Yusof Kamisah

Atherosclerosis is the principal underlying pathology of cardiovascular diseases (CVDs), with endothelial dysfunction representing one of the earliest events in its initiation and progression. Oxidised low-density lipoprotein (oxLDL) plays a pivotal role in this process by promoting inflammatory activation and endothelial dysfunction. Squalene and tocotrienol-rich fraction (SQTRF), both derived from palm oil, possess antioxidant and anti-inflammatory properties. However, their combined effects on endothelial dysfunction remain poorly understood. This study investigated the protective effects of SQTRF against oxLDL-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to oxLDL (50 μg/mL) and treated with SQTRF or TRF, with atorvastatin included as a positive control. Endothelial function was assessed by measuring cell viability, proliferation, migration, angiogenesis, and inflammatory gene expression using established in vitro assays and quantitative real-time PCR (qRT-PCR). OxLDL significantly enhanced endothelial migration and inflammatory gene expression without causing marked cytotoxicity. SQTRF preserved cell viability and significantly attenuated oxLDL-induced migration and angiogenesis. SQTRF demonstrated enhanced attenuation of endothelial proliferation and migration compared with TRF alone. These functional improvements were accompanied by downregulation of NF-κB, suggesting suppression of NF-κB-mediated inflammatory activation. Collectively, these findings demonstrate that SQTRF mitigates oxLDL-induced endothelial dysfunction through modulation of inflammatory and angiogenic responses. This study provides mechanistic evidence supporting the potential of SQTRF as a natural therapeutic candidate for attenuating early endothelial dysfunction associated with atherogenesis, warranting further validation in in vivo models and clinical studies.

Managing acute coronary syndrome (ACS) and atherosclerotic cardiovascular disease remains clinically challenging, requiring a careful balance between ischemic protection and bleeding risk. Antiplatelet therapy is central to the management, with aspirin serving as the cornerstone; however, selection of the second antiplatelet agent in dual antiplatelet therapy (DAPT) remains complex. Clopidogrel, a purinergic receptor subtype Y, G protein–coupled, 12 (P2Y ₁₂ ) inhibitor, is widely used but is limited by substantial interindividual variability in antiplatelet response, particularly in populations with a high prevalence of CYP2C19 loss‐of‐function polymorphisms. These limitations prompted the development of more potent P2Y ₁₂ inhibitors, including prasugrel and ticagrelor, which provide faster and more consistent platelet inhibition. However, clinical experience—especially in Asian populations—has highlighted that a “one‐size‐fits‐all” dosing strategy may not be appropriate, as heightened bleeding risk can offset ischemic benefit. This review reexamines the contemporary role of prasugrel, focusing on evidence supporting dose optimization, careful patient selection, and population‐specific considerations. Current evidence suggests that prasugrel remains a valuable antiplatelet option when tailored to individual ischemic and bleeding risks, particularly in patients undergoing complex percutaneous coronary intervention and selected Asian populations requiring individualized antiplatelet strategies.

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the heart’s pumping ability in failing hearts ex vivo. Thus, this study aimed to investigate the potential use of SNA209 as a treatment for isoprenaline (ISO)-induced heart failure in rats. Methods: Forty male Wistar rats were randomly divided into five groups. Heart failure was induced by isoprenaline (ISO, 10 mg/kg/s.c) for 14 days daily, followed by SNA209 treatment (5 mg/kg; p.o) for another 14 days daily. Control rats were given saline as a vehicle for ISO and DMSO as a vehicle for SNA209. Results: Systolic and diastolic blood pressure (SBP and DBP) in all ISO-treated groups were significantly increased compared to the control group (p < 0.05), and SNA209 treatment managed to reduce the SBP and DBP. Additionally, SNA209 treatment significantly increased the heart rate and normalized the ECG parameters in ISO-treated rats. Pro-B-type natriuretic peptide and troponin T level, a cardiac injury markers, was remarkably reduced by SNA209 in the ISO-treated group. Cardiac hypertrophy was evident in increased cardiomyocyte size in ISO groups; however, SNA reduced the cardiomyocyte size. The left ventricular developed pressure (LVDP) in ISO treated with SNA209 was significantly raised, indicating a chronotropic effect. Cardiac Na⁺/K⁺-ATPase expression of the α1 subunit, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a), and sodium–calcium exchanger subunit were significantly increased in the SNA treatment groups. Conclusions: The SNA 209 treatment improved cardiac function and structure, likely via modulating intracellular calcium management, so underscoring its potential as an adjuvant therapy for heart failure.

Parkia speciosa Hassk. is a plant that grows wild in the lowland forests of Southeast Asia. The plant is traditionally used for its medicinal purposes, including treating hypertension and diabetes mellitus. It contains bioactive compounds, such as flavonoids, steroids, and cyclic polysulfide. Pharmacologically, it possesses anti-inflammatory, antidiabetic, antihypertensive, antihypertrophic, and antioxidant properties. The activities may be owing to the existence of bioactive substances in the plant. This chapter collates studies investigating the pharmacological properties of P. speciosa.

Diabetic cardiomyopathy is a significant and severe complication of diabetes that affects a large portion of the global population, with its prevalence continuing to rise. Secondary metabolites, including quercetin, have shown promising effects in mitigating the progression of diabetic cardiomyopathy by targeting multiple pathological mechanisms, including impaired insulin signaling, glucotoxicity, lipotoxicity, oxidative stress, inflammation, fibrosis, apoptosis, autophagy, mitochondrial dysfunction, cardiac stiffness, and disrupted calcium handling. Addressing these mechanisms is crucial to prevent left ventricular diastolic and systolic dysfunction in advanced stages of diabetic heart disease. Scientific evidence has highlighted the cardioprotective properties of quercetin at both the myocardial and cellular/molecular levels in diabetic models. Therefore, this review aims to present a comprehensive overview of the proposed mechanisms underlying quercetin’s beneficial effects, providing valuable insights that could inform future drug discovery efforts specific to diabetic cardiomyopathy.

Cardiovascular diseases (CVD) are the number one cause of death worldwide, with atherosclerosis, which is the formation of fatty plaques in the arteries, being the most common underlying cause. The activation of inflammatory events and endothelium dysfunction are crucial for the development and pathophysiology of atherosclerosis. Elevated circulating levels of low-density lipoprotein (LDL) have been associated with severity of atherosclerosis. LDL can undergo oxidative modifications, resulting in oxidised LDL (oxLDL). OxLDL has been found to have antigenic potential and contribute significantly to atherosclerosis-associated inflammation by activating innate and adaptive immunity. Various inflammatory stimuli such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) play major roles in atherosclerosis. To date, studies have provided valuable insights into the role of oxLDL in the development of atherosclerosis. However, there remains a gap in understanding the specific pathways involved in this process. This review aims to provide and discuss the mechanisms by which oxLDL modulates signalling pathways that cause cardiovascular diseases by providing in vitro and in vivo experimental evidence. Its critical role in triggering and sustaining endothelial dysfunction highlights its potential as a therapeutic target. Advancing the understanding of its atherogenic role and associated signalling pathways could pave the way for novel targeted therapeutic strategies to combat atherosclerosis more effectively.

Endothelial dysfunction is a hallmark of cardiovascular diseases, contributing to impaired vasodilation, altered hemodynamics, and atherosclerosis progression. Trimetazidine, traditionally used for angina pectoris, exhibits diverse therapeutic effects on endothelial dysfunction. This review aims to elucidate the mechanisms underlying trimetazidine’s actions and its potential as a therapeutic agent for endothelial dysfunction and associated cardiovascular disorders. Trimetazidine enhances vasodilation and hemodynamic function by modulating endothelial nitric oxide synthase activity, nitric oxide production, and endothelin-1. It also ameliorates metabolic parameters, including reducing blood glucose, mitigating oxidative stress, and dampening inflammation. Additionally, trimetazidine exerts antiatherosclerotic effects by inhibiting plaque formation and promoting its stability. Moreover, it regulates apoptosis and angiogenesis, fostering endothelial cell survival and neovascularization. Understanding trimetazidine’s multifaceted mechanisms underscores its potential as a therapeutic agent for endothelial dysfunction and associated cardiovascular disorders, warranting further investigation for clinical translation.

Editorial: Be positive about the negative in pharmacology: Ethnopharmacology 2022

Cardiac diseases, such as myocardial infarction and heart failure, have become a major clinical problem globally. The accumulating data demonstrate that bioactive compounds with antioxidant and anti-inflammatory properties have favorable effects on clinical problems. Kaempferol is a flavonoid found in various plants; it has demonstrated cardioprotective properties in numerous cardiac injury models. This review aims to collate updated information regarding the effects of kaempferol on cardiac injury. Kaempferol improves cardiac function by alleviating myocardial apoptosis, fibrosis, oxidative stress, and inflammation while preserving mitochondrial function and calcium homeostasis. However, the mechanisms of action of its cardioprotective properties remain unclear; therefore, elucidating its action could provide insight into directions for future studies.

Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel (I_f) inhibitor, is used in patients with chronic heart failure as an adjunct to other heart failure medications. This review aims to gather updated information regarding the therapeutic use and mechanism of action of ivabradine in heart failure. The drug reduces elevated resting heart rate, which is linked to increased morbidity and mortality in patients with heart failure. Its use is associated with improved cardiac function, structure, and quality of life in the patients. Ivabradine exerts several pleiotropic effects, including an antiremodeling property, which are independent of its principal heart-rate-reducing effects. Its suppressive effects on cardiac remodeling have been demonstrated in animal models of cardiac remodeling and heart failure. It reduces myocardial fibrosis, apoptosis, inflammation, and oxidative stress as well as increases autophagy in the animals. It also modulates myocardial calcium homeostasis, neurohumoral systems, and energy metabolism. However, its role in improving heart failure remains unclear. Therefore, elucidating its molecular mechanisms is imperative and would aid in the design of future studies.