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Aloe dhufarensis Lavranos is an important medicinal plant, however, the endophytic microorganisms associated with this plant and their antagonistic activities are not known. In this study, endophytic fungi and bacteria were isolated from the leaf tissues of A. dhufarensis and their antagonistic activity against the plant pathogens Fusarium sp. and Cladosporium sp. were evaluated using a dual culture assay. A total of 3 fungal endophytes and 12 bacterial endophytes were isolated from the leaf tissue segments of A. dhufarensis. Among them, two endophytic fungal isolates designated as SQUCC-F2-2 and SQUCC-F3-1 exhibited inhibitory activity against the phytopathogenic fungi tested. In addition, scanning electron microscopy analysis showed that they induced shriveling, pit formation and disintegration of the hyphae of the phytopathogenic fungi. These two endophytic fungal isolates were identified as Sarocladium kiliense (SQUCC-F2-2) and Penicillium oxalicum (SQUCC-F3-1) on the basis of nuclear ribosomal DNA internal transcribed spacer (ITS) region. Analysis of the metabolites produced by these endophytes revealed the presence of fatty acids, fatty acid methyl esters, furfuryl alcohol, 1,2-diols and amide, which have been identified in the literature as antimicrobial compounds. P. oxalicum produced 7 compounds, of which 2-Furanmethanol, Dodecanoic acid and Tetradecanoic acid were dominant. S. kiliense produced 8 compounds with 2,3-Butanediol as the main constituent. This is the first report of endophytic fungi of A. dhufarensis with antagonistic activity against phytopathogenic fungi.

This study investigated the ameliorating effect of exogenous proline on some physiological responses of salt acclimated and non-acclimated Aloe vera plants against subsequent salt stress (EC 21 dS/m). Compared to control, salinity decreased leaf growth and relative water content (RWC), leaf contents of chlorophyll a, carotenoids, K/Na ratio, photosystem performance index (PIabs), while promoted leaf contents of hydrogen peroxide (H2O2), maloendialdehyde (MDA) and Na, which subsequently induced oxidative stress. However, foliar applied proline was effective in alleviating the deleterious effects of salinity. Maximum amelioration of salt stress by exogenous proline was found only in salt-acclimated plants, which was attributed to the reduced leaf Na accumulation together with enhanced K content. Proline pretreatment improved plant relative water content, which was correlated with enhancement in leaf proline concentration. We showed that application of proline on salt-acclimated stressed plants alleviated the damage to PSII functioning induced by salinity, contributing to the improvement of the oxygen-evolving complex efficiency of PSII (Fv/Fo) and the quantum yield of electron transport (ΦEo). This improvement of PSII activity was achieved by higher carotenoids and phenolic accumulation. Additionally, proline treatment reduced the accumulation of H2O2 and MDA, indicating that proline pretreatment was more effective in lowering oxidative damage in salt-exposed acclimated plants, which was associated with the activation of SOD, CAT and APX enzymes. Thus, proline pretreatment could protect salt acclimated Alo vera plants against subsequent salt stress through improving K/Na ratio and water relations attributes as well as enhancing antioxidant systems, resulting in better photosynthesis under salt stress.

The genus Aloe is widely used for medicinal purposes throughout its predominantly African distribution, but detailed knowledge of the contemporary value of aloes is patchy. The main aim of this study was to determine the value of Aloe in the Highlands of Ethiopia, a region of rich Aloe diversity, by documenting local uses and perceptions of the sustainability of the species used. Amhara and Tigray community members participated in semi-structured interviews from 110 respondents aged 24-72. Eleven species of Aloe were recorded for medicine, social and environmental uses, animal food, and as bee plants managed for honey production. Of these, the majority of use records were for human medicine to treat malaria and wounds. We found no evidence of non-sustainable harvesting for medicine, but extensive habitat loss and interest in the commercial uses of Aloe present acute threats and indicate the vulnerability of Aloe species in the central and northern Highlands of Ethiopia.

The genus Aloe (family: Xanthorrhoeaceae) encompasses 490 shrubby-succulent-perennial species which are native to Africa. Among these, Aloe vera has grabbed the limelight in the arena of herbal medicine due to the presence of unique phytochemicals such as Aloin A and B, Homonataloin, Aloe emodin, acemannan etc. in its latex. Moreover, its leaf extract contains 99% water, and 75 active compounds including vitamins (A, B1, B2, B3, B6, B9, B12, C, and E), minerals (Zn, Se, Na, Mn, Mg, K, Cu, Cr, Ca), amino acids, and enzymes (peroxidase, lipase, cellulase, catalase, carboxypeptidase, bradykinase, amylase, alkaline phosphatase). Thus, Aloe vera is revered as a ‘wonder plant’ as it possesses multiple pharmaceutical properties such as anti-oxidant, anti-inflammatory, anti-tumor, anti-fungal, anti-diabetic, anti-ulcer, anti-hypertensive and its juice helps to cure gastrointestinal disorders, and dermal diseases, it also strengthens the immune system. Being a xerophyte, Aloe vera is commercially cultivated in many countries which include South Africa, America, Australia, India etc. The Aloe gel, is meticulously extracted, processed and stabilized before using it in preparation of various health care products. This review focuses on the explicit information on origin, botanical description, phytochemistry, nutritional and medicinal benefits, with special emphasis on value-added products of Aloe vera. The review revealed 46 value-added Aloe-products that are being manufactured by different companies worldwide. Thus, sustainable Aloe-cultivation must be ensured to meet the rising global demands for Aloe vera gel and allied products.

Heavy metals like cadmium (Cd) are a serious threat for living organisms due to increased global environmental pollution. Aloe ferox Mill. is a very important species of the genus Aloe, especially from a medical point of view, because it is a source of biologically active substances and it is often used in the traditional medicine. Since the knowledge about the effect of heavy metals, like Cd on growth of Aloe species is scarce, this study showed the effect of Cd on anatomical, morphological and physiological properties of this important medicinal plant species. We found that Cd affected the leaf morphology and decreased biomass of the aboveground plant part. Cd also affected cuticle deposition and increased the number of stomata in the abaxial and adaxial epidermis of leaves. Roots treated with Cd showed lower lignification and decreased level of membrane lipids peroxidation than control roots. Cadmium concentration was the highest in the roots; however, relatively high portion of Cd is being translocated to the leaves. This might be dangerous as Aloe is well known medicinal plant with content of active secondary metabolites mainly in the leaves.

Aloe vera (Aloe barbadensis Miller) is a perennial drought tolerant medicinal species. This research study investigates the influence of biofertilizers on mycorrhizal fungi colonization, leaf number and width, plant height, offset number, leaf relative elongation rate (RER), leaf dry weight and leaf gel weight, water productivity (WP) for the gel, and aloin content in Aloe vera plants. The experiments were carried out in the warm and dry climate of Bushehr Province, Iran during 2016–2018. Treatments are reported to include irrigation regimes and biofertilizers at four levels. In terms of irrigation regimes, 25%, 50%, 75%, and 100% of water requirement accompanied the following treatments for biofertilizers, phosphorus-solubilizing bacteria (PSB), mycorrhizal fungi (MF), PSB+MF, and control (without any biofertilizers). The PSB includes Pseudomonas putida strain P13 and Pantoea agglomerans strain P5, in addition to Glomus mosseae as MF. The biofertilizer benefits (remarkably PSB+MF) on investigated traits were observed in three harvests. The results confirm the positive impacts of biofertilizers on important traits such as offset number (an economical part of Aloe vera planting), water productivity with less water consumption, and root colonization, which is the main reason of increasing the mentioned traits. Considering the minimal difference between 100%, 75% and 50% of water requirement in terms of gel fresh weight and more aloin content in 50% of our experiments, Aloe vera is reported as a high drought tolerant plant which merely requires an acceptable gel yield and aloin content. Moreover, better water productivity and consumption is possible in warm and arid regions by applying 50% of Aloe vera water requirement as well as biofertilizers.

Aloe vera L. is used largely in the pharmaceutical, cosmetic, and agro-food industries. The in vitro technique was proposed as an alternative method for large-scale propagation and/or conservation breeding programmes in response to the increasing demand for Aloe vera. Unfortunately, a major problem in the application of plant tissue culture is the browning of cultured tissues and microbial contamination. This work investigates for the first time the efficacy of using Essential Oils (EOs) to control enzymatic browning and contamination of cultures from Aloe vera. Murashige and Skoog (MS) (1962) medium supplemented with 1 mg/L β-indole butyric acid (IBA) was used as a basic medium for A. vera for in vitro culture. The effect of the addition of charcoal (at 0.5 g/L), thyme (Thymus vulgaris L.) and rosemary (Rosmarinus officinalis L.) essential oils (at concentrations of 0.1 and 0.2%) to the basic medium was assessed. While thyme Essential Oil (EO) inhibited explant growth, rosemary EO induced the highest explant survival percentage, the lowest browning diffusion and contamination percentage. Moreover, a second experiment was conducted to determine the optimal rosemary EO concentration (0.025, 0.05, 0.075, and 0.1%). Explant survival percentage was 100% after four weeks of culture with rosemary EO concentrations of 0.05, 0.075, and 0.1% with no signs of browning. The lowest infection percentage (10%) was observed for media containing 0.075 and 0.1% of rosemary EO. The highest average number of leaves per explant was 3.71 with 0.1% rosemary EO and the greatest leaf length was 3.18 cm with 0.05%. The analytical techniques used to detect rosemary EO compounds were GC-FID (gas chromatography - flame ionization detection) and GC–MS (gas chromatography-mass spectrometry). The main constituents found were 1,8-cineole (53.92%), α-pinene (15.86%), β-pinene (10.79%), and camphor (7.99%). Additionally, the antioxidant activity of the rosemary EO was determined by the DPPH (Free radical-scavenging activity) (24.66 µg mL−1) and FRAP (Ferric reducing antioxidant power) (35.16 mmol Fe2+L − 1) tests. The chemical composition together with the antioxidant effect and the most widely recognized anti-infectious properties of the used rosemary EO could explain its role in the inhibition of both enzymatic browning and microbial growth in culture media. These results could be a scope for further screening of EOs to be used for the improvement of in vitro culture of A. vera and other industrial crops.

Background: Inflammation is a critical component of many disease progressions, such as malignancy, cardiovascular and rheumatic diseases. The inhibition of inflammatory mediators synthesis by modulation of cyclooxygenase (COX) and lipoxygenase (LOX) pathways provides challenging strategy for development of more effective drugs. Objective: The aim of this study was to design dual COX-2 and 5-LOX inhibitors with iron-chelating properties using a combination of ligand-based (three-dimensional quantitative structure-activity relationship (3D-QSAR)) and structure-based (molecular docking) methods. Methods: The 3D-QSAR analysis was applied on a literature dataset consisting of 28 dual COX-2 and 5- LOX inhibitors in Pentacle software. The quality of developed COX-2 and 5-LOX 3D-QSAR models were evaluated by internal and external validation methods. The molecular docking analysis was performed in GOLD software, while selected ADMET properties were predicted in ADMET predictor software. Results: According to the molecular docking studies, the class of sulfohydroxamic acid analogues, previously designed by 3D-QSAR, were clustered as potential dual COX-2 and 5-LOX inhibitors with ironchelating properties. Based on the 3D-QSAR and molecular docking, 1j, 1g and 1l were selected as the most promising dual COX-2 and 5-LOX inhibitors. According to the in silico ADMET predictions, all compounds had ADMET_Risk score less than 7 and CYP_Risk score lower than 2.5. Designed compounds were not estimated as hERG inhibitors and 1j had improved intrinsic solubility (8.704) in comparison to the dataset compounds (0.411-7.946). Conclusion: By combining 3D-QSAR and molecular docking, three compounds (1j, 1g and 1l) were selected as the most promising designed dual COX-2 and 5-LOX inhibitors, for which good activity, as well as favourable ADMET properties and toxicity, are expected.

Herein, we report a computational algorithm that follows a spectroscopist-driven elucidation process of the structure of an organic molecule based on IR, $^1$H and $^{13}$C NMR, and MS tabular data. The algorithm is independent from database searching and is based on a bottom-up approach, building the molecular structure from small structural fragments visible in spectra. It employs an analytical combinatorial approach with a graph search technique to determine the connectivity of structural fragments that is based on the analysis of the NMR spectra, to connect the identified structural fragments into a molecular structure. After the process is completed, the interface lists the compound candidates, which are visualized by the WolframAlpha computational knowledge engine within the interface. The candidates are ranked according to the predefined rules for analyzing the spectral data. The developed elucidator has a user-friendly web interface and is publicly available (http://schmarnica. si).

Rosmarinus tournefortii is an aromatic evergreen shrub endemic to North Africa, including Algeria. Reports on phytochemicals of this species and related biological activities remain scarce. The essential oils (EOs) and ethanol extracts (EEs) of five populations collected in Algeria are investigated for their antioxidant and antimicrobial properties through different multivariate statistical methods. EOs analysis by GC and GC-MS showed that the main constituents (α-pinene, camphor, camphene and limonene) were almost comparable. The antioxidant capacity was evaluated by the ferric reducing power and the inhibition of free radicals DPPH● and ABTS●+. The free radical scavenging effectiveness of EEs was about 2 times higher than the standard antioxidant (BHT). EOs exhibited weaker antioxidant activity insofar they failed to scavenge 50% radicals. The antimicrobial activity evaluated by determining the minimum inhibitory/bactericidal concentrations towards fifteen multi-drug resistant microorganisms showed that EEs were the most active. The Gram-positive bacteria were the most susceptible. Both EEs and EOs exhibited antifungal and anti-yeast activities.

Drought and low organic carbon content are two main problems for agriculture in arid and semiarid regions. Application of hydrogels and compost may decrease adverse effects of drought on plants. A factorial experiment with a randomized complete block design with three replicates was conducted to evaluate the effect of hydrogels and compost application on yield and growth parameters of Roselle (Hibiscus sabdariffa L.) under drought stress (DS). These factors manipulated with seven treatments of soil amendments with 0, 150 (H1) and 300 (H2) kg ha−1 hydrogel, 10 (C1) and 20 (C2) ton ha−1 compost, 150 kg ha−1 hydrogel + 10 ton ha−1 compost (H1C1), and 150 kg ha−1 hydrogel + 20 ton ha−1 compost (H1C2) upon three DS levels (D1: 25% depletion of available soil moisture (DASM) as no-stress condition, D2: 50% DASM as mild-stress and D3: 75% DASM as severe-stress treatment). Results showed that drought stress significantly decreased growth parameters and relative water content (RWC) while increased ion leakage (IL), antioxidant activity (AA), and total phenolic content (TPC). H1, H1C1, and H1C2 Treatments significantly increased chlorophyll content index (CCI), leaf area (LA), leaf water potential (LWP), RWC, AA, and TPC compared to control under mild and severe stress conditions. In addition, only H1C2 treatment significantly increased calyx yield (CY) under mild and severe drought conditions. Interaction between 150 kg.h−1 hydrogel and 20 ton ha−1 compost compared to the each treatment alone led to the highest SDW, LA, and CY amounts under severe DS treatment. The CCI showed a strong positive correlation with CY (R2 = 0.61, p = 0.01), while revealed a negative correlation with TPC (R2 = -0.72, p = 0.01) and AA (R2 = -0.68, p = 0.01). These results confirm that hydrogel and compost could be suitable for agricultural use under DS conditions. The amount of hydrogel and compost application is very important on plant performance under DS.

Noodles are a popular starchy food among youth and children. However, they are not nutritionally adequate as a single meal. The aim of the study was to determine the effect of Amaranthus leaf powder (ALP) addition on the nutritional composition, physical quality and consumer acceptability of instant noodles. Instant noodle samples were developed by partially substituting wheat flour used in a common noodle recipe with 1, 2 and 3% (w/w) of ALP. The samples were analyzed for nutritional composition using AOAC methods. Physical quality was evaluated in terms of color (CIELAB color values) and texture (g cutting force). Consumer acceptability was evaluated by 60 panelists using a 9-point hedonic scale. Increasing ALP from 0% to 3% had a non-significant effect on the total glycemic carbohydrate, protein, fiber and mineral contents of the noodles. However, the fat content significantly increased (from 1.55% to 4.57%) with the inclusion of ALP, leading to a higher energy value. ALP-fortified noodle samples were significantly softer in texture (271.39 g) than standard noodles (control) (609.08 g), and a significantly greener color was observed with ALP addition. All noodle samples were as acceptable as the control, which suggests that ALP could be used to improve the nutritional value of instant noodles.

Aqueous and hydroethanoic extracts prepared from leaves of Aloysia triphylla (L'Her.) Britton (lemon verbena) and Trigonella foenum-graecum L. (fenugreek) seeds were evaluated for in vivo hypocholesterolemic and anti-inflammatory effects. The results of administration of A.triphylla leaf and T. foenum-graecum extracts on serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low density lipoprotein (VLDL) in hypocholesterolemic mice were evaluated. Mice groups treated with both aqueous and hydroethanoic extracts of A. triphylla showed reduced total cholesterol (161.60 and 162.60 mg/dl, for mice groups treated with respective extracts) and LDL (79.16 and 99.04 mg/dl, for mice groups treated with respective extracts) levels as compared to the hypercholesterolemic group (253.00 and 160.00 mg/dl for TC and LDL, respectively). A similar trend was observed with the aqueous and hydroethanoic extracts of T. foenum-groecum seeds. Mice treated with hydroethanoic extracts (200 mg/kg body weight) of A. triphylla leaves and T. foenum-groecum seeds showed significantly reduced triglyceride and VLDL levels compared to the group treated with atorvastatin (18.76 and 18.20 mg/dl, respectively). In terms of phytochemical composition, caffeic acid were detected in both A. triphylla leaves and T. foenum-graecum seeds extracts. However, rutin and luteolin have not been detected in any extracts of A. triphylla and T. foenum-graecum. Data collected from this study support the fact of future development of novel botanical remedies from A. triphylla leaves and T. foenum-graecum seeds for managing hypercholesterolemia and atherosclerosis.

Abstract: Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs. Research over the past few years has led to a new understanding regarding the pathogenesis of myositis. The new insights include different pathways of the innate and adaptive immune response during the pathogenesis of myositis. The importance of non-inflammatory mechanisms such as cell stress and impaired autophagy has been recently described. New target-specific drugs for myositis have been developed and are currently being tested in clinical trials. In this review, we discuss the mechanisms of action of pharmacological standards in myositis and provide an outlook of future treatment approaches.

Blood fruit is a tropical liana bearing edible fruit rich in anthocyanins. The species is distributed in many Asian countries, wherein it provides livelihood and nutritional security to native dwellers. However, in many of these regions produce is harvested from the wild by employing destructive harvesting practices, thereby damaging the natural stand. Systematic studies were initiated to popularize this species as a novel crop in the humid tropical parts of the world. Present study aims at studying four collections (HV/NE/TRI, HV/MA/KAL, HV/MA/SNU and HV/MA/SND) for morphological and biochemical traits. Results revealed considerable variability for fruit and seed traits, total soluble solids and pH. Total anthocyanin content among the collections varied between 183.63 and 328.28 mg CE/ 100 g pulp. Strong positive correlation was noticed between fruit dimensions with fruit weight, while negative correlation was noticed between pulp content and peel thickness. Ratio of material: solvent for obtaining better anthocyanins recovery was optimized to 1:15 (w/v). Promising genotype (HV/MA/SND) with superior fruit size, TSS content and total anthocyanins content was identified for further exploitation.

Objective The study aimed to assess the efficacy of formulated wound healing hydrogel based on a hydroalcoholic extract of Moringa oleifera seeds. Methods In vitro antioxidant (using DPPH method) and antimicrobial activity (using agar well diffusion method) was studied. Male Swiss albino mice of weight 20- 30g were used. The hydrogel containing 5% and 10% of hydroalcoholic extract of Moringa oleifera seeds was used, whereas Povidone-iodine (5%) was used as standard. The wound healing efficacy of formulated hydrogel based on a hydroalcoholic extract of Moringa oleifera seeds was studied using excision and incision wound models. Assessments were taken on the 1st, 4th, 6th, 9th, 12th, 13th and 14th day in the excision model and on the 8th day in the incision model. Histopathological assessments were also done to support the study. Results Hydroalcoholic extract of Moringa oleifera seeds showed significant scavenging of free radicals showing antioxidant activity. Plant extract showed significant antimicrobial activity using the agar well diffusion method. The formulated hydrogels using the hydroalcoholic extract of Moringa oleifera seeds showed significant wound healing activity compared to both control (p Conclusion The study presented here proved the hydrogels formulated using the hydroalcoholic extract of Moringa oleifera seeds could be used as an alternative therapy to manage wounds effectively.

The fruits of Coccinia grandis (L.) Voigt have been used to treat several aliments in traditional medicine whereas Coccinia rehmannii Cogn. fruits are consumed as food due to their high starch content. Coccinia rehmannii are also known to contain vast amounts of indispensable bioactive compounds that are used in various cosmetics, foods, and medicines. Among these compounds are hydroxycinnamic acids (HCAs) which are usually conjugated/esterified to quinic acid (QA), tartaric acid, citric acid, shikimic acid and sugars and are collectively referred to as chlorogenic acids (CGAs). Over the years, metabolite profiling has been used in plant taxonomy and species classification. Herein, UPLC-qTOF-MS/MS semi-targeted approached was use to profile HCA conjugates from two closely related plant species i.e. C. grandis and C. rehmannii leaves in order to distinguish them from each other. Examination of their relative metabolite contents showed that the two closely related Coccinia species utilise contrasting means of HCA conjugations as means of metabolite diversification strategy. C. grandis was found to conjugate its HCA derivatives to a QA, whilst C. rehmannii conjugates its HCA derivatives to mainly flavonoid glycosides and to QA, even though present in low concentration in this plant. These results shows that plants from the same genus can utilise different chemical diversification means for storage of their metabolites and that processes such as conjugation and isomerization can be exploited as chemotaxonomic markers. Future studies can also be designed to look at the pharmacological potency of these plants as a function of their contrasting chemical differences.

Sonchus oleraceus (L.) L. (sow thistle) is an underutilised functional leafy vegetable with both high nutritional and pharmacological values. In the current study, high performance liquid chromatography ion trap time-of flight mass spectrometry (HPLC-IT-Tof-MS)-based metabolomics in combination with principal component analysis (PCA) were used to provide an overall phytochemical composition of different tissues (leaf, stem and roots) of this underutilised plant. A total of 32 phytochemicals, comprising hydroxycinnamic acids, flavonoids and terpene classes were identified across the three different tissues of S. oleraceus. The study used the new approach of colour coded PCA models to info-graphically depict the metabolic profiles across different parts of the plant. The results of the current study indicate S. oleraceus as a potential source of metabolites with highly claimed nutraceutical properties. As such, the results herein can be used as a template reference for further biological studies aimed at the evaluation of nutraceutical properties of the S. oleraceus plant.

Prunus cerasoides D. Don is a plant of great venerative value in the Himalayan region. The fruits and seed kernels of this plant are traditionally used for the treatment of urinary stones. Present study was aimed to demonstrate the in vitro and preclinical antilithic potential of the hydroethanolic extract of Prunus cerasoides fruits against calcium oxalate urolithiasis. In vitro antiurolithiatic screening was done by nucleation, and aggregation assay, while preclinical evaluation was carried out on ethylene glycol (0.75% v/v) and ammonium chloride (1% w/v) rendered urolithiasic male Wistar rats. P. cerasoides fruit extract induced nucleation of multiple small sized calcium oxalate crystals and inhibited their aggregation in the metastable solutions. P. cerasoides fruit extract to a large extent prevented lithogenic treatment induced anorexia, weight loss, polydipsia, polyuria, crystalluria, hypercalciuria, hyperoxaluria, hyperuricosuria, hyperphosphaturia, hypocitraturia and hypomagnesuria. It also showed preventive effect on the deposition of calcium, oxalate and phosphate in kidney tissues and exhibited ameliorative effect on serum urea, creatinine and uric acid. Moreover, inhibitory effect on oxidative stress induced degeneration of renal tissue was also recorded from histopathological analysis of the kidneys. PCFE showed promising outcomes as an antiurolithiatic both prophylactically and curatively. The effects can be attributed to its ability to restore the equilibrium between the urinary promoters and inhibitors of CaOx crystallization, its anticrystallization activity and its ameliorating effects on renal cellularity, urine and serum chemistry.

Background: Pancreatic ductal adenocarcinoma (PDAC), which ranks forth on the cancer-related death statistics still is both a diagnostic and a therapeutic challenge. Adenocarcinoma of the exocrine human pancreas originates in most instances from malignant transformation of ductal epithelial cells, alternatively by Acinar-Ductal Metaplasia (ADM). RA96 antibody targets to a mucin M1, according to the more recent nomenclature MUC5AC, an extracellular matrix component excreted by PDAC cells. In this study, we tested the usability of multimodal nanoparticle carrying covalently coupled RA96 Fab fragments for pancreatic tumor imaging. Methods: In order to make and evaluate a novel, better targeting, theranostic nanoparticle, iron nanoparticles and the optical dye indocyanin green (ICG) were encapsulated into the cationic sphingomyelin (SM) consisting liposomes. RA-96 Fab fragment was conjugated to the liposomal surface of the nanoparticle to increase tumor homing ability. ICG and iron nanoparticle-encapsulated liposomes were studied in vitro with cells and (i) their visibility in magnetic resonance imaging (MRI), (ii) optical, (iii) Magnetic particle spectroscopy (MPS) and (iv) photoacoustic settings was tested in vitro and also in in vivo models. The targeting ability and MRI and photoacoustic visibility of the RA-96-nanoparticles were first tested in vitro cell models where cell binding and internalization was studied. In in vivo experiments liposomal nanoparticles were injected into a tail vain using an orthotopic pancreatic tumor xenograft model and subcutaneous pancreas cancer cell xenografts bearing mice to determine in vivo targeting abilities of RA-96-conjugated liposomes. Results: Multimodal liposomes could be detected by MRI, MPS and by photoacoustic imaging in addition to optical imaging showing a wide range of imaging utility. The fluorescent imaging of ICG in pancreatic tumor cells Panc89 and Capan-2 revealed increased association of ICG-encapsulated liposomes carrying RA-96 Fab fragments in vitro compared to the control liposomes without covalently linked RA-96. Fluorescent molecular tomography (FMT) studies showed increased accumulation of the RA96-targeted nanoparticles in the tumor area compared to non-targeted controls in vivo. Similar accumulation in the tumor sites could be seen with liposomal ferric particles in MRI. Fluorescent tumor signal was confirmed by using an intraoperative fluorescent imaging system which showed fluorescent labeling of pancreatic tumors. Conclusion: These results suggest that RA-96-targeted liposomes encapsulating ICG and iron nanoparticles can be used to image pancreatic tumors with a variety of optical and magnetic imaging techniques. Additionally, they might be a suitable drug delivery tool to improve treatment of PDAC patients.

Background: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules, they can easily interact with biomolecules of living systems. Objective: A series of substituted 2-thiobezimidazoles has been synthesized .Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell-lines. Methods: The spectral data of the synthesized compounds were characterized. Docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib were performed. Results: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in CDK-ATP binding pocket. 3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. Conclusion: Against all tested compounds ; two compounds 3c &3l were found active against two types of cell-lines.

Background: The Covid-19 virus emerged a few months ago in China and infections rapidly escalated into a pandemic. Objective: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential. Method: In this work two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds. Result: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets – S2, TMPRSS2 and furin – simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza. Conclusion: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.

Breast cancer is the second most commonly identified cancer in women in the United States after skin cancer. The past few years have seen a substantial increase in breast cancer awareness campaigns and active research in fields of diagnosis and targeted therapy. These factors have led to a better mechanistic understanding of the disease, detection at earlier stages, and a more personalized approach to treatment, ultimately causing a crucial increase in the survival rates after detection. However, with the advances in treatment, cases of patients developing primary resistance and acquired resistance are increasing. Most of the breast cancers which develop resistance to therapy are ER+ and are typically treated with tamoxifen and fulvestrant. These drugs either lower the levels of estrogen or inhibit the receptors for estrogen and prevent the tumor from spreading. Around one-third of women treated with these drugs develop resistance to them, lowering their chances of survival. This has directed the search for newer drug therapies to target advanced breast cancer and resistance. One of these efforts has resulted in the development of Palbociclib, a first in class inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6), which was granted accelerated approval from the FDA for combination therapy in postmenopausal women with ER+, HER2- metastatic breast cancer. This review is focused on the various aspects of “Palbociclib” including its synthesis, molecular modeling studies, and efficacy and safety profile with data obtained from various clinical trials.

Infections caused by virus are one of the foremost causes of morbidity and mortality in the world. Although a number of antiviral drugs are currently used for treatment of various kinds of viral infection diseases, there is still no available therapeutic agent for the most of virus in clinical practice. Coumarin is a chemical compound which is found naturally in a variety of plants, as well as it can be synthetically produced possessing diverse biological effects. More recently, reports have highlighted the potential role of coumarin derivatives as antiviral agents. This review outlines the advances in coumarin-based compounds against various viruses including human immunodeficiency virus, hepatitis virus, herpes simplex virus, Chikungunya virus and Enterovirus 71, the structure activity relationship and the possible mechanism of action of the most potent coumarin derivatives are also discussed.

Sophora alopecuroides L. are commonly used in traditional Chinese medicine for the treatment of various ailments such as refractory tinea, eczema, dermatitis, colpitis, bacillary dysentery, and other gastrointestinal diseases. The aim of this study was to investigate the chemical composition, antioxidant, and enzyme inhibitory activity of the aerial part, flower, leaf, root, and stems extracts of S. alopecuroides var. alopecuroides. Major compounds of the extracts were found to be ferulic acid, luteolin, hesperidin and pinoresinol. In many of the antioxidant activity assays, the root extract exhibited high activity. In CUPRAC reducing, phosphomolybdenum, ABTS, and DPPH tests, the activity of the root extract was 1.42, 2.45, 1.25, and 8.41 mg/mL, respectively. Root extract also exhibited significant activity in enzyme inhibitory assays. Tyrosinase, α-amylase, α-glucosidase, and acetyl cholinesterase (AChE) inhibitory activities of the extract were determined as 1.22, 2.97, 1.03, and 0.97 mg/mL, respectively. Chromatographic analysis showed that the root extract contained 462.25 µg/g pinoresinol and 256.23 µg/g vanillic acid as the major compounds. Pearson correlation analysis showed that besides flavonoids/phenolics, these phytochemicals also contributed to the activity of root extract. Therefore, it was concluded that these phytochemicals may be responsible for the activity of the root extract. The root extract of S. alopecuroides var. alopecuroides was thought to be an effective antioxidant and enzyme inhibitory agent.

The study aimed to assess the phytochemical composition and enzyme inhibitory potential of methanol, n-hexane, chloroform, and n-butanol extracts/fractions of Indigofera argentea Berm. f. (whole plant), a medicinal plant from Pakistan. Chemical profiling of I. argentea crude methanol extract was done via ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS) in both the positive and negative ionization modes. Standardin vitro bioassays were used to evaluate the enzyme inhibition potential against carbonic anhydrase, xanthine oxidase, and α-glucosidase. Additionally, nine dominant compounds as tentatively identified by UHPLC-MS profiling were docked against the tested enzymes to provide additional insights into the binding affinities against the target enzymes. UHPLC-MS chemical profiling showed the tentative presence of seventy-six secondary metabolites. The identified compounds include flavonoids and lithocholic acid derivatives of steroids in major amounts along with terpenes. Lithocholic acid derivatives were first reported from this plant and consider being potential candidates for treating diabetes. All extracts showed promising results against α-glucosidase with percentage inhibition of 82.8–21.2%, while for the xanthine oxidase the percentage inhibition values varying from 67.8–47.3%. Furthermore, moderate inhibition was observed against carbonic anhydrase. The methanolic extracts showed good inhibition against B. subtilis, K. pneumonia, P. vulgaris and P. aeruginosa as compared to Ciprofloxacin. Docking studies showed that atalanine showed higher inhibition affinity against the three studied enzymes as compared to morphine. Indigofera argentea showed promising enzyme inhibitory activities and can be considered as a potential source of bioactive secondary metabolites. Isolation of the bioactive compounds and further mechanistic studies could provide further insights into the biopharmaceutical potential of this plant as a nutraceutical and/or dietary supplement.

Sideritis species have been used for centuries for their antimicrobial, digestive, anti-ulcerogenic and anti-inflammatory properties. Therefore, in this study, it was aimed to evaluate the chemical composition, antioxidant and enzyme inhibitory activities of solvent extracts of S. leptoclada O. Schwarz & P.H. Davis, an endemic species. It was determined that methanol (MeOH) and water extracts contained high amounts of chlorogenic acid and verbascoside, while the ethyl acetate (EtOAc) extract contained high amounts of 4-hydroxybenzoic and vanilic acids. The water extract showed the highest antioxidant activity in almost all parameters. Inhibitory activity of the MeOH extract on tyrosinase was 1.04 mg/ml, which was the highest value in this experiment. On the other hand, in α-amylase inhibitory assay, the EtOAc extract showed an activity of 2.21 mg/ml. Docking analysis showed that verbascoside can be an effective tyrosinase and α-amylase inhibitory agent.

Allium ursinum L. is a perennial herbaceous plant belonging to the Alliaceae family. Several classes of bioactive compounds have been isolated from A. ursinum so far, among them sulfur and phenolic compounds as quantitatively the most distributed constituents, responsible for pharmaceutical effects of the plant. Small amounts of steroidal glucosides, lecitins, fatty acids and several amino acids, as well as the essential oil are also present in A. ursinum. Th is plant species is characterized by a long history of use in traditional medicine in the prevention and treatment of cardiovascular disease, as digestive stimulant, antimicrobial agent, as a remedy in respiratory problems, insomnia and fainting. Despite its widespread use for medicinal purposes since the ancient time, studies referring to its pharmacological activity are still lacking. In this review, we summarized the current knowledge related to the phytochemical and pharmacological properties of Allium ursinum. Th is study may be a starting point for future researches in this field, which would fully clarify therapeutic potential of A. ursinum and make it a possible candidate for medicinal product.

Renal diseases have been documented as one of the massive health challenges, ranked as the 12th most common cause of death globally. This study was carried out to assess the chemopreventive effects of Vernonia amydalina on nitrobenzene mediated renal damage in rats. Rats were exposed to 100 mg/kg body weight of nitrobenzene via oral administration and treated with 200 mg/kg body weight (BW) and 400 mg/kg BW of methanol leaf extract of Vernonia amydalina (MLVA) and Vitamin E for 14 consecutive days. Nitrobenzene significantly induced a renal injury with a significant increase in the serum levels of urea and creatinine with the concomitant altered serum electrolyte profile. Also, nitrobenzene mediated the oxidative stress and lipid peroxidation with a significant increase in the renal level of malondialdehyde (MDA), hydrogen peroxide (H2O2), with a concomitant decrease in the level of reduced glutathione (GSH), Catalase (CAT) and Superoxide dismutase (SOD). Furthermore, an inflammation was observed in the nitrobenzene-treated rats with the elevated level of nitric oxide (NO) and myeloperoxidase (MPO). However, the treatment with methanol leaf extract of Vernonia amydalina reversed all the nitrobenzene-associated renal damage, electrolyte imbalance, oxidative stress, lipid peroxidation, inflammation and altered antioxidant defence system. Taken together, methanol leaf extract of Vernonia amydalina offers protection which may be beneficial for the treatment and management of kidney diseases or other related disorders via enhancing the serum electrolyte homeostasis, protecting the structural integrity of the kidney, antioxidant, anti-inflammatory mechanisms.

Pharmacological studies have indicated that flavonoids are crucial compounds to eliminate drug resistance. In this report, the activity of ethyl acetate (EAE), methanol (ME) and water (WE) extracts of Coronilla varia L. on antioxidant and enzyme inhibitory activities, DNA protective effects, antiproliferative activities, apoptotic; autophagic and telomerase gene activity analysis in breast cancer cells and inhibitory effects on cell migration ability of malignant breast cancer cells were examined. In addition, HPLC-MS-MS was used for detection of chemical profiles of all extracts. Results showed that the highest concentration of the bioactive components was detected in EAE (50.86 mg GAE/g for phenolics and 25.66 mg RE/g for flavonoid). Also, EAE displayed significant antioxidant properties in radical scavenging and reducing power assays. Regarding enzyme inhibitory effects, EAE and ME were more active than WE. Some significant compounds such as, vitamin B5, riboflavin, citric acid, and isoflavonoid derivate – medicarpin, noscapine were detected only in WE. Apigenin was determined in all extracts. WE indicated the most shield effect on pDNA against oxidative damage. Half-maximal inhibitory concentrations of extracts on breast cancer cells were calculated with MTT cell viability test. Bax gene was up-regulated and anti-apoptotic gene known as Bcl-2 was down-regulated on MDA-MB-231 cells after treated with WE. TERT-1 gene was down-regulated after treated with EAE and ME for MDA-MB-231 and MCF-7 cells, respectively. Cell migration ability of both MDA-MB-231 and MCF-7 cells was prevented with EAE and ME. A more effective treatment strategy can be applied by combining these extracts with commercial chemotherapy drugs which cause apoptosis and cell migration inhibition in vitro.

In this study, it was aimed to determine the in vitro antioxidant and enzyme inhibitory activities of methanol (MeOH) extracts isolated from Onosma gracilis (Trautv.) and O. oreodoxa (Boiss. & Heldr.). O. oreodoxa was found to be richer in both phenolics and flavonoids than O. gracilis. The amounts of total phenolics and flavonoids in O. oreodoxa were 53.76 mg GAEs/g and 25.29 mg QEs/g, respectively. In addition to spectrophometric analysis, in chromatographic analyzes, twenty-four and twenty-six compounds were identified in O. gracilis and O. oreodoxa, respectively. High amounts of hesperidin (6647.2 and 5260.75 µg/g extract, respectively), hyperoside (7153.26 and 10216.74 µg/g extract, respectively) and rosmarinic acid (21824.33 and 87493.19 µg/g extract, respectively) were found in O. gracilis and O. oreodoxa. While O. oreodoxa showed higher activity in cupric reducing antioxidant power (CUPRAC), ferric reducing antioxidant power (FRAP), phosphomolybdenum, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and ferrous ion chelating assays (324.22, 175.41, 719.50, 125.60 mg TEs/g extract and 25.11 mg EDTAEs/g extract, respectively), ABTS radical scavenging activity of O. gracilis (164.55 mg TEs/g extract) was higher than that of O. oreodoxa. O. gracilis also exhibited higher inhibitory activity on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) (2.57 mg GALAEs/g extract) and α-glucosidase (1674.24 mg ACEs/g extract). On the other hand, the sample showing the most effective inhibition on α-amylase and tyrosinase was O. oreodoxa (417.34 mg ACEs/g extract and 136.18 mg KAEs/g extract, respectively). As a result of the molecular docking analysis performed to determine the contribution of hesperidin, hyperoside and rosmarinic acid to the enzyme inhibitory activity, the binding affinity and inhibition constant of hyperoside to all enzymes were quite high and therefore it was concluded that it may be the compound that contribute to the activity.

Lathyrus species are economically important as food, fodder, and folk medicine. The antioxidant properties (radical scavenging effectiveness, reducing power potentials, metal chelating ability, phosphomolydenum capacity) phytochemical characterization (phenolic composition), and enzyme inhibition abilities of the water and ethyl acetate extracts of Lathyrus czeczottianus (LC) were tested. The phenolic ingradients of LC extracts were evaluated by HPLC-DAD (High-performance liquid chromatography with diode array detector). Chlorogenic acid, epicatechin, and benzoic acid were found as main phenolic compounds in both extracts. Generally, the water extract revealed strong antioxidant potential. The antioxidant effectiveness could be explained by high total phenolic level in the extract. Regarding enzyme inhibitory results, the ethyl acetate extract indicated good inhibitory activities on cholinesterase (for AChE: Acetylccholinesterase 1.15 mg galathamine equivalents (GALAE/g extract) and for BChE: Butyrylcholinesterase 0.19 mg GALAE/g extrac), tyrosinase (54.48 mg kojic acid equivalents (KAE/g)), and alpha-amylase (0.34 mmol acarbose equivalents (ACEs/g)), while the water extract had just good inhibition on alpha-glucosidase (6.49 mmol ACEs/g). In conclusion, L. czeczottianus could be good valuable of bioactive molecules for pharmaceuticals, food and agriculture, and nutraceutical applications. (C) 2020 SAAB. Published by Elsevier B.V. All rights reserved.

The genus Salvia is regarded as an important medicinal plant and also as spice worldwide. Current report might be counted as one of the first investigations to reveal the enzyme inhibitory and antiglycation activities, together with phenolic and antioxidant profiles of 80% methanolic extract prepared from the aerial parts of S.virgata (SVM). Furthermore, the bioavailability parameters of major phenolic compounds in SVM were evaluated. An in vitro human digestion simulation model composed of both gastric and intestinal phases was used for this purpose. Total phenolic, phenolic acid and flavonoid components of each of these phases were calculated in order to assess the phenolic profile of the samples. In addition, quantitative analysis of major bioactive compounds (rutin and rosmarinic acid), before and after the simulation, was practiced by employing High Performance Thin Layer Chromatography (HPTLC) system. Moreover, the potential of non-digested (ND) and bioavailable (IN) phases on the inhibition of diabetes-related enzymes (α-amylase and α-glucosidase) was determined. Also, the inhibitory effect of the samples on the advanced glycation end products (AGEs), formed due to hyperglycemia, was detected. In addition, cholinesterase enzyme inhibition activity of both ND and IN samples was determined. Since, the role of oxidative stress on diabetes and neurodegenerative diseases is well-known, the antioxidant potential of the samples was also estimated by different methods: DPPH and DMPD tests for free radical scavenging activity, FRAP and CUPRAC tests for metal reducing activity and total antioxidant capacity test, as well. The results showed that total phenolic contents, antioxidant potential and diabetes-related and cholinesterase enzymes inhibition of the bioavailable phase were lower than non-digested sample. Besides, in vitro human digestion simulation system had a declining influence on the concentrations of the major bioactive metabolites (rutin and rosmarinic acid).

Abstract: Breast cancer is the most frequent diagnosed cancer in women and the second most common form of cancer, causing death after lung cancer, all across the globe at an alarming rate. The level of estrogens, in breast cancer tissues of postmenopausal women is 10-40 folds higher than the non-carcinogenic breast tissues. As a result of this greater level of estrogen, breast tissue becomes more prone to develop breast cancer; mainly estradiol plays a significant role in the initiation and development of hormone dependent breast cancer. Androstenedione, Adrenal dehydroepiandrosterone sulfate and estrone-sulfate also plays an important role of precursor for estrogen biosynthesis. Estrogens deprivation exhibits an attractive phenomena in the advancement of most ideal therapeutics for the treatment of breast cancer. Inhibition of aromatase and sulphatase emerged as attractive therapy for the treatment of hormone dependent breast cancer via deprivation of estrogen by different pathways. The cocktail of aromatase and sulphatase inhibitors known as dual aromatase-sulphatase inhibitors (DASIs) emerged as an attractive approach for the effective estrogen deprivation. The present review article focused on the journey of dual aromatase-sulphatase inhibitors from the beginning to till date (2020). Keeping in view the key observations, this review may be helpful for medicinal chemists to design and develop new and efficient dual aromatase-sulphatase inhibitors for the possible treatment of hormone-related breast cancer.

The current research investigated the chemical profiling and biological activities of Emex australis Steinh. aerial and fruit parts (methanol and dichloromethane-DCM extracts). Chemical composition was established by determining the amounts of phenolic and flavonoid contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolites profiling to understand the observed biological activities. Antioxidant evaluation was performed utilizing six different assays (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation). Moreover, enzyme inhibition abilities against cholinesterases, α-amylase, α-glucosidase, and tyrosinase were also determined. The fruit methanol extract contained the highest phenolic (157.96 mg GAE/ g extract) and flavonoid contents (41.43 mg QE/g extract), which could justify the observed significant antioxidant (except metal chelating), α-amylase, α-glucosidase, and tyrosinase inhibitory potentials. The other extracts were active against cholinesterases and tyrosinase. The HPLC-PDA polyphenolic analysis quantified a number of 11 phenolic secondary metabolites. The fruit-MeOH extract was found to quantify the maximum phenolics with catechin (4.27 μg/g extract) and gallic acid (4.84 μg/g extract) in higher amounts. Similarly, rutin present in maximum quantity in the aerial-MeOH extract (2.93 μg/g extract). Furthermore, the UHPLC-MS study of aerial and fruit methanol extracts reveals the existence of 22 secondary metabolites, most of which were flavonoid derivatives. Besides that, Pearson coefficient analysis (PCA) was also carried to determine a possible correlation between bioactive contents and observed biological assays. Thus, it is concluded that E. australis extracts contain important classes of secondary metabolites and also exhibited considerable antioxidant and inhibition potential against clinically relevant enzymes.

Since the advent of modern-day screening collections in the early 2000s, various aspects of our knowledge of good handling practices have continued to evolve. Some early practices, however, continue to prevail due to the absence of defining data that would bust the myths of tradition. The lack of defining data leads to a gap between plate-based screeners, on the one hand, and compound sample handling groups, on the other, with the latter being the default party to blame when an assay goes awry.In this paper, we highlight recommended practices that ensure sample integrity and present myth busting data that can help determine the root cause of an assay gone bad. We show how a strong and collaborative relationship between screening and sample handling groups is the better state that leads to the accomplishment of the common goal of finding breakthrough medicines.

Syzygium cumini L. (Jamun) is a Pakistani indigenous plant, which exhibits various diseases biological activities including antidiabetic, antiulcer, hepatoprotective, and even diuretic. The present work was carried out to provide a scientific justification to its use in folk medicine. In the current research work, the crude methanol extract and subsequent fractions of S. cumini fruits were subjected to phytochemical studies, along with urease, α-glucosidase, and phosphodiesterase inhibition profiling. Results showed that the plant is a rich source of various classes of compounds such as alkaloids, steroids, flavonoids, carbohydrates, phenols, glycosides, saponins, and tannins. In addition, results indicated that the crude extract and fractions significantly inhibit the aforementioned enzymes at tested concentrations. The observed urease inhibitory activity (IC50 values) of methanol, ethyl acetate, n-butanol, and chloroform were 10.17 ± 1.00, 7.09 ± 2.00, 8.32 ± 1.76, and 12.23 ± 1.09 µg, respectively. Similarly, the crude methanol extract, ethyl acetate, chloroform, and n-butanol factions exhibited significant α-glucosidase inhibitory potential with IC50 values of 129.98 ± 1.23, 702.74 ± 1.65, 430.21 ± 1.98, and 650.11 ± 1 0.00 µg, respectively, as compared to the standard. On the other hand, the ethyl acetate and n-butanol factions showed excellent phosphodiesterase inhibitory effect with IC50 values of 270.77 ± 1.98 and 87.09 µg, respectively. The antagonistic effect of these samples is attributed to the presence of different phytochemicals. Moreover, the inhibition of these enzymes provided a sound scientific backup to the mentioned folklores.

Medicinal plants are a key source of important natural products, which are used for discovery of new drugs. The aim of this work was to explore the natural compounds having in vitro antiglycation and lipoxygenase inhibition potential. Consequently, compounds such as di-naphthodiospyrols A (1), di-naphthodiospyrols B (2), di-naphthodiospyrols C (3), di-naphthodiospyrols D (4), di-naphthodiospyrols E (5), di-naphthodiospyrols F (6), di-naphthodiospyrols g (7), 8-hydroxyisodiospyrin (8), and diospyrin (9) were isolated for the first time from Diospyros lotus Linn. In vitro antiglycation and lipoxygenase inhibitory activity results indicated that compound 4 exhibits the highest antiglycation activity with inhibition IC50 = 287.45 ± 1.60 μM), followed by compound 5 with an IC50 value of 248.72 ± 2.09 μM respectively. Similarly, compounds 7 and 8 showed moderate activity with IC50 values of 234.87 ± 2.00 , and 228.98 ± 1.98 μM, respectively, when compared with rutin (IC50 = 295.22 ± 1.55 μM). . The isolated compounds (1‒9) were also subjected to lipoxygenase inhibitory activity. Results revealed that secondary metabolites (1‒7) exhibit an excellent inhibitory effect against lipoxygenase, with IC50 values of 90.35 ± 0.96, 87.09 ± 1.00, 84.01 ± 1.01, 40.49 ± 0.49, 44.70 ± 0.49, 79.04 ± 0.86, and 62.09 ± 0.18 μM, for compounds 1, 2, 3, 4, 5, 6, and 7, respectively. The standard drugs Baicalein and Tenidap sodium exhibited inhibitory effect with IC50 values of 40.98 ± 0.08 μM and 23.00 ± 0.05 µM, respectively. Within this context, compounds with high inhibition potential against lioxygenase can be regarded as lead compounds in drug discovery. Furthermore, these compounds can be further studied as antiglycating agents to increase the chemical space for new chemical entities having drug-like properties.

Compound-dependent assay interferences represent a continued burden in drug and chemical probe discovery. The open-source National Institutes of Health/National Center for Advancing Translational S...

The aim of the present study was focused on experimental analysis for medicinal use of Micromeria biflora Benth. The plant was collected and subjected to extraction and fractionation; the chloroform fraction resulted in the isolation of a new constituent salicylalazine, using preparative HPLC. The Chemical structure of salicylalazine was confirmed through NMR and high-resolution mass spectrometry. Salicylalazine was evaluated (in vitro) against various biological targets such as urease, phosphodiesterase-1, tyrosinase, and anti-glycation studies. Furthermore, the binding orientation and interaction pattern of salicylalazine with crucial amino acid residues of the respective targets were used to explore the mechanism of enzymes inhibition. Results indicated that salicylalazine caused potent urease inhibition with an IC50 value of 12.4 ± 1.10 µM, in comparison of standard thiourea (IC50 = 21.0 ± 0.21 µM). The compound exhibited excellent inhibition potential against tyrosinase (89.4%), phosphodiesterase-1 (94.7%) compared to the standards kojic acid (86.3%) and EDTA (86.4%), respectively. Besides, salicylalazine possessed good anti-glycation activity with % inhibition of 86% and IC50 value of 248.7 ± 2.09 µM, compared to the standard Rutin (96%, IC50 value of 295 ± 3.14). Thus, it is concluded that salicylalazine, the active constituent Micromeria biflora Benth, exhibited remarkable in vitro inhibition of urease, phosphodiesterase-1, tyrosinase, and anti-glycation.

The study aimed to validate the folkloric medicinal uses of Viburnum grandiflorum. The column chromatography led to the isolation of a compound from the chloroform soluble fraction of V. grandiflorum which was characterized as 2, 3-dihydro-2-(4ʹ-hydroxy, 3ʹ-methoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl) 7-hydroxybenzofuran (benzofuran) on the basis of various spectroscopic techniques. When benzofuran was studied for xanthine oxidase inhibition, it caused significant concentration dependent inhibition of the enzyme with IC50: 49.52 µM, however, it was found less potent than standard xanthine inhibitor allopurinol (IC50: 0.59 µM). Binding orientation and binding energy of benzofuran and allopurinol were predicted via docking studies. Docking simulations revealed that both studied molecules interact with key amino acid residues through hydrogen bond (Arg 880, Glu 1261, Thr1010 with Allopurinol & Thr 1010 with benzofuran) and hydrophobic interactions (Phe914, Phe1009 with Allopurinol & Phe 910, Phe 1009 with benzofuran). A fair correlation between the computed binding energy and experimental values was observed. Thus, it is concluded that the isolated compound, benzofuran had inhibition on xanthine oxidase, need further detail studies.

Urease is a metallo-protein in which two nickel (Ni) atoms are present at the active site. It is found in all the organisms such as, bacteria, fungi, plants, and in algae. Urease enzymes are also involved in catalyzing the hydrolysis of urea into CO2 and NH3. Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. Current research work aimed to purify the three di-naphthodiospyrols namely; 5,4 -dihydroxy-1-methoxy-6,6 -dimethyl7,3-binaphthyl-1,4,5,8-tetraone (1), 5,8 -dihydroxy-5-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4 -tetraone (2) and 8,5,8-trihydroxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (3) from the chloroform fraction of Diospyros lotus roots. The pure constituents (1-3) were evaluated for their urease inhibitory activity. Compounds (1-3) exhibited potent activity with IC50 value of 28.27 ± 1.68, 20.57 ± 2.00, 27.12 ± 2.45 µM respectively, when compared with standard thiourea (IC50 = 21.23 ± 0.12 µM). The pure isolated compounds (1-3) were also subjected to in silico studies to know their binding pattern with enzyme. The binding orientation and interactions with the important residues of urease enzyme revealed that the three compounds inactivate the enzyme activity by interacting with Ni bi-center as well as with the tailpiece residues.

Background: Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18β-Glycyrrhetinic acid (GA) is the main active metabolite of GL. Objective: Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for promising lead compound for further identification of anti-HCV terpenoid candidate. Methods: GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation, etc. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis were performed via “pkCSM” and “SwissADME” platforms. Results: Eighteen GA derivatives were synthesized and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with IC50 value of 0.79 μM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. Conclusion: Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidate.

Stem bark of Sterculia setigera Delile, family Sterculiaceae, is used in traditional medicine in Sudan and other African countries to treat various diseases. This study aimed to investigate the chemical constituents, antioxidant, enzyme inhibition and antiproliferative activities of stem bark extracts and an isolated compound. Compounds were extracted using hexane and dichloromethane: ethanol (DE) (1:1). Chromatographic techniques were performed to characterize the phenolic compounds. We isolated lupeol as a bioactive compound in S. setigera from DE extract. The antioxidant and enzyme inhibitory properties of each extract were evaluated. The antiproliferative activity of the DE extract was determined. Results showed that five known compounds namely; procyanidins as dimer B, trimer C1 and tetramer, 3,4-dimethoxyphenol s-D-apiofuranosyl (1″→6″)- s -D-glucopyranoside and (+)- catechin were identified or tentatively elucidated, in addition to the isolation and characterization of lupeol. DE extract showed significantly (p

The plants of the Erythrina genus possess tremendous pharmacological properties and thus are utilized in traditional medicines owing to their bioactivities. In the present study, methanolic extract (EsM) of flowers of Erythrina suberosa Roxb. and its fractions (n-hexane (EsH), chloroform (EsC) and aqueous (EsW) parts) were tested for preliminary phytochemical analysis, antioxidant and urease inhibition activities. The EsM extract was found to be most active for antioxidant activity, whereas the EsH extract showed the highest anti-urease potential with an inhibition value of 62.9 % (at a concentration of 100 µg/ml), while the other extracts were least active. The EsH extract being most active against urease enzyme, was further subjected to gas chromatography-mass spectrometry (GC-MS) analysis, which revealed the tentative presence of 18 secondary metabolites of various classes. Furthermore, the in-silico studies of the major compounds as detected in EsH extract by GC-MS analysis were performed to correlate the potential interaction of compounds with the active site of the enzyme. The selected compounds were docked against the urease enzyme, and their affinities were compared. Binding affinity data and interaction patterns of all the studied phytochemicals indicated that these compounds could inhibit urease enzyme synergistically and can be further studied to prevent ulcer and related problems. It is, therefore concluded that E. suberosa flowers possess interesting antioxidant and anti-urease potential and thus could further be adopted for industrial and biopharmaceutical applications.

Resumen Cuba tiene una larga tradición en el control de epidemias. En Cuba, se presentó la situación de la covid-19 seis meses después de su comienzo. Se tomaron medidas diferentes para controlar la pandemia: diversas intervenciones comunitarias, el aislamiento de contactos de casos sospechosos y de personas regresando del extranjero, la aplicación de estrategias terapéuticas. La primera fase epidémica tuvo un pico a finales de abril y en mayo presentó el mayor número de casos acumulados. Hubo un control de la epidemia en junio y julio. Se inició la desescalada a mediados de junio. Se constató un aumento de casos en el mes de agosto, que se interpreta como un rebrote de la misma.

Stachys species have traditionally been used by the people for thousands of years to treat various diseases. In this study, the chemical composition and enzyme inhibitory activities of the various extracts of Stachys germanica subsp. heldreichii (Boiss.) Hayek (Lamiaceae), which were isolated using solvents with different polarities, were investigated. Antioxidant activities of the extracts were analyzed by phosphomolybdenum, radical scavenging [on DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)], reducing power [CUPRAC (cupric-reducing antioxidant capacity) and FRAP (ferric reducing antioxidant power)] and ferrous ion chelating tests, while tyrosinase and α-amylase were used for enzyme inhibitory activity assays. RACI (relative antioxidant capacity index) analysis showed that the ranking of the extracts was MeOH (methanol) > Water > EtOAc (ethyl acetate). In ABTS radical scavenging (2.26 mg/mL), phosphomolybdenum (1.68 mg/mL), CUPRAC (1.35 mg/mL) and FRAP tests (0.75 mg/mL), the MeOH extract showed the highest activity. However, the water extract exhibited the highest activity in DPPH radical scavenging and ferrous ion chelating tests. Tyrosinase inhibition potential of the MeOH extract was significant (IC50: 2.90 mg/mL). On the other hand, in α-amylase inhibition assay, EtOAc extract showed the highest activity (2.24 mg/mL). Amount of phenolics was higher in all extracts than flavonoids. MeOH extract was the richest one in phenolics and flavonoids. The major compounds of the extracts were chlorogenic acid and verbascoside. Pearson correlation analysis showed that these compounds were responsible especially for radical scavenging activity. Correlation between chemical composition and activity findings showed that verbascoside and apigenin contributed to tyrosinase and α-amylase inhibition, respectively.

Vitex agnus-castus, is a famous botanical remedy and a nutritional supplement to manage a panoply of human ailments. The impact of V. agnus-castus fruits aqueous-alcoholic crude extract and its fractions were evaluated for possible in vitro antioxidant, anti-inflammatory, and in vivo antitumor efficacy. The inhibitory action of the tested extract and fractions on cyclooxygenase enzymes (COX-1&2) were assessed. In addition, scavenging ability on different radicals and molecule were evaluated together with the chelating character, lipid peroxide inhibitory action and reducing power. The efficient fraction was then evaluated for possible anti-tumor agent in immunomodulatory model (Ehrlich Ascites Carcinoma). The aqueous-alcoholic extract and ethyl acetate fractions significantly (p

Salvia sclarea L. or clary sage is cultivated worldwide in temperate and sub-tropical climates, as an ornamental and essential oil (EO) bearing plant. EO is obtained from fresh spikes in full flowering stage and is recognized as an important commercial product for food, beverage and cosmetic industries. This study investigated the EO composition of S. sclarea grown in Serbia (Southeast Europe) obtained by two different methods, steam (SD) and hydrodistillation (HD). GC-MS analysis identified oxygenated monoterpenes as the main class of compounds for all EOs (between 81.8% and 88.2% depending on the distillation process). The most abundant oxygenated monoterpenes were linalyl acetate and linalool. In addition, in vitro antimicrobial (modified resazurin microtitre-plate assay) and antioxidant activities (DPPH· assay) and total polyphenol content of obtained EOs were also evaluated. According to the assay used for the evaluation of the antibacterial activity, Gram-negative bacteria were more sensitive to S. sclarea EO in comparison to Gram-positive bacteria. EOs exhibited low antioxidant capacity, below 3% neutralized DPPH· radicals, reaching up to approximately 400 µg AAE mL-1. This study also investigated a possibility for predicting retention indices (RIs) of compounds isolated from EOs. In total, 78 experimentally obtained RIs were applied to construct the prediction model. The quantitative structure-chromatographic retention relationship (QSRR) model was used to anticipate the experimentally obtained RIs. Five molecular descriptors were selected by factor analysis and genetic algorithm to predict RIs. The obtained accuracy of the QSRR model reached r2 = .912, which showed that these models might be applied for predicting retention indices. This is the accepted peer-reviewed version of the published article [https://doi.org/10.1002/ffj.3684]. Due to publisher`s embargo it will be available after 2 November 2022.