Extracellular vesicles (EVs) are those with a double-membrane structure that contains proteins, lipids, nucleic acids, and other biologically active substances that play an important role in cell–cell and cell–environment communication. They have also become an important mechanism for exchanging biologically active substances for cellular molecules. As many studies on EVs have been conducted, plant-derived extracellular vesicles (PDEVs) have also started attracting attention. The biological activity and stability of PDEVs are closely related to the extraction and separation methods, and choosing a separation method that meets the requirements of PDEVs is important. The extraction methods of PDEVs include ultracentrifugation, ultrafiltration, size-exclusion chromatography, etc. In recent years, it has been found through research that PDEVs possess biological properties, such as anti-inflammatory, anti-cancer, and anti-infective properties, and that they show unique advantages as therapeutic agents and drug carriers. Therefore, we have collected the scientific literature related to EVs derived from more than a dozen fruits and vegetables, and summarized and analyzed their extraction, separation, and roles in disease treatment, aiming to provide reference and inspiration for the in-depth study of the efficacy of new drugs.

Natural products (NPs) have long been a cornerstone of pharmaceutical innovation, contributing to approximately 50% of FDA-approved drugs over the past four decades. However, traditional NP drug discovery faces significant hurdles, including laborious isolation processes, biodiversity constraints, and low hit rates in high-throughput screening. These hurdles often extend the development timelines to 10–15 years with costs exceeding $2 billion per drug. Artificial intelligence (AI) emerges as a transformative force, leveraging machine learning (ML), deep learning (DL), and generative models (Gen. AI) to expedite these processes. AI facilitates virtual screening of vast chemical libraries, predicts molecular interactions with unprecedented accuracy, and designs novel NP-inspired scaffolds, potentially reducing discovery time by up to 70%. This interdisciplinary approach not only addresses unmet medical needs but also aligns with global sustainability goals, potentially increasing success rates from <1% in traditional pipelines to over 10%. Ultimately, AI hints at revitalizing NP drug discovery, fostering innovative, eco-friendly therapeutics. This study reviews recent advancements in AI applications for NP drug discovery, including the challenges such as NPs representing only ~5% of screened compounds in many datasets, interpretability issues in “black-box” models, and ethical concerns over bioprospecting in biodiverse regions.

Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically determine their physicochemical properties. Experiments were conducted in vitro with Human Umbilical Vein Endothelial Cells (HUVECs) to verify the therapeutic impact of BELNSs on atherosclerosis. The isolated BELNs exhibited a distinctive teacup-shaped exosome morphology. The extraction yield was approximately 2.1 × 10¹³ particles per milliliter, and the average particle size was measured to be 179.1 nm. These nanovesicles were lipid-rich. The protein content predominantly comprised cytoplasmic proteins. In-depth analysis revealed the presence of five highly conserved plant microRNAs: miR166, miR156, miR399, miR171, and miR395. These miRNAs are involved in regulating plant growth and responses to both biotic and abiotic stresses. Functional assays demonstrated that Berberis kaschgarica Rupr.-derived exosome-like nanovesicles substantially decreased the lipid deposition in HUVECs that was triggered by Palmitic Acid (PA). This research establishes the inaugural utilization of multi-omics platforms to systematically elucidate the bioactivity profile of BELNs from Berberis kaschgarica Rupr., thereby laying the groundwork for advancing its therapeutic potential.

Background: Heart failure (HF) has a complex pathogenesis involving oxidative stress, inflammation, and energy metabolism disorders, and requires multi-target agents. Berberis kaschgarica Rupr. (BKR) is used in Uyghur folk medicine to improve cardiovascular health, but its cardioprotective mechanisms against HF remain unclear. Methods: UPLC-MS/MS was used to identify BKRE components; DPPH/ABTS assays evaluated antioxidant activity. The MTC of BKRE was determined in zebrafish, and its effects on ISO-induced HF zebrafish were assessed via cardiac function, apoptosis, oxidative stress, and inflammation indicators. Network pharmacology, molecular docking, transcriptomics, and qRT-PCR clarified targets and pathways. Results: BKRE contained 14 bioactive flavonoids/alkaloids with favorable drug-likeness, showing concentration-dependent DPPH and ABTS scavenging. In HF zebrafish, BKRE (5/10/20 μg/mL) dose-dependently improved cardiac function, inhibited apoptosis, reduced ROS and TNF-α/IL-6, restored GSH/T-SOD, activated the AMPK-PPARα-PGC-1α pathway by binding ALOX5/NQO1, etc. Conclusions: BKRE exerts multi-mechanistic cardioprotective effects, validating BKR’s ethnopharmacological value and highlighting it as a promising HF agent/functional food.

Plant-derived extracellular vesicles (PDEVs) are a novel category of natural nanocarriers with widespread availability, low immunogenicity, high biocompatibility, and inherent pharmacological activity. These features underscore their value as dual-function systems capable of serving as both carriers and bioactive agents. Unlike previous reviews that focused primarily on disease-specific applications or on individual engineering techniques, this review established a conceptual framework integrating three interconnected dimensions: (i) engineering strategies that address the inherent limitations of PDEVs (targeting, stability, loading efficiency); (ii) the carrier-performance-synergy paradigm linking PDEV composition to therapeutic outcomes; and (iii) gel-composite design principles that transform local retention into a controllable delivery platform. This review delves into various engineering methodologies, including targeted modification, enhanced stability, and optimized drug loading, while elucidating the performance characteristics of PDEVs as drug carriers, focusing on their protective, targeting, and controlled-release properties. It notably investigates the synergistic interactions between the intrinsic bioactivity of PDEVs and the drugs they deliver. Furthermore, this review highlights advanced applications of PDEV gel composites in localized drug delivery, specifically emphasizing their clinical potential for treating dermatological conditions. Finally, it highlights the current challenges faced by PDEVs and anticipates future research directions, such as synthetic biology, multi-omics analysis, and clinical translation. This review provides a theoretical framework for the rational design and clinical translation of PDEVs. It thereby promotes their innovative development in precision nanomedicine.

Plant-derived extracellular vesicles (PDEVs) have emerged as promising natural nanocarriers for biomedical applications owing to their distinctive ability to facilitate intercellular communication and transport bioactive molecules. In this review, we employ bibliometric analysis to identify research hotspots and trends, providing a comprehensive overview of these core themes. The bibliometric results reveal a sustained increase in annual publications in this field, with keyword analysis identifying drug delivery, cross-kingdom regulation, immunomodulation, engineering modification, and gut microbiota as five major research themes. The focus of research has evolved from early basic biological characteristics into engineered smart delivery platforms, with the application areas expanding from intestinal inflammation to neurological, metabolic, dermatological, and oncological diseases. This review systematically examines the core directions in this field. It compares the strengths and limitations of mainstream isolation methods and highlights the value of multi-omics integration, covering the molecular mechanisms of ferroptosis and gut microbiota regulation by PDEVs along with engineering strategies such as drug loading, surface modification, and membrane fusion. It also discusses the latest progress in frontier therapeutic applications of PDEVs, including cancer, inflammatory diseases, tissue regeneration and aesthetics, and neurological disorders. Finally, this review summarizes the key challenges confronting the field, including the lack of standardized protocols, production bottlenecks, and engineering obstacles. It also delineates future directions, including establishing international standardization definitions, advancing multi-omics and AI-driven mechanistic elucidation, developing scalable and efficient purification technologies, and executing systematic preclinical safety and pharmacokinetic evaluations to facilitate clinical translation.