Pre-clinical toxicological investigations are pivotal in the development of safer and more efficacious chemotherapeutic agents. Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid, has demonstrated anticancer potential but is often limited by the toxic side effects of its derivatives. In the current study, we carried out the facial synthesis of a modified OA analogue, OD2, and studied its cytotoxicity and efficacy analysis across several cell lines. Mechanistic toxicology was explored through fluorescence-based assays. Annexin V/Propidium Iodide (A-V/PI) staining and TUNEL assays, were used to confirm apoptosis. OD2 exhibited dose-dependent cytotoxicity, with a pronounced effect on A549 lung cancer cells compared to other cancerous and non-cancerous cell lines. Apoptosis was found to be the predominant mode of cell death, evidenced by Fluorescence imaging analysis of chromatin condensation and mitochondrial dysfunction. This was further validated by an increase in Annexin-V-positive and TUNEL-positive cells in treated groups. OD2 activated the intrinsic mitochondrial apoptotic pathway as evidenced by increased Bax and decreased Bcl2 protein abundance levels. While the current study showcases the therapeutic potential of the selective toxicological activity of OD2, future studies will focus on the deconvolution of its potential polypharmacological mode of action and decoding the basis of its selective action, so as to glean important lessons that can be applied in the development of chemotherapeutic agents with favourable toxicological profiles.

Lung cancer and breast cancer both are extremely threatening to humans, so it is needed to develop safe and effective drugs for the treatment of these two ailments. To improve the activity and selectivity of bioactive natural product oleanolic acid (OA), triphenylphosphonium moieties were introduced at different sites of the OA core skeleton. The antiproliferative activity screening results displayed that the anticancer activity of all target compounds was significantly improved, and some derivatives displayed strong selectivity for breast cancer cells (MCF-7) and lung cancer cells (A549) over the human normal liver cells (QSG-7701 cells). Compounds (for A549 cells) and (for MCF-7 cells) demonstrated the best selectivity (with SI of 12.18 and 7.72, respectively). The docking results showed that and could bind to and interact with PI3K protein through hydrogen bonds and intermolecular hydrophobic forces. These compounds are potential anti-MCF-7 agents and deserve further study.

Fruit surface cuticular waxes of grape berries are important in stress response and fruit quality. Despite extensive studies on the biosynthesis, regulation and composition of fruit surface waxes, knowledge of the compositional variation and genetic mechanisms underlying grape berry cuticular wax formation remains limited. This study aimed to characterise grape berry cuticular wax composition and identify contributing genes. The wax composition of two grape cultivars ('Deckrot' and G1-7720) and their progeny shifted from aldehyde to fatty acid accumulation during ripening while the composition was shown to influence Botrytis cinerea susceptibility. Alcohols and aldehydes contributed to the glaucous wax appearance while the bioactive triterpene, oleanolic acid, was found to be the most abundant wax monomer. Metabolic quantitative trait locus analysis identified several genomic regions associated with wax monomer formation, including a cluster on chromosome nine linked to triterpene content, which included eight putative triterpene synthases. Molecular phylogenetic analysis suggested these genes code for amyrin synthases. Co-expression analysis, and subsequent heterologous expression in yeast, confirmed the involvement of VvTTPS12 in oleanolic acid formation. This study explores the role of grape berry wax composition and enhances understanding of genetic contributors to wax formation.

The separation of different types of bioactive compounds in olive leaf is demonstrated with a tailored adsorbent functionalized with pyridyl moieties and sorption-desorption processes developed to use only hydroalcoholic solvents. The competitive binding isotherms of mixtures of vanillic acid, oleuropein, quercetin, maslinic, and oleanolic acids in water/ethanol solvents, with the composition ranging from 50/50 up to 100% ethanol, prove the feasibility of the separation of such different classes of molecules. The bioactive compounds in two industrial olive leaf extracts with different crude compositions were separated with the pyridyl-based polymer particles in packed columns, employing multicycle sorption/desorption processes. A polyphenol-rich extract was subjected to separation, resulting in the isolation of fractions containing varying concentrations of specific compounds. For example, a fraction enriched with oleuropein exhibited a concentration of approximately 80% (an enrichment factor of ∼4 in comparison with the crude extract), while glycosylated flavonoids were present at a concentration of around 60% in another fraction (an enrichment factor of ∼12). Additionally, aglycone flavonoids were present in fractions at a concentration of approximately 83% (an enrichment factor of ∼49). On the other hand, the separation of polyphenols and triterpene acids in an olive leaf extract with a high triterpene content was also demonstrated, with a ratio of flavonoids to triterpenoids of approximately 23 in isolated fractions, as compared to approximately 1 observed in the crude extract. The developed approach yielded luteolin with an enrichment factor of approximately 7. These novel achievements are intended to contribute to sustainability and a circular bioeconomy through the efficient industrial valorization of agricultural byproducts.

Gastric ulcers (GC) are prevalent gastrointestinal disorders with complex etiologies, including Helicobacter pylori infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Curcumin (CUR), with its established anti-inflammatory and antioxidant properties, is limited in clinical application due to poor bioavailability. This study developed oleanolic acid-coated CUR nanoparticles (OC NPs) to enhance the efficacy of CUR in GC prevention. OC NPs were characterized by a spherical shape, demonstrating remarkable improvements in solubility and stability, maintaining structural integrity within biological systems and exhibiting excellent biocompatibility. In vitro studies showed OC NPs reduced inflammation and oxidative stress in GES-1 cells. In vivo, OC NPs effectively prevented ethanol-induced GC in mice by lowering inflammatory cytokines, while increasing antioxidant levels. Histological analysis confirmed enhanced gastric mucosal protection and reduced fibrosis and apoptosis. OC NPs demonstrated prolonged retention in the stomach, offering a targeted drug delivery system. These findings suggested OC NPs as a promising low-toxicity alternative for preventing GC.

Mesangial proliferative glomerulonephritis (MsPGN) is a common form of glomerulonephritis characterized by mesangial cell proliferation and inflammatory responses. However, current clinical treatment options for MsPGN are rather limited. Oleanolic acid (OA), a natural pentacyclic triterpenoid compound, exhibits anti-tumor and anti-inflammatory properties and has been proven to have renal protective effects. We speculate that OA could potentially serve as an alternative therapy for MsPGN.

Oleanolic acid (OA) ischaracterized by its low water solubility, poor permeability and majorly metabolized by cytochrome P450 (CYP) isozymes in the intestinal tract, particularly CYP3A, which contribute to the low oral bioavailability. OA has multiple pharmacological actions including hepatoprotective, anti-inflammatory, antidiabetic and antiviral effects. OA classified as a BCS IV drug which have restricted its potential clinical application. In this study D-α-Tocopheryl polyethylene glycol succinate (TPGS) and Pluronics F68 based stabilized OA loaded mixed micellar system (OA-MMs) developed to improve the solubility and permeability. Mixed micelles were characterized by dynamic light scattering studies as a function of temperature, salt addition, and OA solubilisation followed byXRD, FE-SEM and IR analysis confirmed the formation of stabilized OA-MMs with the least size and PDI (10.041 ± 1.35 nm, 0.313 ± 0.012). Scattering studies results demonstrates the formation of stable micelles with no significant alterations insize upon salt addition (up to 150mM NaCl), OA incorporation (up to 150 mM) and temperature rise till 40 °C.Solubility of the pure OA and OA-MMs was found to be 0.042 mg/ml and 1.98 mg/ml. The % cumulative release of drug from alone OA, OA + TPGS and OA-MMs was found to be 4.363 ± 0.025%, 57.18 ± 0.034% and 92.269 ± 0.017% respectively up to 24 h. Single-pass intestinal perfusion studies (SPIP) showed that K and P of OA-MMs was improved30 fold as compared with that of pure OA and this was mainly due to the improved permeability and inhibitory effect of Pluronic F68 on CYP3A. The in vivo Pharmacokinetic study showed that C increased markedly from 12.76 to 20.49 and 39.17 µg/ml in case of OA alone, OA + TPGS and OA-MMs. Parallel to the C there was an increase in the AUC133.68 to 164.56 and 296.50 respectively. All of the produced OA-MMs formulation's results demonstrated a notable increase in OA's bioavailability through increased permeability and solubility along with metabolic inhibition OA.

Depression is a prevalent, chronic, and debilitating disorder characterized by high treatment resistance. Symplocos racemosa, containing phenols and triterpenoids, acts as an antidepressant by elevating brain monoamine levels.

Triple-negative breast cancer (TNBC) is a type of breast cancer characterized by high molecular heterogeneity. Owing to the lack of effective therapeutic strategies, patients with TNBC have a poor prognosis. L. has the effects of reducing swelling, dissolving knots and treating breast carbuncles and mammary rocks. Modern pharmacological studies have reported that it can effectively inhibit the growth of breast cancer. The main active antitumor components of are triterpenoids (PVT); however, the role and potential mechanism of PVT in TNBC remain unexplored. Our study aimed to further explore the inhibitory effects of PVT on TNBC and the associated mechanism. The results showed that 19 compounds associated with PVT were identified, 9 of which were triterpenoids. The percentages of ursolic acid and oleanolic acid in PVT were 34.51% and 11.32%, respectively. Triterpenes of significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells and promoted their apoptosis in a concentration-dependent manner. PVT could also effectively downregulate the mRNA and protein expression levels of , , and and upregulate the mRNA and protein expression levels of in MDA-MB-231 cells. In mice with tumors of TNBC, PVT significantly reduced tumor growth and the expression levels of PTP1B, CXCL12, CXCR4, PI3K, AKT, mTOR and other proteins in TNBC tumor tissue and upregulated the expression of IL-24. This study showed that PVT played an anti-TNBC role by regulating the PTP1B/PI3K/AKT/mTOR signaling pathway and the IL-24/CXCL12/CXCR4 signaling axis.

Calenduloside E (CE) and chikusetsusaponin IVa (ChIVa) are triterpene saponins with multidirectional bioactivity. In this study, the contents of CE and ChIVa were determined in the roots, stems, leaves, and fruits of ten wild-growing species of Amaranthaceae. To achieve optimal extraction conditions for both saponins, maceration, shaking-assisted maceration, and ultrasound-assisted and heat reflux extraction were compared. A sensitive, specific, and rapid UPLC-MS/MS method was developed and validated for the simultaneous quantification of CE and ChIVa. The results showed that CE and ChIVa coexisted in most of the species analyzed, except for . For the first time, the presence of CE and ChIVa was noted in , , , , and . Of the species analyzed, the highest ChIVa content was found in the fruit of (13.15 mg/g dw), (12.20 mg/g dw), and (10.0 mg/g dw), and in the fruit and roots of (5.52 and 7.77 mg/g dw, respectively). The highest amount of CE was determined in the fruit of (7.84 mg/g dw) and (6.54 mg/g dw). These saponin-abundant plant parts of Amaranthaceae spp. may be considered convenient sources of these bioactive saponins.