Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway

Abstract

Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo, rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury. In vitro, primary cultured neonatal ventricular myocytes exposed to hypoxia/reoxygenation (H/R) were applied to further discuss the anti-H/R injury property of GC. The results revealed that GC significantly improved the symptoms of MI/R injury, as evidenced by reducing infarct size, preventing myofibrillar degeneration and reversing the mitochondria dysfunction. Moreover, histological analysis and Myeloperoxidase (MPO) activity measurement showed that GC remarkably suppressed Polymorphonuclears (PMNs) infiltration and ameliorated the histopathological damage. Furthermore, GC pretreatment was shown to improve H/R-induced ventricular myocytes viability and enhance tolerance of inflammatory insult, as evidenced by suppressing expression of CD40, translocation of NF-κB p65 subunit, phosphorylation of IκB-α, as well as the activity of IKK-β. In addition, downstream inflammatory cytokines modulated by NF-κB signaling were effectively down-regulated both in vivo and in vitro, as determined by immunohistochemistry and ELISA. In conclusion, these results indicate that GC possesses a beneficial effect against MI/R injury via inflammation inhibition that may involve suppression of CD40-NF-κB signal pathway and downstream inflammatory cytokines expression, which may offer an alternative medication for MI/R diseases.

Cardioprotection of Ginkgolide B on Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Regulation of A20-NF-κB Pathway

“…Both MI/RI and CI/RI are hypoxic and anoxic diseases, which have similar characteristics in pathogenesis and treatment, suggesting that GB may possess a potential value in the treatment strategy of MI/RI. Meanwhile, we have just proved that Ginkgolide C (GC) which possessed the similarity chemical structure to GB could exert a protective effect against MI/RI via inhibiting inflammation which might involve in blocking CD40-NF-κB signal pathway (21). However, it has not been illuminated whether GB has the similar effect of improving MI/RI yet.…”

“…The third heart slice was stained with hematoxylin-eosin (H&E) and analyzed by light microscopy in three random fields. The intensity of histopathological damage was evaluated via pathological scores in accordance with the criteria reported by the previous study (21): (1) score 0: no damage; (2) score 1: mild damage; (3) score 2: moderate damage; (4) score 3: severe damage; (5) score 4: highly severe damage. The mean of the absolute number of PMNs was also recorded in three random high-power fields (HPF).…”

“…Rat ventricular myocytes were separated from the hearts of 1–4-day-old Sprague-Dawley rats according to trypsin enzymic digestion and differential attachment methods as described previously (21). Three days later, the cells were finally purified at a density of 1 × 10 5 /mL in DMEM medium supplemented with 10% fetal calf serum in 95% air/5% CO 2 at 37°C.…”

“…Nuclear and Cytoplasmic Protein Extraction Kit (Beyotime Biotechnology, Beijing, China) was applied to extract the cytoplasmic and nuclear proteins from cells according to the manufacturer's instruction as described previously (21). The protein concentrations were determined by BCA assay.…”

Role of Ginkgolides in the Inflammatory Immune Response of Neurological Diseases: A Review of Current Literatures

“…GC also shows a beneficial effect against myocardial I/R injury via inhibition of inflammation, possibly via suppression of the CD-40-NF-κB signaling pathway and downstream inflammatory cytokine expression. These may offer an alternative treatment for myocardial I/R diseases (Zhang et al, 2018 ; Figure 3 ).…”