Loganin alleviates myocardial ischemia–reperfusion injury through GLP‐1R/NLRP3‐mediated pyroptosis pathway

Abstract

Myocardial ischemia–reperfusion (I/R) injury is one of main pathological manifestations of cardiovascular outcomes related to NLRP3 inflammasome‐mediated pyroptosis pathway. Loganin is an iridoid glycoside extracted from traditional Chinese medicines, which has multiple activities. However, the roles and mechanism of loganin in myocardial I/R injury remain largely unknown. The models of myocardial I/R injury were established using I/R‐treated rats or OGD/R‐treated H9C2 cardiomyocytes. Myocardial damage was assessed by TTC and hematoxylin–eosin staining. Pyroptosis‐related marker levels were detected by immunohistochemistry, immunofluorescence and western blotting assays. Cell proliferation was examined via EdU assay. Cell apoptosis was investigated by LDH release and flow cytometry. The integrity of cell membrane was analyzed via Dil staining. GLP‐1R and NLRP3 levels were detected by immunofluorescence and western blotting assays. Our results showed that loganin suppressed I/R‐induced myocardial damage in rats by reducing myocardial infarct, injury and pyroptosis. In addition, loganin attenuated OGD/R‐induced cardiomyocyte apoptosis through increasing cell proliferation and reducing LDH release and apoptotic rate. Loganin also mitigated OGD/R‐induced cardiomyocyte pyroptosis by reducing cell membrane damage and levels of cleaved caspase‐1, IL‐1β and IL‐18. Furthermore, loganin repressed GLP‐1R/NLRP3 pathway activation in OGD/R‐treated H9C2 cardiomyocytes by enhancing GLP‐1R expression and decreasing NLRP3 level. GLP‐1R/NLRP3 activation by GLP‐1R inhibition or NLRP3 overexpression reversed the suppressive effects of loganin on OGD/R‐induced cardiomyocyte pyroptosis. These data indicated that loganin prevented OGD/R‐induced proliferation inhibition, apoptosis and pyroptosis in OGD/R‐treated cardiomyocytes by inhibiting GLP‐1R/NLRP3 activity, indicating the therapeutic potential of loganin in myocardial I/R injury.

Pyroptosis in Diabetic Peripheral Neuropathy and its Therapeutic Regulation

“… 242 Li and co-workers also indicated that LGN treatment attenuated OGD/R-induced cardiomyocyte pyroptosis by alleviating cell membrane damage and inhibiting the pyroptosis-related protein expression level of Cleaved Caspase-1, IL-1β and IL-18. 243 Furthermore, LG intervention blocked GLP-1R/NLRP3 pathway activation in OGD/R-stimulated H9C2 cardiomyocytes by promoting GLP-1R expression and obstructing NLRP3 inflammasome stimulation. 243 Intriguingly, LGN treatment mitigates ROS production, inhibits NF-κB–P2RX7–TNXIP protein expression and alleviates NLRP3 inflammasome-mediated RSC96 cell damage.…”

“… 243 Furthermore, LG intervention blocked GLP-1R/NLRP3 pathway activation in OGD/R-stimulated H9C2 cardiomyocytes by promoting GLP-1R expression and obstructing NLRP3 inflammasome stimulation. 243 Intriguingly, LGN treatment mitigates ROS production, inhibits NF-κB–P2RX7–TNXIP protein expression and alleviates NLRP3 inflammasome-mediated RSC96 cell damage. Previous research has indicated that LGN mitigates the generation of inflammatory mediators including IL-1β by restricting the activation of NF-κB signaling pathway in the spinal cord tissue of PDN rat models.…”

Loganin exerts neuroprotective effect by inhibiting neuronal pyroptosis in rat with cerebral haemorrhage

“…12,13 It has shown that loganin was able to ameliorate high glucoseinduced Schwann cells pyroptosis by inhibiting reactive oxygen species (ROS) production as well as NLRP3 inflammasome activation and attenuated myocardial ischemia-reperfusion injury through the GLP-1R/NLRP3-mediated thermoprotein deposition pathway. 14,15 However, only a few studies have demonstrated the neuroprotective effects of loganin on brain diseases such as Alzheimer's disease. 16,17 Existing research on loganin has hinted at its capacity to influence key signalling pathways involved in neuroprotection, including the ADORA2A and MLCK pathways, which play pivotal roles in the regulation of cerebral oedema and neuronal survival post-ICH.…”

“…Particularly, adenosine A2A receptor (ADORA2A) agonists, improve experimental autoimmune encephalomyelitis (EAE) by inhibiting the myosin light chain kinase (MLCK) signalling pathway and are associated with blood–brain barrier dysfunction induced by Th1 cytokines 12,13 . It has shown that loganin was able to ameliorate high glucose‐induced Schwann cells pyroptosis by inhibiting reactive oxygen species (ROS) production as well as NLRP3 inflammasome activation and attenuated myocardial ischemia–reperfusion injury through the GLP‐1R/NLRP3‐mediated thermoprotein deposition pathway 14,15 . However, only a few studies have demonstrated the neuroprotective effects of loganin on brain diseases such as Alzheimer's disease 16,17 .…”

Loganin inhibits Liver Cancer Cell Proliferation and Metastasis via Blocking Mitogen-Activated Protein Kinase Signaling Pathway

“…Loganin alleviated the pathologies and cognitive impairment, as well as molecular deficits in Alzheimer's disease mouse models [8] . Li et al [9] showed that loganin inhibited ischemia-reperfusion-evoked myocardial injury by reducing pyroptosis and myocardial infarct. Importantly, loganin impeded cell proliferation, cell cycle and induced death in liver cancer [10] .…”