2026· Advances in Protein Chemistry and Structural Biology· Vol 153, pp.
409-436
· 0 citations
Medicine
TL;DR
This review highlights recent mechanistic findings, targets, and translational advancements of marine-derived bioactives with a focus on the importance of these advancements in the development of next-generation therapeutics based on their revolutionary nature.
Cancer prevention through dietary intervention utilizing bioactive natural compounds has garnered significant attention due to the therapeutic limitations of conventional cancer treatments. These plant-derived active compounds, including polyphenols, terpenoids, organosulfur compounds, bioactive peptides, and alkaloids, possess potent anticancer properties. This systemic review addresses a critical gap in the scientific literature by elucidating the precise multitargeted oncogenic regulatory mechanisms of these molecules. A comprehensive methodology was employed, involving a systematic literature search across major electronic databases (including PubMed, Web of Science, Embase, and SCOPUS) to identify relevant original peer-reviewed studies. The evidence gathered demonstrates that these active compounds deliver significant health benefits and protect cells by modulating crucial molecular targets involved in cell cycle regulation, apoptosis, oncogenic signaling, epigenetic control, angiogenesis, oxidative stress, and inflammation. Specifically, they operate via multi-targeted cascades, such as inhibiting the PI3K/Akt, NF-κB, and STAT3 pathways. To provide a clear structural overview, these active compounds are categorized comprehensively based on their botanical and structural origins, including spices, fruits, and rhizomes. However, despite their promising bioactivities, these compounds have not yet been fully translated into clinical therapy due to challenges such as low bioavailability, rapid metabolism, limited systematic exposure, and a lack of convincing evidence from large-scale clinical trials. Although most current evidence remains rooted in in vitro and experimental animal models, clinical validation through high-quality trials is still required. Ultimately, this review underscores the potential of these active compounds and highlights how advances in formulation and nano delivery strategies offer promising solutions for effective cancer prevention.
Medicinal plants represent a valuable source of structurally diverse bioactive compounds with significant potential for the development of multi-target therapeutics against complex diseases. Unlike conventional single-target drugs, phytochemicals can simultaneously modulate multiple molecular pathways, offering improved therapeutic efficacy and reduced susceptibility to drug resistance. Recent advances in phytochemistry have facilitated the isolation and characterization of a wide range of secondary metabolites, while computational biology has transformed natural product research through molecular docking, molecular dynamics simulations, network pharmacology, artificial intelligence, and multi-omics approaches. The integration of these technologies enables efficient target identification, virtual screening, pharmacokinetic prediction, and lead optimization, thereby accelerating phytopharmaceutical discovery. This review highlights recent progress in medicinal plant-derived multi-target therapeutics, emphasizing the complementary roles of phytochemical diversity and computational biology in modern drug discovery. Furthermore, it discusses current challenges, emerging opportunities, and future perspectives for translating plant-based bioactive compounds into safe, effective, and evidence-based therapeutic agents.
R. Gharal· Natural Resources for Human...· 1 citation
Molecular glues (MGs) are small molecules that modulate protein – protein interactions by inducing or stabilizing ternary complexes, thereby reprogramming cellular networks rather than inhibiting single targets. Natural products, shaped by evolutionary selection and characterized by exceptional structural diversity, constitute a rich and underexplored source of glue-like compounds. Here, we propose a conceptual framework for rationalizing the multi-target efficacy of traditional medicines through molecular glue mechanisms. Diverse classes of natural products, including polyketides, terpenoids, steroids, lignans, organic acids, and alkaloids, have been shown to promote proximity-driven regulation of signaling pathways and targeted protein degradation. This interaction-based mode of action provides a molecular explanation for the systems-level therapeutic effects of traditional formulations that act through multiple pathways simultaneously. Integration of molecular glue theory with network pharmacology and modern chemical biology approaches offers a strategy to decode the complex pharmacology of herbal medicines and to expand the druggable proteome. Advances in proximity-based screening technologies and machine learning are expected to further accelerate the discovery of natural product-derived molecular glues for next-generation therapeutics.
Hamid Sheikha, Seyed Hossein Hashemi Najafabadi, A. Divsalar· Traditional Medicine Researc...· 0 citations
The bioactive peptides derived from food have proven to be of great potential as natural therapeutic agents for the prevention of chronic diseases and for health maintenance. The field of computational biology, which is evolving at an astounding pace, has transformed the peptide discovery process and brought together the tools of bioinformatics, artificial intelligence (AI) and machine learning (ML) into a streamlined in silico pipeline, alongside molecular docking, molecular dynamics (MD) simulations and prediction of ADMET properties. They can be used to rapidly identify, screen, optimize, and characterise bioactive peptides derived from a wide range of food proteins and can reduce the time, cost, and experimental effort, compared to laboratory methods. Bioactive peptides from foods possess different biological roles, including antioxidant, anti-inflammatory, antimicrobial, antihypertensive, antidiabetic, immunomodulatory, and anticancer activities, which are associated with several molecular targets and signaling pathways. They have been shown to regulate oxidative stress, inflammation, immune response, glucose metabolism, and cellular homeostasis, which highlights their therapeutic potential in various diseases, including cardiovascular diseases, cancer, metabolic disorders, neurodegenerative diseases, gastrointestinal diseases, etc. Also, structure–activity relationship (SAR) analysis and AI-assisted molecular optimization can be applied to enhance the stability, specificity, and bioavailability of peptides, thereby paving the way for functional foods, nutraceuticals, and peptide-based therapeutics. Although considerable advances have been made, there are still issues of peptide stability, oral bioavailability, large-scale production, regulatory approval, and clinical validation. The application of multi-omics, generative AI, precision nutrition, and improved food delivery systems will likely lead to increased advances in food bioactive peptide research into personalized medicine and new therapeutic options.
Priyadarshani A. Patil· Natural Resources for Human...· 0 citations
The global burden of infectious and non-communicable diseases presents a critical challenge, highlighting the urgent need for novel, safe, and effective therapies. Bioactive compounds from medicinal plants, especially flavonoids, offer a promising resource for drug discovery due to their diverse and potent pharmacological effects documented in preclinical studies. This comprehensive review summarizes current knowledge of flavonoids, including their classification into 14 main groups and their production via biosynthesis, chemical synthesis, modification, and extraction. While structural modification remains a key aspect of drug development, biosynthesis is increasingly seen as a potential transformative strategy for sustainable large-scale production. However, it requires a deeper understanding of metabolic pathways and optimization of synthetic methods. Aside from production challenges, a major translational hurdle is the inherently low bioavailability of many flavonoids. This review critically examines innovative solutions under investigation, such as advanced nanoparticles and colloidal drug delivery systems designed to address challenges in solubility, stability, and absorption. It also summarizes the current understanding of the mechanisms of action underlying their broad biological activities, primarily as evidenced by preclinical models, including nutritional, immunological, and disease-specific effects, and discusses potential drug interactions warranting clinical attention. Lastly, the review highlights key research gaps, including the need for more robust in vivo validation, standardized extracts to improve reproducibility, and well-designed clinical trials to verify efficacy in humans. Future directions include leveraging metabolic engineering and artificial intelligence to optimize biosynthesis, as well as targeted clinical studies of advanced delivery systems. By integrating these approaches, this review aims to establish a framework for ongoing research on flavonoids to inform future translational efforts that may eventually support their development as clinical therapies.
M. El-Saadony, A. Saad, Mohamed A. Fahmy et al.· Frontiers in Nutrition· 0 citations
Bioactive peptides (BAPs), derived from both natural and synthetic sources, are increasingly recognized as multifunctional agents with potential roles in the management of cancer and inflammatory conditions, in addition to their well‐established antimicrobial activity. Their biological activity is critically governed by their sequence‐dependent physicochemical properties, including charge hydrophobicity, amphipathicity, and well‐defined three‐dimensional conformation, such as α‐helices, β‐sheets, and coils, which collectively determine target specificity, membrane interaction, and intracellular activity, ultimately determining therapeutic effectiveness and safety.
Aside from in vitro models, animal models further validated their efficacy, enabling mechanistic insights and high‐throughput screening.
In cancer models, BAPs induce anti‐cancer activity through various mechanisms such as membrane disruption, mitochondrial dysfunction, ROS generation, apoptosis, inhibition of invasion, migration, and angiogenesis across multiple cancer types, including breast cancer, particularly triple‐negative breast cancer, colorectal, lung and melanoma, highlighting BAPs broad antitumor properties. Concurrently, BAPs regulate the immune system through cytokine modulation, NF‐κB signalling suppression, reduced immune cell infiltration and macrophage polarization promotion.
However, despite these advances, clinical translation remains limited due to poor stability, short half‐life, cytotoxicity, high production costs and optimized drug delivery systems. An integrated multidisciplinary approach with AI‐guided design places BAPs as promising precision medicine tools for specific, immunomodulatory, and personalized anticancer and anti‐inflammatory therapies.
N. Doha, R. Gill, S. Crovella et al.· Clinical and Translational D...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
