Susan Lucia Bonnet

Prunus L. is a diverse genus of deciduous and evergreen trees and shrubs belonging to the family Rosaceae (subfamily Amygdaloideae), comprising approximately 400–430 species widely distributed across temperate regions. Several species are cultivated globally for ornamental purposes and for commercially important fruits such as plums, almonds, peaches, nectarines, cherries, and apricots. Beyond their economic value, numerous Prunus species have a long history of use in traditional healthcare systems for their ethnomedicinal properties. This review synthesizes current knowledge on the ethnomedicinal applications, phytochemical composition, pharmacological activities, and therapeutic potential of 30 selected Prunus species. An extensive literature survey was conducted across major scientific databases, including PubMed, Scopus, Google Scholar, and SciFinder, as well as published books and proceedings. Chemical and taxonomic data were verified through PubChem and World Flora Online. Phytochemical investigations reveal that Prunus species are rich in phenolic acids, flavonoids, anthocyanins, tannins, terpenoids, and cyanogenic glycosides, which contribute to a broad spectrum of biological activities. Experimental studies report significant anticancer, antioxidant, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, antihyperlipidemic, antibacterial, and diuretic properties. However, comprehensive mechanistic studies and clinical validations remain limited to a few well-studied species, highlighting substantial research gaps. Future research should focus on the isolation and structural characterization of bioactive constituents, elucidation of molecular mechanisms, integration of omics-based approaches, and the conduct of well-designed clinical and toxicological studies. Sustainable utilization and conservation strategies are also essential to preserve genetic diversity. Overall, this review underscores the significant pharmacological promise of Prunus species and provides a framework for advancing their therapeutic applications.

Background/Objectives: Diabetes is a chronic metabolic disorder that leads to elevated blood sugar levels and has become a global concern. Though there has been an increase and evolution of antidiabetic drugs and therapeutics, they fall short of the desired efficacy and are often associated with adverse effects. This study explores reduced chalcone as a scaffold to design and synthesize potential antidiabetic drugs with improved efficacy through glycosylation and supplemented by in silico evaluation. Methodology: The 3ʹ-hydroxychalcone was initially reduced to 1-phenyl-3-(3ʹ-hydroxyphenyl)propane (2), followed by direct C-glycosylation at C-4ʹ under temperature control from -78 ℃ to room temperature (RT) and afforded the C-4ʹ glucosylated 1,3-diaryl propane. The first step in the mechanism was 3ʹ-O-glycosylation, and the resultant 3ʹ-O-a,b-glucose isomer mixture was isolated at -40 ℃ . NMR spectroscopy and mass spectrometry were used to characterise and validate compound structures. These compounds' antidiabetic potentials and drug-likeness were evaluated through integrated computational techniques. Results: The main compound (5) showed no inhibitory activity against α-glucosidase and α-amylase. However, all the compounds showed higher probable antidiabetic activities and improved drug-likeness relative to aspalathin. Their binding affinity assessment showed they are potential ‘pan-binders’ with high binding affinities to several proteins implicated in the advancement of diabetes, including AKT, AMPK, GLUT4, SGLT2, and SIRT6. Furthermore, they were observed to stabilise within the binding pocket of AKT, underscored by strong hydrogen and hydrophobic bonds resulting in protein conformational changes, thus highlighting their antidiabetic potential. Conclusion: The synthesised glucosyl chalcones could be potential lead compounds for developing novel antidiabetic compounds.

This study aimed to investigate the glycaemic control potential and modulation of GABA-induced chloride currents (I_GABA) of H. revolutum and the possible bioactive xanthones. Fractions from the leaf and stem extracts (dichloromethane and methanol) were assessed for in vitro α-glucosidase-inhibitory potential and their ability to modulate I_GABA (GABAergic effect) through GABA_A receptors heterologously expressed in Xenopus oocytes. Xanthones 4-hydroxy-2,3-dimethoxy-9H-xanthen-9-one (1), 3-hydroxy-2,4-dimethoxy-9H-xanthen-9-one (2) and trans-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy-2,3-dihydro-7H-[1,4]dioxino[2,3-c]xanthen-7-one (3) were isolated from the stem and tested in the GABA_A receptors assay, but only 3 was assessed for α-glucosidase-inhibitory action. Compared to acarbose (IC₅₀ = 6.16 µM), 3 showed a mild to moderate α-glucosidase-inhibitory activity (IC₅₀ = 45.1 µM), which may be attributed to the absence of a hydroxyl group at its xanthone core. Isomeric compounds 1 and 2 significantly enhanced I_GABA with similar efficacy, while 3 was inactive, which may be attributed to its notable structural difference (cyclic ether substitution) compared to compounds 1 and 2. H. revolutum stem contains xanthones with α-glucosidase-inhibitory potential, which also enhance I_GABA and could be further studied as a medicinal plant for managing GABA_A receptor-mediated mental disorders and/or diabetes.

Bioactive flavonoid epicatechin has been reported in the peel of litchi fruit but isolated from its hydroalcoholic extracts. This study isolated epicatechin with cellular glucose uptake modulatory and ROS production inhibitory properties from the ethyl acetate (EtOAc) extract using a bioassay-guided approach. The fruit peel was defatted with hexane and sequentially extracted using dichloromethane (DCM), EtOAc, methanol (MeOH) and water. In vitro phytochemical models, namely antioxidant (Fe³⁺ reducing, radical scavenging and anti-linoleic acid peroxidative) and glycaemic control (α-glucosidase and α-amylase inhibitory and glucose uptake modulatory), were employed for the bioassay-guided isolation, while the isolated compound was characterised using NMR and mass spectrometry and assessed for dose-dependent inhibition of α-glucosidase and lipopolysaccharide (LPS)-induced cellular ROS production, as well as modulation of cellular glucose uptake. Relative to the other extracts, the EtOAc extract had appreciable phenol and flavonoid contents, which perhaps influenced its potent anti-lipid peroxidative (65.0%) and α-glucosidase inhibitory (52.4%) effects. The α-glucosidase inhibitory potency of the fractions (1–8) from the EtOAc extracts correlated with their flavonoid contents, with fraction 5 outperforming other fractions. The fraction comprised a pool of fractions obtained from the DCM:MeOH:water (7:3:0.281 v/v/v) solvent system. LC-MS revealed the predominant presence of epicatechin in fraction 5, which was later isolated from one of the sub-fractions (sub-fraction 4) of fraction 5. This sub-fraction had stronger anti-lipid peroxidative (65.5%), α-glucosidase inhibitory (65.8%) and glucose uptake modulatory (38.2%) effects than the other sub-fractions from fraction 5, which could have been influenced by the isolated epicatechin. Moreover, the isolated epicatechin inhibited α-glucosidase (IC₅₀ = 35.3 µM), modulated cellular glucose uptake (EC₅₀ = 78.5 µM) and inhibited LPS-induced ROS production in RAW 264.7 macrophages in a dose-dependent fashion [IC₅₀ = 18.9 µM; statistically comparable (p > 0.05) to ascorbic acid, IC₅₀ = 9.57 µM]. Epicatechin from litchi peel EtOAc extract could potentiate glucose uptake modulatory, α-glucosidase inhibitory and ROS suppressive capacities, which could be influential in the use of litchi fruit peel for managing diabetes and associated oxidative damage.

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1–3), along with four known ones (4–7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC₅₀ = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC₅₀ = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC₅₀ = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 had the highest binding score (−121.8 and −131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (−116 and −100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds 1 and 2 showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds 1 and 2 for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.

An antiplasmodial activity-guided isolation was carried out on the dichloromethane extract of Tithonia diversifolia dried leaves. A total of five germacranolide type sesquiterpene lactones and a new flavonol, 3,6-dihydroxy-2-(4′-hydroxyphenyl)-7-methoxy-4H-chromen-4-one, were isolated. The flavonol reported an IC₅₀ above 6.00 µM against the chloroquine sensitive strain, NF54. The antimalarial activity of the Tithonia diversifolia dichloromethane leaf extract was attributed to orizabin and tagitinin C.

Proanthocyanidins (PACs) are natural plant-derived polymers consisting of flavan-3-ol monomers. Quebracho (Schinopsis lorentzii and balansae) heartwood and mimosa (Acacia mearnsii) bark extracts are the major industrial sources of PACs. These commercial extracts are often sulfited to reduce their viscosity and increase their solubility in water. The chemical process of sulfitation is still poorly understood regarding stereochemical influences during the reaction and during the cleavage of the interflavanyl bond of oligomers. To gain a better understanding of sulfitation, two diastereomeric flavan-3-ol monomers were sulfited under industrial conditions, and procyanidin B-3 (catechin-4α→8-catechin) were sulfited to investigate interflavanyl bond cleavage with sulfitation at C-4. Treatment of diastereomeric flavan-3-ols 2R,3S-catechin and 2R,3R-epicatechin with NaHSO₃ at 100 °C in aqueous medium afforded the enantiomeric (1R,2S)- and (1S,2R)-1-(3,4-dihydroxyphenyl)-2-hydroxy-3-(2,4,6-trihydroxyphenyl)propane-1-sulfonic acid, respectively. Utilizing computational NMR PD4 calculations it was determined that the direction of stereoselective nucleophilic attack is controlled by the C-3 configuration of the flavan-3-ols catechin and epicatechin. Sulfitation of the catechin-4α→8-catechin dimer 7 (procyanidin B-3) under the same conditions led to the cleavage of the interflavanyl bond yielding the C-4 sulfonic acid substituted catechin momomer. From the heterocyclic ring coupling constants it was determined that nucleophilic attack occurs from the β-face of the dimer leading to the 2,3-trans-3,4-cis isomer as product.

Flavonoids and their photochemical transformations play an important role in biological processes in nature. Synthetic photochemistry allows access to molecules that cannot be obtained via more conventional methods. This review covers all published synthetic photochemical transformations of the different classes of flavonoids. It is first comprehensive review on the photochemistry of flavonoids.