Cardioprotective Effect of Hydroxysafflor Yellow A via the Cardiac Permeability Transition Pore

Abstract

Myocardial ischemia damages cardiac myocytes in part via opening of the mitochondrial permeability transition pore. Preventing this pore's opening is therefore a useful therapeutic goal in treating cardiovascular disease. Hydroxysafflor yellow A has been proposed as a nontoxic alternative to other agents that modulate mitochondrial permeability transition pore opening. In this study, we proposed that hydroxysafflor yellow A prevents mitochondrial permeability transition pore formation in anoxic cardiac myocytes, and thus protects the cell from damage seen during reoxygenation of the cardiac myocytes. Experiments with hydroxysafflor yellow A transport in aerobic myocytes show that roughly 50% of the extracellular dye concentration crosses the cell membrane in a 2-h incubation. In our anoxia/reoxygenation protocol, hydroxysafflor yellow A modulated both the reduction of viability and the loss of rod-shaped cells that attend anoxia and reoxygenation. Hydroxysafflor yellow A's protective effect was similar to that of cyclosporin A, an agent known to inhibit mitochondrial permeability transition pore opening. In additional experiments, plated myocytes were loaded with calcein/MitoTracker Red, then examined for intracellular dye distribution/morphology after anoxia/reoxygenation. Hydroxysafflor yellow A-containing cells showed a cardioprotective pattern similar to that of cyclosporin A (an agent known to close the mitochondrial permeability transition pore). We conclude that hydroxysafflor yellow A can enter the cardiac myocyte and is able to modulate anoxia/reoxygenation-induced damage by interacting with the mitochondrial permeability transition pore.

Therapeutic Potential of Hydroxysafflor Yellow A on Cardio-Cerebrovascular Diseases

“…Beside inflammation and apoptosis, MI/R damages cardiomyocytes in part via the opening of the mitochondrial permeability transition pore (mtPTP), a non-selective pore that penetrates the inner and outer mitochondrial membranes (Bhosale and Duchen, 2019). HSYA has the capability to enter the cardiomyocytes and then inhibit mtPTP opening to alleviate H/R-induced myocardial injury through the enhanced endothelial nitric oxide synthase (eNOS)-produced NO (Liu et al, 2008;Huber et al, 2018).…”

“…Decreases JAK2/signal transducer and activator of transcription 1 activity, enhances antioxidant capacity and decreases apoptosis (Zhou et al, 2019) Hyperlipidemia combined with MI/R model in male Wistar rats 8, 16, 32 mg•kg -1 i.p. Suppresses the over-expression of TLR4 (Han et al, 2016) H/R and LPS-induced neonatal rat ventricular myocytes 1, 3, 10 mmol•L -1 / Decreases excessive secretion of inflammatory cytokines, down-regulates over-expression of TLR4 and NF-kB (Han et al, 2016) H/R-induced H9c2 cells 6.25, 12.5, 25 mmol•L -1 / Improves cardiomyocyte viability, maintains mitochondrial membrane potential, reduces apoptotic cardiomyocytes, decreases Caspase-3 activity, and inhibits NLRP3 inflammasome activation (Ye et al, 2020) H/R-induced H9c2 cells 1.25, 5, 20 mmol•L -1 / Activates the hexokinase II proteins, restores mitochondrial energy, reduces ROS generation (Min and Wei, 2017) H/R-induced H9c2 cells 20 mmol•L -1 / Inactivates the JAK2/signal transducer and activator of the transcription 1 pathway (Zhou et al, 2019) H/R-induced H9c2 cells 5, 20, 80 mmol•L -1 / Up-regulates HO-1 expression through the PI3K/Akt/Nrf2 signaling pathway (Liu et al, 2012) MI/R model in hearts isolated from male SD rats 50, 100, 200 mmol•L -1 / Enhances NO production by eNOS activation (Liu et al, 2008) H/R-induced cardiomyocytes isolated from SD rat hearts 100, 200 mmol•L -1 / Modulates the reduction of viability and the loss of rodshaped cells, and interacts with the mtPTP (Huber et al, 2018) Hypertension Male spontaneous hypertension rat and normotensive Wistar-Kyoto rats…”

Жирнокислотний Склад Міокарду Гусей За Дії Вікасолу

“…Виходячи з цих даних, вікасол може викликати в міокарді зміни жирнокислотного складу тканин, а правильно підібрана доза препарату забезпечить підвищення опірності організму до негативних чинників, що може бути використано при виборі технології годування та лікування сільськогосподарської птиці. У той же час позитивний ефект на функціональний стан міокарду підтверджується широким застосуванням хінонів як кардіопротекторних препаратів [9,15,21,34].…”

Hydroxysafflor Yellow A: A Promising Therapeutic Agent for a Broad Spectrum of Diseases

“…The protective effect of HSYA on the myocardial ischemia/reperfusion (MI/R) rats and the ventricular myocytes isolated from those animals could be attenuated by a MPTP opener called atractyloside and a restrainer of nitric oxide synthase (NOS) named L-NAME [ 12 ]. Meanwhile, in the isolated cardiac myocytes stimulated by anoxia/reoxygenation or ionomycin, HYSA increased rod shape cells in the closed MPTP condition and decreased round cells with open MPTP [ 13 ]. Another two targets of HYSA against MI or MI/R damage are hemeoxygenase-1 (HO-1) and hemeoxygenase-2 (HO-2).…”