Procyanidin B2 inhibits lipopolysaccharide‑induced apoptosis by suppressing the Bcl‑2/Bax and NF‑κB signalling pathways in human umbilical vein endothelial cells

Abstract

Human umbilical vein endothelial cells (HUVECs) serve a critical role in maintaining normal vascular function. Lipopolysaccharide (LPS), which is released from pathogenic bacteria in the blood, induces HUVEC apoptosis and injury to cause vascular dysfunction and infectious vascular diseases. Procyanidin B2 (PB2) possesses numerous functions, including antioxidant, antitumor, anti-inflammatory and antiapoptosis effects, but the molecular mechanism is not completely understood. The present study investigated the effects of PB2 on LPS-induced cytotoxicity and apoptosis in HUVECs, as well as the underlying mechanisms. The effects of PB2 on LPS-mediated alterations to cytotoxicity, mitochondrial membrane potential, apoptosis were assessed by performing Cell Counting Kit-8, JC-1 fluorescence, Hoechst 33258 staining assays, respectively. IL-1β, IL-6 and TNF-α mRNA expression and protein levels were measured by performing reverse transcription-quantitative PCR and ELISAs, respectively. Bcl-2, Bax, cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, phosphorylated (p)-IκB-α, p-IκB-β, p-NF-κB-p65 and total NF-κB p65 protein expression levels were determined via western blotting. NF-κB p65 nuclear translocation was assessed via immunofluorescence. PB2 pretreatment markedly attenuated LPS-induced cytotoxicity and apoptosis in HUVECs. PB2 also significantly downregulated the expression levels of IL-1β, IL-6, TNF-α, Bax, cleaved caspase-3, cleaved caspase-7, cleaved caspase-9 and p-NF-κB-p65, but upregulated the expression levels of Bcl-2, p-IκB-α and p-IκB-β in LPS-induced HUVECs. Moreover, PB2 markedly inhibited LPS-induced NF-κB p65 nuclear translocation in HUVECs. The results suggested that the potential molecular mechanism underlying PB2 was associated with the Bax/Bcl-2 and NF-κB signalling pathways. Therefore, PB2 may serve as a useful therapeutic for infectious vascular diseases.

Procyanidin B2 Alleviates Heat-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells

“…Hence, low concentrations (5, 10, and 25 μM) of PB2 were used in the study to detect its protective effects under heat exposure. This study found that 5, 10, and 25 μM of PB2, effectively dose-dependently, alleviated the decline in cell viability induced by high temperature, which is consistent with the research results, which suggest that PB2 can ameliorate the reduction in neuronal cell viability caused by cypermethrin [ 23 ] and defense the viability loss of human umbilical vein endothelial cells under lipopolysaccharide (LPS)-stimulated condition [ 24 ].…”

“…However, there are also research findings that show that choline protects bovine mammary epithelial cells from HS-induced oxidative stress by inhibiting the expression and nuclear translocation of Nrf2 [ 46 ]. Similarly, PB2 was reported to protect mice cerebral cortex neurons from cypermethrin-induced oxidative stress by reducing Nrf2 expression and nuclear translocation [ 24 ]. The reason for this difference might be related to the intensity of oxidative stress.…”

CircTMEM165 facilitates endothelial repair by modulating mitochondrial fission via miR-192/SCP2 in vitro and in vivo

“…LPS has been mostly used to study inflammatory responses 42 , 43 , 44 and recently reported to induce HUVEC apoptosis. 45 Recent studies have shown a close relationship between mitochondria and phagosomes following bacterial invasion. 46 Here, we observed that LPS strongly affected mitochondrial dynamics by targeting DRP1 and MFN1 in HUVECs, with circTMEM165 participating in the regulation of this process.…”

Proanthocyanidins may be potential therapeutic agents for the treatment of carotid atherosclerosis: A review

“…Pre-treatment of the cells with PC markedly attenuated LPS-induced cytotoxicity and apoptosis. 37 The authors concluded that the potential molecular mechanism underlying the effects of PC was associated with the Bax/Bcl-2 and NF-κB signalling pathways. They suggested that PC may be useful as a novel therapeutic agent for infectious vascular diseases.…”