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Magnolia Officinalis Ekstraktının Kardiyak Yaşlanmada Gözlenen Mitokondri Fonksiyon Bozukluğu Üzerindeki Düzenleyici Etkileri

Amaç: Bu çalışmada Magnolia Officinalis’ten elde edilen bitkisel bir materyal olan ve anti-enflamasyon, antioksidatif stres ve antiapoptozda önemli rollere sahip olduğu ileri sürülen magnolia ekstraktının (ME), kardiyomiyositlerde yaşlanmaya bağlı artan reaktif oksijen türleri (ROS) üretimi ve mitokondri membran potansiyelinin (MMP) depolarize olması ile koruyucu etkisinin incelenmesi amaçlanmıştır. Bu amaç doğrultusunda, yaşlı kardiyomiyositlerde bu maddenin apoptoz ve endoplazmik retikulum (ER) stresi üzerindeki baskılayıcı etkisinin hangi biyobelirteçler üzerinden olduğunun moleküler düzeyde incelenmesi hedeflenmiştir. Gereç ve Yöntem: Çalışmada sıçan sol ventrikül hücre hattı H9c2’ler kullanılarak in vitro yaşlanma modeli oluşturulmuştur. D-galaktoz (D-Gal; 50 mg/mL) ile 48-saat muamele edilen H9c2 hücreleri, 18 saat boyunca 5 µM ME ile inkübe edilmiş ve yaşlı kardiyomiyositlerdeki ROS üretimi ve MMP depolarizasyonuna etkileri incelenmiştir. ROS ve MMP ölçümleri floresans boyalar olan dichlorofluorescin diacetate (DCFDA) ve carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) kullanılarak konfokal mikroskobunda gerçekleştirilmiştir. ER-stresi belirteçleri Calregulin ve glucose-regulated protein 78 ve apoptoz belirteci olarak ise dengeleyici nükleosit taşıyıcı 1 ifadesindeki ME muamelesi sonrasındaki değişim qRT PCR ölçümleri ile analiz edilmiştir. Bulgular: Yaşlanma modeli oluşturulmuş kardiyomiyositlerin, ME ile inkübasyonu yaşlanmaya bağlı artan ROS üretiminin belirgin şekilde baskılanmasına, depolarize olan MMP’nin normal değerlere dönmesine neden olmuştur. Ayrıca, mitokondri fonksiyon bozukluğu ile gelişen ER-stres ve apoptozun ME muamelesi ile baskılandığı ve bu etkinin altında yatan nedenler arasında oksidatif stres ve apoptoz belirteç genlerinin ifadelerinin normal değerlere doğru iyileştiği gözlenmiştir. Sonuç: Çalışma bulguları, kalp koruyucu etkileri bilinen magnolia officinalis ekstraktının kalp yaşlanması ile kontrolsüz olarak gelişen mitokondri fonksiyon bozukluğunu fonksiyonel ve moleküler düzeyde düzenleyerek yaşlanmaya bağlı artan kalp yetmezliğinde yeni bir tedavi yaklaşımı olarak uygulanabileceğini işaret etmektedir.

The Regulatory Effects of Magnolia Officinalis Extract on Aging-induced Mitochondrial Dysfunction in Cardiomyocytes

Objectives: In this study, it is aimed to examine the protective effect of magnolia extract (ME), a herbal material obtained from Magnolia Officinalis, which is claimed to have an important role in anti-inflammation, antioxidative stress and antiapoptosis, with increased reactive oxygen species (ROS) production due to aging and depolarized mitochondrial membrane potential (MMP) in cardiomyocytes and its suppressive effect on apoptosis and endoplasmic reticulum (ER) stress at the molecular level. Materials and Methods: In the study, an in vitro aging model was created using rat left ventricular cell line H9c2. H9c2 cells treated with D-galactose (D-Gal; 50 mg/mL) for 48 hours were incubated with 5 µM ME for 24 hours and their effects on ROS production and MMP depolarization in aged cardiomyocytes were examined. ROS and MMP measurements were performed under confocal microscopy using fluorescent dyes dichlorofluorescin diacetate (DCFDA) and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP). With the ER- stress markers Calregulin and glucose-regulated protein 78, qRT-PCR measurements of the change in expression of the apoptosis marker equilibrative nucleoside transporter 1 after ME treatment were analyzed.Results: Incubation of aging-modeled cardiomyocytes with ME provides significant suppression of aging-related ROS production and regulation of depolarized MMP. In addition, we observed that ER-stress and apoptosis developed by mitochondrial dysfunction were suppressed by ME treatment, by examining the expressions of stress and apoptosis marker genes. Conclusion: Our findings show that Magnolia officinalis extract, known for its cardioprotective effects, can be applied as a new treatment approach in aging-related heart failure by regulating mitochondrion dysfunction that develops uncontrollably with cardiac aging at the functional and molecular level.

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