Metabolomics based mechanistic insights to vasorelaxant and cardioprotective effect of ethanolic extract of Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds in isoproterenol induced myocardial infraction.

BACKGROUND: Cardiovascular diseases (CVDs) are a significant cause of morbidity and death in the current world, posing a challenge to both developing and industrialized nation's health systems. Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds have long been utilized to supplement and enhance health and treat cardiovascular illnesses. However, its treatments for CVDs are still unknown. More research is required to fully comprehend the impact of C. lanatus seeds on vasorelaxation and myocardial infractions. PURPOSE: Therefore, an integrated metabolomics profiling technique was used to investigate possible pathways of C. lanatus in isoproterenol (ISO)-induced myocardial infarction (MI). Isoproterenol causes long-term cardiac hypertrophy by causing cardiomyocyte compensatory loss, eventually leading to heart failure. METHODS: In vitro models of vasoconstriction, atrium, and in vivo models of invasive blood pressure measurement and isoproterenol (ISO) induced cardiac hypertrophy in rats were used to understand underlying mechanistic by LC-MS/MS based dynamic metabolomics analysis of the serum and heart samples to be investigated the effect of ethanolic extract of C. lanatus (Cl.EtOH). RESULTS: Cl.EtOH exhibited vasorelaxant, negative chronotropic, and inotropic effects in in-vitro models whereas, a potent hypotensive effect was observed in normotensive rats. The Cl.EtOH protected the animals from ISO-induced myocardial infarction (MI) with therapeutic interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, biochemical assays, and metabolomic profiling of serum and heart tissues. CONCLUSIONS: For the first time, our study confirmed that C. lanatus seeds (Cl.EtOH) possess significant antihypertensive and prevent ISO-induced myocardial infarction. These findings comprehensively demonstrated mechanistic insights of Cl.EtOH in vasorelaxation and myocardial infarction. The current study provides evidence for further mechanistic studies and the development of C. lanatus seeds as a potential therapeutic intervention for patients with cardiovascular disorders.

Metabolomics analysis delineates the therapeutic effects of hydroethanolic extract of Cucumis sativus L. seeds on hypertension and isoproterenol-induced myocardial infarction.

Cucumis sativus L., widely cultivated as an edible vegetable. Its seeds are well reputed for cardiovascular preventive properties. However, the mechanisms underlying for cardiovascular protection of C. sativus are still unidentified. Therefore, this study utilized a metabolomics approach to investigate putative mechanisms of C. sativus seeds in myocardial infarction (MI) and in vitro models of vasoconstriction, atrium, and invasive blood pressure measurement. Results showed that Cu.EtOH extract showed a vasorelaxant response with potent hypotensive effect in normotensive rats and L-NAME induced hypertension. Cu.EtOH caused a negative inotropic and positive chronotropic effect on the atrium. Cu.EtOH protected the animals from ISO-induced myocardial infarction (MI) interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, and biochemical assays. The metabolomics data suggested that Cu.EtOH mainly affected amino acid metabolism, BCAA degradation, ketone bodies degradation, and oxidative stress. Our study showed that Cu.EtOH suppressed inflammation with a strong anti-myocardial infarction impact. Additionally, our findings indicated Cu.EtOH reverted the amino acid metabolism, BCAA, and ketone bodies degradation. The findings show the antihypertensive mechanism of Cu.EtOH may include the modulation of endothelium-derived relaxing factor (EDRF) produced from nitric oxide (NO) and is connected with vascular endothelial function. C. sativus seeds, in particular, played a pivotal role in the treatment of myocardial and vascular disorders by enhancing the EDRF mechanism, energy generation, and antioxidant capacity. In summary, our findings showed the mechanistic insights on the therapeutic potential of C. sativus seeds for cardiovascular disorders.

Cardioprotective, hypotensive and toxicological studies of Populus ciliata (Wall. ex Royle).

Populus ciliata Wall ex. Royle has folkloric repute to treat various cardiovascular ailments and related disorders. The current study was designed to evaluate the toxic profile, cardioprotective and hypotensive effects of Populus ciliata (Wall. ex Royle). Populus ciliata crude ethanolic extract (Pc. Cr) and its aqueous (Pc. Aq) & organic (Pc. Dcm) fractions were tested on isolated aorta of rat and rabbit having intact and non-intact endothelium respectively. Pc. Cr & Pc. Aq relaxed the contractions induced by PE (1 µM)-induced and K+ (80 mM)-induced on aorta, possibly by mediating endothelium derived relaxing factor (EDRF) in intact endothelium and voltage dependent L-type calcium channels blocking (CCB) mechanism in non-intact endothelium. Pc. Cr showed anti-hypertensive & cardioprotective activity by decreasing force of contraction & heart rate on isolated rabbit paired atria and reduced blood pressure in anesthetized rat. Cardioprotective effect of Pc. Cr was assessed in isoproterenol induced acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) in Sprague Dawley rats. In LVH, Pc. Cr exerted positive effects by decreasing angiotensin II & renin and increasing cGMP & nitric oxide (NO) with reduced cardiac fibrosis, necrosis and cardiac cell size. In AMI, Pc. Cr responded effectively by decreasing cardiac markers creatinine kinase (CK), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LD) in blood associated with less edema and necrosis. Presence of catechin, vinallic acid, P-coumeric acid and quercitin identified through HPLC support the effectiveness of Pc. Cr in hypertension, AMI and LVH. Pc. Cr showed no significant adverse effects in Sprague Dawley albino rats after acute & sub-acute treatment in histopathological investigation. Extract of Populus ciliata showed vasorelaxant, hypotensive and cardioprotective effect in Sprague Dawley albino rats and white albino rabbit by mediating EDRF and voltage dependent L-type CCB mechanism respectively.

Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents.

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases.