AUTHOR=Anajirih Nuha , Abdeen Ahmed , Taher Ehab S. , Abdelkader Afaf , Abd-Ellatieff Hoda A. , Gewaily Mahmoud S. , Ahmed Nashwa E. , Al-Serwi Rasha H. , Sorour Safwa M. , Abdelkareem Heba M. , Ebrahim Elturabi , El-Sherbiny Mohamed , Imbrea Florin , Imbrea Ilinca , Ramadan Mahmoud M. , Habotta Ola A. TITLE=Alchemilla vulgaris modulates isoproterenol-induced cardiotoxicity: interplay of oxidative stress, inflammation, autophagy, and apoptosis JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1394557 DOI=10.3389/fphar.2024.1394557 ISSN=1663-9812 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.