Bioprospecting Dodonaea viscosa Jacq.; a traditional medicinal plant for antioxidant,cytotoxic, antidiabetic and antimicrobial potential

Purpose of studyDodonaea viscosa Jacq. is an ethnomedicinal plant that has been extensively used for the treatment of gout, rheumatism and pain. Current study was undertaken to mine its antioxidant, antimicrobial, cytotoxic and antidiabetic potential. Chromogenic assays were employed to establish plant’s multimode antioxidant profile whereas HPLC fingerprinting was performed to quantify polyphenols. Standard brine shrimp lethality, MTT and SRB assays proved its cytotoxicity potential.ResultsAmong all the extracts (flower, leaf, stem and root), maximum extract recovery (22% w/w), gallic acid equivalent total phenolic content (20.11 ± 0.11 ug GAE/mg DW), ascorbic acid equivalent total antioxidant capacity (22.5 ± 0.07 µg/mg DW) and total reducing power (31.1 ± 1.13 µg/mg DW) were recorded in the distilled water + acetone extract of leaf. The acetone extract of leaf showed maximum quercetin equivalent total flavonoid content (4.78 ± 0.13 µg/mg DW). HPLC-DAD analysis revealed significant amount of rutin, vanillic acid, coumaric acid, ferulic acid, gallic acid, syringic acid, cinnamic acid, gentisic acid, catechin, caffeic acid, apigenin and myricetin in the different plant parts. Maximum scavenging potential was exhibited by methanol + ethyl acetate stem extract (IC₅₀ = 23.8 µg/ml). The highest antibacterial potential was found in flower (85.7%) and root (71.4%) extracts. The ethanol + ethyl acetate (1:1) leaf extract showed noteworthy toxicity against brine shrimps (LC₅₀ = 95.46 µg/ml) while a notable antiproliferative activity against THP-1 (IC₅₀ = 3.4 µg/ml) and Hep G2 (IC₅₀ = 20 µg/ml) cell lines was shown by ethanol + ethyl acetate extracts (1:1) of stem and root, respectively. A moderate inhibition of α-amylase enzyme was observed in all parts of the plant.ConclusionThe results of the present study suggest D. viscosa as a potential source of antioxidant, anticancer and α-amylase inhibitory phytochemicals.     

Polyphenolic characterization and evaluation of multimode antioxidant,cytotoxic, biocompatibility and antimicrobial potential of selected ethno-medicinal plant extracts

IntroductionScientific evidence about biological profile of natural products can support their traditional uses. The current work was aimed to assess phytochemical and biological profile of nine medicinal plants collected from Herbalists.MethodsExtracts prepared in different solvents were subjected to phytochemical, antioxidant, enzyme inhibitory, cytotoxic, and antimicrobial activities. Reverse phase-high performance liquid chromatography (RP-HPLC) analysis was performed for the quantification of polyphenols.ResultsResults showed methanol extract (M) being potent as compared to others. Gentian lutea M showed maximum extract recovery (15.00 ± 0.11 % w/w) and TFC (30.82 ± 0.21 μg QE/mg extract). Nigella sativa M displayed highest TPC (44.99 ± 0.43 μg GAE/mg extract) and TAC (334.72 ± 0.35 μg AAE/ mg extract). Results showed noteworthy quantities of vanillic acid, rutin, kaempferol, emodin in ethyl acetate (EA) and methanol (M) extracts of plants assessed by RP-HPLC. Gentisic acid was highest (11.75 µg/mg extract) in T. arjuna M extract. Similarly, maximum %FRSA (82.28 ± 0.03 %) and TRP (160.40 ± 0.38 μg AAE/ mg extract) were depicted by Terminalia chebula and Chamomilla recutita, respectively. Moreover, Mentha longifolia and G. lutea M demonstrated noteworthy (p < 0.05) antibacterial activity against Staphylococcus aureus (14 ± 0.7 mm) and Klebsiella pneumoniae (12 ± 0.3 mm), respectively. Curcuma amada, C. recutita, Murraya koenigii and G. lutea M had significant α-glucosidase activity. Another good solvent for extraction was ethyl acetate (EA), whose extracts were secondary to methanol in producing significant biological profile. For example, EA of N. sativa (TPC: 1.46 ± 0.45 µg GAE/ mg extract), G. lutea (TRP: 160.33 ± 0.52 μg AAE/mg extract: ZOI of 12 ± 0.5 mm in K. pneumoniae) and Mormodica charantia (α-amylase inhibition: 39.5 ± 0.10 %) showed significant bioactivities. All extracts displayed mild antifungal protein kinase inhibition activities and were significantly (greater than80 %: p < 0.05) cytotoxic to brine shrimps with negligible hemolytic activity.ConclusionBriefly, variable polarity solvent extracts of studied plants will be processed for isolation of antioxidant, cytotoxic, carbohydrate enzyme inhibitory and antibacterial compounds.     

Molecular docking of phenolic compounds and screening of antioxidant and antidiabetic potential of Olea europaea L. Ethanolic leaves extract

Oxidative stress has a crucial role in diabetic pathophysiology, therefore consuming naturally derived antioxidants as a remedial target. This study examines the naturally occurring antioxidant and antidiabetic of Olea europaea L. ethanolic leaves extract. Olea europaea L. leaves were macerated (OLE) by using absolute ethanol. Phytochemical and physiochemical analysis of OLE was screened using standard methods. The antioxidant effects were examined by DPPH (1, 1-diphenyl-2-picrylhydrazil) radical scavenging assay. In vitro antidiabetic was assayed by α-amylase enzyme inhibition study. Ethanolic extraction of OLE by maceration technique, 10% yield. Loss on drying, foreign organic matters and total ash value of OLE showed 2%, 0.2% and 16.5%, respectively. Phytochemical test on OLE confirmed saponin, flavonoid, glycoside, tannin, phenol and carbohydrate presences. The total phenolic and flavonoid contents of OLE is 490 mg GAE/g and 855 mg RUE/g of extract, respectively. OLE (IC₅₀ 38.37 ± 0.26 µg/ml) showed functional DPPH scavenging assay comparable to ascorbic acid (IC₅₀ 30.37 ± 0.17 µg/ml). In the alpha-amylase inhibitory activity, Acarbose showed an IC₅₀ value of 20.06 ± 0.19 µg/ml, while OLE portrayed an IC₅₀ value of 37.99 ± 0.15 µg/ml. The kinetic studies revealed that all samples at high concentrations reacted within a very short time, and a steady state was reached almost immediately. The lowest concentration showed slow kinetic behaviour implied longer periods before the constant state was reached. Molecular docking studies evidenced that most of the phenolic compounds of OLE interact with the active site of Human pancreatic α-amylase through the hydrogen bonding and hydrophobic interaction confirming the alpha-amylase inhibitory effect. The results suggest that Olea europaea L. has been a conceivable natural bioactive source as an antioxidant and an antidiabetic agent.     

Polarity guided extraction,HPLC based phytochemical quantification,and multimode biological evaluation of Otostegia limbata (Benth.) Boiss

Purpose of studyOtostegia limbata (Benth.) Boiss. (Family: Lamiacae) is an important underexplored ethnomedicinal plant that has been used as antinflammatory, anticancer and antibacterial herbal remedy previously. The present work was aimed to evaluate the antioxidant, antimicrobial, antileishmanial, and anticancer prospective of O. limbata stem and leaf extracts.ResultsThe highest amount of phenolic and flavonoid content was obtained in the methanol-acetone and methanol stem extracts i.e., 53.29 ± 1.33 and 28.64 ± 1.16, respectively with highest DPPH scavenging in MeH stem extract (IC₅₀ = 34.5 ± 1.34 μg/ml). Significant amount of catechin, gallic acid, apigenin and rutin was quantified. A moderate antibacterial and substantial antifungal activity was observed. Cytotoxicity against brine shrimps categorized 21% of stem (3 out of 14 extracts) and 57% (8 out of 14 extracts) of leaf extracts as potent. Substantial cytotoxicity against THP-1 cell line (IC₅₀ = 3.46 ± 0.25 μg/ml) and Leishmania (IC₅₀ = 1.50 ± 0.23 μg/ml) was exhibited by methanol-distilled water leaf extract while noteworthy antiproliferative activity against Hep-G2 (IC₅₀ = 0.44 ± 0.45 μg/ml) was manifested by n-hexane stem extract. Absence of hemolysis in normal RBCs signified plant’s selective cytotoxicity. Methanol-distilled water and chloroform stem extracts displayed prominent protein kinase inhibition and antidiabetic potential of plant.ConclusionThe results of present study recommend O. limbata as a potential source of antifungal, antileishmanial, anticancer, and α-amylase inhibitory agents.     

UPLC-ESI-QTOF-MS phenolic compounds identification and quantification from ethanolic extract of Myrtus communis ‘Variegatha’: In vitro antioxidant and antidiabetic potentials

Global public health is seriously threatened by diabetes and its complications. Although several synthetic drugs are currently employed for managing diabetes, however, the adverse effects associated with their use cannot be underestimated. Thus, the quest for a safe and cost-effective alternative is highly imperative. In the present study, the phenolic contents, antioxidant, antidiabetic, and cytotoxic potentials of 70% ethanolic crude extract of Myrtus communis ‘Variegatha’ were investigated using in vitro biochemical protocols. The total polyphenols content was 116.44 mg GAE/g, flavonols (6.74 mg QE/g), flavanols (2.46 mg CE/g) and the ferric reducing antioxidant power (FRAP) value was 1267.28 µmol AAE/g, 2,2-diphenyl-1-picrylhydrazyl (DPPH) (1165.37 µmol TE/g), and Trolox equivalent antioxidant capacity (TEAC) (775.52 µmol TE/g). High-resolution ultra-performance liquid chromatography coupled with electrospray ionisation/quadrupole-time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was explored to identify the phenolic compounds, most of which were flavonoids. The extract demonstrated a strong α-glucosidase inhibition potential in a concentration-dependent manner with IC₅₀ (3.159 µg/mL), which was higher than epigallocatechin gallate (EGCG) (6.208 µg/mL), a positive control antidiabetic drug. A slight increase in glucose utilization was observed after 24 h of treatment in C3A hepatocytes at 25 μg/mL whereas an increase in glucose uptake was recorded at 25 and 50 μg/mL. The extract exhibited a cytotoxic effect (IC₅₀ 76.85 µg/mL) against C3A hepatocytes at 100 µg/mL, which correlates to the glucose utilization and uptake recorded. The findings from the study show the prospect of M. communis ‘Variegatha’ as a promising source of bioactive compounds that could be used in the development of new anti-diabetic agents, thus, further research into the plant is recommended.     

One-pot multicomponent synthesis of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives and their biological evaluation as potential antioxidants,enzyme inhibitors,antimicrobials, cytotoxic and anti-inflammatory agents

A series of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives with substituted amine moieties (1–13) and substituted aldehyde (S) were designed and synthesized by a reflux condensation reaction in the presence of an acid catalyst to get N-Mannich bases. Mannich bases were evaluated pharmacologically for their antioxidant, α-amylase enzyme inhibition, antimicrobial, cell cytotoxicity and anti-inflammatory activities. Most of the compounds exhibited potent activities against these bioassays. Among them, SH1 and SH13 showed potent antioxidant activity against DPPH free radical at IC₅₀ of 9.94 ± 0.16 µg/mL and 11.68 ± 0.32 µg/mL, respectively. SH7, SH10 and SH13 showed significant results in TAC and TRP antioxidant assays, comparable to that of ascorbic acid. SH2 and SH3 showed potent activity in inhibiting α-amylase enzyme at IC₅₀ of 10.17 ± 0.23 µg/mL and 9.48 ± 0.17 µg/mL, respectively, when compared with acarbose (13.52 ± 0.19 µg/mL). SH7 was the most active against gram-positive and gram-negative bacterial strains, SH13 being the most potent against P. aeruginosa by inhibiting its growth up to 80% (MIC = 11.11 µg/mL). SH4, SH5 and SH6 exhibited significant activity against some fungal strains. Among the thirteen synthesized compounds (SH1-SH13), four were screened out based on the results of brine shrimp lethality assay (LD₅₀) and cell cytotoxicity assay (IC₅₀), to determine their anti-cancer potential against Hep-G2 cells. The study was conducted for 24, 48, and 72 h. SH12 showed potent results at IC₅₀ of 6.48 µM at 72 h when compared with cisplatin (2.56 µM). An in vitro nitric oxide (NO) assay was performed to shortlist compounds for in vivo anti-inflammatory assay. Among shortlisted compounds, SH13 exhibited potent anti-inflammatory activity by decreasing the paw thickness to the maximum compared to the standard, acetylsalicylic acid (ASA).     

Design,synthesis of new novel quinoxalin-2(1H)-one derivatives incorporating hydrazone,hydrazine, and pyrazole moieties as antimicrobial potential with in-silico ADME and molecular docking simulation

A series of 6-(morpholinosulfonyl)quinoxalin-2(1H)-one based hydrazone, hydrazine, and pyrazole moieties were designed, synthesized, and evaluated for their in vitro antimicrobial activity. All the synthesized quinoxaline derivatives were characterized by IR, NMR (¹H /¹³C), and EI MS. The results displayed good to moderate antimicrobial potential against six bacterial, and two fungal standard strains. Among the tested derivatives, six quinoxalin-2(1H)-one derivatives 4a, 7, 8a, 11b, 13, and 16 exhibited a significant antibacterial activity with MIC values (0.97–62.5 µg/mL), and MBC values (1.94–88.8 µg/mL) compared with Tetracycline (MICs = 15.62–62.5 µg/mL, and MBCs = 18.74–93.75 µg/mL), and Amphotericin B (MICs = 12.49–88.8 µg/mL, and MFC = 34.62–65.62 µg/mL). In addition, according to CLSI standards, the most active quinoxalin-2(1H)-one derivatives demonstrated bactericidal and fungicidal behavior. Moreover, the most active quinoxaline derivatives showed a considerable antibacterial activity with bactericidal potential against multi-drug resistance bacteria (MDRB) strains with MIC values ranged between (1.95–15.62 µg/mL), and MBC values (3.31–31.25 µg/mL) near to standard Norfloxacin (MIC = 0.78–3.13 µg/mL, and MBC = 1.4–5.32 µg/mL. Further, in vitro S. aureus DNA gyrase inhibition activity were evaluated for the promising derivatives and displayed potency with IC₅₀ values (10.93 ± 1.81–26.18 ± 1.22 µM) compared with Ciprofloxacin (26.31 ± 1.64 µM). Interestingly, these derivatives revealed as good immunomodulatory agents by a percentage ranging between 82.8 ± 0.37 and 142.4 ± 0.98 %. Finally, some in silico ADME, toxicity prediction, and molecular docking simulation were performed and showed a promising safety profile with good binding mode.     

Phenolic composition,antioxidant and enzyme inhibitory activities of Parkia biglobosa (Jacq.) Benth., Tithonia diversifolia (Hemsl) A. Gray,and Crossopteryx febrifuga (Afzel.) Benth

Medicinal plants from Chad grow under special climatic conditions in between the equatorial forest of Central Africa and the desert of North Africa and are understudied. Three medicinal plants from Chad (T. diversifolia, P. Biglobosa and C. Febrifuga) were evaluated for their phenolic composition, antioxidant and enzyme inhibition activities. The total phenolic composition varied from 203.19 ± 0.58 mg GAE/g DW in the ethyl acetate extract of P. biglobosa, to 56.41 ± 0.89 mg GAE/g DW in the methanol extract of C. febrifuga while the total flavonoid content varied from 51.85 ± 0.91 mg QE/g DW in the methanol extract of P. biglobosa to 08.56 ± 0.25 mg QE/g DW in the methanol extract of C. febrifuga. HPLC-DAD revealed that rutin, gallic acid and protocatechuic acid were the most abundant phenolics in T. diversifolia, P. Biglobosa and C. Febrifuga respectively. The antioxidant activity assayed by five different methods revealed very good activity especially in the DPPH^?, ABTS^?+ and CUPRAC assays where the extracts were more active than the standard compounds used. Good inhibition was exhibited against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with methanol (IC₅₀: 15.63 ± 0.72 µg/mL), ethyl acetate (IC₅₀: 16.20 ± 0.67 µg/mL) extracts of P. biglobosa, and methanol (IC₅₀: 21.53 ± 0.65 µg/mL) and ethyl acetate (IC₅₀: 30.81 ± 0.48 µg/mL) extracts of T. diversifolia showing higher inhibition than galantamine (IC₅₀: 42.20 ± 0.44 µg/mL) against BChE. Equally, good inhibition was shown on α-amylase and α-glucosidase. On the α-glucosidase, the ethyl acetate (IC₅₀ = 12.47 ± 0.61 µg/mL) and methanol extracts (IC₅₀ = 16.51 ± 0.18 µg/mL) of P. biglobosa showed higher activity compared to the standard acarbose (IC₅₀ = 17.35 ± 0.71 µg/mL) and on α-amylase, the ethyl acetate (IC₅₀ = 13.50 ± 0.90 µg/mL) and methanol (IC₅₀ = 18.12 ± 0.33 µg/mL) extracts of P. biglobosa showed higher activity compared to acarbose (IC₅₀ = 23.84 ± 0.25 µg/mL). The results indicate that these plants are good sources of antioxidant phenolics and can be used to manage oxidative stress linked illnesses such as Alzheimer’s disease and diabetes.     

Total phenolic and flavonoid contents,antioxidant, antidiabetic and antiplasmodial activities of Garcinia forbesii King: A correlation study

Garcinia forbesii King belongs to Clusiaceae is a source of secondary metabolites especially xanthones with various biological activities. G. forbesii King is also known for its empirical use for malaria and diabetes. This study investigated the total phenolic and flavonoid contents, in vitro antioxidant, antidiabetic and antiplasmodial activities of four extracts attained from the stem bark of G. forbesii King. The total phenolic and flavonoid contents were determined by spectrophotometric methods and antioxidant activity was evaluated by DPPH, ABTS, FRAP assays. In vitro antidiabetic activity was assessed by α-glucosidase and α-amylase assays and antiplasmodial activity was studied against chloroquine sensitive Plasmodium falciparum strain 3D7. The highest value of total phenolic (187.37 ± 0.06 mg GAE/g) and flavonoid (35.97 ± 0.02 mg QE/g) contents were recorded in n-hexane and methanolic extracts. n-Hexane extract showed the highest DPPH activity with IC₅₀ of 8.12 ± 0.02 μg/mL. Ethyl acetate extract exhibited better scavenging ability for ABTS with IC₅₀ of 3.88 ± 0.04 μg/mL. The FRAP assay showed better activity in methanol extract with an inhibition value of 73.68 ± 3.66 µM Fe²⁺/g. The strong inhibition against α-glucosidase and α-amylase were displayed by dichloromethane extract with IC₅₀ of 35.13 ± 2.01 μg/mL and 4.83 ± 0.20 μg/mL. n-Hexane and methanol extracts showed significant antiplasmodial activity with IC₅₀ of 0.23 ± 0.01 μg/mL and 0.73 ± 0.01 μg/mL, respectively. The correlation analysis indicated a positive relationship of total phenolic and flavonoid contents with antiplasmodial activity. The results revealed that n-hexane and methanol extracts could be used as a potential natural antiplasmodial, while dichloromethane extract is a promising natural antidiabetic.     

Antioxidant potential in the leaves of grape varieties (Vitis vinifera L.) grown in different soil compositions

Grape plant (Vitis vinifera L.) is a species of the family Vitaceae. It is an economically important fruit plant abundantly grown all over the world. Vitaceae comprised of 900 species distributed across tropical, sub-tropical and partially temperate sorts of climatic zones. In the current study we aimed to evaluate the antioxidant activities of grape leaves extract from different Pakistani varieties.We have analyzed the crude methanolic extract from the leaves of Pakistani grape varieties (i.e. NARC Black, Sundar Khani, Shogran-1, Shogran-2, Haita, Sheghali, Perlette, and Sultania-C) cultivated in various soil compositions. Total phenolic contents (TPC) of the extract were determind by using Folin-ciocalteu reagent method. Total flavonoid contents (TFC) were determind by the Aluminum Chloride Calorimetric method. Antioxidant activities of the extracts of different concentration were evaluated using Phosphomolybdenum method, Reducing power and DPPH (2, 2-disphenyl-1-picryl-hydrazyl) assays. Assays performed for grape varieties showed great antioxidant potential. All varieties significantly depicted with variation in polyphenolic contents and antioxidant potential with changes in the soil conditions. The highest TPC and TFC were quantified in Shogran-1 97.58 ± 0.09 (GAE, g⁻¹) and Sultania-C 97.47 ± 0.12 (µg QE/g DE) varieties respectively which were grown in (T6) and (T5), while lower were recorded in Sundar khani 5.16 ± 0.23 in (T6). Likewise, Shogran-1 128.26 ± 0.23 (µg AAE/g extract) variety grown in (T6) depicted highest total antioxidant capacity, NARC black 182.06 ± 0.24 (µg AAE/g extract) variety grown in (T6) resulted in maximum reducing power while DPPH free radical scavenging potential were determinded in Sultania-C 80.91 ± 0.10 (T4) equivalent µg/g. In the terms of bioassays, the promising results were showed by compost + sand + clay (T4), compost + clay + dung (T5) and sand + clay + dung (T6). Therefore, we conclude that variation in soil composition has a significant contribution in the quantity of phytochemicals and antioxidants expression. Our study further suggest that use of organic fertilizer (Compost) and loamy sort of soil enhance functioning of most of the varieties in terms of important phytochemicals.     

Evaluation of in vitro,in silico antidiabetic and antioxidant potential of bioactivity based isolated “Pakistanine” from Berberis baluchistanica

Bioassay based fractionation of methanolic extract of Berberis baluchistanica (Berberidaceae), used traditionally for internal injuries, led to the isolation of known compounds (1–4). The structure of these compounds was elucidated by different spectroscopic analysis and available literature data. Antidiabetic and antioxidant potentials of B. baluchistanica fractions and isolated compounds were evaluated using in vitro alpha- amylase and DPPH assays. The isolated compounds were identified as obamegine (1), pakistanine (2), 8-oxyberberine (3) and baluchistine (4). Obamegine was reported from many other species of this genus but it is first time isolated from B. baluchistanica in present study. Moreover, in vitro pakistanine (2) was found as bioactive lead molecule for hypoglycemic (IC₅₀:40.26 µg/ml) and antioxidant (IC₅₀:14.15 µg/ml) activities compared to acarbose (IC₅₀:33.68 µg/ml) and ascorbic acid (IC₅₀:0.41 µg/ml). To the best of our knowledge, no previous data were available for these biological activities. Additionally, in silico antidiabetic and antioxidant activity of pakistanine against two proteins, α-amylase (-9.7 kcal/mol) and tyrosinase (-8.7 kcal/mol) are reported here for the first time. The molecular docking binding interactions authenticate and support the above-mentioned activities and are helpful in predicting the mechanism of action of pakistanine (2).     

Phytochemical,antioxidant, enzyme inhibitory,thrombolytic, antibacterial,antiviral and in silico studies of Acacia jacquemontii leaves

The main objective of this work was to gain insight into biological propensities, and bioactive phytochemicals of Acacia jacquemontii Benth, a wild plant providing medicinal components, as well as to establish a link between its phytochemical profile and biological activities. Phytochemical profiling revealed the presence of a higher amount of total phenolic (271.44 ± 4.41 mg GAE/g) and flavonoid contents (216.47 ± 5.82 mg QE/g) in methanolic extract (MEAJ), and as compared to n-hexane fraction (HEAJ) and stronger biological activities of MEAJ were possibly linked to the higher bioactive contents. The freshly collected plant leaves showed a strong antioxidant potential (total antioxidant capacity 1.03 ± 0.19 mmol TE/g), which was found even stronger in dried methanolic extract (TAC; 4.36 ± 1.12 mmol TE/g), moreover, MEAJ also showed strong antioxidant potential when investigated by different antioxidant assays (DPPH; 154.04 ± 2.47, ABTS; 122.36 ± 0.80, FRAP; 453.18 ± 5.9, CUPRAC; 1389.97 ± 5.32 mg TE/g). The MEAJ showed good tyrosinase inhibition activity (71.69 %), compared with 83 % inhibition by kojic acid. Ten major compounds identified by GC–MS were docked and eight legends showed lower binding energies (-6 to ?7.8 kcal/mol) compared with kojic acid (-5.9 kcal/mol), which shows the possible role of these compounds in the anti-tyrosinase activity of the extract, and the ADMET analysis predicted the drug-likeness and safety profile of the studied compounds. The thrombolytic effect of MEAJ was 56.41 ± 0.75 to 57.15 ± 1.41 % which was comparable with streptokinase (82.44 ± 1.15 to 84.14 ± 0.95 %). Antibacterial activity of MEAJ was also good (MEAJ; 0.5–2.0 mg/mL, and co-amoxiclav; 5.0–12.5 µg/mL), and the highest activity was observed against Bacillus subtilis (MEAJ; 0.5 mg/mL, co-amoxiclav; 5.0 µg/mL). The antiviral activity of MEAJ was highly strong (HA titer; 00 to 08) against all the tested strains. It can be concluded that A. jacquemontii is a prospective source of phytochemicals with strong biological activities, and their usage in formulations of natural products and pharmaceuticals is recommended, however, further research may address the discovery and development of novel drugs for the pharmaceutical industry.     

Phytochemical and Biological Characterization of Tephrosia nubica Boiss. Growing in Saudi Arabia

The chloroform (TNC), ethyl acetate (TNE) and n-butanol (TNB) fractions of Tephrosia nubica Bioss. growing in Saudi Arabia were investigated for the first time using UPLC-ESI-MS/MS in two ionization modes. The analysis revealed the tentative identification of 107 compounds. Moreover, the therapeutic potential of T. nubica fractions was determined by in vitro evaluation of their cytotoxic, antioxidant, and anti-obesity activities using MTT assay, DPPH radical scavenging activity and pancreatic lipase inhibitory assay, respectively. The results showed that TNE, TNB, TNC fractions revealed weak antioxidant activity with SC₅₀ 139.9 ± 0.8, 144.9 ± 1.5, 148.9 ± 1.3 µg/mL, respectively compared to ascorbic acid 14.2 ± 0.5 µg/ml. Moreover TNE, TNC fractions showed more significant cytotoxic activity against HepG-2 with IC₅₀ 82.1 ± 3.1, 101 ± 2.8 µg/mL and MCF-7 with IC₅₀ 114 ± 3.2, 124 ± 3.9 µg/mL respectively. The TNB fraction showed weak cytotoxic activity against both cell lines compared to the other fractions. Ultimately, TNE fraction showed a remarkable anti-obesity activity with IC₅₀ 62.4 ± 1.5 µg/mL compared to chloroform fraction with IC₅₀ 535.6 ± 2.1 µg/mL and n-butanol fraction which did not show any activity. In conclusion, these findings represent the first insights into the phytochemical constituents and pharmacological properties of T. nubica. The ethyl acetate fraction of T. nubica might be a promising source of functional constituents with antioxidant, cytotoxic and anti-obesity potentials. It might be a natural alternative therapy and nutritional strategy, for obesity treatment without dangerous side effects. Isolation of the bioactive compounds from the ethyl acetate fraction of T. nubica and evaluating their biological activities are recommended.     

Green synthesis of iron (Fe) nanoparticles using Plumeria obtusa extract as a reducing and stabilizing agent: Antimicrobial,antioxidant and biocompatibility studies

In the current study, a green and facile route for the synthesis of iron nanoparticles (FeNPs) was adopted. The FeNPs were fabricated via a single step green route using aqueous leaves extract of Plumeria obtusa (P. obtusa) as a capping/reducing and stabilizing agents. The FeNPs were characterized by UV/Vis (Ultraviolet/Visible), FTIR (Fourier Transform Infra-Red spectroscopy), TEM (Transmission Electron Microscopy), SEM (Scanning Electron Microscopy) and XRD (X-Ray Diffraction) techniques. The FeNPs were of spheroidal shape with average size of 50 nm. The biosynthesized FeNPs were further evaluated for their biological activities like antimicrobial, antioxidant and biocompatibility. The FeNPs displayed auspicious antimicrobial activity against bacterial (E. coli, B. subtilis) and fungal strains (A. niger) and S. commune. The test performed against red blood cells (RBCs) lysis (1.22 ± 0.02%) and macrophage (31 ± 0.09%) showed biocompatible nature of FeNPs. In vitro cytotoxicity against AU565 (82.03 ± 0.08–23.65 ± 0.065%) and HeLa (88.61 ± 0.06–33.34 ± 0.06%) cell lines showed cell viability loss in dose dependent manner (FeNPs 25–100 μg/mL). The antioxidant activities values were determined through DPPH, TRPA, NO and H₂O₂ assays with values 70.23 ± 0.02%, 76.65 ± 0.02 μg AAE/mg, 74.43 ± 0.04% and 67.34 ± 0.03%, respectively. Based on the bioactivities, the green synthesized FeNPs have potential for therapeutic applications.     

Phytochemical,Antimicrobial, Antidiabetic,Thrombolytic, anticancer Activities,and in silico studies of Ficus palmata Forssk

Ficus palmata Forssk. (Moraceae family) is medicinally valuable plant that is mostly used as folk medicine for the treatment of different diseases. Phytochemical composition was evaluated by preliminary phytochemical investigation, GCMS analysis, and total bioactive contents (TPC and TFC). The antioxidant, enzyme inhibition, antimicrobial, thrombolytic and anticancer activities were performed for biological evaluation. The extract exhibited the maximum total phenolic (49.24 ± 1.21 mg GAE/g) and total flavonoid contents (29.9 ± 1.13 mg QE/g) which may be correlated to higher antioxidant potential of extract. The GCMS investigation identified the presence of 27 phytocompounds of different classes related to aldehydes, esters of fatty acids, triterpenes, steroids, triterpenoid. The extract possessed the strong α-glucosidase (73.4 ± 4.65 %) and moderate α-amylase inhibition activity (47.1 ± 3.29 %). Significant results were observed in case of antiviral, antifungal, and antibacterial activities. F. palmata extract inhibited the growth of HepG2 cancer cells in a dose-dependent manner. The extract also exhibited moderate in vitro thrombolytic activity. In addition, the phytocompounds identified by GCMS were subjected to in silico molecular docking studies to analyze the binding affinity between phytocompounds and enzymes (α-glucosidase and α-amylase). Moreover, the best docked compounds were selected for ADMET studies which provide information about pharmacokinetics, physicochemical properties, drug-likeness, and toxicity of identified phytocompounds. The outcome of our research revealed that ethanolic extract of F. palmata possessed good antidiabetic, antimicrobial, thrombolytic and anticancer potential. This plant should be further explored to isolate the bioactive compounds for new drug development.     

Anti-pathogenic,anti-diabetic,anti-inflammatory,antioxidant, and wound healing efficacy of Datura metel L. leaves

Datura metel L. is an important medicinal plant of Solanaceae family which has extensive pharmacological properties. The present investigation was aimed to identify the presence of phytoconstituents and assess in vitro antibacterial, anti-biofilm, anti-diabetic, anti-inflammatory, antioxidant, cytotoxicity, and wound healing efficacy of D. metel leaves extract. Among different solvent extracts, methanolic extract showed higher amount of phenolic (124.61 ± 0.68 mg GAE/g), alkaloid (88.77 ± 1.01 mg AE/g), flavonoids (42.24 ± 0.18 mg QE/g), and tannins contents (38.72 ± 0.51 mg GAE/g). The extract exhibited not only significantly (P < 0.05) different antibacterial activities against pathogens tested but also showed maximum biofilm inhibition of 94, 88, and 92% against B. subtilis, MRSA, and E. coli, respectively. Anti-diabetic assay depicted 22.55 ± 0.62–79.41 ± 1.13% and 24.31 ± 1.47–72.59 ± 0.22% of α-amylase and α-glucosidase inhibition abilities of methanolic extract, respectively at varied concentrations. The methanolic extract showed potential anti-inflammatory effect (P < 0.05) by showing 28.11 ± 0.13, 34.94 ± 1.11, 55.73 ± 0.42, 73.28 ± 0.72, and 92.62 ± 1.33% of inhibition of protein denaturation at different concentrations with an IC₅₀ value of 52.45 µg/mL. The extract revealed significant (P < 0.05) rate of ABTS scavenging, DPPH degradation, and reducing power assay in a concentration dependent manner. The cytotoxicity assay was demonstrated on L929 mouse fibroblast cell line and found > 90% of cell viability in the presence of methanolic extract, thereby indicating its non-toxicity effect. Wound healing assay indicated that methanolic extract at 50 µg/mL closed 100% of wound gap after 24 h with high rate of migration and proliferation. Furthermore, GC–MS chromatogram revealed the presence of several components in methanolic extract, including neophytadiene, hexadecanoic acid, and hentriacontane as principal phytoconstituents. In conclusion, methanolic extract of D. metel leaves could be used as potent therapeutic agent not only for treating metabolic diseases but also superficial chronic diabetic wounds.     

Volatile constituents of Amomum argyrophyllum Ridl. and Amomum dealbatum Roxb. and their antioxidant,tyrosinase inhibitory and cytotoxic activities

The volatile components from fresh rhizomes and leaves of Amomum argyrophyllum Ridl. and Amomum dealbatum Roxb. were performed using HS-SPME and charac-terized by GC–MS. A total of 49, 47, 49, and 34 compounds were identified from the rhizomes and leaves of A. argyrophyllum and A. dealbatum, respectively. The major components were β-pinene, α-pinene, and o-cymene. The rhizome extracts exhibited total phenolic content of 2.9 ± 0.5 and 2.1 ± 0.6 mg gallic acid equivalents. The IC₅₀ values of DPPH and ABTS were 179.8 ± 3.9 µg/mL, 392.9 ± 2.6 µg/mL, 120.3 ± 2.5 µg/mL, and 328.6 ± 3.3 µg/mL, respectively. The FRAP values were 76.5 ± 7.8 and 84.9 ± 4.4 µM ascorbic acid equivalents. The extracts showed weak antibacterial activity and tyrosinase inhibitory activity of 69.0 ± 3.6 and 53.7 ± 7.4 mg kojic acid equivalents. The cytotoxicity effect was assessed with the MTT assay at 200 µg/mL. The extracts showed no toxicity. In addition, the anti-inflammatory properties of extracts were evaluated, and showed potential to inhibit nuclear factor-κB (NF-κB) activity.     

Design,synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial,antioxidant and anti-inflammatory agents

In an attempt to rationalize the search for new potential anti-inflammatory and anti-infection agents, a new series of 1,4-and 1,5-disubstituted 1,2,3-triazoles linked benzoxazine conjugates have been synthesized via “Click Chemistry” reaction, were designed, synthesized and characterized by means of spectral and elemental data. The newly synthesized compounds have been assessed for their antimicrobial, antioxidant and anti-inflammatory potential. Results revealed that all synthesized compounds display superior activities to the standard drug against different bacterial strains especially S. aureus, M. luteus, and P. aeruginosa, with good to moderate activity towards the tested E. coli bacteria, in respect to the commercial antibiotic, tetracycline. Moreover, the antifungal activity was screened against C. albicans and C. krusei yeasts and results demonstrate potent activity as compared to the standard drug, ampicillin. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, whose results indicate that analogues 4a (IC₅₀ 1.88 ± 0.07 µM and 2.17 ± 0.02) followed by 4b (IC₅₀ 2.19 ± 0.09 µM and 2.38 ± 0.43 µM), 4d (IC₅₀ 2.30 ± 0.01 µM and 4.07 ± 0.57 µM), and 4f (2.98 ± 0.02 µM and 3.80 ± 0.01 µM), respectively, exhibited the strongest activity when compared to the standard reference, butylated hydroxytoluene (BHT) (3.52 ± 0.08 µM and 4.64 ± 0.11 µM). In addition, their anti-inflammatory activity was assessed using the xylene-induced ear edema standard technique and the results demonstrated the potency of 4a, 4b and 4d as excellent anti-inflammatory agents. Preliminary structure–activity relationship studies (SARs) provide those biological activities can be modulated by the presence of unsubstituted aromatic ring as well as the position of substituents on the phenyl moiety via electron withdrawing groups (EWGs) or electron donating groups (EDGs) effects. Docking studies on the most promising compounds 4a, 4b, and 4d into the active sites of S. aureus tyrosyl-tRNA synthetase, Candida albicans N-Myristoyltransferase, Human COX-2 enzyme, and Human Peroxiredoxin 5 revealed good binding profiles with the target proteins. The interaction's stability was further assessed using a conventional atomistic 100 ns dynamic simulation study. Hence, our results recommended the rationalized targets 4a, 4b and 4d, to be promising lead candidates for the discovery of novel dual anti-inflammatory and anti-infection agents.     

Physical properties,biological applications and biocompatibility studies on biosynthesized single phase cobalt oxide (Co3O4) nanoparticles via Sageretia thea (Osbeck.)

Cobalt oxide nanoparticles were successfully biosynthesized by complete green process using aqueous leaf extracts of Sageretia thea as chelating agent. Diverse techniques were applied for characterization. Antibacterial (with and without UV illumination), antileishmanial, antioxidant and enzyme inhibition applications were assessed, while freshly isolated macrophages and red blood cells were used for biocompatibility studies. Good antibacterial nature and enhancement of bactericidal nature upon UV modulation is reported. Staphylococcus aureus and Escherichia coli are indicated as most susceptible bacterial strains. Significant cytotoxic potential is revealed with IC₅₀ calculated as 12.82 µg/ml and 3.16 µg/ml against the axenic leishmanial promastigote and amastigote cultures respectively. Biogenic cobalt oxide nanoparticles indicated DPPH free radical scavenging potential, while moderate antioxidant capacity and reducing power was demonstrated. Bioinspired cobalt oxide also demonstrated alpha amylase and protein kinase inhibition at higher concentrations. Biogenic cobalt oxide was found as more cytotoxic to macrophages (IC₅₀ = 58.55 µg/ml) then to RBC’s (IC₅₀ >200 µg/ml). Our results indicate green synthesis as an alternative, effective and eco-friendly method for the biosynthesis of cobalt oxide nanoparticles with numerous biological applications.     

Synthesis and cytotoxic activity of new indolylpyrrole derivatives

The current approach described the synthesis of a new series of indolylpyrrole derivatives through multicomponent reaction of α-cyano chalcones, appropriate aldehydes, and ammonium acetate in refluxed acetic acid. The chemical structures of the designed compounds were confirmed with spectroscopic data and elemental analysis and then tested for their in vitro cytotoxic activity by SRB assay method towards three cell lines involving human Prostate adenocarcinoma; metastatic cells (PC-3), human ovary adenocarcinoma (SKOV3) and human dukes' type B, colorectal adenocarcinoma (LS 174 T). Most significant activity provided with compounds 5c, 5h and, 5j against prostate cancer cells (PC-3) with IC50s of 3.30 ± 0.20, 3.60 ± 0.10, and 3.60 ± 0.90 µg/ml, respectively. In human ovarian carcinoma (SKOV3), the compounds 5a, and 5i have stronger cytotoxicity with IC50s of 1.20 ± 0.04, 1.90 ± 0.50 µg/ml, respectively than the standard doxorubicin (IC50 = 2.20 ± 0.02 µg/ml). On the other hand, only compound 5a has the ability to diminish the viability of LS174T cells in an active manner with IC50 2.80 ± 0.10 µg/ml. Consequently, this effort offers groundwork for additional examination of nominated indolylpyrroles as antiproliferative agents.