This study focused on the biological evaluation and chemical characterization of Geranium pyrenaicum Burm. f. Different solvent extracts (hexane, ethyl acetate, methanol, and water extracts) were prepared. The phytochemical profile, antioxidant, and enzyme inhibitory activity were investigated. Cytotoxicity was assessed using VERO, FaDu, HeLa and RKO cells. The antiviral activity was carried out against HSV-1 (Herpes simplex virus 1) propagated in VERO cell line. The aqueous extract, possessing high phenolic content (170.50 mg gallic acid equivalent/g extract), showed the highest reducing capacity (613.27 and 364.10 mg Trolox equivalent/g extract, for cupric reducing antioxidant capacity and ferric reducing antioxidant power, respectively), radical scavenging potential (469.82 mg Trolox equivalent/g extract, against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), metal chelating ability (52.39 mg ethylenediaminetetraacetic acid equivalent/g extract) and total antioxidant capacity (3.15 mmol Trolox equivalent/g extract). Liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (LC-ESI-QTOF-MS/MS) alloved to tentatively identify a total of 56 compounds in the extracts, including ellagitannins, gallic acid and galloyl derivatives amongst others. The ethyl acetate extracts substantially depressed cholinesterase enzymes (4.49 and 12.26 mg galantamine equivalent/g extract against AChE and BChE, respectively) and α-amylase enzyme (1.04 mmol acarbose equivalent/g extract). On the other hand, the methanolic extract inhibited tyrosinase (121.42 mg kojic acid equivalent/g extract) and α-glucosidase (2.39 mmol acarbose equivalent/g extract) activities. The highest selectivity towards all cancer cell lines (SI 4.5–10.8) was observed with aqueous extract with the FaDu cells being the most sensitive (CC₅₀ 40.22 µg/mL). It can be concluded that the presence of certain bioactive antiviral molecules may be related to the high anti HSV-1 activity of the methanolic extract. This work has generated vital scientific data on this medicinal plant, which is a prospective candidate for the creation of innovative phyto-pharmaceuticals.

Ethyl acetate (EA), methanol (MeOH), and aqueous extracts of aerial parts of Anthemis tinctoria var. pallida (ATP) and A. cretica subsp. tenuiloba (ACT) were investigated for their phenol and flavonoid content, antioxidant, and key enzyme inhibitory potentials. All extracts displayed antiradical effects, with MeOH and aqueous extracts being a superior source of antioxidants. On the other hand, EA and MeOH extracts were potent against AChE and BChE. Enzyme inhibitory effects against tyrosinase and α-glucosidase were observed, as well. We also studied Anthemis extracts in an ex vivo experimental neurotoxicity paradigm. We assayed extract influence on oxidative stress and neurotransmission biomarkers, including lactate dehydrogenase (LDH) and serotonin (5-HT), in isolated rat cortex challenged with K⁺ 60 mM Krebs-Ringer buffer (excitotoxicity stimulus). An untargeted proteomic analysis was finally performed in order to explore the putative mechanism in the brain. The pharmacological study highlighted the capability of ACT water extract to blunt K⁺ 60 mM increase in LDH level and 5-HT turnover, and restore physiological activity of specific proteins involved in neuron morphology and neurotransmission, including NEFMs, VAMP-2, and PKCγ, thus further supporting the neuroprotective role of ACT water extract.

Anacamptis pyramidalis (L.) Rich. forms part of the Orchidaceae family that is highly valued for its horticultural as well as therapeutic benefits. The present study set out to investigate the inhibitory activity of A. pyramidalis tubers against key biological targets for the management of type 2 diabetes, Alzheimer disease, and skin hyperpigmentation. In addition, the antioxidant potential of the extracts was also assessed using multiple methods. The detailed phytochemical profiles of the extracts were determined using high-performance liquid chromatography. Based on qualitative phytochemical fingerprint, a network pharmacology analysis was conducted as well. Parishin was identified from the water extract only, whereas gastrodin and caffeic acid derivatives were present in the methanol extract. The methanol extract exhibited high inhibitory activity against tyrosinase (69.69 mg kojic acid equivalent/g extract), α-amylase (15.76 mg acarbose equivalent/g extract), and α-glucosidase (20.07 mg acarbose equivalent/g extract). Similarly, the methanol extract showed highest antioxidant potential (22.12, 44.23, 45.56, and 29.38 mg Trolox equivalent/g extract, for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), CUPric Reducing Antioxidant Capacity (CUPRAC), and Ferric Reducing Antioxidant Power (FRAP) assays, respectively). Finally, the results of network pharmacology analysis, besides corroborating traditional uses of plant extracts in the management of cold and flu, confirmed a direct involvement of identified phytochemicals in the observed enzyme inhibitory effects, especially against tyrosinase, α-amylase, and α-glucosidase. Furthermore, based on the results of both colorimetric assays and network pharmacology analysis related to the activity of A. pyramidalis extracts and identified phytocompounds on enzymes involved in type 2 diabetes, a docking study was conducted in order to investigate the putative interactions of oxo-dihydroxy octadecenoic acid trihydroxy octadecenoic acid against aldose reductase, peroxisome proliferator-activated receptor (PPAR)-α, dipeptidyl peptidase (DPP)-IV, and α-glucosidase. Docking analysis suggested the inhibitory activity of these compounds against the aforementioned enzymes, with a better inhibitory profile shown by oxo-dihydroxy octadecenoic acid. Overall, the present findings supported the rationale for the use of A. pyramidalis as source of bioactive metabolites and highlight, today more than ever, for the strong necessity of linkage strategy between wild resource valorization and conservation policy.

Fibigia clypeata (L.) Medik. is a poorly studied plant species belonging to the Brassicaceae family, and usually used as cress in the salads. The current investigation aimed at assessing the antioxidant potential and inhibitory activity of ethyl acetate, methanol, and aqueous extracts of F. clypeata against key enzymes targeted in the management of type II diabetes (α-amylase and α-glucosidase), Alzheimer’s disease (acetylcholinesterase and butyrylcholinesterase), and skin hyperpigmentation (tyrosinase). Cytotoxicity of the extracts was also determined using normal VERO and cancer FaDu and SCC-25 cell lines. Besides, LC-MS was employed to investigate the detailed phytochemical profiles of the extracts. The methanol extract showed potent enzyme inhibitory activity (4.87 mg galantamine equivalent/g, 3.52 mg galantamine equivalent/g, 126.80 mg kojic acid equivalent/g, and 24.68 mg acarbose equivalent/g, for acetylcholinesterase, butyrylcholinesterase, tyrosinase, and α-glucosidase, respectively) and antioxidant potential (96.52, 109.10, 154.02, and 104.85 mg trolox equivalent/g, for DPPH, ABTS, CUPRAC, and FRAP assays, respectively). Interestingly, caffeic acid-O-hexoside derivative, caffeyl alcohol O-glucopyranoside, and ferulic acid derivative were identified in all extracts. F. clypeata extracts showed no cytotoxicity towards VERO cell line and a weak cytotoxic potential against FaDu and SCC-25 cell lines. Interesting scientific evidence gathered from the present study support further investigation on F. clypeata in the view of designing and developing a novel therapeutic agent for the management of Alzheimer’s disease, type II diabetes, skin hyperpigmentation problems, as well as cancer.

The present study investigates the chemical profile and biological activities of Polygonum istanbulicum M. Keskin, a species endemic to Turkey, aiming to explore its potential applications in pharmacology. We assessed its phenolic and flavonoid content by employing ethyl acetate, methanol, and water as extraction solvents. The methanol extract demonstrated the highest concentrations of these compounds, with liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (LC-MS-qTOF) analysis identifying a wide range of bioactive substances, such as derivatives of quercetin and myricetin. Antioxidant capacity was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), cupric-reducing antioxidant capacity (CUPRAC), ferric-reducing antioxidant power (FRAP), and phosphomolybdenum assays, with the methanol extract showing the most potent activity (DPPH: 892.22 mg Trolox equivalent (TE)/g; ABTS: 916.21 mg TE/g; CUPRAC: 1082.69 mg TE/g; FRAP: 915.05 mg TE/g). Enzyme inhibition assays highlighted the efficacy of P. istanbulicum extracts against key enzymes, with potential implications for managing Alzheimer’s disease, hyperpigmentation, and type 2 diabetes. Cytotoxicity tests against various cancer cell lines showed notable activity, particularly with the aqueous extract on the HGC-27 cell line (IC₅₀: 29.21 µg/mL), indicating potential for targeted anti-cancer therapy. Molecular docking and molecular dynamics simulations further supported the binding affinities of quercetin and myricetin derivatives to cancer-related proteins, suggesting significant therapeutic potential. This study underscores the value of P. istanbulicum as a source of bioactive compounds with applications in antioxidant, anti-cancer, and enzyme-inhibitory treatments.