Background: Oxidative stress and maladaptive cardiac remodeling are key contributors to heart failure progression. Xestospongia testudinaria, a marine sponge rich in bioactive compounds, possesses antioxidant and lipid-modulating properties. This study investigated the cardioprotective and antioxidant effects of Xestospongia testudinaria methanolic extract (Xesto) in an isoprenaline-induced rat model of heart failure. Methods: Thirty-five healthy male Wistar rats weighing 200-250 g were used in this study. Heart failure was induced in rats via subcutaneous administration of isoprenaline (10 mg/kg/day) for 14 days. Rats were subsequently treated with Xesto (15 mg/kg/day, oral gavage), digoxin (10 mg/kg/day), or saline for an additional 14 days. Hemodynamic parameters, serum NT-proBNP, oxidative stress biomarkers, biochemical indices, hematological parameters, and histopathological changes were evaluated. Molecular docking was performed to assess the interaction of Xesto constituents with Kelch-like ECH-associated protein 1 (KEAP1). Results: Isoprenaline administration significantly increased blood pressure, NT-proBNP, malondialdehyde, hepatic enzymes, and urea levels, while reducing superoxide dismutase and catalase activities. Xesto treatment significantly improved hemodynamic parameters, restored antioxidant enzyme activities, reduced lipid peroxidation, and normalized biochemical and hematological alterations. Histological analysis demonstrated reduced cardiomyocyte hypertrophy and collagen deposition in Xesto-treated rats. Docking analysis showed favorable binding of trans-phytol within the KEAP1 Kelch domain, suggesting possible modulation of antioxidant regulatory pathways. Conclusions:Xestospongia testudinaria exhibited significant cardioprotective and antioxidant effects in isoprenaline-induced heart failure, potentially through enhancement of endogenous antioxidant defenses and attenuation of pathological cardiac remodeling. These findings support its potential as a marine-derived therapeutic candidate for oxidative stress-associated cardiovascular disorders.

Acute kidney injury secondary to myocardial ischemia-reperfusion is a serious complication driven by oxidative stress and inflammation. Although reperfusion restores oxygenation, it also increases reactive oxygen species generation, worsening renal injury. S-allyl cysteine, a garlic-derived organosulfur compound, exerts antioxidative effects by enhancing endogenous antioxidant defenses. Hence, this study investigates the effects of S-allyl cysteine in ovariectomized rats subjected to myocardial ischemia-reperfusion injury. Thirty-two female Wistar rats underwent either ovariectomy (n=24) or sham surgery (n=8). After a 3-week recovery, myocardial ischemia-reperfusion injury was induced by 30 min of left anterior descending coronary artery ligation followed by 2 h of reperfusion. S-allyl cysteine or propargylglycine was administered via the right carotid artery at reperfusion onset. Kidney tissues were analyzed biochemically and histologically. S-allyl cysteine significantly reduced malondialdehyde levels and insignificantly increased both glutathione level and catalase activity in renal tissues. However, no changes were observed in superoxide dismutase activity and hydrogen sulfide levels. Renal histology revealed that S-allyl cysteine preserved renal morphology in ovariectomized rats, likely via reactive oxygen species scavenging and Nrf2 pathway activation. This study concludes that S-allyl cysteine attenuates myocardial ischemia-reperfusion-induced kidney injury in estrogen-deficient rats by reducing oxidative stress and enhancing antioxidant defenses, suggesting potential as a therapeutic supplement to reduce risk of acute kidney injury in menopausal women.

Background:The incidence of haze from Indonesian forest and peatland fires is a major concern due to its adverse health effects, particularly due to fine particulate matter (PM2.5) exposure, leading to adverse effects on the lungs. Aim:This study designed a whole-body PM2.5 exposure chamber to develop a PM2.5 exposure model with varying concentrations and durations, and then evaluated its impact on lung tissue. Methods:Thirty-six male Wistar rats were randomly divided into four groups: a control group and three treatment groups with PM2.5 exposure at concentrations of 300, 500, and 700 µg/m³ for 10, 20, and 30 days. The morphology of PM2.5 was characterized using a scanning electron microscope (SEM) equipped with an energy-dispersive X-ray spectroscopy (EDS) detector. Lung tissue histology was assessed using hematoxylin and eosin for lung injury scoring and Masson's trichrome for the percentage of fibrotic areas. Results:SEM-EDS results showed particles deposited within the alveolar cavity. The highest PM2.5 exposure group (700 µg/m³) had significantly higher lung tissue injury scores and fibrotic areas than the control group across all durations (p < 0.05). Conclusion:Exposure to PM2.5 from peat land-burning smokecauses significant lung tissue injury and fibrosis in a dose-dependent manner in Wistar rats.

Metabolic syndrome (MetS) is a growing global health problem characterized by central obesity, dyslipidemia, hypertension, and insulin resistance. It poses a major burden, particularly in low- and middle-income countries where lifestyle changes and limited healthcare access accelerate its rise. This review highlights advances from 2014–2024 in understanding MetS, with a focus on the therapeutic promise of natural phytochemicals such as polyphenols, flavonoids, and alkaloids. Evidence was drawn from preclinical, clinical, and population-based studies retrieved from PubMed, Scopus, and Web of Science databases using search terms including combinations of ''metabolic syndrome,'' ''phytochemicals,'' ''polyphenols,'' ''flavonoids,'' ''alkaloids,'' and related metabolic markers, with inclusion criteria focusing on original research articles, systematic reviews, and clinical trials published between 2014 and 2024. Across 152 studies, phytochemicals consistently improved markers of MetS. They lowered triglycerides, raised high-density lipoprotein cholesterol (HDL-C), reduced fasting glucose and homeostatic model assessment for insulin resistance (HOMA-IR), and improved blood pressure regulation. Mechanistic data show polyphenols like resveratrol and epigallocatechin gallate (EGCG) enhance AMP-activated protein kinase (AMPK) signaling and glucose transporter type 4 (GLUT4) activity; flavonoids such as quercetin reduce nuclear factor kappa B (NF-κB)-driven inflammation; and alkaloids like berberine modulate gut microbiota and insulin receptor signaling. These compounds act on overlapping molecular pathways including AMPK, peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and microbial communities, giving them broad protective potential. Despite promising results, issues of bioavailability, dosage, and inconsistent study designs limit translation. Safety profiles remain favorable, but large-scale, long-term clinical trials are needed. Phytochemicals represent a cost-effective and complementary approach to managing MetS and reducing its cardiovascular and diabetic complications.

The α7nAchR gene is expressed in immune cells, including macrophages, and is linked to cardiovascular diseases. The cardioprotective effects of α7nAchR activation against inflammation in isoprenaline-induced myocardial injury are unclear. This study aims to assess the cardioprotective effects of α7nAChR activation on isoprenaline-induced myocardial injury rats. We hypothesized that α7nAChR activation provides cardioprotection against the myocardial injury via the cholinergic anti-inflammatory pathway. Isoprenaline hydrochloride (85 mg/kg) was injected subcutaneously in rats to induce myocardial injury and activated the a7nAchR through daily transcutaneous tragus stimulation for 14 days at 20 Hz, 0.2 ms, and 2 mA. Examination on Langendorff isolated heart perfusion technique showed improvement in cardiac functions. The electrical stimulation affected collagen deposition, circulating troponin T, and circulating inflammatory marker TNFα. The effects were abolished with pharmacological inhibition of α7nAChR. Further, the role of α7nAChR in ischemia-induced inflammation was studied in RAW264.7 macrophages. Inflammation was activated in RAW264.7 macrophages that were treated with glucose-free media, flushed with 95% N2, and 5% CO2 for 1 h, and reoxygenated in a normoxic incubator for 24 h. a7nAchR stimulation in the activated macrophages reduced pro-inflammatory markers (NO, TNFα) but did not affect anti-inflammatory (IL10, TGFb) expression levels. The reduction in pro-inflammatory factors was linked to the modulation of the transcriptional regulator NFκB, but not STAT3. Our findings suggest that activation of the cholinergic anti-inflammatory pathway may protect against isoprenaline-induced cardiac injury by improving cardiac performance and regulating inflammatory macrophage activity potentially via the NFκB/TNFα pathway.

Ethnopharmacological relevance: Eriobotrya japonica (Thunb.) Lindl. (EJ), commonly known as loquat, is a fruit tree from the Rosaceae family, traditionally used in various cultures for its medicinal properties. Originating from Southeast China, it has been utilized in traditional medicine across countries like Indonesia, Japan, India, and Turkey. The leaves and fruits of Eriobotrya japonica are known for their expectorant, anti-inflammatory, and antidiabetic effects, among others. The plant contains a rich profile of phytochemicals including phenolic compounds, flavonoids, and triterpenes, which contribute to its pharmacological activities. Aim of the study: This study aims to provide a comprehensive analysis of the phytochemical constituents, traditional uses, and therapeutic potentials of Eriobotrya japonica. The study evaluates the scientific evidence supporting the ethnopharmacological relevance of the plant and identifies areas for future research. Materials and methods: A literature review was conducted, querying several databases for research articles published in English from 1960 to February 2024. Studies included were those investigating the phytochemistry, biological activity, traditional use, and pharmacological properties of Eriobotrya japonica. The methodology involved the extraction and isolation of bioactive compounds, in vitro and in vivo assays to determine pharmacological effects, and toxicity studies to assess safety. Results and discussion: This study reveals that Eriobotrya japonica contains a wealth of bioactive compounds, exhibiting notable antioxidant, anti-inflammatory, antidiabetic, and antitumor properties. Traditional uses in various cultures align with the pharmacological properties observed in scientific studies. However, the mechanisms of action of many compounds remain partially understood, and comprehensive toxicity studies are lacking. The potential for drug development from Eriobotrya japonica compounds is substantial, given their diverse therapeutic effects. Conclusion: Eriobotrya japonica exhibits a wide range of pharmacological activities that support its traditional uses. The presence of bioactive phytochemicals makes it a promising candidate for the development of new therapeutic agents. Future research should focus on elucidating the mechanisms of action, conducting clinical trials to confirm efficacy and safety, and exploring the potential for developing novel drugs from its constituents.

Cardiovascular diseases are a major global health issue, particularly among menopausal women who experience hormonal fluctuations and increased oxidative stress. Estrogen, a key hormone in females, provides cardioprotection by upregulating cystathionine γ-lyase expression and enhancing hydrogen sulfide production. S-allyl cysteine, found abundantly in aged garlic extract, has been shown to protect against vascular dysfunction through the antioxidative mechanism. Thus, this study aims to investigate the vasodilatory effects of S-allyl cysteine in ovariectomized rats, a model for estrogen deficiency in menopausal women. Female Wistar rats (170–220 g, n = 32) underwent either ovariectomy or sham operations and were given a 21-day recovery period before being sacrificed. The rats’ aortic rings were isolated and suspended in a tissue bath and placed between two tungsten wires, connected to an isometric force transducer. Pre-constriction with phenylephrine (PE, 10−6 M) was followed by S-allyl cysteine incubation and a cumulative dose–response curve using acetylcholine (10−9 to 10−4 M). Statistical analysis was performed using one-way and two-way ANOVA with significance set at p < 0.05. The results indicated a significant increase in aortic relaxation after S-allyl cysteine incubation, which also led to a higher percentage of potassium chloride–induced contraction, suggesting activation of potassium ion channels in the endothelium. This was supported by the observation that dl-propargylglycine, a cystathionine γ-lyase inhibitor, blocked S-allyl cysteine’s vasodilatory effect. The study concludes that S-allyl cysteine modulates vascular function, likely through the cystathionine γ-lyase/hydrogen sulfide signaling pathway. These findings highlight S-allyl cysteine can be a natural supplement that aids in cardioprotection for menopausal women.

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.

The integration of nanotechnology and flavonoid research represents a novel approach to deliver and stabilize flavonoid, potent natural antioxidants present in various fruits and vegetables, renowned for their beneficial effects on cardiovascular function. This review provides an overview of the latest advancements nanotechnology to enhance flavonoid bioavailability, delivery, and efficacy. We examined various nanocarriers, including liposomes, nanoparticles, and nanoemulsions, that are utilized for encapsulating flavonoids. This encapsulation serves to protect flavonoids from degradation and enable their effective biodistribution in cardiovascular tissues. Recent research indicates that nanoencapsulated flavonoids improve therapeutic effets by lowering oxidative stress and inflammation; and improving lipid profiles in cardiovascular diseases. Moreover, we investigated the mechanism contributing to the cardiovascular advantages of flavonoids, including their ability to regulate endothelial function, blood pressure, and atherosclerosis prevention. Additionally, we analyzed challenges in translating these discoveries into clinical practice, such as ensuring safety, optimizing dosage, and addressing regulatory requirements. Future prospects include increasing production capacity, conducting extensive toxicity research over an extended period, and executing comprehensive clinical trials to confirm the efficacy of flavonoid based nanotherapeutics in maintaining cardiovascular health and managing related diseases. The integration of nanotechnology and flavonoid research represents a novel approach to deliver and stabilize flavonoids, potent natural antioxidants renowned for their cardiovascular benefits. This review provides an overview of the latest advancements in nanotechnology to enhance flavonoid bioavailability, delivery, and efficacy. We examined various nanocarriers, including liposomes, nanoparticles, and nanoemulsions, for encapsulating flavonoids to protect them from degradation and enable effective biodistribution in cardiovascular tissues. Nanoencapsulated flavonoids improve therapeutic effects by lowering oxidative stress and inflammation and improving lipid profiles in cardiovascular diseases. We also analyzed challenges in translating these discoveries into clinical practice, such as ensuring safety, optimizing dosage, and addressing regulatory requirements. However, issues related to large-scale production and long-term stability of nanomaterials still present significant obstacles. Future prospects include increasing production capacity and conducting extensive toxicity research and comprehensive clinical trials.

Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L-NG-nitro arginine methyl ester (L-NAME), an analog of L-arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L-NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L-NAME-induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L-NAME-induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin-converting enzyme (ACE) and endothelin-1. Moreover, they exhibit anti-inflammatory effects, attenuating inflammation-mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L-NAME-induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.

Carvacrol, called CA, is a dynamic phytoconstituent characterized by a phenol ring abundantly sourced from various natural reservoirs. This versatile scaffold serves as a pivotal template for the design and synthesis of novel drug molecules, harboring promising biological activities. The active sites positioned at C-4, C-6, and the hydroxyl group (-OH) of CA offer fertile ground for creating potent drug candidates from a pharmacological standpoint. In this comprehensive review, we delve into diverse synthesis pathways and explore the biological activity of CA derivatives. We aim to illuminate the potential of these derivatives in discovering and developing efficacious treatments against a myriad of life-threatening diseases. By scrutinizing the structural modifications and pharmacophore placements that enhance the activity of CA derivatives, we aspire to inspire the innovation of novel therapeutics with heightened potency and effectiveness.

The characteristics of early and advanced stages of diabetic cardiomyopathy (DCM) are well-understood; however, the time points by which these stages are developed in animal models vary and depend on the hyperglycaemic status and duration of diabetes. This study was aimed to determine the time points for the development of early and advanced stages of DCM from the induction of type 1 diabetes mellitus by identifying the functional and histological changes that occurred. Type 1 diabetes was induced via streptozotocin injection, and rats were divided into 4-week and 8-week diabetic groups. A group of non-diabetic rats served as the normal control. Cardiac functions and structural changes were analysed. Results showed that after four weeks, all diabetic rats displayed early DCM characteristics, including pronounced left ventricular diastolic dysfunction and cardiomyocyte hypertrophy (P < 0.05) compared to the normal control. After eight weeks, there was a significant deterioration in both left ventricular systolic and diastolic function compared to the normal control, along with marked cardiomyocyte hypertrophy and myocardial fibrosis (P < 0.05), signifying the development of advanced DCM. In summary, this findings revealed the development of early and advanced stages of DCM at four weeks and eight weeks of diabetes respectively in diabetes melitus type 1 rat model.

Lupeol, a naturally occurring lupane-type pentacyclic triterpenoid, is widely distributed in various edible vegetables, fruits, and medicinal plants. Notably, it is found in high concentrations in plants like Tamarindus indica, Allanblackia monticola, and Emblica officinalis, among others. Quantitative studies have highlighted its presence in Elm bark, Olive fruit, Aloe leaf, Ginseng oil, Mango pulp, and Japanese Pear bark. This compound is synthesized from squalene through the mevalonate pathway and can also be synthetically produced in the lab, addressing challenges in natural product synthesis. Over the past four decades, extensive research has demonstrated lupeol’s multifaceted pharmacological properties, including anti-inflammatory, antioxidant, anticancer, and antibacterial effects. Despite its significant therapeutic potential, clinical applications of lupeol have been limited by its poor water solubility and bioavailability. Recent advancements have focused on nano-based delivery systems to enhance its bioavailability, and the development of various lupeol derivatives has further amplified its bioactivity. This review provides a comprehensive overview of the latest advancements in understanding the pharmacological benefits of lupeol. It also discusses innovative strategies to improve its bioavailability, thereby enhancing its clinical efficacy. The aim is to consolidate current knowledge and stimulate further research into the therapeutic potential of lupeol and its derivatives.