Among them, p38 MAPK, a member of the MAPK family, is an important pathway mediating cellular force transduction. It can be activated by extracellular mechanical stress or stretch to participate in physiological and pathological processes such as cytoskeletal remodeling, proliferation, and differentiation [20,21]. However, the role of p38 MAPK in the mechanical signaling mechanism of acupuncture needs to be further investigated.…”

Section: Introductionmentioning

confidence: 99%

The Role of p38 Mitogen-Activated Protein Kinase-Mediated F-Actin in the Acupuncture-Induced Mitigation of Inflammatory Pain in Arthritic Rats

Zhou,

Zhang,

et al. 2024

Brain Sciences

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The analgesic efficacy of acupuncture has been widely recognized. However, the mechanism by which manual acupuncture-generated mechanical stimuli translate into biological signals remains unclear. This study employed a CFA-induced inflammatory pain rat model. Acupuncture intervention was then performed following standardized procedures. Enzyme-linked immunosorbent assay (ELISA) assessed inflammatory cytokines levels, while immunofluorescence and qRT-PCR screened the level of p38 and F-actin expression in the ST36 acupoint area of rats. Results indicated increased inflammatory factors, including IL-1β and TNFα, with reduced paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) in CFA rats compared to unmodeled rats. After acupuncture intervention, the heightened expression level of F-actin and p38 mRNA and the phosphorylation of p38 in the acupoint area was observed alongside decreased inflammatory factors in diseased ankle joints. The application of lifting and thrusting manipulations further enhanced the effect of acupuncture, in which the molecular expression level of muscle and connective tissue increased most significantly, indicating that these two tissues play a major role in the transformation of acupuncture stimulation. Moreover, antagonizing p38 expression hindered acupuncture efficacy, supporting the hypothesis that p38 MAPK-mediated F-actin transduces mechanical signals generated by acupuncture and related manipulation into biological signals.

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Esculin alleviates lipopolysaccharide (LPS)–induced pneumonia by regulating the USP7/MAPK14 axis

Wang,

Li,

Wang

et al. 2024

J of Applied Toxicology

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Pneumonia is a serious and life‐threatening lung inflammation with high morbidity and mortality. Accumulating evidence has suggested that esculin, a derivative of coumarin, possesses potent anti‐inflammatory effects. This study is designed to explore the pharma role and underlying mechanism of esculin against lipopolysaccharides (LPS)‐induced pneumonia. TC‐1 cells were stimulated by LPS to mimic the inflammatory injury model in vitro. Cell viability, proliferation, and apoptosis were determined using MTT assay, 5‐ethynyl‐2′‐deoxyuridine assay, and flow cytometry. Interleukin‐1β and tumor necrosis factor α levels were analyzed using an enzyme‐linked immunosorbent assay. Reactive oxygen species and superoxide dismutase were examined using special assay kits. Macrophage polarization was detected using flow cytometry. Mitogen‐activated protein kinase 14 (MAPK14) level was detected by real‐time quantitative polymerase chain reaction. MAPK14 and ubiquitin‐specific protease 7 (USP7) protein levels were determined using western blot assay. After Ubibrowser database prediction, the interaction between USP7 and MAPK14 was verified using a Co‐immunoprecipitation assay. The biological role of esculin was verified in LPS‐challenged ALI mice in vivo. Here, we found that esculin significantly relieved LPS‐induced TC‐1 cell proliferation inhibition, and apoptosis, inflammatory response, oxidative stress, and M1‐type macrophage polarization promotion. MAPK14 and USP7 expressions were enhanced in LPS‐treated TC‐1 cells, which was partly abolished by esculin treatment. Overexpressing MAPK14 attenuated the repression of esculin on LPS‐triggered TC‐1 cell injury. At the molecular level, USP7 interacted with MAPK14 and maintained its stability by removing ubiquitin. Moreover, esculin repressed the progression of pneumonia in vivo by regulating MAPK14. Taken together, esculin exposure could mitigate LPS‐induced TC‐1 cell injury partly by targeting the USP7/MAPK14 axis, providing a better understanding of the role of esculin in the anti‐inflammatory therapeutics for pneumonia.

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Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases

Cited by 16 publications

References 190 publications

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

The Role of p38 Mitogen-Activated Protein Kinase-Mediated F-Actin in the Acupuncture-Induced Mitigation of Inflammatory Pain in Arthritic Rats

Esculin alleviates lipopolysaccharide (LPS)–induced pneumonia by regulating the USP7/MAPK14 axis

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