Panax Notoginseng Saponins Protect H9c2 Cells From Hypoxia-reoxygenation Injury Through the Forkhead Box O3a Hypoxia-inducible Factor-1 Alpha Cell Signaling Pathway.

Panax notoginseng saponins (PNS) are commonly used in the treatment of cardiovascular diseases. Whether PNS can protect myocardial ischemia-reperfusion injury by regulating the forkhead box O3a hypoxia-inducible factor-1 alpha (FOXO3a/HIF-1α) cell signaling pathway remains unclear. The purpose of this study was to investigate the protective effect of PNS on H9c2 cardiomyocytes through the FOXO3a/HIF-1α cell signaling pathway. Hypoxia and reoxygenation of H9C2 cells were used to mimic MIRI in vitro, and the cells were treated with PNS, 2-methoxyestradiol (2ME2), and LY294002." Cell proliferation, lactate dehydrogenase, and malonaldehyde were used to evaluate the degree of cell injury. The level of reactive oxygen species was detected with a fluorescence microscope. The apoptosis rate was detected by flow cytometry. The expression of autophagy-related proteins and apoptosis-related proteins was detected by western blot assay. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway. Furthermore, the protective effects of PNS were abolished by HIF-1α inhibitor 2ME2 and PI3K/Akt inhibitor LY294002. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway.

Liu XW ，Lu MK ，Zhong HT ，Liu JJ ，Fu YP ... -  《-》

Panax Notoginseng Saponins Attenuate Myocardial Ischemia-Reperfusion Injury Through the HIF-1α/BNIP3 Pathway of Autophagy.

Liu XW ，Lu MK ，Zhong HT ，Wang LH ，Fu YP ... -  《-》

Panax quinquefolius saponins and panax notoginseng saponins attenuate myocardial hypoxia-reoxygenation injury by reducing excessive mitophagy.

Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2',7'-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway.

Xia J ，Chen C ，Sun Y ，Li S ，Li Y ，Cheng BR ，Pang Y ，Li Y ，Li D ，Lin Q ... -  《-》

Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes.

Chen S ，Liu J ，Liu X ，Fu Y ，Zhang M ，Lin Q ，Zhu J ，Mai L ，Shan Z ，Yu X ，Yang M ，Lin S ... -  《-》

Sevoflurane postconditioning attenuates cardiomyocytes hypoxia/reoxygenation injury via PI3K/AKT pathway mediated HIF-1α to regulate the mitochondrial dynamic balance.

Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects. The H9C2 cardiomyocytes were cultured to establish the hypoxia-reoxygenation (H/R) model and randomly divided into 4 groups: Control group, H/R group, sevoflurane postconditioning (H/R + SpostC) group and PI3K/AKT blocker (H/R + SpostC + LY) group. Cell survival rate was determined by CCK-8; Apoptosis rate was determined by flow cytometry; mitochondrial membrane potential was evaluated by Mito Tracker™ Red; mRNA expression levels of AKT, HIF-1α, Opa1and Drp1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR); Western Blot assay was used to detect the protein expression levels of AKT, phosphorylated AKT (p-AKT), HIF-1α, Opa1 and Drp1. Compared with the H/R group, the survival rate of cardiomyocytes in the H/R + SpostC group increased, the apoptosis rate decreased and the mitochondrial membrane potential increased. qRT-PCR showed that the mRNA expression of HIF-1α and Opa1 were higher in the H/R + SpostC group compared with the H/R group, whereas the transcription level of Drp1 was lower in the H/R + SpostC group. In the H/R + SpostC + LY group, the mRNA expression of HIF-1α was lower than the H/R + SpostC group. There was no difference in the expression of Opa1 mRNA between the H/R group and the H/R + SpostC + LY group. WB assay results showed that compared with the H/R group, the protein expression levels of HIF-1α, Opa1, P-AKT were increased and Drp1 protein expression levels were decreased in the H/R + SpostC group. HIF-1α, P-AKT protein expression levels were decreased in the H/R + SpostC + LY group compared to the H/R + SpostC group. SpostC mediates HIF-1α-regulated mitochondrial fission and fusion-related protein expression to maintain mitochondrial dynamic balance by activating the PI3K/AKT pathway and increasing AKT phosphorylation, thereby attenuating myocardial I/R injury.

Ma H ，Hou T ，Wu J ，Zhao J ，Cao H ，Masula M ，Wang J ... -  《BMC Cardiovascular Disorders》