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.

Feijoa sellowiana leaves and fruits have been investigated as a source of diverse bioactive metabolites. Extract and eight metabolites isolated from F. sellowiana leaves were evaluated for their enzymatic inhibitory activity against α-glucosidase, amylase, tyrosinase, acetylcholinestrerase and butyrylcholinesterase both in vitro and in silico. Feijoa leaves' extract showed strong antioxidant activity and variable levels of inhibitions against target enzymes with a strong anti-tyrosinase activity (115.85 mg Kojic acid equivalent/g). Additionally, α-tocopherol emerged as a potent inhibitor of AChE and BChE (5.40 & 10.38 mmol galantamine equivalent/g, respectively). Which was further investigated through molecular docking and found to develop key enzymatic interactions in AChE and BChE active sites. Also, primetin showed good anti BChE (11.70 mmol galantamine equivalent/g) and anti-tyrosinase inhibition (90.06 mmol Kojic acid equivalent/g) which was also investigated by molecular docking studies. Highlights Isolation of eight bioactive constituents from Feijoa sellowiana leaves. In vitro assays using different enzymatic drug targets were investigated. In silico study was performed to define compound interactions with target proteins. Feijoa leaf is an excellent source of anti-AChE and antityrosinase bioactives.

Spondias species have been used in traditional medicine for different human ailments. In this study, the effect of different solvents (ethyl acetate, methanol, and water) and extraction methods (infusion, maceration, and Soxhlet extraction) on the enzyme inhibitory activity against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, α-glucosidase, and antioxidant properties of S. mombin and S. dulcis leaves and stem bark were evaluated. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) yield in the identification and/or annotation of 98 compounds showing that the main secondary metabolites of the plant are gallic and ellagic acids and their derivatives, ellagitannins, hydroxybenzoic, hydroxycinnamic, acylquinic acids and flavonols, flavanones, and flavanonols. The leaves infusion of both Spondias species showed highest inhibition against acetylcholinesterase (AChE) (10.10 and 10.45 mg galantamine equivalent (GALAE)/g, for S. dulcis and S. mombin, respectively). The ethyl acetate extracts of the stem bark of S. mombin and S. dulcis actively inhibited α-glucosidase. Methanolic extracts of the leaves and stem bark exhibited highest tyrosinase inhibitory action. Antioxidant activity and higher levels of phenolics were observed for the methanolic extracts of Spondias. The results suggested that the Spondias species could be considered as natural phyto-therapeutic agents in medicinal and cosmeceutical applications.

Nepeta baytopii is a poorly studied, endemic Nepeta species (Lamiaceae) of Turkey. For the first time, the biological activities (antioxidant, enzyme inhibition, and cytotoxicity properties) of the hexane, ethyl acetate, methanol, water/methanol, and water extracts and essential oil prepared from N. baytopii aerial parts were assessed. Hydro-methanol (41.25 mg gallic acid equivalent (GAE)/g) and water extracts (50.30 mg GAE/g), respectively showed the highest radical scavenging (94.40 and 129.22 mg Trolox equivalent (TE)/g, for 2,2-diphenyl-1-picrylhydrazyl radical and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid radical scavenging assays) and reducing (229.37 and 129.55 mg TE/g, for ferric-reducing antioxidant power and cupric-reducing antioxidant capacity assays) capacities in vitro. An interestingly high inhibition was observed for ethyl acetate extract against butyrylcholinesterase (10.85 mg galantamine equivalent/g). The methanol extract showed high cytotoxicity (31.7%) against HepG2 cells. Caryophyllene oxide was identified in high concentrations in the essential oil (39.3%). Luteolin and apigenin and their derivatives were identified from the methanol and water extracts. The results obtained from this study highlighted that the abundance of highly bioactive compounds from Nepeta baytopii ensures the multiple biological activities of the tested extracts, and this suggests a potential use in the pharmaceutical and nutraceutical fields, and therefore should be investigated further.

Bridelia species have been used in traditional African medicine for the management of diverse human ailments. In the current work, the detailed phytochemical profiles of the extracts of the stem bark of B. speciosa were evaluated and the antioxidant and enzyme inhibitory properties of the extracts were assessed. The anti-bacterial and anti-mycotic effects of the extracts were evaluated against selected pathogen strains. Additionally, the anti-proliferative effects were studied on the liver cancer HepG2 cell line. Finally, the putative protective effects were assessed on isolated rat liver that was challenged with lipopolysaccharide (LPS). The results revealed the presence of 36 compounds in the ethyl acetate extract, 44 in the methanol extract, and 38 in the water extract. Overall, the methanol extract showed the highest antioxidant activity, particularly in LPS-stimulated rat liver. Additionally, this extract exerted the highest antimycotic effect on C. albicans, whereas the water extract showed a promising anti-proliferative effect on liver cancer HepG2 cells. The methanol extract was also the most active as enzyme inhibitor, against acetylcholinesterase and butyrylcholinesterase. The current study appraises the antioxidant and enzyme inhibition properties of B. speciosa methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses.

In a world where an eco-friendlier approach is becoming more and more necessary, it is essential to reduce waste production and to reuse residues of the company's supply chain. Coffee silverskin (CS) and spent coffee ground (SCG), two by-products of coffee production, are important sources of bioactive compounds and, for this, some authors have proposed their reuse in the nutraceutical, food, and cosmetic sector. However, their potential enzyme inhibitory properties have been poorly investigated. Hence, the objective of the current work was to study the enzymatic inhibitory activities against acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, and tyrosinase of different extracts of CS and SCG. Before these in vitro bioassays, the phytochemical composition of each extract was investigated via colorimetric assays and HPLC-MS/MS analysis. In addition, the antioxidant activities were evaluated by different chemical approaches. SCG extracts contained a higher content of bioactive compounds, notably the SCG EtOH:H2O extract was the richest in caffeine and possessed the highest antioxidant activities. The hydroalcoholic and methanolic extracts were shown to be the most active against all tested enzymes, while the water extracts displayed lower activity. Our results showed a weak correlation between bioactive compounds and enzyme inhibitory effects, proving inhibitory activities likely due to non-phenolic molecules such as alkaloids and terpenoids. Obtained findings could be a starting point to develop novel nutraceuticals from CS and SCG.

This study focused on the biological evaluation and chemical characterisation of Ficus sur Forssk. (F. sur) (Family: Moraceae). The methanolic and aqueous extracts' phytochemical profile, antioxidant, and enzyme inhibitory properties were investigated. The aqueous stem bark extract yielded the highest phenolic content (115.51 ± 1.60 mg gallic acid equivalent/g extract), while the methanolic leaves extract possessed the highest flavonoid content (27.47 ± 0.28 mg Rutin equivalent/g extract). In total, 118 compounds were identified in the tested extracts. The methanolic stem bark extract exhibited the most potent radical scavenging potential against 2,2-diphenyl-1 picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (475.79 ± 6.83 and 804.31 ± 4.52 mg Trolox equivalent/g extract, respectively) and the highest reducing Cu2+ capacity (937.86 ± 14.44 mg Trolox equivalent/g extract). The methanolic stem bark extract substantially depressed tyrosinase (69.84 ± 0.35 mg kojic acid equivalent/g extract), α-amylase (0.77 ± 0.01 mmol acarbose equivalent/g extract), acetylcholinesterase and butyrylcholinesterase (2.91 ± 0.07 and 6.56 ± 0.34 mg galantamine equivalent/g extract, respectively) enzymes. F. sur extracts were tested for anticancer properties and antiviral activity towards human herpes virus type 1 (HHV-1). Stem bark infusion and methanolic extract showed antineoplastic activity against cervical adenocarcinoma and colon cancer cell lines, whereas leaf methanolic extract exerted moderate antiviral activity towards HHV-1. This investigation yielded important scientific data on F. sur which might be used to generate innovative phytopharmaceuticals.

The widespread genus Cirsium Mill. (Asteraceae) is renowned in traditional medicine. In the present study, an innovative biochemometric-assisted metabolite profiling of the flower heads, aerial parts and roots of Cirsium appendiculatum Griseb. (Balkan thistle) in relation to their antioxidant and enzyme inhibitory potential was developed. The workflow combines ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) with partial least-square analysis to discriminate the herbal extracts and identify the most prominent biological activities. The annotation and dereplication of 61 secondary metabolites were evidenced, including 15 carboxylic (including hydroxybenzoic and hydroxycinnamic) acids and their glycosides, 11 acylquinic acids, 26 flavonoids and 9 fatty acids. All compounds were reported for the first time in the studied species. The root extract revealed the highest cupric and ferric reducing power (618.36 ± 5.17 mg TE/g and 269.89 ± 8.50 mg TE/g, respectively) and antioxidant potential in phosphomolybdenum (3.36 ± 0.15 mmol TE/g) as well as the most prominent enzyme inhibitory potential on α-glucosidase (0.72 ± 0.07 mmol ACAE/g), acetylcholinesterase (4.93 ± 0.25 mg GALAE/g) and butyrylcholinesterase (3.80 ± 0.26 mg GALAE/g). Nevertheless, the flower heads were differentiated by their higher metal chelating activity (32.53 ± 3.51 mg EDTAE/g) and total flavonoid content (46.59 ± 0.89 mgRE/g). The partial least-square discriminant and heat-map analysis highlighted the root extract as the most active and a promising source of bioactive compounds for the therapeutic industry.

Hypericum triquetrifolium and H. neurocalycinum were evaluated for their phytochemical content and in vitro bioactivity. NMR analyses were performed on the methanol extract of the aerial parts of H. triquetrifolium to establish the main classes of phytoconstituents. Then, LC-DAD-MSn analyses were performed in order to compare the composition of aerial parts and roots extracts of both Hypericum species, obtained using either methanol or water as solvents. Results, processed using multivariate data analysis, showed a significantly higher phenolic content of methanol extracts compared to water extracts, while minor qualitative differences were observed between the two. Distinctive flavonoid and PAC patterns were observed for H. triquetrifolium and H. neurocalycinum, and specific compounds were exclusively detected in one or the other species. Specifically, the phloroglucinols 7-epiclusianone, hyperfirin and hyperforin were present only in H. neurocalycinum, while hyperforin was detected only in H. triquetrifolium. Extracts were assayed using different in vitro tests to evaluate their antioxidant properties and their inhibitory activity against several enzymes, showing significant antioxidant and metal chelating activities. Furthermore, inhibitory properties against acetylcholinesterase, butyrylcholinesterase and tyrosinase were observed. Multivariate approaches were used to correlate biological data with the phytochemical composition of the different extracts. The results, showing positive correlations between specific chemical constituents and the measured bioactivities, represent preliminary data that could guide future studies aimed at isolating bioactive constituents from H. neurocalycinum and H. triquetrifolium for further pharmacological evaluations.

Heliotropium is one of the most important plant genera to have conventional folklore importance, and hence is a potential source of bioactive compounds. Thus, the present study was designed to explore the therapeutic potential of Heliotropium crispum Desf., a relatively under-explored medicinal plant species. Methanolic extracts prepared from a whole plant of H. crispum were studied for phytochemical composition and possible in vitro and in silico biological properties. Antioxidant potential was assessed via six different assays, and enzyme inhibition potential against key clinical enzymes involved in neurodegenerative diseases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), diabetes (α-amylase and α-glucosidase), and skin problems (tyrosinase) was assayed. Phytochemical composition was established via determination of the total bioactive contents and reverse phase ultra-high performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis. Chemical profiling revealed the tentative presence of 50 secondary metabolites. The plant extract exhibited significant inhibition against AChE and BChE enzymes, with values of 3.80 and 3.44 mg GALAE/g extract, respectively. Further, the extract displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 43.19 and 41.80 mg TE/g extract, respectively. In addition, the selected compounds were then docked against the tested enzymes, which have shown high inhibition affinity. To conclude, H. crispum was found to harbor bioactive compounds and showed potent biological activities which could be further explored for potential uses in nutraceutical and pharmaceutical industries, particularly as a neuroprotective agent.

Lupin seeds can represent a valuable source of phenolics and other antioxidant compounds. In this work, a comprehensive analysis of the phytochemical profile was performed on seeds from three Lupinus species, including one cultivar (Lupinus albus) and two wild accessions (Lupinus cossentinii and Lupinus luteus), collected from the northern region of Tunisia. Untargeted metabolomic profiling allowed to identify 249 compounds, with a great abundance of phenolics and alkaloids. In this regard, the species L. cossentinii showed the highest phenolic content, being 6.54 mg/g DW, followed by L. luteus (1.60 mg/g DW) and L. albus (1.14 mg/g DW). The in vitro antioxidant capacity measured by the ABTS assay on seed extracts ranged from 4.67 to 17.58 mg trolox equivalents (TE)/g, recording the highest values for L. albus and the lowest for L. luteus. The DPPH radical scavenging activity ranged from 0.39 to 3.50 mg TE/g. FRAP values varied between 4.11 and 5.75 mg TE/g. CUPRAC values for lupin seeds ranged from 7.20 to 8.95 mg TE/g, recording the highest for L. cossentinii. The results of phosphomolybdenum assay and metal chelation showed similarity between the three species of Lupinus. The acetylcholinesterase (AChE) inhibition activity was detected in each methanolic extract analyzed with similar results. Regarding the butyrylcholinesterase (BChE) enzyme, it was weakly inhibited by the Lupinus extracts; in particular, the highest activity values were recorded for L. albus (1.74 mg GALAE/g). Overall, our results showed that L. cossentinii was the most abundant source of polyphenols, consisting mainly in tyrosol equivalents (5.82 mg/g DW). Finally, significant correlations were outlined between the phenolic compounds and the in vitro biological activity measured, particularly when considering flavones, phenolic acids and lower-molecular-weight phenolics.

In the quest for novel therapeutic agents from plants, the choice of extraction solvent and technique plays a key role. In this study, the possible differences in the phytochemical profile and bioactivity (antioxidant and enzyme inhibitory activity) of the Alstonia boonei leaves and stem bark extracted using water, ethyl acetate and methanol, and different techniques, namely infusion, maceration and Soxhlet extraction, were investigated. Data collected showed that methanol extracts of both A. boonei leaves (48.34-53.08 mg gallic acid equivalent [GAE]/g dry extract) and stem bark (37.08-45.72 mg GAE/g dry extract) possessed higher phenolic content compared to the ethyl acetate extracts (leaves: 30.64-40.19 mg GAE/g; stem bark: 34.25-35.64 mg GAE/g). The methanol extracts of A. boonei leaves showed higher radical scavenging and reducing capacity, and these findings were in accordance with phenolic content results. In general, water extracts of A. boonei leaves and stem bark obtained by infusion were poor inhibitors of acetylcholinesterase, α-amylase, α-glucosidase, and tyrosinase, except for butyrylcholinesterase. The chemical profiles of the extracts were determined by UHPLC-MS and the presence of several compounds, such as phenolic acids (caffeic, chlorogenic and ferulic acids, etc.), flavonoids (rutin and isoquercetin) and flavonolignans (Cinchonain isomers). Cell viability was tested using the human peripheral blood monocytic cell line (THP-1), and the extracts were safe up to 25 μg/mL. In addition, anti-inflammatory effects were investigated with the releasing of IL-6 TNF-α and IL-1β. In particular, stem bark extracts exhibited significant anti-inflammatory effects. Data presented in this study highlight the key role of solvent choice in the extraction of bioactive secondary metabolites from plants. In addition, this study appraises the antioxidant and enzyme inhibitory action of A. boonei leaves and stem bark, which are extensively used in traditional medicine.

Currently, there is a renewed interest towards the development of plant-based pharmacophores. In this work, 16 extracts prepared from the leaves, twigs, roots and fruits of a hydro-halophyte, Rhizophora mucronata Lam. (Family: Rhizophoraceae), were studied for possible antioxidant activity and the phenolic profiles established. Thereafter, enzymatic inhibitory activities (α-amylase, α-glucosidase, tyrosinase, acetyl- (AChE), butyrylcholinesterase (BChE), lipase, and elastase) were assessed. The total phenolic, flavonoid, phenolic acid, tannin, flavanol and triterpenoid content were estimated using standard assays. An untargeted metabolomics-based approach, based on ultra-high-pressure liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS) followed by multivariate statistics, was then used to comprehensively profile and describe the phenolics present. UHPLC-QTOF-MS allowed for putatively annotating 104 phenolic acids, 103 flavonols, 94 flavones, 71 anthocyanins, 66 tyrosols, 29 lignans, 15 alkylphenols and 10 stilbenes in the extracts. Nine strains (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA), Salmonella enteritidis, Sarcina lutea, Proteus mirabilis, Bacillus cereus and Candida albicans) were then used to investigate the antimicrobial properties. The methanolic twig extract exhibited significant reducing potential towards Cu (II)/Cu (I) and Fe (III)/Fe (II) (1336.88 ± 15.70 and 710.18 ± 21.04 mg TE/g, respectively) and was the most potent DPPH radical scavenger (807.07 ± 6.83 mg TE/g). Additionally, the methanolic twig extract showed significant inhibition against most targeted enzymes. Anti-microbial results showed that all extracts were active against MRSA. Multivariate analysis demonstrated that the phenolic profile of ethyl acetate extracts and leaves were the two most discriminative parameters in terms of solvents and organs, respectively. The present findings indicated that R. mucronata may be further explored for the management/prevention of oxidative stress, neurodegenerative complications and hyperpigmentation.