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.

(1) Background: OSU-2S is a derivative of FTY720 and exhibits significant inhibitory effects on various cancer cells. There is currently no research on the mechanism of the impact of OSU-2S on NSCLC development. We analysed and validated the hub genes and pharmacodynamic effects of OSU-2S to treat NSCLC. (2) Methods: The hub genes of OSU-2S for the treatment of NSCLC were screened in PharmMapper, genecard, and KM Plotter database by survival and expression analysis. The effect of OSU-2S on hub gene expression was verified by Western blot analysis. The ex vivo and in vivo efficacy of OSU-2S on tumour growth was verified using A549 cells and a xenografted animal model. (3) Results: A total of 7 marker genes for OSU-2S treatment of NSCLC were obtained. AURKA and S1PR1 were screened as hub genes. Significant differences in the expression of AURKA and S1PR1 between normal and lung adenocarcinoma (LUAD) tissues were found in the GEPIA2 database; Western blot showed that OSU-2S could affect p-AURKA and S1PR1 protein expression. OSU-2S significantly inhibited tumour growth in A549 cells and xenografted animal models. (4) Conclusions: Our study confirms the inhibitory effect of OSU-2S on NSCLC, screens and demonstrates its potential targets AURKA(p-AURKA) and S1PR1, and provides a research basis for treating NSCLC with OSU-2S.

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.

Background: Atherosclerosis (AS) has one of the highest rates of morbidity and death globally. Cydonia oblonga Mill. (quince, COM) and Ocimum basilicum L. (basil, OB) are Uyghur medicines that are often used for anti-inflammatory, anti-tumor, and cardiovascular disease treatment. This study aimed to uncover the hub genes of the quince-basil co-administration against AS and validate them. Methods: Network pharmacology analysis and bioinformatics analysis methods were utilized to map the network and obtain four hub genes. Experiments were performed in vivo and in vitro using HUVEC and zebrafish to validate the therapeutic effect of COM-OB co-administration against AS. Finally, the hub genes were validated by Western blot. Results: Screening by network pharmacology analysis and bioinformatics analysis obtained a total of 3302 drug targets, 1963 disease targets, and 1630 DEGs. A series of bioinformatic analyses were utilized to ultimately screen four hub genes, and the stability was also verified by molecular docking and molecular dynamics. COM-OB total flavonoids co-administration significantly decreased PA-induced lipid deposition in HUVEC and reduced high cholesterol-induced fat accumulation in zebrafish. Western blot results showed that COM-OB co-administration significantly affected the expression of hub genes. Conclusions: The study identified and validated four hub genes, COL1A1, COL3A1, BGLAP, and NOX4, thus providing a rationale for the treatment of AS with COM and OB co-administration.