The First Records of the In Silico Antiviral and Antibacterial Actions of Molecules Detected in Extracts of Algerian Fir (Abies numidica De Lannoy) Using LC-MS/MS Analysis.

(1) Background: Due to the wide application in medicinal and pharmaceutical chemistry of flavonoid molecules, which are one of the most famous types of secondary plant metabolites, our work has come within the framework of bio-consulting to help in the identification of the molecule(s) responsible for the antibacterial effect which will be the active principle of a natural antibiotic developed from Algerian fir using bioinformatics tools. (2) Methods: The docking method was used to test the antiviral activity on SARS-CoV-2 virus and the antibacterial activity on Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli of 12 polyphenolic molecules present in the ethyl acetate and n-butanol extracts of Numidian fir leaves, and identify the molecules responsible for these specific biological activities. (3) Results: The findings revealed that it is possible that two molecules, hyperoside and quercitrin, have a high capacity to inhibit SARS-CoV-2, and it is important to mention that they are the most quantitatively abundant molecules in the extract. The molecule luteolin-7-glucoside is probably responsible for the antibacterial activity in the extract against Gram-negative bacteria such as Escherichia coli, and the molecule hesperidin is responsible for the antibacterial activity in the extract against Gram-positive bacteria such as Staphylococcus aureus.

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice.

This study aimed to investigate the chemical composition and antidiabetic properties of cultivated Hyoscyamus albus L. The ethanol extract was analyzed using LC-MS/MS, and 18 distinct phenolic compounds were identified. Among these, p-coumaric acid (6656.8 ± 3.4 µg/g), gallic acid (6516 ± 1.7 µg/g), luteolin (6251.9 ± 1.3 µg/g), apigenin (6209.9 ± 1.1 µg/g), and rutin (5213.9 ± 1.3 µg/g) were identified as the most abundant polyphenolic molecules. In the in vitro antidiabetic experiment, the ability of the plant extract to inhibit α-glucosidase and α-amylase activities was examined. The results indicated that the extract from H. albus L. exhibited a higher inhibitory effect on α-amylase compared to α-glucosidase, with an IC50 of 146.63 ± 1.1 µg/mL and 270.43 ± 1.1 µg/mL, respectively. Docking simulations revealed that luteolin, fisetin, and rutin exhibited the most promising inhibitory activity against both enzymes, as indicated by their high contrasting inhibition scores. To further investigate the in vivo antidiabetic effects of H. albus L., an experiment was conducted using STZ-induced diabetic mice. The results demonstrated that the plant extract effectively reduced the levels of cholesterol and triglycerides. These findings suggest that H. albus L. may have therapeutic potential for managing hyperlipidemia, a common complication associated with diabetes. This highlights its potential as a natural remedy for diabetes and related conditions.

Effects of Nigella sativa Oil Fractions on Reactive Oxygen Species and Chemokine Expression in Airway Smooth Muscle Cells.

BACKGROUND: many previous studies have demonstrated the therapeutic potential of N. sativa total oil fractions, neutral lipids (NLs), glycolipids (GLs), phospholipids (PLs), and unsaponifiable (IS) in asthma patients. We therefore tested its effect on airway smooth muscle (ASM) cells by observing its ability to regulate the production of glucocorticoid (GC)-insensitive chemokines in cells treated with TNF-α/IFN-γ, and its antioxidative and reactive oxygen species (ROS) scavenging properties. MATERIALS AND METHODS: the cytotoxicity of N. sativa oil fractions was assessed using an MTT assay. ASM cells were treated with TNF-α/IFN-γ for 24 h in the presence of different concentrations of N. sativa oil fractions. An ELISA assay was used to determine the effect of N. sativa oil fractions on chemokine production (CCL5, CXCL-10, and CXCL-8). The scavenging effect of N. sativa oil fractions was evaluated on three reactive oxygen species (ROS), O2•-, OH•, and H2O2. RESULTS: our results show that different N. sativa oil fractions used at 25 and 50 µg/mL did not affect cell viability. All fractions of N. sativa oil inhibited chemokines in a concentration-dependent manner. Interestingly, the total oil fraction showed the most significant effect of chemokine inhibition, and had the highest percentage of ROS scavenging effect. CONCLUSION: these results suggest that N. sativa oil modulates the proinflammatory actions of human ASM cells by inhibiting the production of GC-insensitive chemokines.

Evaluation of In Vitro and In Silico Anti-Alzheimer Potential of Nonpolar Extracts and Essential Oil from Mentha piperita.

The anticholinesterase and antioxidant activities with chemical composition and molecular docking of essential oil and nonpolar extracts of Mentha piperita were evaluated using enzymatic and chemical methods. Molecular docking tools were used to explain the interaction of the major chemical constituents with the enzymes. GC/MS analyses revealed that the main compounds in M. piperita essential oil were l-menthone (43.601%) followed by pulegone (21.610%), linolenic acid (25.628%), and l-menthone (10.957%), representing the major compounds of the petroleum ether extract. Imidazoquinoline (7.767%) and 17-N-acetyl-oroidine (5.363%) were the major constituents of the chloroform extract. Linolenic acid (19.397%) and l-menthone (6.336%) were the most abundant compounds in the hexane extract. The M. piperita essential oil and nonpolar extracts showed moderate antioxidant activity. The essential oil showed the most promising anticholinesterase activity with IC50 = 10.66 ± 0.12 µg/mL and IC50 = 16.33 ± 0.03 µg/mL against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively, close to galantamine in AChE and more active in BChE, followed by the interesting activity in the petroleum ether extract with IC50 = 23.42 ± 3.06 µg/mL in AChE and IC50 = 62.00 ± 3.22 µg/mL in BChE. The docking experiments showed that among the seven major identified compounds, N-acetyl-17-oroidine showed the highest binding score (63.01 in AChE and 63.68 in BChE). This compound was found to bind the catalytic and peripheral sites, resulting in more potent inhibitory activity than galantamine, which only binds to the catalytic site. These findings suggested the possible use of M. piperita essential oil and nonpolar extracts as a potential source of alternative natural anti-Alzheimer compounds.

Process Optimization of Phytoantioxidant and Photoprotective Compounds from Carob Pods (Ceratonia siliqua L.) Using Ultrasonic Assisted Extraction Method.

The current study first describes the extraction of phytoantioxidant polyphenols from Carob byproducts (pods) using maceration and heating-assisted extraction as traditional methods and ultrasonic-assisted extraction (UAE) as an innovative method to determine the most efficient extraction process in terms of four targeted responses: total phenolic content (TPC), antioxidant activities (TAC and DPPH), and photoprotective properties as measured by the sun protection factor (SPF). Second, we used response surface methodology (RSM) with a central composite rotatable design (CCDR) approach to investigate the influence of process variables (extraction time, extraction temperature, and solvent concentration) on UAE, which was found to be the most effective extraction technique in our study. Carob byproduct extracts had a TPC ranging from 6.21 to 21.92 mg GAE/g dw, a TAC ranging from 22.00 to 49.30 mg AAE/g dw, DPPH scavenging activity ranging from 56.35 to 90.50%, and SPF values ranging from 8.62 to 22.37. The optimal UAE conditions for maximum TPC, TAC, DPPH, and SPF responses were determined to be 38.90% ethanol, 53.90 °C, and 50.92 min. Using Carob as a source for sustainable and bioactive products in conjunction with optimized UAE is a promising contribution to the cosmetic industry that will help to strengthen the concept of environmentally-friendly "green chemistry". Given that Carob pulp or seeds are considered food byproducts, the research presented here encourages the use of these agri-food waste materials in cosmetics.

Ultrasound-Assisted Extraction, LC-MS/MS Analysis, Anticholinesterase, and Antioxidant Activities of Valuable Natural Metabolites from Astragalus armatus Willd.: In Silico Molecular Docking and In Vitro Enzymatic Studies.

The Astragalus armatus Willd. plant's phenolic constituent extraction and identification were optimized using the ultrasound-assisted extraction (UAE) method and the LC-MS/MS analysis, respectively. Additionally, cupric reducing antioxidant capacity (CUPRAC), beta carotene, reducing power, DMSO alcalin, silver nanoparticle (SNP)-based method, phenanthroline, and hydroxyl radical tests were utilized to assess the extract's antioxidant capacity, while the neuroprotective effect was examined in vitro against acetylcholinesterase enzyme. This study accurately estimated the chemical bonding between the identified phenolic molecules derived from LC-MS/MS and the AChE. The extract was found to contain sixteen phenolic substances, and rosmarinic, protocatechuic, and chlorogenic acids, as well as 4-hydroxybenzoic, hyperoside, and hesperidin, were the most abundant substances in the extract. In all antioxidant experiments, the plant extract demonstrated strong antioxidant activity and a significant inhibitory impact against AChE (40.25 ± 1.41 µg/mL). According to molecular docking affinity to the enzyme AChE, the top-five molecules were found to be luteolin, quercetin, naringenin, rosmarinic acid, and kaempferol. Furthermore, these tested polyphenols satisfy the essential requirements for drug-like characteristics and Lipinski's rule of five. These results highlight the significance of the A. armatus plant in cosmetics, as food additives, and in the pharmaceutical industry due to its rosmarinic and chlorogenic acid content.

RP-HPLC-ESI-QTOF-MS Qualitative Profiling, Antioxidant, Anti-Enzymatic, Anti-Inflammatory, and Non-Cytotoxic Properties of Ephedra alata Monjauzeana.

An investigation was conducted to study the beneficial effects of Ephedra alata monjauzeana crude extract (EamCE). The chemical profile was determined using RP-HPLC-ESI-QTOF-MS analysis, revealing the presence of twenty-one flavonoids and phenolic acids. A series of antioxidant assays was carried out using ten different methods. The EamCE has demonstrated a significant antioxidant potential, with interesting IC50 values not exceeding 40 µg/mL in almost activities. Likewise, a significant inhibition of key enzymes, involved in some health issues, such as Alzheimer's disease, diabetes, hyperpigmentation, dermatological disorders, gastric/urinary bacterial infections, and obesity, was observed for the first time. The IC50 values ranged from 22.46 to 54.93. The anti-inflammatory and non-cytotoxic activities were assessed by heat-induced hemolysis and cell culture methods, respectively; the EamCE has shown a prominent effect in both tests, notably for the anti-inflammatory effect that was superior to the reference compound "diclofenac" (IC50: 71.03 ± 1.38 > 70.23 ± 0.99 (µg/mL)). According to these results, this plant could be used in a large spectrum as a food supplement, as a natural remedy for various physiological disorders and pathologies; and it might serve as a preventive and health care agent.

HPLC-DAD-ESI/MS profiles of bioactive compounds, antioxidant and anticholinesterase activities of Ephedra alata subsp. alenda growing in Algeria.

Ephedra (Ephedraceae) is used in medicine for various purposes as having, antioxidant, anticarcinogen, antibacterial, anti-inflammatory hepatoprotective, anti-obesity, antiviral and diuretic activities. In this study the aim was to investigate chemical constituents of Ephedra alata and understand the possible effects of those constituents in antioxidant activity and alzheimer's disease essay. For this purpose, natural compounds from E.alata were characterized by LC-DAD-ESI-MS/MS using negative and positive ionization modes, while the bioactivity was assessed by acetylcholinesterase (AChE) inhibition study and determining of antioxidant activity; DPPH radical scavenging and ß-carotene bleaching assays were used to assess the antioxidant potential. The proposed method of spectrometry provided tentative identification of 27 compounds including alkaloids and phenolic compounds as flavonoids. The methanolic extract showed high contents of total phenolic and exhibited an important antioxidant potential and demonstrated a potent inhibitory effect against acetylcholinesterase (IC50: 11,25 ± 0,25 µg/mL). The results showed that the plant possesses a therapeutic effect.

The Cosmetic Potential of The Medicinal Halophyte Tamarix Gallica L. (Tamaricaceae) Growing in The Eastern Part of Algeria: Photoprotective and Antioxidant Activities.

AIM AND OBJECTIVE: Currently, the use of ingredients from natural sources has gained great attention in the cosmetic field, especially for the development of new photoprotective formulations. Therefore, the present study aimed to evaluate the cosmetic potential of the crude methanol extract and the ethyl acetate fraction of the medicinal halophyte Tamarix gallica L. (Tg) growing in the area of Tebessa in the eastern part of Algeria, by assessing their phenolic and flavonoid contents, photoprotective and antioxidant activities. METHODS: The research approach consisted of determining phenolic and flavonoid contents of aerial parts via Folin-Ciocalteu and aluminum chloride methods, respectively. The antioxidant activity was measured through two in vitro methods, DPPH radical scavenging activity and total antioxidant capacity test (TAC). The in vitro photoprotective effect was evaluated according to the parameter SPF (Sun Protection Factor) by using the UV spectroscopic method in the UV-B region (290-320 nm). RESULTS: The methanol extract (Tg-MeOH) and ethyl acetate (Tg-EtOAc) fraction showed good antioxidant activity with IC50 values of 14.05±0.66, 27.58±1.98 µg/mL respectively in the DPPH test. Furthermore, both extracts displayed strong total antioxidant capacity (287.01±7.85, 246.7±1.12 mg AAE/g, respectively) in the TAC test. Both extracts exhibited high photoprotective activity, with sun protection factor (SPF) values 37.03±0.22 and 36.08±0.03. The antioxidant and photoprotective activities of these extracts were probably related to polyphenols content (190.27±0.74 mg AGE /g and 121.77±1.29 mg AGE /g, respectively) and flavonoids (78.75±0.06 mg QE /g and 58.67±1.19mg/g). CONCLUSION: Our findings show that extracts of Tamarix gallica L. could be a promising source to be mixed as a natural sunscreen and antioxidant agents into photoprotective cosmetic formulations.

New approach in the characterization of bioactive compounds isolated from Calycotome spinosa (L.) Link leaves by the use of negative electrospray ionization LITMSn, LC-ESI-MS/MS, as well as NMR analysis.

Two novel compounds were isolated for the first time from Calycotome spinosa (L.) Link, an alkaloid 5-Hydroxy-1H-indole (4) and a cyclitol D-pinitol (5), together with the three well-known flavonoids; Chrysin-7-O-(ß-D-glucopyranoside) (1), Chrysin-7-O-ß-D-(6″-acetyl)glycopyranoside (2) and Apigenin-7-O-ß-D-glycopyranoside (3). The chemical structures of the isolated compounds were elucidated by spectroscopic data and mass spectrometric analyses; including a fresh approach 1D-NMR, 2D-NMR with LC-ESI-MS/MS. In this study, the new compound (4) that has been obtained from the leaves MeOH extract presented the best radical scavenging activity (DPPH) (IC50 < 10 µg/mL) compared to the standard butylated hydroxytoluene (BHT, IC50 = 34.73 ± 0.23 µg/mL) and showed the highest total antioxidant capacity (TAC = 985.54 ± 0.13 mg AAE/g extract) in contrast to ascorbic acid (TAC = 905.95 ± 0.07 mg AAE/g extract). Furthermore, the strongest reducing power (EC50 = 344.82 ± 0.02 µg/mL), as well as the remarkable scavenging potential by ABTS assay (IC50 = 7.8 ± 0.43 µg/mL), were exhibited by the same composite (4). Followed by the methanol crude extract and the compound (3) that also showed a potent antioxidant (DPPH; IC50 = 41.04 ± 0.15 and 47.36 ± 0.21 µg/mL, TAC; 671.02 ± 0.21 and 608.67 ± 0.34 mg AAE/g extract, FRAP; EC50 = 763.73 ± 0.32 and 814.61 ± 0.31 µg/mL, ABTS; IC50 = 19.18 ± 0.06 and 63.72 ± 0.64 µg/mL, respectively), but less than the previous samples. On the opposite side, compound (5) had the lowest activity, in which its values were less interesting to determine. Moreover, compound (4) has equally exerted an attractive antibacterial activity against Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC- 27853) and Salmonella abony (NCTC 6017), as measured by the disc diffusion assay, with inhibition zones of 16 ± 0.5, 9.83 ± 0.29 and 8 ± 0.28 mm, in that order. To the best of our knowledge, 5-Hydroxy-1H-indole was isolated from plants for the second time in our current work. Thus, the obtained results from this investigation propose that the leaves of C. spinosa are a rich natural source for value molecules as potential antioxidants and antimicrobial agents for best human health.

A nutraceutical extract from Inula viscosa leaves: UHPLC-HR-MS/MS based polyphenol profile, and antioxidant and cytotoxic activities.

Nowadays, advanced extraction techniques and highly sensitive metabolic profiling methods are effectively employed to get new information on plant chemical constituents. Among them wild medicinal plants or their parts, with large and ancient use in folk medicine, are investigated for their potential functional use and cultivation. In this context, Inula viscosa leaves engaged our attention. A simple experimental design, based on Soxhlet extraction and chromatographic fractionation, allowed us to obtain the investigated polyphenol fraction (IvE). UHPLC-HRMS analyses revealed shikimoyl depsides of caffeic acid and unusual dihydrobenzofuran lignans as main secondary metabolites. These compounds, together with cinchonain-type phenols, and hydroxycinnamoyl flavonol glycosides, are reported for the first time in inula. Overall, forty-three secondary metabolites were identified. The extract exerted a remarkable antiradical activity towards DPPH• and ABTS+•. Furthermore, it was able to inhibit cell viability and mitochondrial redox activity of neuroblastoma, hepatoblastoma and colon carcinoma cells, whereas it did not affect cell density of HaCaT cells immortalized human keratinocytes. As detected by the oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate, the inhibitory responses seemed to be related to IvE-induced increase of intracellular reactive oxygen species (ROS). The obtained results highlighted that inula leaves, nowadays even undervalued and unexplored, could be considered a renewable source of nutraceutical compounds.

Antiproliferative and Antioxidant Activities of Two Extracts of the Plant Species Euphorbia dendroides L.

Background: These days, the desire for naturally occurring antioxidants has significantly increased, especially for use in foodstuffs, cosmetics, and pharmaceutical products, to replace synthetic antioxidants that are regularly constrained due to their carcinogenicity. Methods: The study in hand aimed to appraise the antioxidant effect of two Euphorbia dendroides extracts using reducing power, anti-peroxidation, and DPPH (1,1 Diphenyl 2 Pycril Hydrazil) scavenging essays, in addition to the anticancer activity against two tumor cell lines, namely C6 (rat brain tumor)cells, and Hela (human uterus carcinoma)cell lines. Results: The results indicated that the ethyl acetate extract exhibited antiradical activity of 29.49%, higher than that of n-butanol extract (18.06%) at 100 µg/mL but much lower than that of gallic acid (78.21%).The ethyl acetate extract exhibits better reducing capacity and lipid peroxidation inhibitory activity compared to n-butanol extract but less than all tested standards. Moreover, the ethyl acetate extract was found to have an antiproliferative activity of more than 5-FU (5-fluoro-Uracil) against C6 cells at 250 µg/mL with IC50 and IC75 of 113.97, 119.49 µg/mL, respectively, and good cytotoxic activity against the Hela cell lines at the same concentration. The HPLC-TOF-MS (high performance liquid chromatography-Time-of-flight-Mass Spectrometry) analyses exposed the presence of various compounds, among which Gallic and Chlorogenic acids functioned as major compounds. Conclusions: The two extracts exhibited moderate anticancer abilities and behaved somewhat as average antioxidant agents. Based on the total phenolics and flavonoids contents, as well as HPLC results, it could be concluded that antiproliferative and antioxidant activities depend upon the content of different phenolics and flavonoids.

Chemical characterization of polyphenols from Daucus muricatus growing in Algeria by RP-UHPLC-ESI-QTOF-MS/MS.

In the present work, reversed phase (RP) ultra-high-performance liquid chromatography (UHPLC) coupled to quadrupole-time-of-flight (QTOF) mass spectrometry in tandem has been used for the identification of the main phenolic compounds in the aerial parts of Daucus muricatus. The characterisation of the compounds was carried out taking into account retention time, mass accurate measurements, the generated molecular formulae and fragmentation pattern. These data were contrasted with literature and databases, as well as with those of authentic standards when possible. The proposed method provided tentative identification of 30 phenolic and other polar compounds, including hydroxycinnamic acid derivatives, flavonoids and hydroxybenzoic acid derivatives. As a note, hydroxycinnamic acid derivatives were found to be the most diverse phenolic class of Daucus muricatus.

A novel benzimidazole and other constituents with antiproliferative and antioxidant properties from Thymelaea microphylla Coss. et Dur.

A new compound (microphybenzimidazole, 7) along with the six known compounds matairesinol (1), prestegane B (2), umbelliferone (3), daphnoretin (4), microphynolide A (5) and microphynolide B (6) were isolated from Thymelaea microphylla. The structures of the pure compounds were elucidated by spectroscopic and mass-spectrometric analyses, including 1D-, 2D-NMR, and HPLC-TOF/MS. Compounds 2 and 4, as well as three fractions (F6, F6-C5, and F6-W42) obtained from a 50% (v:v) CH2Cl2:MeOH extract exhibited a selective activity against rat brain glioma cells (C6). Moreover, compound 1 and other fractions obtained from 50% (v:v) CH2Cl2:MeOH and 70% (v:v) MeOH:H2O extracts exhibited dose- and time-dependent effects on human cervical cancer cell (HeLa), as measured by xCELLigence assay. Compound 2 (IC50 = 14.0 ± 0.2 µg/mL) and fraction F5 (IC50 = 12.4 ± 0.1 µg/mL) showed higher radical scavenging ability than the synthetic agent butylated hydroxytoluene (BHT, IC50 = 22.7 ± 0.6 µg/mL).

Antioxidant and antigenotoxic properties of compounds isolated from Marrubium deserti de Noé.

In our continual course toward the valorization of traditionally used endemic flora through the analysis of its chemobiodiversity, the phytochemical analysis of aerial parts of Marrubium deserti de Noé was undertaken. Dichloromethane and methanol extracts led to the isolation of terpenoid derivatives among which two were new labdane diterpenes named marrulibacetal A and desertine, respectively. Six of them were known compounds (a mixture of the isomers cyllenin A and 15-epi-cyllenin A, marrubiin, marrulactone, marrulibacetal and ß-stigmasterol) and seven known phenolic compounds were also isolated: apigenin and several 7-O-substituted derivatives (apigenin-7-O-ß-neohesperidoside, apigenin-7-O-glucoside, terniflorin and apigenin-7-O-glucuronide) together with two phenylethanoid glucosides (acteoside and forsythoside B). The structures and relative configurations of the new compounds were elucidated by MS and a series of 1D and 2D NMR analyses. Some pure compounds have been evaluated for their antioxidant activities through different methods: DPPH and ABTS assays as well as CUPRAC assay. Genotoxic and antigenotoxic activities of extracts and pure compounds were also evaluated in vitro on Escherichia coli PQ37 cells by the SOS Chromotest. Some of the isolated compounds like phenylethanoid derivatives showed stronger antioxidant capacity than trolox and were also able to significantly inhibit ß-galactosidase induction caused by the mutagen agent nitrofurantoin.

Chemical composition and antimicrobial activity of essential oil of Bupleurum montanum and B. plantagineum.

The hydrodistilled oils from the aerial parts of Bupleurum montanum and B. plantagineum, which are endemic to North Africa, including Algeria, were analyzed by gas chromatography-mass spectrometry (GC-MS). Ninety-eight compounds were detected in the oil of B. montanum, representing 98.6% of the total oil, and 68 in the oil of B. plantagineum, representing 99.8% of the total. Megastigma-4,6-(E),8(2)-triene was the major constituent of B. montana oil (25.3%). Other important compounds were myrcene, alpha-pinene and benzyl tiglate. Conversely, the major constituents of the oil of B. plantagineum were alpha-pinene (31.9%), cis-chrysanthenyl acetate (28.2%), and myrcene (24.8%), followed by the monoterpene hydrocarbon limonene (5.1%). The mutagenic, antiplasmodial and antimicrobial activities of the essential oils were individually evaluated against eleven microorganisms, using the agar diffusion method, by determination of MIC values. The investigated oils exhibited moderate antimicrobial activity. Maximum activity of the oils was observed against Nocardia asteroides, Staphylococcus aureus and Enterococcus faecalis. Fungicidal activity against Candida albicans was also found for both oils.