Neogambogic acid relieves myocardial injury induced by sepsis via p38 MAPK/NF-κB pathway

Abstract

Sepsis-associated myocardial injury, an invertible myocardial depression, is a common complication of sepsis. Neogambogic acid is an active compound in garcinia and exerts anthelmintic, anti-inflammatory, and detoxification properties. The role of neogambogic acid in sepsis-associated myocardial injury was assessed. Firstly, mice were pretreated with neogambogic acid and then subjected to lipopolysaccharide treatment to induce sepsis. Results showed that lipopolysaccharide treatment induced up-regulation of biomarkers involved in cardiac injury, including lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and troponin I (cTnI). However, pretreatment with neogambogic acid reduced levels of LDH, CK-MB, and cTnI, and ameliorated histopathological changes in the heart tissues of septic mice. Secondly, neogambogic acid also improved cardiac function in septic mice through reduction in left ventricular end-diastolic pressure, and enhancement of ejection fraction, fractional shortening, and left ventricular systolic mean pressure. Moreover, neogambogic acid suppressed cardiac apoptosis and inflammation in septic mice and reduced cardiac fibrosis. Lastly, protein expression of p-p38, p-JNK, and p-NF-κB in septic mice was decreased by neogambogic acid. In conclusion, neogambogic acid exerted anti-apoptotic, anti-fibrotic, and anti-inflammatory effects in septic mice through the inactivation of MAPK/NF-κB pathway.

Molecular targets and mechanisms of cortex mori for lung cancer treatment: A network pharmacology study, molecular docking and experimental validation

“…signaling pathway can inhibit the cell cycle and cell apoptosis of lung cancer. A number of studies have been conducted on the PI3K-AKT-mTOR signaling pathway, which is an important pathway in signal transduction in cells, and it is closely related to the occurrence and development of lung cancer by in uencing the activation state of various effector molecules downstream (Fu et al 2022. Han et al 2022).…”

Caged Polyprenylated Xanthones in Garcinia hanburyi and the Biological Activities of Them

“… 55 Studies have concluded that the activated pro-inflammatory cytokines, oxidative stress and inflammation and C-reactive protein (CRP) are key mechanisms in the development of CVD. 56 Fu et al 57 evaluated the role of neoglycyrrhetinic acid in sepsis-associated myocardial injury, and they discovered that GNA exerts anti-apoptotic, anti-fibrotic and anti-inflammatory effects in septic mice through inactivation of the MAPK/NF-κB pathway. Studies have shown that GA can inhibit cardiac hypertrophy and fibrosis induced by pressure or isoprenaline infusion by inhibiting the NF-κB pathways and proteasome, indicating that GA therapy may a new strategy for the treatment of cardiac hypertrophy and fibrosis.…”

“…Recent research has shown that GNA ameliorates cardiac injury and dysfunction in LPS-induced septic mice by inhibiting cardiac apoptosis, fibrosis and inflammation through downregulation of p-JNK and p-NF-κB. 57 In a recent work, binding affinities of xanthone compounds which including morellic acid, gambogellic acid, GNA, moreollic acid with SARS-CoV-2 main protease (Mpro) were predicted using the molecular docking technique, the results showed that morellic acid has a high-binding affinity towards SARS-CoV-2 Mpro, and this suggests that MA is a promising candidate for anti-COVID-19; however, this requires further detailed in vivo experimental estimation and clinical evaluation. 64 …”

PTX3 mediates PI3K/AKT/mTOR signaling to downregulate apoptosis and autophagy to attenuate myocardial injury in sepsis

“…However, mitigating cardiomyocyte autophagy can attenuate sepsis-induced myocardial damage ( Yang et al, 2021 ). In a similar vein, cardiomyocyte apoptosis plays a significant role in the pathological cascade that culminates in myocardial injury during sepsis ( Fu et al, 2022 ). Nonetheless, evidence suggests that curbing cardiomyocyte apoptosis may offer therapeutic benefits in mitigating myocardial damage within the septic milieu ( Li et al, 2019 ).…”