HIV remains a major global health challenge with antiretroviral therapy (ART) effectively suppressing viral replication. However traditional ART does not eliminate viral reservoirs and is limited by systemic toxicity, long-term adherence burdens, and incomplete tissue penetration. These limitations highlight an important scientific problem in the inability of conventional ART to achieve durable remission or cure. Nanoparticle-mediated drug delivery systems have emerged as a transformative approach to address these limitations by improving drug solubility, stability, and targeted delivery to infected cells and viral sanctuaries such as the brain, lymphoid organs, and gastrointestinal mucosa. Different nanocarrier platforms including liposomes, polymeric nanoparticles, dendrimers, and lipid-based vesicles enable both passive and active targeting strategies. Functionalization with ligands such as antibodies, peptides, aptamers, and sugar moieties enhance cellular uptake, reduces off-target effects, and optimizes pharmacokinetics and biodistribution. Controlled-release formulations extend drug half-life and reduce dosing frequency, supporting long-acting regimens. Beyond drug delivery, nanoparticles also facilitate immunomodulatory therapies, therapeutic vaccines, and advanced gene-editing technologies such as CRISPR–Cas9. The convergence of nanotechnology, mRNA platforms, and artificial intelligence-driven drug development represents a paradigm shift toward individualized and precision HIV treatment. Despite these advances, significant translational challenges remain, including nanotoxicity, long-term safety, large-scale GMP manufacturing, regulatory barriers, and cost-effectiveness. Addressing these barriers is essential to unlock the full potential of nanoparticle-based strategies and translate them into equitable and sustainable clinical solutions. This review synthesizes evidence on nanoparticle-mediated antiretroviral delivery, focusing on pharmacokinetics, biodistribution, and viral reservoir targeting. Lipid- and polymer-based nanoparticles demonstrate measurable improvements in lymphoid tissue penetration and sustained plasma concentrations in preclinical models. Long-acting nanosuspensions of cabotegravir and rilpivirine provide clinical proof-of-concept for bi-monthly injectable HIV therapy. Emerging nanoplatforms enable integration with RNA therapeutics, immunomodulators, and CRISPR-based gene editing for future personalized interventions. Key translational challenges include nanotoxicity, GMP-scale manufacturing, regulatory frameworks, and cost-effectiveness, particularly in resource-limited settings.

Pseudocereals, such as buckwheat (Fagopyrum esculentum), are non-grass seeds that can be milled into flour and utilized similarly to traditional cereals. Buckwheat, a member of the Polygonaceae family, is gluten-free and recognized for its exceptional nutritional profile. It is particularly valued for its high-quality protein, boasting a superior amino acid composition, particularly in lysine, compared to most cereal grains. The therapeutic potential of buckwheat showcases its anti-inflammatory, anti-hyperglycemic, anti-hypertensive, neuroprotective, and anticancer properties. Furthermore, buckwheat has been identified as a functional food with prebiotic and antioxidant activities, contributing to the management of various chronic diseases, including cardiovascular conditions, diabetes, and celiac disease. This review aims to explore the bioactive components of buckwheat and their mechanisms of action, integrating emerging mechanistic evidence with clinical insights to clarify how specific buckwheat-derived compounds contribute to disease modulation. Additionally, the applications of buckwheat in gluten-free diets and its potential to alleviate common health issues will be discussed.

Background and Aims:Low birth weight (LBW) persistently poses a substantial public health risk throughout Kenya, most intensely within lower-middle-income groups. The research aimed at determining the prevalence of LBW in Kenya while conducting an evaluation of maternal and sociodemographic factors related to its development. A systematic review of observational studies (cross-sectional and cohort) was conducted to assess LBW prevalence together with risk factors. Methods:The research utilized multiple databases to run a thorough literature search in accordance with PRISMA guidelines from 2000 up to November 2024. The research included sixteen studies that satisfied the established criteria. A random-effects model was utilized to evaluate both LBW prevalence as well as risk factor prevalence levels. The statistical approach for assessing heterogeneity consisted of both Cochran's Q-test and the I² statistic. The study analyzed variation by using subgroup assessments together with meta-regression evaluation methods. Results:Research findings indicated a combined prevalence of 11.7% (95% CI: 8.9%-15.1%) for LBW in Kenya alongside significant variability (I² = 98%). Mothers without formal education demonstrated the peak rate of 13.2% LBW, while mothers with tertiary education showed the lowest LBW rate at 8.5%. Rates of Low birth weight demonstrated a connection with birth order position since sixth or higher birth order infants, along with first-born infants, presented greater LBW risk (8.6% and 8.1%) than fourth or fifth order delivery (5.9%). Conclusions:This systematic review and meta-analysis confirm that LBW, with a prevalence of 11.7% in Kenya, remains a major issue that varies by region and maternal factors. The most at-risk are uneducated mothers and firstborns of high birth order. There should be region-specific policies to improve maternal health services and quality prenatal care. Additionally, promoting female education is crucial to reducing LBW and its long-term impacts.

This study systematically reviewed research on heavy metal contamination in environmental and food systems in Uganda using the PRISMA 2020 data reporting method and the PICOS framework. An extensive literature search of published papers on heavy metal contamination in Uganda's environment and food systems was conducted in PubMed, Web of Science, and Scopus databases up to May 21, 2024. Boolean operators (AND/OR/NOT) were applied to develop search strategies tailored to each database. Following duplicate removal, title and abstract screening, and full-text assessment using the Rayyan platform, 39 articles were included in the final review. Data were extracted from each study using a standardized template that captured metal type, contamination source, concentration levels, affected food or environmental matrix, geographic location, and toxicological impact. Data were synthesized using a descriptive and narrative approach. Key sources of contamination include industrial and municipal waste, agricultural practices, and emissions from transport and manufacturing. Among the metals, lead was the most mentioned across studies. Regional analysis revealed that Central Uganda had the highest reports on heavy metals, while Northern Uganda remains critically understudied. Ecologically, heavy metals threaten soil fertility, aquatic biodiversity, and agricultural sustainability. Contamination of staple foods with lead, cadmium, and mercury poses significant public health risks, particularly for children and pregnant women. Strengthened environmental monitoring, targeted regional investigations, and improved food safety surveillance within a One Health framework are urgently recommended.

Background Maize ( Zea mays L. ) is a significant cereal crop, which, due to its nutritious content, especially in terms of dietary energy and nutrients, is globally important. Its nutritive status does not just end with macronutrients, but it also encompasses nutrient status that promotes health-giving micronutrients and phytochemicals. Objective This review aims to consolidate recent advancements in maize nutrient profiling and highlight current challenges in optimizing its nutritional potential across global food systems. Methods A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar for peer-reviewed articles published between 2010 and 2024 in English. Search terms included “Zea mays nutrition,” “maize macronutrients,” “maize micronutrient biofortification,” and “phytochemicals in maize”. Studies included both empirical and review papers reporting on maize nutritional quality, bioavailability, and impacts on human health. Results Maize is composed primarily of carbohydrates, with starch as the dominant fraction, alongside moderate protein and low lipid content concentrated in the germ. Biofortified varieties, including Quality Protein Maize (QPM), provide enhanced levels of lysine, tryptophan, and provitamin A. Maize also supplies essential B vitamins and minerals such as iron, zinc, and magnesium; however, their bioavailability is reduced by antinutrients like phytates. In addition, maize is shown to be rich in phytochemicals, including ferulic acid, flavonoids, and carotenoids, which exhibit antioxidant and therapeutic properties. Conclusion Maize is more than a staple food crop; it is an indispensable crop for global food and nutrition security. However, challenges such as low bioavailability due to antinutritional factors limit its full nutritional potential. Therefore, strengthening genetic and agronomic interventions to improve its nutritional quality is essential to address hidden hunger and enhance population health worldwide.

Background Maize (Zea mays L.) is a significant cereal crop, which, due to its nutritious content, especially in terms of dietary energy and nutrients, is globally important. Its nutritive status does not just end with macronutrients, but it also encompasses nutrient status that promotes health-giving micronutrients and phytochemicals. Objective This review aims to consolidate recent advancements in maize nutrient profiling and highlight current challenges in optimizing its nutritional potential across global food systems. Methods A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar for peer-reviewed articles published between 2010 and 2024 in English. Search terms included “Zea mays nutrition,” “maize macronutrients,” “maize micronutrient biofortification,” and “phytochemicals in maize”. Studies included both empirical and review papers reporting on maize nutritional quality, bioavailability, and impacts on human health. Results Maize is composed primarily of carbohydrates, with starch as the dominant fraction, alongside moderate protein and low lipid content concentrated in the germ. Biofortified varieties, including Quality Protein Maize (QPM), provide enhanced levels of lysine, tryptophan, and provitamin A. Maize also supplies essential B vitamins and minerals such as iron, zinc, and magnesium; however, their bioavailability is reduced by antinutrients like phytates. In addition, maize is shown to be rich in phytochemicals, including ferulic acid, flavonoids, and carotenoids, which exhibit antioxidant and therapeutic properties. Conclusion Maize is more than a staple food crop; it is an indispensable crop for global food and nutrition security. However, challenges such as low bioavailability due to antinutritional factors limit its full nutritional potential. Therefore, strengthening genetic and agronomic interventions to improve its nutritional quality is essential to address hidden hunger and enhance population health worldwide.

Stress is a major concern with significant impacts on mental and physical health. Moderately stressed people's perceived stress, physiological reactions, and biomarkers related to stress. For this purpose, in this randomized clinical trial, a total of 108 females (25-45 years old) with moderate stress were enrolled and randomly divided into three groups: T-0 (placebo tea), T-1 (green tea 1 g/day), and T-2 (green tea 1.5 g/day) for twelve weeks. The effects of green tea were measured using stress, physiological parameters, salivary cortisol, melatonin, alpha-amylase, glucose, liver enzymes, and C-reactive protein at baseline and post-intervention. Statistical analysis was conducted using SPSS, employing ANOVA (p < 0.05). The results showed that green tea, especially at a dose of 1.5 g, reduced stress, blood glucose, cortisol, and alpha-amylase levels while increasing melatonin levels and improving liver function. Green tea may support stress relief, metabolism, and liver health, but larger studies are needed to confirm.

Tulsi (Ocimum sanctum L.) is an aromatic medicinal herb abundant in nutrients and bioactive constituents. This study aimed to assess the nutritional, phytochemical, antioxidant, and therapeutic attributes of Tulsi leaf powder (TLP), focusing on its capacity to regulate hyperlipidemia, liver function, and oxidative stress. Proximate analysis demonstrated elevated levels of crude fiber (18.76

Seed oils from the Cucurbitaceae family represent a promising yet under-reviewed class of natural products for therapeutic development. This review provides a comprehensive synthesis linking their distinctive phytochemistry to pharmacological mechanisms and biotechnological applications. We detail characteristic profiles rich in polyunsaturated fatty acids and unique Δ7-phytosterols, chemotaxonomic markers serving as distinctive chemical fingerprints. Evidence is synthesized demonstrating how these components drive anti-inflammatory, antioxidant, and wound-healing activities via key pathways like NF-κB and Nrf2. Furthermore, we explore how biotechnology leverages genetic diversity and molecular tools, such as marker-assisted selection and DNA barcoding, to enhance oil yield, ensure authenticity, and support sustainable production. While preclinical evidence is compelling, translating these oils into validated therapeutics requires focused clinical trials and standardized formulations. By integrating phytochemical, pharmacological, and biotechnological evidence, this review establishes a robust foundation for developing Cucurbitaceae seed oils into next-generation nutraceuticals and plant-based pharmaceuticals, offering a transformative paradigm for sustainable therapeutic development.

Gut microbiota resilience, the capacity of intestinal microbial communities to resist, adapt, and recover from perturbations has emerged as a critical determinant of human health and longevity. Environmental stressors such as antibiotics, pollutants, poor diet, infections, and psychosocial stress challenge this resilience, often leading to dysbiosis (a sustained disruption of microbial community structure and/or function), impaired metabolism, chronic inflammation, and increased disease susceptibility across the lifespan. While dysbiosis has been extensively studied, the resilience dimension remains underexplored, particularly in the context of cumulative and repeated stress exposures. This narrative review explores microbial resilience, identifying environmental disruptors, and their manifestation at life stages, highlighting its hidden yet crucial role in optimizing lifespan. We critically evaluate the consequences of reduced resilience for chronic disease, frailty, and therapeutic response, while emphasizing the protective roles of diversity, functional redundancy, and host–microbe feedback loops. Translational strategies including dietary modulation, microbial therapeutics, behavioral interventions, and precision tools such as multi-omics and biosensors, are assessed for their potential to strengthen resilience and promote healthy aging. By reframing gut microbiota resilience as both a biological property and a public health target, this work advances a novel perspective: that fostering resilience may mitigate environmental insults, personalize interventions, and extend healthspan. This review looks at how the trillions of microbes living in our gut cope with “stress” from the world around us, such as antibiotics, pollution, ultra-processed foods, infections, poor sleep, and chronic psychological stress. We refer to this coping ability as “microbiota resilience,” meaning the ability of the gut community to resist damage, adapt, and bounce back while still doing its key jobs (facilitating digestion, training the immune system, protecting the gut lining, and sending signals that influence the brain and metabolism). When resilience is weakened, the balance of microbes can tip toward inflammation and disease across life, raising risks for problems such as obesity and diabetes, bowel disease, liver disease, mood disorders, neurodegeneration, infections, cancer treatment side-effects, and age-related frailty. The paper pulls together evidence across the lifespan. Early life (birth and feeding) sets the foundation; childhood and adolescence can strengthen resilience through diet and diverse environmental exposure; adulthood brings stability but also lifestyle-related threats; older age often shows declining diversity and resilience. The review also outlines practical ways to bolster resilience: fiber-rich, plant-based and fermented foods; targeted probiotics, prebiotics/synbiotics, and (in special cases) fecal microbiota transplantation; regular physical activity; good sleep and circadian routines; stress-reduction; minimizing unnecessary antibiotics and exposure to pollutants; and emerging “precision” tools (multi-omics testing, personalized nutrition, and postbiotic metabolites). Finally, the authors highlight research gaps, especially the need for clear, standardized measures of resilience and inclusive studies across diverse populations, so clinicians and public health programs can track and improve gut resilience to extend healthy years of life.

MicroRNAs (miRNAs) are increasingly recognized as central regulators of gene expression, cellular adaptation, and disease progression. This is fundamentally reshaping current understanding of disease molecular pathogenesis and therapeutic intervention. Beyond their established roles in development and metabolism, miRNAs actively participate in oncogenesis, metabolic dysfunction, inflammation, and redox homeostasis. Emerging evidence shows that phytochemicals can modulate miRNA-mediated regulatory networks by influencing miRNA biogenesis, expression, stability, and functional activity through transcriptional, epigenetic, and post-transcriptional mechanisms. Among these pathways, the thioredoxin-interacting protein (TXNIP) axis has attracted considerable attention because of its critical involvement in oxidative stress, inflammation, metabolic reprogramming, apoptosis, and cancer-associated signalling. For instance, dysregulated TXNIP expression is strongly associated with metabolic dysfunction-associated fatty liver disease (MAFLD), diabetes, cardiovascular diseases, neurodegenerative disorders, and multiple cancers, making it an attractive therapeutic target. This narrative review discussed emerging trends on phytochemical-mediated regulation of TXNIP-associated miRNAs, including miR-148b, miR-33a/b, miR-17-5p, miR-224, and miR-20a. Particular emphasis was placed on the conserved miRNA seed region as the principal determinant of target recognition, while discussing the emerging hypothesis that phytochemicals may allosterically modulate structurally accessible RNA motifs to influence miRNA conformation, stability, RNA-induced silencing complex loading, and target accessibility without disrupting canonical Watson-Crick base pairing. We further discussed molecular docking, RNA-specific molecular dynamics simulations, and complementary structural validation approaches as emerging tools for investigating RNA-ligand interactions. Therefore, this review has provided a mechanistic and translational framework integrating RNA biology, redox signalling, and precision medicine to guide future development of RNA-targeted phytochemical therapeutics for cancer, metabolic disorders, and other chronic diseases.

Fruits, especially bananas and their products, play a vital role in enhancing human health due to their abundance of bioactive compounds, fibers, resistant starch, and essential nutrients. This pilot study uniquely evaluated whether consuming muffins containing 35

Antimicrobial resistance (AMR) is a global health and environmental challenge, driven by complex interactions among microbial communities, resistance genes, and selective pressures in various ecological niches. Traditional surveillance procedures often fall short in capturing the full diversity and dynamics of resistance reservoirs in the environment. This review examines the integration of artificial intelligence (AI) and machine learning (ML) with next-generation sequencing (NGS) technologies for comprehensive resistome profiling. We discuss advances in multi-omics approaches, particularly metagenomics, microbiome-based analytics, and metatranscriptomics. We also highlight computational workflows that enable high-resolution mapping of resistance genes, their mobile genetic elements, and host associations. The role of AI/ML in resistome prediction, classification, and source tracking, as well as the incorporation of environmental metadata for contextual interpretation is discussed based on the selected literature. Moreover, we assess current challenges and propose future directions for developing standardized, scalable, and interpretable bioinformatic pipelines in AMR surveillance. This review primarily elucidates the potential of integrated AI-omics platforms to revolutionize aquatic environmental AMR monitoring and inform risk assessment and mitigation strategies.

Background: Cognitive decline and neurodegenerative diseases are growing public health issues, especially in aging populations. This study observed how dietary patterns are associated with cognitive performance and neurodegenerative biomarkers among older adults in aging populations. Methods: A retrospective study of 500 adults aged >= 65 years in Lahore examined associations between dietary patterns, cognitive outcomes, and neurodegenerative biomarkers, with participants classified into Mediterranean or non-Mediterranean (Western, plant-based, or mixed) dietary groups based on FFQ-and 24-hour recall-derived pattern scores, alongside standardized cognitive assessments and clinical neuroimaging measures. Results: Mediterranean and plant-based diets were associated with improved cognitive performance and lower levels of neurodegenerative biomarkers compared to Western diets. Adherence to a Mediterranean diet was associated with reduced MMSE decline (beta = 0.37, 95% CI: 0.18-0.56, p < 0.001), higher MoCA scores (beta = 1.20, 95% CI: 0.75-1.65, p < 0.001), and improved memory and executive function (beta = 0.31, 95% CI: 0.12-0.50, p = 0.002). Diets based on plants were associated with cognitive outcomes. Neuroimaging showed associations with increased hippocampal volume (beta = 0.42-0.48, p < 0.001), FDG-PET metabolism (beta = 0.07-0.09, p <= 0.001), and associations with decreased WMH volume (beta = -0.35 to 0.41, p <= 0.005). Plant-based and Mediterranean diets were associated with reduced neurofilament light levels. Mixed/other diets showed moderate associations. Conclusion: Mediterranean and plant-based diets are associated with more favorable neuroimaging profiles, neurodegenerative biomarkers, and elderly cognition, while Western diets are associated with neurodegeneration and cognitive loss.

Background Diabetes mellitus is a severe metabolic disease in the world, and therefore significant research has been conducted on food‐derived bioactive compounds capable of antidiabetic effects. The Azadirachta indica (neem) plant, which is widely used in traditional food and ethnomedicine, contains a variety of phytochemicals that have potential applications in nutrition as nutraceuticals. Aims This meta‐analysis and systematic review assessed the antidiabetic effects of A. indica preparations in rodents with diabetes and more so in relevancy in terms of translation to food biochemistry, nutraceutical formulation and molecular nutrition pathway. Methods In accordance with PRISMA 2020, we performed a systematic search of PubMed, Scopus, Web of Science and Google Scholar to identify controlled studies on antidiabetic effects of A. indica on rodent diabetes models. The SYRCLE tool was used to determine the risk of bias. Primary outcome: improvement of fasting blood glucose (FBG). Secondary outcomes: glycated haemoglobin (HbA1c), insulin, oxidative stress biomarkers (SOD, catalase, GSH, GPx, MDA) and lipid profile parameters. Random‐effects meta‐analyses estimated the standardized mean differences (SMDs) using the g correction of Hedges. Duration, dose, extract type and diabetes induction method were analysed as subgroups. The I 2 statistics and tau‐squared ( τ 2 ) were used to measure heterogeneity. Results The meta‐analysis comprised the studies that were conducted on the different A. indica preparations in the diabetic rats. A. indica had a significant effect of reducing FBG with a pooled effect size of −6.702 (95% CI: −7.621–5.165, p = 0.001), but with high heterogeneity ( I 2 = 92.6). A. indica had a significant pooled effect of improving oxidative stress markers, improving SOD activity (SMD = 2.222, 95% CI: 0.999 to 3.450), favourable lipid profile changes included reduced total cholesterol (SMD = −3.632, 95% CI: −4.814 to −2.450), triglycerides (SMD = −4.842, 95% CI: −6.206 to −3.477), LDL cholesterol (SMD = −3.471, 95% CI: −4.701 to −2.241) and increased HDL cholesterol (SMD = 3.280, 95% CI: 2.112 to 4.447). Conclusion A. indica exhibits strong nutraceutical potential for diabetes management through its multitarget actions on glycaemic control, enhancement of antioxidant defence and regulation of lipid metabolism. These effects are largely attributed to key bioactive constituents, including quercetin, nimbin and azadirachtolide, which appear to act through pathways involving AMPK activation, GLUT4 translocation and PPARγ modulation. Together, these findings provide solid preclinical support for the development of A. indica as a functional food ingredient or complementary dietary supplement aimed at improving metabolic health.

Bisphenol A (BPA), which is a common ingredient of plastics and epoxy resins, is among the most commonly found endocrine-disrupting chemicals in the human environment. Chronic human exposure has raised concerns over its effects on reproductive health. There is growing evidence showing that BPA causes epigenetic changes, primarily DNA methylation, histone changes, and non-coding RNA changes that result in hormonal imbalances, a disruption in gametogenesis, and fertility impairment. This review summarizes current understanding of how BPA alters male reproductive performance in exposed individuals, including impaired spermatogenesis and sperm quality, endocrine imbalance, and disruption of hypothalamic-pituitary-gonadal (HPG) signaling, often in concert with oxidative stress and altered steroidogenesis. We then discuss evidence that BPA exposure, especially during critical developmental windows, can reprogram the paternal germline, such that epigenetic alterations carried by sperm, such as DNA methylation changes, abnormal histone acetylation (H3K9ac, H3K27ac, H4K12ac), disrupted histone-to-protamine transition, and altered sperm small RNAs/miRNA profiles, can contribute to fertility defects in subsequent generations. Moreover, various therapeutic methods, like epigenetic drugs and natural products such as resveratrol, naringenin, and genistein, are being studied to reverse or alleviate the impact of BPA. Given BPA's ubiquity, these findings also highlight the necessity of stricter regulation, health education to the general population, along with research into potential safer alternatives. Learning the ways BPA is remodeling the epigenome and fertility through generations is essential to protecting reproductive health and the basis of policy intervention.

In the pharmaceutical sciences, particularly in network pharmacology and computer-aided drug design (CADD), successful multidisciplinary collaboration is crucial for sustainable capacity growth. This systematic study investigates how interdisciplinary research methods can be strengthened and creative technology integration may be fostered sustainably through educational leadership. For papers published between 2010 and 2024, a systematic literature search was carried out in the Scopus and Web of Science (WoS) databases. "Network pharmacology," "interdisciplinary collaboration," "pharmaceutical sciences," "computer-aided drug design," and "educational leadership" were among the search phrases used. Peer-reviewed papers, case studies, and reports discussing leadership in multidisciplinary pharmaceutical sciences research or instruction were among the eligible studies. Out of 558 identified records, 109 studies were included in accordance with PRISMA requirements (WoS = 476; Scopus = 82). With 10% of research focusing on CADD, 22% on educational leadership, and 68% on more general, multidisciplinary viewpoints, the results indicated a paradigm shift towards interdisciplinary collaboration. However, limitations were found because educational leadership was not included in CADD and network pharmacology frameworks in several studies. The main challenges to productive cooperation were identified as resource limitations, policy gaps, and communication difficulties. This analysis highlights how institutional frameworks, regulatory support, and adaptive leadership techniques are necessary to facilitate long-term knowledge sharing, innovation absorption, and better research outcomes in the pharmaceutical sciences. Therefore, enhancing educational leadership opens the door to long-term effects and sustained capacity building in multidisciplinary pharmaceutical research.

Introduction:The central role of oxidative stress in neuronal injury and the progression of neurological disorders underscores the need to identify multi-target agents capable of restoring redox homeostasis. This study evaluated the antioxidant and pharmacological potential of Syzygium aromaticum ethyl acetate fraction (SEAF) using integrated phytochemical, computational, and experimental approaches. Methods:GC-MS was used to characterize the phytochemical composition of the ethyl acetate fraction of Syzygium aromaticum (SEAF). Thirteen phytometabolites with relative peak areas ≥1.0% were selected for ADME-Tox profiling and molecular docking against monoamine oxidase B (MAO-B) and 5-lipoxygenase (5-LOX). In vitro antioxidant assays, acute oral toxicity testing, and in vivo evaluation of cerebellar oxidative stress biomarkers were subsequently performed. Results:GC-MS identified eugenyl acetate (43.08%), eugenol (18.86%), and β-caryophyllene (1.64%) as the predominant metabolites. The prioritized phytometabolites exhibited favorable predicted ADME-Tox profiles and notable binding energies for MAO-B (up to -8.4 kcal/mol) and 5-LOX (up to -6.8 kcal/mol), involving key interactions with HIS367 and HIS372 in MAO-B and GLN363, TYR435, and CYS172 in 5-LOX, comparable to the standard ligands. Although ascorbic acid exhibited greater radical-scavenging and ferric-reducing potencies than SEAF in the DPPH and FRAP assays, respectively, SEAF showed higher total antioxidant activity than ascorbic acid. In vivo, SEAF administration was relatively safe up to 2000 mg/kg and significantly increased cerebellar superoxide dismutase and catalase activities while reducing malondialdehyde levels in HgCl2-treated mice, with effects comparable to vitamin E. SEAF preserved cerebellar cortex histoarchitecture and Nissl substance in Purkinje cells against mercuric chloride-evoked oxidative damage. Conclusion:Syzygium aromaticum exhibited potent antioxidant effects through combined radical scavenging, enzymatic enhancement, modulation of oxidative stress-related targets, and preservation of cerebellar histoarchitecture, supporting its potential as a candidate for further preclinical development.

Hesperidin, a flavonoid predominantly found in citrus fruits, has gained attention as a potential nutraceutical for managing various components of metabolic syndrome, including obesity, hypertension, dyslipidemia, and insulin resistance. This review aims to provide a comprehensive overview of the pharmacological properties of hesperidin, emphasizing its therapeutic potential in combating metabolic syndrome through both in vivo and in silico investigations. Preclinical studies have demonstrated that hesperidin exerts anti-inflammatory, antioxidant, and lipid-lowering effects, contributing to the improvement of metabolic parameters. Mechanistically, hesperidin is known to modulate key signaling pathways, including the peroxisome proliferator-activated receptor gamma (PPAR-γ), AMP-activated protein kinase (AMPK), and nuclear factor-kappa B (NF-κB), to restore metabolic homeostasis. Moreover, recent in-silico studies have identified potential protein targets of hesperidin, shedding light on its molecular mechanisms and enabling the prospect for the design of more effective therapeutic strategies. Consistently, this current report integrates findings from experimental models and computational approaches to narratively outline the promise of hesperidin as a multi-target agent for managing metabolic syndrome. Therefore, this report has elucidated the need for clinical trials to validate these preclinical outcomes and establish hesperidin as a viable therapeutic option for patients with metabolic syndrome.

Genetic or epigenetic changes that lead to abnormal development of signalling through cellular pathways such as MAPK, PI3K/AKT/mTOR, Wnt/β-catenin play an important role in driving cancer. These signalling pathways control how cells grow, divide and die (apoptosis). Thus, the continued activation of these pathways represents a characteristic of oncogenesis as well as a suitable target for treatment. This review will highlight how natural products have been shown to modify the molecular pathways involved with these signalling cascades in preclinical cancer models. Data derived from an array of preclinical studies showcase how the bioactive phytochemicals that comprise these products are implemented in the form of targeting cancer cells through specific inhibition of signalling pathways, induction of apoptosis, inhibition of tumour growth and alteration of oncogenic crosstalk. Despite the significant body of evidence, there are still several limitations that exist in regards to variability between studies in terms of the methods used for validation of the mechanism by which these compounds function, differences in their bioavailability and overall robustness of those studies. Using a pathway-centered understanding of the mechanisms by which natural compounds exert their therapeutic effects will support the development of targeted phytopharmaceutical approaches and promote the integration of these therapies into evidence-based oncology practices.