Alchemilla vulgaris modulates isoproterenol-induced cardiotoxicity: interplay of oxidative stress, inflammation, autophagy, and apoptosis
Nuha Anajirih, Ahmed Abdeen, Ehab S. Taher, Afaf Abdelkader, Hoda A. Abd-Ellatieff, Mahmoud S. Gewaily, Nashwa E. Ahmed, Rasha Hamed Al‐Serwi, Safwa M. Sorour, Heba M. Abdelkareem, Elturabi Ebrahim, Mohamed El‐Sherbiny, Florin Imbrea, Ilinca Imbrea, Mahmoud M. Ramadan, Ola A. Habotta
Abstract
Introduction: Isoproterenol (ISO) is regarded as an adrenergic non-selective β agonist. It regulates myocardial contractility and may cause damage to cardiac tissues. Alchemilla vulgaris (AV) is an herbal plant that has garnered considerable attention due to its anti-inflammatory and antioxidant bioactive components. The present investigation assessed the cardioprotective potential of AV towards ISO-induced myocardial damage. Methods: Four groups of mice were utilized: control that received saline, an ISO group (85 mg/kg, S.C.), ISO + AV100, and ISO + AV200 groups (mice received 100 or 200 mg/kg AV orally along with ISO). Results and discussion: ISO induced notable cardiac damage demonstrated by clear histopathological disruption and alterations in biochemical parameters. Intriguingly, AV treatment mitigates ISO provoked oxidative stress elucidated by a substantial enhancement in superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) content, as well as a considerable reduction in malondialdehyde (MDA) concentrations. In addition, notable downregulation of inflammatory biomarkers (IL-1β, TNF-α, and RAGE) and the NF-κB/p65 pathway was observed in ISO-exposed animals following AV treatment. Furthermore, the pro-apoptotic marker Bax was downregulated together with autophagy markers Beclin1 and LC3 with in ISO-exposed animals when treated with AV. Pre-treatment with AV significantly alleviated ISO-induced cardiac damage in a dose related manner, possibly due to their antioxidant and anti-inflammatory properties. Interestingly, when AV was given at higher doses, a remarkable restoration of ISO-induced cardiac injury was revealed.