Abstract

Natural products black cumin—Nigella sativa (N. sativa) and wild garlic—Allium ursinum (AU) are known for their potential role in reducing cardiovascular risk factors, including antracycline chemotherapy. Therefore, this study investigates the effect of N. sativa and AU water and methanolic extracts in a cellular model of doxorubicin (doxo)-induced cardiotoxicity. The extracts were characterized using Ultraviolet-visible (UV-VIS) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and Gas Chromatography coupled with Mass Spectrometry (GC-MS) techniques. Antioxidant activity was evaluated on H9c2 cells. Cytosolic and mitochondrial reactive oxygen species (ROS) release was evaluated using 2′,7′-dichlorofluorescin-diacetate (DHCF-DA) and mitochondria-targeted superoxide indicator (MitoSOX red), respectively. Mitochondrial membrane depolarization was evaluated by flow cytometry. LC-MS analysis identified 12 and 10 phenolic compounds in NSS and AU extracts, respectively, with flavonols as predominant compounds. FT-IR analysis identified the presence of carbohydrates, amino acids and lipids in both plants. GC-MS identified the sulfur compounds in the AU water extract. N. sativa seeds (NSS) methanolic extract had the highest antioxidant activity reducing both intracellular and mitochondrial ROS release. All extracts (excepting AU methanolic extract) preserved H9c2 cells viability. None of the investigated plants affected the mitochondrial membrane depolarization. N. sativa and AU are important sources of bioactive compounds with increased antioxidant activities, requiring different extraction solvents to obtain the pharmacological effects.

Highlights

  • Cardiovascular diseases (CVDs) are continuing to be the leading cause of death

  • The quantity of total polyphenolic compounds generally assumed to be responsible for the antioxidant properties of plant extracts, as well as their antioxidant activity, was determined for both N. sativa seeds (NSS) and Allium ursinum (AU) extracts (Table 1)

  • The highest Total Polyphenol Content (TPC) value registered for AU methanolic extract was approximately 17% higher than the highest value registered for NSS methanol extract

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Summary

Introduction

Cardiovascular diseases (CVDs) are continuing to be the leading cause of death. Among the most common risk factors with importance in CVDs etiology and development, are the existing comorbidities such as hypertension, hyperlipidemia, obesity, diabetes mellitus, or others such as genetic factors, age and gender, pharmacological treatments, dietary factors, tobacco use, excessive alcohol use and physical inactivity [2,3]. Antracycline chemotherapy is a well-known high-risk factor for cardiomyopathy since the development of heart failure may occur in up to 65% of doxorubicin The existing ways used to reduce antracyclyne cardiotoxicity, primary or secondary, by the use of classical treatments or by counselling the patients to dietary and lifestyle changes, still needs improvements [6]

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