Biological Properties of Oleanolic Acid Derivatives Bearing Functionalized Side Chains at C-3.

Triterpene acids are a class of pentacyclic natural carboxylic compounds endowed with a variety of biological activities including antitumor, antimicrobial, and hepatoprotective effects. In this work, several oleanolic acid derivatives were synthesized by structurally modifying them on the C-3 position. All synthesized derivatives were evaluated for possible antibacterial and antiviral activity, and among all the epimers, 6 and 7 demonstrated the best biological activities. Zone-of-inhibition analyses were conducted against two strains, E. coli as a Gram-negative and S. aureus as a Gram-positive model. Subsequently, experiments were performed using the microdilution method to determine the minimum inhibitory concentration (MIC). The results showed that only the derivative with reduced hydrogen bonding ability on ring A possesses remarkable activity toward E. coli. The conversion from acid to methyl ester implies a loss of activity, probably due to a reduced affinity with the bacterial membrane. Before the antiviral activity, the cytotoxicity of triterpenes was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Samples 6 and 7 showed less than 50% cytotoxicity at 0.625 and 1 mg/mL, respectively. The antiviral activity against SARS-CoV-2 and PV-1 did not indicate that triterpene acids had any inhibitory capacity in the sub-toxic concentration range.

Amlou inspired spread: Formulation and characterization of new spread based on Ziziphus lotus L. fruit, argan oil, and honey.

This study explores novel applications of combining natural products by integrating Ziziphus lotus L. (Z. lotus), honey, and argan oil to create a product similar to traditional Moroccan Amlou (a mixture of almonds, honey, and argan oil). Five formulations were developed with varying percentages of these three ingredients, alongside two formulations of traditional Amlou. The nutritional value, mineral composition, fatty acid profile, bioactive compounds, and antioxidant activities of the products were analyzed using standard analytical methods such as gas chromatography and spectrophotometry. Additionally, sensory evaluations were conducted to assess consumer preferences. The results showed that the new formulations are rich in oil (45.15-52.24 g/100 g), carbohydrates (40.26-46.81 g/100 g), and protein (3.15-3.92 g/100 g). Mineral analysis revealed significant amounts of potassium (443-578 mg/100 g), calcium (98-124 mg/100 g), phosphorus (50-65 mg/100 g), and magnesium (38-50 mg/100 g). The Z. lotus-based products exhibited higher phenolic content (7-12 mg GAE/g), flavonoids (7.10-10.18 mg QE/g), and stronger antioxidant activities using DPPH radical scavenging activity (3.55-11.14 mg AAE/g) and FRAP (5.39-8.55 mg AAE/g). Moreover, the new product retains the beneficial fatty acid profile of argan oil, with a high content of oleic acid (48 %) and linoleic acid (32 %). Sensory evaluation indicated that the formulation consisting of 45 % Z. lotus powder, 50 % argan oil, and 5 % honey was the most appreciated for taste and texture. These findings suggest that incorporating Z. lotus into traditional Amlou recipes not only enhances nutritional and antioxidant properties but also meets consumer acceptance in terms of flavor and texture.

Cannabis sativa essential oils orally administered to CD1 mice: Tissue distribution of main constituents.

The essential oil (EO) obtained from hemp (Cannabis sativa L.) biomass is rich of bioactive constituents and its oral administration can be valuable. In this paper two different hemp EOs were orally administered to CD1 mice. One EO, obtained from the fresh plant material, resulted rich in monoterpenes (monoterpene rich oil, MRO) and the other, obtained from the dried biomass, contained mainly sesquiterpenes and CBD (sesquiterpene rich oil, SRO). The blood levels of the most abundant constituents were evaluated in the animals 30 and 90 min after oral administration of hemp EOs. Furthermore, compounds were also measured in brain, liver, kidney, spleen, and cecum content to evaluate their tissue distribution at the same times. Results showed the easy absorption and the ability of the major hemp EOs constituents to reach brain, liver, and kidney. Oral administration of MRO resulted in blood levels of monoterpenes in the range 45-115 ng/g at 30 min and significant tissue distribution with the detection of monoterpenes in brain, liver, and kidney. Oral administration of SRO resulted in blood levels, at 30 min, in the range 70-80 ng/g of sesquiterpenes and 139 ng/g of CBD. The compounds are still detectable in blood and brain 90 min after oral administration and significant concentrations of terpenoids are observed in liver and kidney. MRO and SRO can be considered as valuable sources of these bioactive compounds and further investigations are needed to evaluate the potential uses of hemp EO as constituent of innovative drug formulations.

Antioxidant, Anti-Inflammatory, Anti-Diabetic, and Pro-Osteogenic Activities of Polyphenols for the Treatment of Two Different Chronic Diseases: Type 2 Diabetes Mellitus and Osteoporosis.

Polyphenols are natural bioactives occurring in medicinal and aromatic plants and food and beverages of plant origin. Compared with conventional therapies, plant-derived phytochemicals are more affordable and accessible and have no toxic side effects. Thus, pharmaceutical research is increasingly inclined to discover and study new and innovative natural molecules for the treatment of several chronic human diseases, like type 2 diabetes mellitus (T2DM) and osteoporosis. These pathological conditions are characterized by a chronic inflammatory state and persistent oxidative stress, which are interconnected and lead to the development and worsening of these two health disorders. Oral nano delivery strategies have been used to improve the bioavailability of polyphenols and to allow these natural molecules to exert their antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic biological activities in in vivo experimental models and in patients. Polyphenols are commonly used in the formulations of nutraceuticals, which can counteract the detrimental effects of T2DM and osteoporosis pathologies. This review describes the polyphenols that can exert protective effects against T2DM and osteoporosis through the modulation of specific molecular markers and pathways. These bioactives could be used as adjuvants, in combination with synthetic drugs, in the future to develop innovative therapeutic strategies for the treatment of T2DM and osteoporosis.

Cladanthus scariosus Essential Oil and Its Principal Constituents with Cytotoxic Effects on Human Tumor Cell Lines.

Cladanthus is a small genus of the Asteraceae family comprising just five species that, apart from Cladanthus mixtus (L.) Chevall., has a large distribution in all the Mediterranean countries, mainly in the North Africa area. Several ethnopharmacological uses have been reported for species of this genus. Notably, Cladanthus scariosus (Ball) Oberpr. & Vogt is endemic to Morocco. Seeking to delve deeper into the phytochemistry and pharmacological aspects of this species, in this work, we investigated the essential oil (EO) obtained from the aerial parts of a locally sourced accession, hitherto unexplored, growing wild near Tizi n'Ticha, Morocco. The chemical composition of the EO, obtained by the hydrodistillation method, was evaluated by GC and GC-MS. The most abundant EO constituent was germacrene D (13.2%), the principal representative of the sesquiterpene hydrocarbons class (27.2%). However, the major class of constituents was monoterpene hydrocarbons (43.0%), with α-pinene (11.9%), sabinene (10.2%), p-cymene (8.5%), and α-phellandrene (5.2%) as the most abundant. The EO and its main constituents have been tested for their possible cytotoxic activity against three human tumor cell lines (MDA-MB 231, A375, and CaCo2) using the MTT assay, with corresponding IC50 values of 13.69, 13.21, and 22.71 µg/mL, respectively. Germacrene D and terpinen-4-ol were found to be the most active constituents with IC50 values between 3.21 and 9.53 µg/mL. The results demonstrate remarkable cytotoxic activity against the three human tumor cell lines studied, and in the future, further analyses could demonstrate the excellent potential of C. scariosus EO as an antitumor agent.

Fractionation of Carlina acaulis L. Root Methanolic Extract as a Promising Path towards New Formulations against Bacillus cereus and Methicillin-Resistant Staphylococcus aureus.

The root of Carlina acaulis L. has been widely used in traditional medicine for its antimicrobial properties. In this study, the fractionation of methanol extract from the root was conducted. Four fractions (A, B, C, and D) were obtained and tested against a range of bacteria and fungi. The results showed promising antibacterial activity, especially against Bacillus cereus, where the minimal inhibitory concentration (MIC) was determined to be equal to 0.08 mg/mL and 0.16 mg/mL for heptane (fraction B) and ethyl acetate (fraction C), respectively. In the case of the methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 strain, the same fractions yielded higher MIC values (2.5 and 5.0 mg/mL, respectively). This was accompanied by a lack of apparent cytotoxicity to normal human BJ foreskin fibroblasts, enterocytes derived from CaCo2 cells, and zebrafish embryos. Further analyses revealed the presence of bioactive chlorogenic acids in the fractionated extract, especially in the ethyl acetate fraction (C). These findings support the traditional use of the root from C. acaulis and pave the way for the development of new formulations for treating bacterial infections. This was further evaluated in a proof-of-concept experiment where fraction C was used in the ointment formulation, which maintained high antimicrobial activity against MRSA and displayed low toxicity towards cultured fibroblasts.

Effect of seed's geographical origin on cactus oil physico-chemical characteristics, oxidative stability, and antioxidant activity.

The aim of this study was the valorisation of cactus (or prickly pear, Opuntia ficus-indica) seeds growing in six different regions of Morocco. Moisture, proteins, lipids profile, total polyphenols content, oxidative stability, and antioxidant activity were investigated. The Folin-Ciocalteu test highlighted the abundant presence of phenolic compounds (165 to 225 mg EAG/100 g of extract) and a significant antioxidant capacity against DPPH free radicals. The seeds contained protein (7-9.25%) and lipids (2.7-5%). Cactus oil quality indices such as acidity and peroxide value were below 1.2% and 10 mEq.O2/kg, respectively. GC analysis revealed that linoleic and oleic acid percentages ranged from 57.1 to 63.8%, and 13.5 to 18.7%, respectively. Cactus seed oil was rich in tocopherols (500-680 mg/kg) and phytosterols (8000-11,100 mg/kg) with a predominance of γ-tocopherols and ß-sitosterol. Triacylglycerols, fatty acids and sterols composition showed small variation depending on the geographical origin, while the individual tocopherol profile was significantly influenced.

Microwave-assisted hydrodiffusion and gravity extraction: An efficient method to produce pomegranate juice.

Green technologies based on microwaves have been developed by the food industry to produce organoleptically acceptable fruit juices without preliminary processing. Microwave irradiation coupled with hydrodiffusion and gravity (MHG) combines microwave heating with the earth's gravity, allowing the collection of hydrophilic substances released from the irradiated matrix. To the best of our knowledge, MHG extraction has never been experimented to produce pomegranate juice. In this work, we have evaluated it as a potential alternative to the conventional squeezing. A central composite design study (CCD) allowed the selection of the best extractive conditions (irradiation power and extraction time) to obtain a pomegranate juice with higher yield, polyphenol (e.g., catechin and delphinidin-3,5-glucoside) content, and related bioactivities (antioxidant and antidiabetic) than the one obtained by squeezing while maintaining the chemical-physical properties. Thus, this technique appears to be a functional alternative to producing high value pomegranate juice.

Exploring the Efficacy of Four Apiaceae Essential Oils against Nine Stored-Product Pests in Wheat Protection.

The Apiaceae family, known for aromatic plants producing bioactive essential oils (EOs), holds significance across sectors, including agrochemicals. This study evaluated the insecticidal potential of four Apiaceae EOs from Crithmum maritimum L., Trachyspermum ammi (L.) Sprague ex Turrill, Smyrnium olusatrum L., and Elwendia persica (Boiss.) Pimenov and Kljuykov against various significant storage pests (Sitophilus oryzae (L.), Trogoderma granarium Everts, Rhyzopertha dominica (F.), Tribolium castaneum (Herbst), T. confusum Jacquelin du Val, Oryzaephilus surinamensis (L.), Alphitobius diaperinus (Panzer), Acarus siro L., and Tenebrio molitor L.) on wheat. Insect mortality rates were monitored at intervals of 1, 2, 3, 4, 5, 6, and 7 days. Smyrnium olusatrum EO exhibited the highest efficacy, followed by T. ammi, C. maritimum, and E. persica EOs, although efficacy varied by species, developmental stage, and concentration. Notably, complete mortality occurred for several pests at 1000 ppm of S. olusatrum and T. ammi EOs. Gas chromatography-mass spectrometry (GC-MS) analysis revealed key compounds in these EOs, including myrcene, germacrone, and curzerene in S. olusatrum EO, and thymol, γ-terpinene, and p-cymene in T. ammi EO. These findings emphasize their potential as botanical insecticides. Smyrnium olusatrum and T. ammi EOs emerge as promising eco-friendly pest management options due to their efficacy, highlighted compound composition, and availability of biomass from both wild and cultivated sources.

Anti-breast cancer activity of the essential oil from grapefruit mint (Mentha suaveolens × piperita).

Grapefruit mint (Mentha suaveolens × piperita) is a hybrid, perennial, and aromatic plant widely cultivated all over the world and used in the food, cosmetics, and pharmaceutical industries mostly for its valuable essential oil. Herein, we evaluated the anticancer activity of the grapefruit mint essential oil, cultivated in Iran. For the chemical composition analysis of essential oil, GC-MS was used. MTT assay was utilized for assessing the cytotoxic activity of the essential oil. The type of cell death was determined by annexin V/PI staining. Essential oil effect on the expression of maternally expressed gene 3 (MEG3), a regulatory lncRNA involved in cell growth, proliferation, and metastasis, was studied using qRT-PCR. Linalool (43.9%) and linalool acetate (40.1%) were identified as the dominant compounds of essential oil. Compared with MCF-7, the MDA-MB-231 cells were more sensitive to essential oil (IC50 = 7.6 µg/ml in MCF-7 and 5.9 µg/ml in MDA-MB-231 after 48 h). Essential oil induced cell death by apoptosis. Wound healing scratch assay confirmed the anti-invasive effect of essential oil. In addition, essential oil upregulated the tumor suppressor MEG3 in breast cancer cells. These results provide new insights into grapefruit mint essential oil potential application as an anticancer adjuvant in combination treatments for breast cancer patients.

Microwave Control of Reynoutria japonica Houtt., Including Ecotoxicological Aspects and the Resveratrol Content in Rhizomes.

Japanese knotweed (Reynoutria japonica Houtt.) is Poland's invasive weed, for which there is no efficient control method. The rhizomes of this species are rich in resveratrol. In this work, we evaluated (1) the effectiveness of electromagnetic microwaves (MV) in destroying Japanese knotweed using an original device, HOGWEED (MV of 2450 MHz), (2) the ecotoxic effect of the MV on the soil environment, and (3) the resveratrol content in knotweed rhizomes after MV treatment. The field studies were carried out in 2022 in southern Poland. Cut plants were MV-treated for times of 5.0-25.0 min. The MV efficiency was checked 10 and 56 days after treatment (DAT). After MV treatment, fresh soil samples were taken to analyze their ecotoxicity. As a result, at 56 DAT, knotweed was controlled if MV was used for at least 20.0 min. The MV did not affect the soil ecotoxicity. The MV-treated soils were classified as non-toxic or low-toxic. To analyze the resveratrol content, healthy knotweed rhizomes were dug out, treated with MV in the laboratory at 2.5-10.0 min, and analyzed for resveratrol content in HPLC-MS/MS. As a result, the resveratrol in the rhizomes significantly decreased in a time-dependent manner following MV exposure.

Metabolite profiling, enzyme inhibitory activity and antioxidant potential of different extracts from Glycyrrhiza foetida Desf. (Fabaceae, Galegeae, Glycyrrhizinae).

Obesity, a risk factor for the development of type 2 diabetes, represents a socio-economic burden for healthcare systems. Consequently multiple studies aiming to facilitate early diagnostic and prevent complications have demonstrated the promising role of phenolic derivatives on diabetes management. In this frame, the present study aimed to establish for the first time the chemical ingredients and to appraise the antioxidant and the enzyme inhibitory properties of Glycyrrhiza foetida aerial parts and roots extracts using methanol, ethyl acetate and chloroform solvents. The phytochemicals were analyzed via (HPLC-MS/MS). In addition, the extracts were tested for inhibitory activities against α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. The antioxidant capabilities were evaluated using various methods (phospho­molybdenum, DPPH, ABTS, FRAP, CUPRAC, and metal chelating assays). Notably, twenty-nine secondary metabolites, namely eleven phenolic acids, seventeen flavonoids and a non-phenolic acid have been identified. Delphinidin 3,5-diglucoside, rutin, isoquercitrin, hyperoside, catechin, phloridzin and hesperidin were the major compounds in the aerial parts extracts while trans-cinnamic acid was the dominant compound in roots. Among phenolic acids, vanillic acid was found to be the main constituent in all extracts. The tested extracts were found to yield TPC in amounts ranging from 34.08 to 49.36 mg GAE/g and TFC ranging from 7.01 to 45.74 mg RE/g. G. foetida extracts showed interesting in vitro antioxidant properties. Additionally, all extracts showed a significant anti-tyrosinase activity, with inhibition values ranging between 52.84 and 80.34 mg KAE/g. Thus, G. foetida remains an exceptional matrix for further investigations and application in cosmetics and food additives.

Fighting Microbial Infections from Escherichia coli O157:H7: The Combined Use of Three Essential Oils of the Cymbopogon Genus and a Derivative of Esculentin-1a Peptide.

The absence of effective therapy against Escherichia coli O157:H7 infections has led to the need to develop new antimicrobial agents. As the use of synergistic combinations of natural antimicrobial compounds is growing as a new weapon in the fight against multidrug-resistant bacteria, here, we have tested new synergistic combinations of natural agents. Notably, we investigated a possible synergistic effect of combinations of essential oils and natural peptides to counteract the formation of biofilm. We chose three essential oils (i.e., Cymbopogon citratus, C. flexuosus and C. martinii) and one peptide already studied in our previous works. We determined the fractional inhibitory concentration (FIC) by analyzing the combination of the peptide derived from esculentin-1a, Esc(1-21), with the three essential oils. We also studied the effects of combinations by time-kill curves, scanning electron microscopy on biofilm and Sytox Green on cell membrane permeability. Finally, we analyzed the expression of different genes implicated in motility, biofilm formation and stress responses. The results showed a different pattern of gene expression in bacteria treated with the mixtures compared to those treated with the peptide or the single C. citratus essential oil. In conclusion, we demonstrated that the three essential oils used in combination with the peptide showed synergy against the E. coli O157:H7, proving attractive as an alternative strategy against E. coli pathogen infections.

Lethal and sublethal effects of carlina oxide on Tetranychus urticae (Acari: Tetranychidae) and Neoseiulus californicus (Acari: Phytoseiidae).

BACKGROUND: Tetranychus urticae Koch, is a polyphagous and damaging pest, presenting several resistant populations worldwide. Among new and more environmentally friendly control tools, botanical pesticides represent a valuable alternative to synthetic ones within integrated pest management strategies. Accordingly, we investigated the lethal and sublethal effects of carlina oxide isolated from Carlina acaulis (Asteraceae) roots on T. urticae and its natural enemy, the predatory mite, Neoseiulus californicus (McGregor). RESULTS: Carlina oxide (98.7% pure compound) was used for acaricidal tests on eggs, nymphs, and adult females of T. urticae (concentrations of 312.5, 625, 1250, 2500 and 5000 µL L-1 ), and eggs and females of N. californicus (1250 and 5000 µL L-1 on eggs and females, respectively). Behavioral two-choice tests were also conducted on phytoseiid females. Carlina oxide toxicity was higher on T. urticae females than nymphs (median lethal dose 1145 and 1825 µL L-1 , respectively), whereas egg mortality and mean hatching time were significantly affected by all tested concentrations. A decreasing daily oviposition rate for T. urticae was recorded with concentrations ranging from 625 to 5000 µL L-1 , whereas negative effects on the population growth rate were recorded only with the three higher concentrations (1250, 2500 and 5000 µL L-1 ). No toxic effect on N. californicus females was found, but a strong repellent activity lasting for 48 h from application was recorded. CONCLUSION: Carlina oxide reduced longevity and fecundity of T. urticae adults, but not of N. californicus. This selective property allows us to propose it as a novel active ingredient of ecofriendly acaricides for T. urticae management. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Phytochemical analysis of Clinopodium candidissimum (Munby) Kuntze growing in Algeria by an integrated HS-SPME-GC-MS, NMR and HPLC-DAD-MSn approach: valorisation of an endemic natural source of bioactive compounds.

Clinopodium candidissimum (Munby) Kuntze (Lamiaceae) is used in traditional medicine and as a food condiment in Algeria, where it is known as Zaater cheleuh and Nabta elbida. Here, we report the comprehensive characterisation of non-volatile polar constituents extracted from C. candidissimum aerial parts (a mixture of inflorescences, stems and leaves), and their aroma profile. Qualitative 1H-NMR and quali-quantitative HPLC-MSn analyses of fractions obtained with solvents at different polarity revealed the presence of aglyconic and glycosylated flavonoids (3.1%), phenylpropanoids (3.6%), gallic acid derivatives (0.76%), and triterpenoids (0.62%), among the others. On the other hand, HS-SPME-GC-MS allowed to identify 38 volatile constituents, among which the oxygenated monoterpenes pulegone (44.8%), piperitenone (6.6%), isopulegone (5.8%) and neo-menthol (3.8%), and the sesquiterpene hydrocarbons germacrene D (16.2%) and bicyclogermacrene (3.0%) were the most abundant. Overall, results indicate that C. candidissimum represents an endemic natural source of antioxidants and bioactive compounds, and they will be useful for further studies on this species.

Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L.

Neuroinflammation, which is mainly triggered by microglia, is a key contributor to multiple neurodegenerative diseases. Natural products, and in particular Cannabis sativa L., due to its richness in phytochemical components, represent ideal candidates to counteract neuroinflammation. We previously characterized different C. sativa commercial varieties which showed significantly different chemical profiles. On these bases, the aim of this study was to evaluate essential oils and aqueous distillation residues from the inflorescences of three different hemp varieties for their anti-neuroinflammatory activity in BV-2 microglial cells. Cells were pretreated with aqueous residues or essential oils and then activated with LPS. Unlike essential oils, aqueous residues showed negligible effects in terms of anti-inflammatory activity. Among the essential oils, the one obtained from 'Gorilla Glue' was the most effective in inhibiting pro-inflammatory mediators and in upregulating anti-inflammatory ones through the modulation of the p38 MAPK/NF-κB pathway. Moreover, the sesquiterpenes (E)-caryophyllene, α-humulene, and caryophyllene oxide were identified as the main contributors to the essential oils' anti-inflammatory activity. To our knowledge, the anti-neuroinflammatory activity of α-humulene has not been previously described. In conclusion, our work shows that C. sativa essential oils characterized by high levels of sesquiterpenes can be promising candidates in the prevention/counteraction of neuroinflammation.

Essential oil of Apium nodiflorum (L.) Lag. growing in Ksob River, Algeria.

The essential oil from the aerial parts of Apium nodiflorum (L.) Lag. (Apiaceae), collected in Ksob River (Algeria) and obtained by hydrodistillation, was analysed by GC-MS. Sixty-seven components have been identified, representing more than 98.7% of the total oil. The essential oil was found to be rich in terpinolene (32.9 ± 4.6%), myristicin (10.6 ± 2.3%), myrcene (6.2 ± 1.1%), limonene (6.0 ± 0.9%), γ-terpinene (5.9 ± 1.2%) and (Z)-caryophyllene (5.3 ± 1.0%).

Editorial for the Special Issue "Antiprotozoal Activity of Natural Products".

Neglected tropical diseases (NTDs), a diverse group of infectious diseases, represent the leading cause of morbidity and mortality among the world's low-income populations [...].

Exploring for HPLC-MS/MS Profiles and Biological Activities of Different Extracts from Allium lycaonicum Siehe ex Hayek from Turkey Flora.

The present study was designed to determine the phenolic constituents, antioxidant, and enzyme inhibition activities of aerial parts and bulbs of Allium lycaonicum (family Amaryllidaceae). Extracts were prepared by maceration and Soxhlet/infusion using hexane, methanol, and water as extraction solvents. Generally, extracts from the aerial parts showed higher total phenolic and individual components and antioxidant activity than their respective bulb extracts. Maceration with water was the best to extract total phenolic content from the aerial parts (29.00 mg gallic acid equivalents (GAE)/g), while the Soxhlet extraction with hexane (22.29 mg GAE/g) was the best for the bulb. Maceration with methanol recovered the highest total flavonoid content from both the aerial parts (41.95 mg (rutin equivalents (RE)/g) and bulb (1.83 mg RE/g). Polar extracts of aerial parts were characterized by higher abundance of kaempferol-3-glucoside (≤20,624.27 µg/mg), hyperoside (≤19,722.76 µg/g), isoquercitrin (≤17,270.70 µg/g), delphindin-3,5-diglucoside (≤14,625.21 µg/g), and rutin (≤10,901.61 µg/g) than the bulb. Aerial parts' aqueous extract, prepared by maceration, exerted the highest anti-ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical activity (64.09 mg trolox equivalents (TE)/g), Cu++ (83.03 mg TE/g) and Fe+++ (63.03 mg TE/g) reducing capacity while that prepared by infusion recorded the highest anti-DPPH (2,2-diphenyl-1-picrylhydrazyl) radical (31.70 mg TE/g) and metal chelating (27.66 mg EDTAE/g) activities. The highest total antioxidant activity (1.46 mmol TE/g) was obtained by maceration of the bulb with water. Extracts obtained by organic solvents showed remarkable enzyme inhibition properties against the tested enzymes. Soxhlet extraction of the bulb with hexane and methanol recorded the highest acetylcholinesterase inhibition (4.75 mg galanthamine equivalents (GALAE)/g) and tyrosinase inhibition (139.95 mg kojic acid equivalents/g) activities, respectively. Extracts obtained by maceration of the bulb with methanol and the aerial parts with hexane exerted the highest glucosidase inhibition (3.25 mmol acarbose equivalents/g) and butyrylcholinesterase inhibition (20.99 mg GALAE/g) activities, respectively. These data indicated that A. lycaonicum is a source of bioactive molecules with potential antioxidant and enzyme inhibition properties. Nonetheless, the extracts obtained through various solvents and extraction techniques showed variations in their phytoconstituent composition and biological properties.

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to their inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances in which vaccination is not accessible or in individuals with compromised immune systems, drugs can provide additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Moreover, targeting host factors allows us to develop compounds that are effective against different viral variants as well as against newly emerging virus strains. In recent years, the globe has experienced climate change, which may contribute to the emergence and spread of infectious diseases through a variety of factors. Warmer temperatures and changing precipitation patterns can increase the geographic range of disease-carrying vectors, increasing the risk of diseases spreading to new areas. Climate change may also affect vector behavior, leading to a longer breeding season and more breeding sites for disease vectors. Climate change may also disrupt ecosystems, bringing humans closer to wildlife that transmits zoonotic diseases. All the above factors may accelerate the emergence of new viral epidemics. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds, including those with anti-viral activity. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Interest in herbal antiviral products has increased. More than 50% of approved drugs originate from herbal sources. Plant-derived compounds offer diverse structures and bioactive molecules that are candidates for new drug development. Combining these therapies with conventional drugs could improve patient outcomes. Epigenetics modifications in the genome can affect gene expression without altering DNA sequences. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses recruit cellular epitranscriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we explore the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing their modulation processes and anti-viral effects on DNA and RNA viruses, as well as addressing future research objectives in this rapidly emerging field.