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.     

Alpha-glucosidase inhibitory activity of ethanol extract,fractions and purified compounds from the wood of Albizia myriophylla

Albizia myriophylla Benth. is a medicinal herb which is used as a traditional remedy for various ailments including diabetes in Thailand. In our continued investigation of the biological activity of A. myriophylla, the ethanol extract, fractions and the isolated compounds from the wood of this plant were evaluated for in vitro α-glucosidase inhibition using spectrophotometric method. The plant ethanol extract and its different fractions possessed α-glucosidase inhibitory activity in a concentration-dependent manner. Dichloromethane fraction of the wood ethanol extract exhibited the highest percent inhibition against α-glucosidase (69.30%) among all fractions. Subsequent α-glucosidase inhibition assay proved that indenoic acid (1), 8-methoxy-7, 3′,4′-trihydroxyflavone (2) and 3,4,7,3′-tetrahydroxyflavan (3) were partially rational for antidiabetic effect of this plant species. Among these compounds, 3 (IC₅₀ 98.59 μg/mL) exhibited potent inhibition of α-glucosidase, compared with a positive control acarbose (IC₅₀ 125 μg/mL). The inhibitory effect towards α-glucosidase of compounds 1–3 was reported herein for the first time.     

Comprehensive Biological Potential,Phytochemical Profiling Using GC-MS and LC-ESI-MS,and In-Silico Assessment of Strobilanthes glutinosus Nees: An Important Medicinal Plant

Plants of the genus Strobilanthes have notable use in folklore medicines as well as being used for pharmacological purposes. The present work explored the biological predispositions of Strobilanthes glutinosus and attempted to accomplish a comprehensive chemical profile through GC-MS of different fractions concerning polarity (chloroform and n-butanol) and LC-ESI-MS of methanolic extract by both positive and negative ionization modes. The biological characteristics such as antioxidant potential were assessed by applying six different methods. The potential for clinically relevant enzyme (α-amylase, α-glucosidase, and tyrosinase) inhibition was examined. The DPPH, ABTS, CUPRAC, and FRAP results revealed that the methanol fraction presented efficient results. The phosphomolybdenum assay revealed that the n-hexane fraction showed the most efficient results, while maximum metal chelation potential was observed for the chloroform fraction. The GC-MS profiling of n-butanol and chloroform fractions revealed the existence of several (110) important compounds presenting different classes (fatty acids, phenols, alkanes, monoterpenes, diterpenes, sesquiterpenoids, and sterols), while LC-ESI-MS tentatively identified the presence of 44 clinically important secondary metabolites. The n-hexane fraction exhibited the highest potential against α-amylase (497.98 mm ACAE/g extract) and α-glucosidase (605.85 mm ACAE/g extract). Significant inhibitory activity against tyrosinase enzyme was displayed by fraction. Six of the prevailing compounds from the GC-MS study (lupeol, beta-amyrin, stigmasterol, gamma sitosterol, 9,12-octadecadienoic acid, and n-hexadecanoic acid) were modelled against α-glucosidase and α-amylase enzymes along with a comparison of binding affinity to standard acarbose, while three compounds identified through LC-ESI-MS were docked to the mushroom tyrosinase enzyme and presented with significant biding affinities. Thus, it is assumed that S. glutinosus demonstrated effective antioxidant and enzyme inhibition prospects with effective bioactive molecules, potentially opening the door to a new application in the field of medicine.     

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.     

Antioxidant and α-Glucosidase Inhibitory Compounds of Centella Asiatica

Centella asiatica, as known as Pegagan was previously reported to have anti-hyperglycemic effects in animal diabetic model rats. However, its α-glucosidase activity in vitro assay not yet reported. Our goal in this study is to isolate and identify active compounds as α-glucosidase inhibitor and antioxidant from aqueous ethanol 70% (v/v) extract of C. asiatica. The extract was partitioned by n-hexane, EtOAc, and n-butanol sequentially. Among the fractions tested, EtOAc fraction was showed the highest antioxidant and α-glucosidase inhibitory activities with an IC₅₀ values of 45.42 and 73.17 μg/mL, respectively. The antioxidant activity was conducted by determination of DPPH radical scavenging activity, whereas α-glucosidase inhibitory activity was determined against yeast α-glucosidase. Furthermore, isolation of the ethyl acetate extract yielded two active compounds, which were identified as kaempferol (1) and quercetin (2). Both of the compounds showed good yeast α-glucosidase inhibitory activity with IC₅₀ values of 16.50 and 21.61 μg/mL, respectively. In addition those compounds also could scavenge DPPH radical activity with IC₅₀ values of 9.64 and 11.97 μg/mL, respectively. Due to its ability in reducing α-glucosidase activity and scavenging free radical activity, the C. asiatica appears to be a potential as a good resource for future development of antioxidant and antidiabetic drug.     

Phytochemical analysis,UPLC-ESI-Orbitrap-MS analysis,biological activity,and toxicity of extracts from Tripleurospermum limosum (Maxim.) Pobed

Tripleurospermum limosum (TL) has been used in folk medicine to treat gastritis. Toward the further development and use of TL, we report the phytochemical profiling, determination of active components, and antioxidant and enzyme inhibitory activities of TL. Nineteen compounds were identified by ultra-performance liquid chromatography-electrospray ionization-orbitrap-mass spectrometry for the first time in this plant. Phytochemical studies indicated that TL contained 11 types of phytochemicals. The active components [total carbohydrate content (TCC), total protein content (TP_roC), total triterpenoid content (TTC), total phenolic content (TP_heC), total flavonoid content (TFC), total phenolic acid content (TPAC), condensed tannin content (CTC), and gallotannin content (GC)] of eight different solvent extracts were determined by ultraviolet–visible spectrophotometry. Aqueous extract had highest TP_roC, TP_heC, and GC values. Methanol extract exhibited highest TCC and TFC values. Ethanol extract showed highest TPAC and CTC values and dichloromethane extract exhibited highest TTC value. Methanol extract showed strongest ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt cation radicals, and hydroxyl radicals, and also exhibited highest antioxidant activity in ferric-reducing antioxidant power and cupric ion-reducing antioxidant capacity assays. Best iron and copper chelating activity and H₂O₂ scavenging ability were shown by aqueous extract. Ethanol extract showed strongest ability to scavenge superoxide radicals and effectively prevent β-carotene bleaching. Acetone extract had highest inhibitory activity toward α-glucosidase, α-amylase, and xanthine oxidase. Ethyl ether extract had highest inhibitory activity towards urease and angiotensin converting enzyme. Aqueous and ethanol extracts had strongest inhibitory activity toward acetylcholinesterase. Methanol extract showed highest inhibitory activity toward tyrosinase. Methanol extract showed good stability and antioxidant capacity during heating, at different pH values, and after in vitro digestion and had low toxicity. The efficacy of methanol extract in stabilizing olive and sunflower oils was studied, the results suggested that methanol extract had a protective effect on the primary oxidation of the two oils. TL may be useful as a source of active components for application in human nutrition and/or phytomedicine and methanol extract of TL could be used as a natural oil stabiliser.     

Phytochemical Analysis,Antioxidant, and Wound Healing Activity of Pluchea indica L. (Less) Branch Extract Nanoparticles

Proliferation and migration of keratinocytes and fibroblasts play an important role in cutaneous wound healing, while oral mucosal squamous cell proliferation and migration are crucial for oral wound healing. In this study, the phytochemical profile of Pluchea indica branch ethanolic extract was characterized. The bioactive compound of Pluchea indica branch ethanolic extract was identified and analyzed by the validated HPLC method. The nanoparticles of P. indica branch extract were formulated by solvent displacement method to increase the solubility and the colloidal stability of the extract. The stability of the nanoparticles was investigated by using the dynamic light scattering technique. Effects of P. indica crude extract and nanoparticles on cell viability, proliferation and migration of primary epidermal keratinocytes, human dermal fibroblasts, and oral mucosal keratinocyte cells were investigated by MTT assay and scratch assay, respectively. The results showed that P. indica branch extract contained a high content of total phenolic and total flavonoids. The HPLC analysis revealed that the main compound in the extract was 4,5-O-dicaffeoylquinic acid. The cell viability of the extract and nanoparticles decreased when cells were exposed to a high concentration of extract and nanoparticles. These results demonstrate that P. indica branch extract and extract nanoparticles at specific concentrations possess in vitro wound healing activity and they may be possibly used to treat different types of wounds including dermal and oral mucosal wounds.     

Bioactive compounds content and their biological properties of acetone extract of Cuscuta reflexa Roxb. grown on various host plants

The present study is aimed to evaluate the total phenolic and flavonoid contents, and free phenolic compounds of acetone extract of Cuscuta reflexa grown on five different hosts: Coccinia grandis, Ficus racemosa, Samanea saman, Streblus asper and Zollingeria dongnaiensis, and to explore the antioxidant activities, α-glucosidase and tyrosinase inhibitory properties of the extracts. The highest level of total phenolic and flavonoid contents were observed in the extract of C. reflexa that was grown on S. asper (65.45 mg GAE/g extract) and C. grandis (97.83 mg QE/g extract), respectively. According to HPLC results, vanillic acid, rutin and quercetin were found in all extracts of C. reflexa grown on diversified hosts. The extract of C. reflexa grown on C. grandis possessed the greatest antioxidant activities (DPPH; 251.64 μg/mL, FRAP; 26.44 mg GAE/g extract), α-glucosidase inhibition accounted for 84.36 per cent and antityrosinase activity was at 18.29 mg KAE/g sample.     

Screening and evaluation of α-glucosidase inhibitors from indigenous medicinal plants in Dak Lak Province,Vietnam

α-Glucosidase inhibitors have received much attention due to their important use in treating diabetes mellitus. Although some synthetic α-glucosidase inhibitors have been available for a long time, they often cause various unexpected side effects. Thus, the present study was aimed at finding a safe, natural source of α-glucosidase inhibitors. Twenty-six samples of 22 medicinal plants were collected in the Dak Lak province of Vietnam and evaluated for α-glucosidase inhibitory activity. Trunk bark extract from Euonymus laxiflorus Champ (ELC extract) was selected as the best α-glucosidase inhibitor with the smallest IC₅₀ = 0.36 mg/mL against rat-derived α-glucosidase. This extract had a stronger inhibitory activity against α-glucosidase from Saccharomyces cerevisiae (IC₅₀ = 1.32 µg/mL) and Bacillus stearothermophilus (IC₅₀ = 5.15 µg/mL). The potential inhibition against some other enzymes were tested, and the results showed that the ELC extract did not inhibit fungal cellulase but strongly inhibited porcine α-amylase (IC₅₀ = 6.7 µg/mL). The ELC extract also inhibited the proteases papain and bromelain, with IC₅₀ = 339 µg/mL and IC₅₀ = 226 µg/mL, respectively. The thermal and pH stabilities of the ELC extract were also investigated.     

Characterization of the Phytochemical Profiles and Biological Activities of Ajuga chamaepitys subsp. chia var. chia and Ajuga bombycina by High-Performance Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry (HPLC–ESI–MSn)

This study investigates into the pharmacological potential of three solvent extracts (ethyl acetate, methanol, and water) of two Ajuga species (Ajuga chamaepitys subsp. chia var. chia and Ajuga bombycina) based on their antioxidant activity and enzyme inhibitory effects along with establishing the phytochemical profile. Spectrophotometric and high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC–ESI–MSⁿ) were used to determine the total and individual phytocompounds, respectively. Antioxidant potential was assessed using different assays such as DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation. Enzyme inhibitory effects were studied against acetylcholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase. The aqueous extract of both plants showed better ABTS scavenging, FRAP, and metal chelating activities. The methanol extracts displayed the highest tyrosinase inhibitory and antioxidant activity in the phosphomolybdenum assay while the ethyl acetate extracts of both plants showed better butyrylcholinesterase (BChE), α-amylase, and α-glucosidase inhibition. The total phenolic content was highest in the aqueous extract of A. chamaepitys while the methanolic extract of A. bombycina showed the highest flavonoid content. Identification by HPLC–ESI–MSⁿ revealed the presence of some individual compounds including phenolic acids, flavonoids, iridoid glycosides, phenylethanoid glycosides, and other compounds. To conclude, both A. chamaepitys and A. bombycina can be considered as rich sources of phytocompounds to manage chronic diseases.     

Anacyclus pyrethrum (L): Chemical Composition,Analgesic, Anti-Inflammatory,and Wound Healing Properties

Background: Anacyclus pyrethrum (A. pyrethrum) is a wild species belonging to the family Asteraceae, which is used in traditional medicines. Aim of the study: This work was undertaken to study the chemical composition, analgesic, anti-inflammatory, and wound healing properties of hydroalcoholic extracts of different parts (roots, seeds, leaves, and capitula) of A. pyrethrum. Material and Methods: The phytochemical analysis of the studied extracts was conducted by GC-MS. The analgesic activity was evaluated in mice using acetic acid and formaldehyde methods. The anti-inflammatory activity was tested using the inhibitory method of edema induced in rats. The healing activity of the hydroethanolic extracts was explored by excision and incision wound healing models in rats. Results: The phytochemical analysis of the studied plant extracts affirmed the presence of interesting compounds, including some newly detected elements, such as sarcosine, N-(trifluoroacetyl)-butyl ester, levulinic acid, malonic acid, palmitic acid, morphinan-6-One, 4,5.alpha.-epoxy-3-hydroxy-17-methyl, 2,4-undecadiene-8,10-diyne-N-tyramide, and isovaleric acid. The extracts of different parts (roots, seeds, leaves, and capitula) exhibited promising anti-inflammatory, analgesic, and wound healing effects, with percentages of inhibition up to 98%, 94%, and 100%, respectively. Conclusion: This study might contribute towards the well-being of society as it provides evidence on the potential analgesic, anti-inflammatory, and wound healing properties of A. pyrethrum.     

Chromatographic Separation of Breynia retusa (Dennst.) Alston Bark,Fruit and Leaf Constituents from Bioactive Extracts

Breynia retusa (Dennst.) Alston (also known as Cup Saucer plant) is a food plant with wide applications in traditional medicine, particularly in Ayurveda. Extracts obtained with four solvents (dichloromethane, methanol, ethyl acetate and water), from three plant parts, (fruit, leaf and bark) were obtained. Extracts were tested for total phenolic, flavonoid content and antioxidant activities using a battery of assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum) and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase as target enzymes. Results showed that the methanolic bark extract exhibited significant radical scavenging activity (DPPH: 202.09 ± 0.15; ABTS: 490.12 ± 0.18 mg Trolox equivalent (TE)/g), reducing potential (FRAP: 325.86 ± 4.36: CUPRAC: 661.82 ± 0.40 mg TE/g) and possessed the highest TAC (3.33 ± 0.13 mmol TE/g). The methanolic extracts were subjected to LC-DAD-MSⁿ and NMR analysis. A two-column LC method was developed to separate constituents, allowing to identify and quantify forty-four and fifteen constituents in bark and fruits, respectively. Main compound in bark was epicatechin-3-O-sulphate and isolation of compound was performed to confirm its identity. Bark extract contained catechins, procyanidins, gallic acid derivatives and the sulfur containing spiroketal named breynins. Aerial parts mostly contained flavonoid glycosides. Considering the bioassays, the methanolic bark extract resulted a potent tyrosinase (152.79 ± 0.27 mg kojic acid equivalent/g), α-amylase (0.99 ± 0.01 mmol acarbose equivalent ACAE/g) and α-glucosidase (2.16 ± 0.01 mmol ACAE/g) inhibitor. In conclusion, methanol is able to extract the efficiently the phytoconstituents of B. retusa and the bark is the most valuable source of compounds.     

In vitro wound healing evaluation,antioxidant and chemical profiling of Baeckea frutescens leaves ethanolic extract

Occurrence of the wound or chronic wound, which results to disability, amputation and diminish quality of life, are leading to increased healthcare expenditure around the globe. Despite effective conventional wound healing medicines, the exploration of alternative medicines are continuing process as researchers seek for the approach to reduce the cost of wound healing management. In present study, wound healing properties of ethanolic extract of Baeckea frutescens leaves were determined by evaluating their cytotoxicity, proliferation and migration rate on two types of cells, keratinocytes (HaCaT) and fibroblasts (BJ). Furthermore, the antioxidant properties of this plant were determined by DPPH scavenging, ferric reducing antioxidant power (FRAP) and total phenolics content (TPC) assays. The phytochemistry of the extract was evaluated by phytochemicals screening and liquid chromatography mass spectrometry (LCMS) analysis. Results of this study indicated Baeckea frutescens extract increased the rate of proliferation and migration on both HaCat and BJ cells within their nontoxic doses. The extract also possessed a very good antioxidant property as demonstrated with high DPPH radical scavenging, FRAP and TPC values, comparable to that of Green tea extract, a widely known antioxidant. The phytochemistry analyses and LCMS exhibited the presence saponins, flavonoids, tannins and steroids in Baeckea frutescens extract possibly responsible to their antioxidant and wound healing properties.     

Trihydroxy-2-thiaquinolizidine derivatives as a new class of bicyclic glycosidase inhibitors

Trihydroxy-2-thiaquinolizidines, a new class of bicyclic dideoxy-iminohexitol glycosidase inhibitor derivatives with nominally the d-gluco, l-ido, d-manno and l-gulo configurations were synthesized. X-ray analyses indicated that the preferred conformation for d-gluco and d-manno derivatives was a flat trans-fused system. Unlike deoxynojirimycin, the compound with d-gluco configuration was selective for α-glucosidases (yeast and rice) and showed no inhibitory activity towards β-glucosidase (almond), α-galactosidase (green coffee beans), α-galactosidase (E. coli) and α-mannosidase (jack bean), while the l-ido derivative was specific for β-glucosidase (almond).     

Schisandra rubriflora Fruit and Leaves as Promising New Materials of High Biological Potential: Lignan Profiling and Effect-Directed Analysis

The effect-directed detection (EDD) of Schisandra rubriflora fruit and leaves extracts was performed to assess their pharmacological properties. The EDD comprised TLC—direct bioautography against Bacillus subtilis, a DPPH assay, as well as α-glucosidase, lipase, tyrosinase, and acetylcholinesterase (AChE) inhibition assays. The leaf extracts showed stronger antioxidant activity than the fruit extract as well as inhibition of tyrosinase and lipase. The fruit extract was found to be extremely active against B. subtilis and to inhibit α-glucosidase and AChE slightly more than the leaf extracts. UHPLC–MS/MS analysis was carried out for the bioactive fractions and pointed to the possible anti-dementia properties of the dibenzocyclooctadiene lignans found in the upper TLC fractions. Gomisin N (518 mg/100 g DW), schisanhenol (454 mg/100 g DW), gomisin G (197 mg/100 g DW), schisandrin A (167 mg/100 g DW), and gomisin O (150 mg/100 g DW) were the quantitatively dominant compounds in the fruit extract. In total, twenty-one lignans were found in the bioactive fractions.     

Greener pastures in evaluating antidiabetic drug for a quinoxaline Derivative: Synthesis,Characterization, Molecular Docking,in vitro and HSA/DFT/XRD studies

In an effort to develop a potent antidiabetic drug, new quinoxaline derivative, 2-(4-((3-methyl-2-oxoquinoxalin-1(2H)-yl)methyl)-4,5-dihydro-1H-1,2,3-triazol-1-yl)-N-(p-tolyl)acetamide (MOQTA) was synthesized and characterized by XRD and various spectroscopic tools (IR, ¹H &¹³C NMR, ESI-MS). The geometric optimization of the molecule was calculated with Density Functional Theory (DFT) method by B3LYP with a 6–311++G(d,p) basis set. Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEP) surfaces of the title compound were generated. Furthermore, Hirshfeld surface analysis (HSA) and 2D fingerprint plots were presented. The calculated MEP and HSA surface interactions were compared in terms of hydrogen bonds and π-π stacking interactions obtained by X-ray packing analyses. X-ray crystallographic structure analysis revealed that the N—HN, C—HO and C—HN intermolecular hydrogen bonds were in agreement with those obtained by HSA. Moreover, MOQTA was assessed for its in vitro anti-diabetic activity. Likewise, molecular docking analyses were conducted to examine the binding mode between MOQTA and the enzymes α-glucosidase and α-amylase. Finally, the physicochemical, pharmacokinetic and toxicological properties of MOQTA have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.     

Facile construction of 1,2-cis glucosidic linkage using sequential oxidation-reduction route for synthesis of an ER processing α-glucosidase I substrate

The fluorescence-labeled hexasaccharide (Glcα1-2Glcα1-3Glcα1-3Manα1-2Manα1-2Manα) was synthesized as a substrate for the processing enzyme α-glucosidase I. To construct the 1,2-cis glucosidic linkages, we employed an α stereoselective coupling using the mannosyl donor by assisted neighboring-group participation, followed by conversion of the stereochemistry of the C-2 hydroxyl group in the mannose residue using sequential oxidation of C-2 hydroxyl group to a 2-keto group and stereoselective reduction of the hydroxyl group to the gluco-configuration to provide the corresponding α-glucoside derivative. Using this strategy, the three consecutive α-glucosidic linkages were easily obtained in a stereoselective manner. Finally, the Dansyl labeled hexasaccharide derivative was used to measure the activity of processing α-glucosidase I.     

Astragalin identification in graviola pericarp indicates a possible participation in the anticancer activity of pericarp crude extracts: In vitro and in silico approaches

Graviola, soursop, or guanabana (Annona muricata L.), is an ethnomedical fruit consumed to alleviate headache, diarrhea, diabetes, and cancer. Pericarp is the inedible part of graviola least studied in comparison to seeds and leaves, even thought, it contains the highest concentration of graviola total polyphenols. Anticancer effect of graviola pericarp has been demonstrated in crude extracts attributing the effect to acetogenins, however, crude extracts contain several active molecules. Thus, the present work aimed to fractionate and purify an ethanolic crude extract from graviola pericarp. Purified graviola pericarp fraction (PGPF) was evaluated on cancerous and non-cancerous cell lines, and then was identified by NMR, TOF-MS, and HPLC. Finally, an in silico analysis was performed to predict targets cancer-related of the molecule detected. Our results revealed IC₅₀ values for cervix adenocarcinoma (HeLa), hepatocellular carcinoma (HepG2), triple-negative breast cancer (MDA-MB-231), and non-cancerous cell line (HaCaT) of 92.85 ± 1.23, 81.70 ± 1.09, 84.28 ± 1.08, and 170.2 ± 1.12 µg PGPF/mL, respectively. In vitro therapeutic indexes estimated as quantitative relationship between safety and efficacy of PGPF were 1.83, 2.08, and 2.02 for HeLa, HepG2, and MDA-MB-231, respectively. The NMR analysis revealed astragalin (kaempferol-3-O-glucoside) in PGPF, a flavonoid not reported in graviola pericarp until now. Astragalin identity was confirmed by TOF-MS and HPLC. In silico results support previous reports about astragalin modulating proteins such as Bcl-2, CDK2, CDK4, MAPK and RAF1. Also, results suggest that astragalin may interact with other cancer-related proteins not associated previously with astragalin. In conclusion, astragalin may be contributing to the anticancer effect observed in graviola pericarp extracts.     

Multifunctional approaches to provide potential pharmacophores for the pharmacy shelf: Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt.

Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt. commonly known as “hogweed” is traditionally used to manage several human ailments. This investigation assessed, for the first time, the enzyme inhibitory properties, antioxidant activity, phytochemical profile, antimutagenic, and antimicrobial potential of the ethyl acetate, methanol, and water extracts of H. sphondylium. We also established the possible interactions of identified phenolic compounds with cholinesterases, amylase, glucosidase, and tyrosinase using in silico docking studies. Chlorogenic acid was found in high amounts in the methanol extract of H. sphondylium. The methanol extract was an effective inhibitor of acetylcholinesterase (1.70 mg galantamine equivalent (GALAE)/g extract) while the ethyl acetate extract showed pronounced inhibitory action against butyrylcholinesterase (1.77 mg GALAE/g extract). The extracts exhibited low inhibition against amylase (0.12-0.84 mmol acarbose equivalent (ACAE)/g extract) and a more pronounced inhibition against glucosidase (2.29–3.65 mmol ACAE/g extract). In silico results showed that rutin and quercetin (-70.4 and -72.2 Kcal/mol, for rutin and quercetin respectively) docked to the enzymatic cavity of acetylcholinesterase but these phenolic compounds showed less affinity with butyrylcholinesterase (-15.0 and -5.2 Kcal/mol, for rutin and quercetin respectively). The extracts did not induce any mutations on the bacterial strains, while they have excellent antimutagenic capacity against well-known mutagens (inhibition values 98%, 97% and 96%). The methanol extract (0.78 mg/ml) showed moderate antifungal activity while the ethyl acetate extract (0.78–3.12 mg/ml) showed weak to moderate antimicrobial activity. This study provides valuable baseline data which might serve for the development of future pharmacophores for the management of human ailments.