Total flavonoids of Dracocephalum moldavica L. inhibit oxidative stress against H9c2 cell ischemia-reperfusion injury via VEGF-B/AMPK pathway
10.16438/j.0513-4870.2022-1449
- VernacularTitle:香青兰总黄酮通过VEGF-B/AMPK通路缓解氧化应激抗H9c2细胞缺血再灌注损伤
- Author:
Kaderyea KADER
1
;
Jian-guo XING
1
;
Di-wei LIU
1
;
Rui-fang ZHENG
2
;
Zu-wen MA
3
Author Information
1. Xinjiang Institute of Materia Medica, Urumqi 830002, China
2. Xinjiang Institute of Materia Medica, Urumqi 830002, China; School of Preclinical Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
3. The Fifth Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China
- Publication Type:Research Article
- Keywords:
total flavonoids of Dracocephalum moldavica L.;
myocardial ischemia reperfusion injury;
hypoxia/re-oxygenation;
oxidative stress;
apoptosis;
vascular endothelial growth factor B;
adenosine 5'-monophosphate (AMP)-activated protein kinase
- From:
Acta Pharmaceutica Sinica
2023;58(9):2685-2693
- CountryChina
- Language:Chinese
-
Abstract:
Total flavonoids of Dracocephalum moldavica L. (TFDM) is an effective component extracted and isolated from the traditional Uighur medicinal herb Cymbidium fragrans. Cymbidium fragrans has the effects of tonifying the heart and brain, promoting blood circulation and resolving blood stasis, and has been widely used in the treatment of cardiovascular and cerebrovascular diseases for a long time. The purpose of this study was to determine the effect of total flavonoids from Cymbidium fragrans on hypoxia/re-oxygenation (H/R) injury in H9c2 (rat cardiomyocytes) cells and its mechanism. A model (H/R) of hypoxia/re-oxygenation injury in H9c2 cells was established using hypoxia and glucose deprivation for 9 h combined with re-oxygenation and rehydration for 2 h to simulate myocardial ischemia-reperfusion injury. The effects of total flavonoids from Cymbidium fragrans on cell viability, markers of myocardial cell damage, oxidative stress levels, and reactive oxygen radical (ROS) content were investigated, Western blot was used to detect the expression of vascular endothelial growth factor B (VEGF-B) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway related proteins. The results showed that the total flavonoids of Cymbidium fragrans significantly increased the viability of myocardial cells after H/R injury, and decreased the content of lactate dehydrogenase (LDH) and creatine kinase isozyme (CK-MB) in the cell supernatant. It significantly reduced malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decreased intracellular ROS and nitric oxide (NO) content. Western blot analysis showed that the total flavonoids of Cymbidium fragrans decreased Bax levels in H9c2 cells damaged by H/R and increased Bcl-2 expression. Total flavones of Cymbidium fragrans upregulate VEGF-B/AMPK pathway related proteins VEGF-B, vascular endothelial growth factor receptor 1 (VEGFR-1), neuropilin 1 (NRP-1), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated adenosine monophosphate activated protein (p-AMPK) and phospho mechanistic target of rapamycin (p-MTOR) levels. The above research results indicate that the total flavonoids of Cymbidium can significantly reduce the H/R injury of myocardial cells, which may be related to the upregulation of VEGF-B/AMPK pathway and inhibition of oxidative stress response.
