In Vitro and Molecular Docking Evaluation of the Anticholinesterase and Antidiabetic Effects of Compounds from Terminalia macroptera Guill. & Perr. (Combretaceae).

Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From 1H and 13C NMR data, the compounds were identified as 3,3'-di-O-methyl ellagic acid (1), 3,3',4'-tri-O-methyl ellagic acid-4-O-ß-D-xylopyranoside (2), 3,3',4'-tri-O-methyl ellagic acid-4-O-ß-D-glucopyranoside (3), 3,3'-di-O-methyl ellagic acid-4-O-ß-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1-4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3'-di-O-methyl ellagic acid, with IC50 values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds (1-5). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for 1-11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of -4.03 to -10.20 kcalmol-1. Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.

The modular architecture of sigma factors in cyanobacteria: a framework to assess their diversity and understand their evolution.

BACKGROUND: Bacterial RNA polymerase holoenzyme requires sigma70 factors to start transcription by identifying promoter elements. Cyanobacteria possess multiple sigma70 factors to adapt to a wide variety of ecological niches. These factors are grouped into two categories: primary sigma factor initiates transcription of housekeeping genes during normal growth conditions, while alternative sigma factors initiate transcription of specific genes under particular conditions. However, the present classification does not consider the modular organization of their structural domains, introducing therefore multiple functional and structural biases. A comprehensive analysis of this protein family in cyanobacteria is needed to address these limitations. RESULTS: We investigated the structure and evolution of sigma70 factors in cyanobacteria, analyzing their modular architecture and variation among unicellular, filamentous, and heterocyst-forming morphotypes. 4,193 sigma70 homologs were found with 59 distinct modular patterns, including six essential and 29 accessory domains, such as DUF6596. 90% of cyanobacteria typically have 5 to 17 sigma70 homologs and this number likely depends on the strain morphotype, the taxonomic order and the genome size. We classified sigma70 factors into 12 clans and 36 families. According to taxonomic orders and phenotypic traits, the number of homologs within the 14 main families was variable, with the A.1 family including the primary sigma factor since this family was found in all cyanobacterial species. The A.1, A.5, C.1, E.1, J.1, and K.1 families were found to be key sigma families that distinguish heterocyst-forming strains. To explain the diversification and evolution of sigma70, we propose an evolutionary scenario rooted in the diversification of a common ancestor of the A1 family. This scenario is characterized by evolutionary events including domain losses, gains, insertions, and modifications. The high occurrence of the DUF6596 domain in bacterial sigma70 proteins, and its association with the highest prevalence observed in Actinobacteria, suggests that this domain might be important for sigma70 function. It also implies that the domain could have emerged in Actinobacteria and been transferred through horizontal gene transfer. CONCLUSION: Our analysis provides detailed insights into the modular domain architecture of sigma70, introducing a novel robust classification. It also proposes an evolutionary scenario explaining their diversity across different taxonomical orders.

In Vitro and In Silico Evaluation of Anticholinesterase and Antidiabetic Effects of Furanolabdanes and Other Constituents from Graptophyllum pictum (Linn.) Griffith.

Graptophyllum pictum is a tropical plant noticeable for its variegated leaves and exploited for various medicinal purposes. In this study, seven compounds, including three furanolabdane diterpenoids, i.e., Hypopurin E, Hypopurin A and Hypopurin B, as well as with Lupeol, ß-sitosterol 3-O-ß-d-glucopyranoside, stigmasterol 3-O-ß-d-glucopyranoside and a mixture of ß-sitosterol and stigmasterol, were isolated from G. pictum, and their structures were deduced from ESI-TOF-MS, HR-ESI-TOF-MS, 1D and 2D NMR experiments. The compounds were evaluated for their anticholinesterase activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BchE), as well as their antidiabetic potential through inhibition of α-glucosidase and α-amylase. For AChE inhibition, no sample had IC50 within tested concentrations, though the most potent was Hypopurin A, which had a percentage inhibition of 40.18 ± 0.75%, compared to 85.91 ± 0.58% for galantamine, at 100 µg/mL. BChE was more susceptible to the leaves extract (IC50 = 58.21 ± 0.65 µg/mL), stem extract (IC50 = 67.05 ± 0.82 µg/mL), Hypopurin A (IC50 = 58.00 ± 0.90 µg/mL), Hypopurin B (IC50 = 67.05 ± 0.92 µg/mL) and Hypopurin E (IC50 = 86.90 ± 0.76 µg/mL). In the antidiabetic assay, the furanolabdane diterpenoids, lupeol and the extracts had moderate to good activities. Against α-glucosidase, lupeol, Hypopurin E, Hypopurin A and Hypopurin B had appreciable activities but the leaves (IC50 = 48.90 ± 0.17 µg/mL) and stem (IC50 = 45.61 ± 0.56 µg/mL) extracts were more active than the pure compounds. In the α-amylase assay, stem extract (IC50 = 64.47 ± 0.78 µg/mL), Hypopurin A (IC50 = 60.68 ± 0.55 µg/mL) and Hypopurin B (IC50 = 69.51 ± 1.30 µg/mL) had moderate activities compared to the standard acarbose (IC50 = 32.25 ± 0.36 µg/mL). Molecular docking was performed to determine the binding modes and free binding energies of Hypopurin E, Hypopurin A and Hypopurin B in relation to the enzymes and decipher the structure-activity relationship. The results indicated that G. pictum and its compounds could, in general, be used in the development of therapies for Alzheimer's disease and diabetes.

Autotrophic denitrification supported by sphalerite and oyster shells: Chemical and microbiome analysis.

This research evaluated the metal-sulfide mineral, sphalerite, as an electron donor for autotrophic denitrification, with and without oyster shells (OS). Batch reactors containing sphalerite simultaneously removed NO3- and PO43- from groundwater. OS addition minimized NO2- accumulation and removed 100% PO43- in approximately half the time compared with sphalerite alone. Further investigation using domestic wastewater revealed that sphalerite and OS removed NO3- at a rate of 0.76 ± 0.36 mg NO3--N/(L · d), while maintaining consistent PO43- removal (∼97%) over 140 days. Increasing the sphalerite and OS dose did not improve the denitrification rate. 16S rRNA amplicon sequencing indicated that sulfur-oxidizing species of Chromatiales, Burkholderiales, and Thiobacillus played a role in N removal during sphalerite autotrophic denitrification. This study provides a comprehensive understanding of N removal during sphalerite autotrophic denitrification, which was previously unknown. Knowledge from this work could be used to develop novel technologies for addressing nutrient pollution.

In vitro α-glucosidase inhibitory activity of isolated compounds and semisynthetic derivative from aerial parts of Erythrina senegalensis DC.

The current study was conducted to isolate the phytoconstituents from Erythrina senegalensis leaves and stem bark and evaluate their inhibitory activity against α-glucosidase, digestive enzyme related to diabetes mellitus. Phytochemical investigation of the leaves resulted in the isolation of three saponins (3-5), two triterpenoids (7 and 8) and two steroids (10a and 10b) as inseparable mixture, while one saponin (6), one triterpenoid (9) and one mixture of two cinnamates (2a and 2b) were isolated from the stem bark. Except for compounds 2 b, 7, 8, 10a and 10 b all the isolated compounds are reported here for the first time from the genus Erythrina. Acetylation of the mixture of two cinnamates (2a and 2b) led to a new diester derivative (1) trivially called erythrinamate. The extracts and pure compounds (3, 4, 6) showed good α-glucosidase inhibitory activity compared to the standard drug acarbose. The findings suggest that saponins of E. senegalensis could be used to develop potential anti-hyperglycemic drugs.

Euphol from Tapinanthus sp. Induces Apoptosis and Affects Signaling Proteins in Glioblastoma and Prostate Cancer Cells

BACKGROUND: Plants play an important role in cancer therapy. They are source of natural molecules which can induce apoptosis in cancer cells by affecting molecular mechanisms implicated in cancer progression. The MAP Kinase/ERK1/2 and PI3K/AKT signaling pathways are two classical signaling pathways implicated in cancer progression and constitute therapeutic targets against cancer. This study aimed to evaluate the effect of euphol on MAP Kinase/ERK1/2 and PI3K/AKT signaling pathways in glioblastoma and prostate cancer cells. Euphol is a tetracyclique triterpene alcohol isolated from Tapinanthus sp. which is a hemi parasitic plant belonging to Loranthaceae family. METHODS: Plant powder was extracted by maceration and euphol was isolated and described using respectively column chromatography separation on silica gel and spectroscopic data. Cytotoxic effect of euphol was evaluated using XTT assay and its effect on MAP Kinase/ERK1/2 and PI3K/AKT protein expression was investigated by Western immunoblot analysis. Apotosis was analyzed by evaluating caspase-3/7 activity. RESULTS: Our investigations demonstrated that this compound has an important cytotoxic effect on C6 and U87 MG glioblastoma (GBM) cells and PC-3 prostate cancer cells. Furthermore, euphol-induced apoptosis revealed by elevated caspase 3/7 activity, was correlated with a significant inhibition of MAP kinase/Erk 1/2 and PI3K/Akt signaling pathway in glioblastoma U87 MG cells. The reverse effect was observed in C6 glioblastoma cells, where apoptosis was correlated with a long-lasting activation of Erk 1/2.  In PC-3 cells, euphol had no or limited effect on Erk 1/2 and Akt activity. CONCLUSION: These results indicate that euphol induces cell death in glioblastoma and prostate cancer cells and regulates significantly Erk1/2 and Akt activity in glioblastoma cells.

A novel pentacyclic triterpene acid from the stem barks of Combretum fragrans F. Hoffm (Combretaceae).

A phytochemical study was carried out on stem bark of Combretum fragrans F. Hoffm., a medicinal plant belonging to the Combretaceae family and used traditionally in the treatment of various ailments. Column chromatography separation on silica gel of the crude methanol extract from stem barks of C. fragrans led to the isolation of a new pentacyclic triterpene acid, with a 3,6-epoxide bridge and trivially named as fragransinic acid (1), along with four known compounds: betulin (2), betulinic acid (3), bellericagenin B (4) and a mixture of ß-sitosterol (5) and stigmasterol (6). Structures were elucidated by extensive spectroscopic analyses including 1D and 2D NMR, mass spectrometry as well as by comparison with literature data. The above compounds were isolated for the first time from C. adenogonium. Implications for chemosystematics and traditional medicine were briefly discussed.

Antibiofilm and Anti-Quorum Sensing Potential of Cycloartane-Type Triterpene Acids from Cameroonian Grassland Propolis: Phenolic Profile and Antioxidant Activity of Crude Extract.

Propolis is very popular for its beneficial health properties, such as antimicrobial activity and antioxidant effects. It is one of the most long-serving traditional medicines to mankind due to its interesting chemical diversity and therapeutic properties. The detailed chemical information of propolis samples is very necessary to guarantee its safety and for it to be accepted into health care systems. The phenolic profile of the hydroethanolic extract was determined using HPLC-DAD, and the antioxidant was evaluated using five complementary methods. Triterpenoids were isolated using column chromatography and characterized using 1H NMR and 13C NMR. The effects of the extract and the isolated compounds on quorum sensing mediated processes and biofilm formation in bacteria were evaluated. Protocatechic acid (40.76 ± 0.82 µg/g), 4-hydroxybenzoic acid (24.04 ± 0.21 µg/g), vanillic acid (29.90 ± 1.05 µg/g), quercetin (43.53 ± 1.10 µg/g), and luteolin (4.44 ± 0.48 µg/g) were identified and quantified. The extract showed good antioxidant activity in the DPPH•, ABTS•+, CUPRAC, and metal chelating assays, and this antioxidant effect was confirmed by cyclic voltammetry. 27-Hydroxymangiferonic acid (1), Ambolic acid (2), and Mangiferonic acid (3) were isolated from anti-quorum sensing activity at MIC, and it was indicated that the most active sample was the extract with inhibition diameter zone of 18.0 ± 1.0 mm, while compounds 1, 2, and 3 had inhibition zones of 12.0 ± 0.5 mm, 9.0 ± 1.0 mm, and 12.3 ± 1.0 mm, respectively. The samples inhibited the P. aeruginosa PA01 swarming motility at the three tested concentrations (50, 75, and 100 µg/mL) in a dose-dependent manner. The propolis extract was able to inhibit biofilm formation by S. aureus, E. coli, P. aeruginosa, C. albicans, and C. tropicalis at MIC concentration. Compound 1 proved biofilm inhibition on S. aureus, L. monocytogenes, E. faecalis, E. coli, and C. tropicalis at MIC and MIC/2; compound 2 inhibited the formation of biofilm at MIC on S. aureus, E. faecalis, E. coli, S. typhi, C. albicans, and C. tropicalis; and compound 3 inhibited biofilm formation on E. faecalis, E. coli, C. albicans, and C. tropicalis and further biofilm inhibition on E. coli at MIC/4 and MIC/8. The studied propolis sample showed important amounts of cycloartane-type triterpene acids, and this indicates that there can be significant intra-regional variation probably due to specific flora within the vicinity. The results indicate that propolis and its compounds can reduce virulence factors of pathogenic bacteria.

From a large-scale genomic analysis of insertion sequences to insights into their regulatory roles in prokaryotes.

BACKGROUND: Insertion sequences (ISs) are mobile repeat sequences and most of them can copy themselves to new host genome locations, leading to genome plasticity and gene regulation in prokaryotes. In this study, we present functional and evolutionary relationships between IS and neighboring genes in a large-scale comparative genomic analysis. RESULTS: IS families were located in all prokaryotic phyla, with preferential occurrence of IS3, IS4, IS481, and IS5 families in Alpha-, Beta-, and Gammaproteobacteria, Actinobacteria and Firmicutes as well as in eukaryote host-associated organisms and autotrophic opportunistic pathogens. We defined the concept of the IS-Gene couple (IG), which allowed to highlight the functional and regulatory impacts of an IS on the closest gene. Genes involved in transcriptional regulation and transport activities were found overrepresented in IG. In particular, major facilitator superfamily (MFS) transporters, ATP-binding proteins and transposases raised as favorite neighboring gene functions of IS hotspots. Then, evolutionary conserved IS-Gene sets across taxonomic lineages enabled the classification of IS-gene couples into phylum, class-to-genus, and species syntenic IS-Gene couples. The IS5, IS21, IS4, IS607, IS91, ISL3 and IS200 families displayed two to four times more ISs in the phylum and/or class-to-genus syntenic IGs compared to other IS families. This indicates that those families were probably inserted earlier than others and then subjected to horizontal transfer, transposition and deletion events over time. In phylum syntenic IG category, Betaproteobacteria, Crenarchaeota, Calditrichae, Planctomycetes, Acidithiobacillia and Cyanobacteria phyla act as IS reservoirs for other phyla, and neighboring gene functions are mostly related to transcriptional regulators. Comparison of IS occurrences with predicted regulatory motifs led to ~ 26.5% of motif-containing ISs with 2 motifs per IS in average. These results, concomitantly with short IS-Gene distances, suggest that those ISs would interfere with the expression of neighboring genes and thus form strong candidates for an adaptive pairing. CONCLUSIONS: All together, our large-scale study provide new insights into the IS genetic context and strongly suggest their regulatory roles.

Interaction network among factors involved in heterocyst-patterning in cyanobacteria.

The genetically regulated pattern of heterocyst formation in multicellular cyanobacteria represents the simplest model to address how patterns emerge and are established, the signals that control them, and the regulatory pathways that act downstream. Although numerous factors involved in this process have been identified, the mechanisms of action of many of them remain largely unknown. The aim of this study was to identify specific relationships between 14 factors required for cell differentiation and pattern formation by exploring their putative physical interactions in the cyanobacterium model Nostoc sp. PCC 7120 and by probing their evolutionary conservation and distribution across the cyanobacterial phylum. A bacterial two-hybrid assay indicated that 10 of the 14 factors studied here are engaged in more than one protein-protein interaction. The transcriptional regulator PatB was central in this network as it showed the highest number of binary interactions. A phylum-wide genomic survey of the distribution of these factors in cyanobacteria showed that they are all highly conserved in the genomes of heterocyst-forming strains, with the PatN protein being almost restricted to this clade. Interestingly, eight of the factors that were shown to be capable of protein interactions were identified as key elements in the evolutionary genomics analysis. These data suggest that a network of 12 proteins may play a crucial role in heterocyst development and patterning. Unraveling the physical and functional interactions between these factors during heterocyst development will certainly shed light on the mechanisms underlying pattern establishment in cyanobacteria.

Antimicrobial and α-glucosidase inhibitory activities of chemical constituents from Gardenia aqualla (Rubiaceae).

An aliphatic alkene namely pentapentacontene (4) was isolated for the first time from a natural source, Gardenia aqualla, along with fourteen other compounds including nonacosanol (1), tetratriacontanol (2), octatriacontanol (3), ß-sitosterol (5) and stigmasterol (6), daucosanol (7), ursolic acid (8), uvaol (9), 3ß,19α,23ß,24α-tetrahydroxyurs-12-en-28-oic acid (10), lupenone (11), oleanolic acid (12), vanillin (13), vanillic acid (14) and D-mannitol (15). α-glucosidase inhibitory assay revealed that MeOH and EtOAc extracts of leaves had the best activity with IC50 of 9.65 and 20.03 µg/ml respectively. All the tested compounds showed dose dependent inhibition of α-glucosidase and some of them were found to be comparable to acarbose. Compound 10 was the most potent with IC50 = 1.72 µM. It also showed the most interesting antibacterial activity, against the isolate strain of S. typhi and P. aeruginosa and also exhibited the most significant antifungal activities against all the tested yeasts.

Heterophynone and methyl ester of Colic acid, two new compounds with antimicrobial activity from Cola heterophylla (Sterculiaceae).

The ethyl acetate fraction, the stem bark and the residual methanolic extracts from the leaves of Cola heterophylla (Sterculiaceae) led to the isolation of two new compounds: Heterophynone (1) and methyl ester of Colic acid (6), along with four known triterpenes: betulinic acid (2), oleanolic acid (3), ursolic acid (4) and chletric acid (5). Structures of compounds were established by different spectroscopic methods that included 1D and 2D NMR experiment. The antimicrobial activity of isolated compounds was evaluated against two yeasts, Candida Albicans NR 29456 and Candida Krusei 1415; and five Gram-positive bacterial, Salmonella enteric Serovar Muenchem, Salmonella enteric Serovar Thyphimurium, Staphylococcus aureus NR 46003, Staphylococcus aureus NR46374 and Pseudomonas aeruginosa HM 601). Among tested compounds, Heterophynone was found to be the most active with significant antimicrobial activity against Salmonella enteric Serovar Thyphimurium (MIC = 7.82 µg/mL and MBC = 62.5 µg/mL) and good activity against Candida Albicans NR 29456 (MIC = 62.5 µg/mL).

A new abietane-type diterpenoid from roots of Burkea africana Hook (Fabaceae) with α-amylase inhibitory potential.

A new abietane-type diterpenoid, rubesanolidic acid (1), alongside six known compounds including ß-sitosterol (2), lupeol (3), betulinic acid (4) ursolic acid (5), ß-sitosterol 3-O-ß-D-glucopyranoside (6) and stigmasterol 3-O-ß-D-glucopyranoside (7) were isolated from the roots of Burkea africana through column chromatography. Their structures were elucidated from spectroscopic analyses (UV, IR, MS, 1D and 2D NMR) data and by comparison with data from previous studies. The extract and compounds were tested for their α-amylase inhibition. The extract was more active than the isolated compounds with a percentage inhibition of 51.0 ± 2.5% at 400 µg/mL and was the only sample showing above 50% inhibition at this dose. Amongst the isolated compounds and at the dose of 400 µg/mL, the new diterpenoid Rubesanolidic acid exibited the highest percentage inhibition of α-amylase of 38.2 ± 2.0% while ß-sitosterol showed the lowest inhibition of 9.6 ± 0.5%. The results indicate that B. africana is a potential source of antidiabetic compounds.

A new flavonoid glycoside from Tapinanthus sp. (Loranthaceae) and evaluation of anticancer activity of extract and some isolated compounds.

The present work describes the isolation and anticancer activity of Tapinanthus sp. which is a hemi parasitic plant harvested on Combretum glutinosum, the host plant. Phytochemical study afforded a new flavonoid glycoside, tapinantoside (1) isolated for the first time from natural source, alongside six known compounds (2-7). Structure of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, mass spectrometry and by comparison with literature data. The anticancer activity of extract and some isolated compounds were evaluated on glioblastoma (U87MG, C6) and prostate (PC-3) cancer cells. The methanol leaves extract showed good anticancer activity against U87 (IC50 = 21.40 µg/mL) and PC-3 cells (IC50 = 10.26 µg/mL). Compound 3 powerfully inhibits the proliferation of C6 (IC50 = 38.84 µM) and PC-3 cells (IC50 = 21.33 µM), while its effect was moderated on U87MG cells. Compound 1 and 7 were not active on all tested cancer cell lines.

Antibacterial and antioxidant activities and phytochemical composition of Stereospermum kunthianum root bark.

A new glycoiridoid (1) together with seven (7) known compounds were isolated from the methanol crude extract of the root bark of Stereospermum kunthianum using chromatography methods. Their structures were elucidated using HR-ESI-MS, 1 D- & 2 D-NMR spectroscopies in comparison with previous literature. The antioxidant activity was investigated by using FRAP, DPPH, ABTS and HRSA methods while the antibacterial activity was assays on Escherichia coli (ATCC25922) and Salmonella typhimurium (ATCC14028) strains. The results showed that the isolated compounds had significantly (p < 0.01) high radical scavenging (IC50) and reducing power activity. All bacteria strains showed important minimal inhibitory concentration activity against isolated compounds started at 5 mg/mL with an inhibition zone of 6 mm. Thus, the isolated compounds in S. kunthianum justify the use of the plant in traditional medicine for the treatment of various diseases in humans. These isolated compounds can be used for formulation of new drug discovery to treat infectious diseases.

In Vitro Evaluation of α-amylase and α-glucosidase Inhibition of 2,3-Epoxyprocyanidin C1 and Other Constituents from Pterocarpus erinaceus Poir.

Diabetes mellitus is a metabolic disorder which is one of the leading causes of mortality and morbidities in elderly humans. Chronic diabetes can lead to kidney failure, blindness, limb amputation, heart attack and stroke. Physical activity, healthy diets and medications can reduce the incidence of diabetes, so the search for more efficient antidiabetic therapies, most especially from natural products, is a necessity. Herein, extract from roots of the medicinal plant Pterocarpus erinaceus was purified by column chromatography and afforded ten compounds which were characterized by EIMS, HR-FAB-MS, 1D and 2D NMR techniques. Amongst them were, a new trimeric derivative of epicatechin, named 2,3-Epoxyprocyanidin C1 (1); two pentacyclic triterpenoids, friedelin (2) and betulin (3); angolensin (4); flavonoids such as 7-methoxygenistein (5), 7-methoxydaidzein (6), apigenin 7-O-glucoronide (8) and naringenin 7-O-ß-D-glucopyranoside (9); and an ellagic acid derivative (10). The extract and compounds were evaluated for their antidiabetic potential by α-amylase and α-glucosidase inhibitory assays. IC50 values of compound 7 (48.1 ± 0.9 µg/mL), compound 8 (48.6 ± 0.1 µg/mL), compound 9 (50.2 ± 0.5 µg/mL) and extract (40.5 ± 0.8 µg/mL) when compared to that of acarbose (26.4 ± 0.3 µg/mL) indicated good α-amylase inhibition. In the α-glucosidase assay, the extract (IC50 = 31.2 ± 0.1 µg/mL), compound 7 (IC50 = 39.5 ± 1.2 µg/mL), compound 8 (IC50 = 40.9 ± 1.3 µg/mL), compound 1 (IC50 = 41.6 ± 1.0 µg/mL), Compound 4 (IC50 = 43.4 ± 0.5 µg/mL), compound 5 (IC50 = 47.6 ± 0.9 µg/mL), compound 6 (IC50 = 46.3 ± 0.2 µg/mL), compound 7 (IC50 = 45.0 ± 0.8 µg/mL), compound 9 (IC50 = 44.8 ± 0.6 µg/mL) and compound 11 (IC50 = 47.5 ± 0.4 µg/mL) all had moderate-to-good inhibitions, compared to acarbose (IC50 = 22.0 ± 0.5 µg/mL). The ability to inhibit α-amylase and α-glucosidase indicates that P. erinaceus and its compounds can lower blood glucose levels by delaying hydrolysis of carbohydrates into sugars, thereby providing a source of natural antidiabetic remedy.

Anticancer Activity of Combretum fragrans F. Hoffm on Glioblastoma and Prostate Cancer Cell Lines.

BACKGROUND: Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. METHODS: The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. RESULTS: C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. CONCLUSION: Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.

Wood and sulfur-based cyclic denitrification filters for treatment of saline wastewaters.

This study investigated the performance and microbiome of cyclic denitrification filters (CDFs) for wood and sulfur heterotrophic-autotrophic denitrification (WSHAD) of saline wastewater. Wood-sulfur CDFs integrated into two pilot-scale marine recirculating aquaculture systems achieved high denitrification rates (103 ± 8.5 g N/(m3·d)). The combined use of pine wood and sulfur resulted in lower SO42- accumulation compared with prior saline wastewater denitrification studies with sulfur alone. Although fish tank water quality parameters, including ammonia, nitrite, nitrate and sulfide, were below the inhibitory levels for marine fish production, lower survival rates of Poecilia sphenops were observed compared with prior studies. Heterotrophic denitrification was the dominant removal mechanism during the early operational stages, while sulfur autotrophic denitrification increased as readily biodegradable organic carbon released from wood chips decreased over time. 16S rRNA-based analysis of the CDF microbiome revealed that Sulfurimonas, Thioalbus, Defluviimonas, and Ornatilinea as notable genera that contributed to denitrification performance.

Two new flavones glycosides with antimicrobial activities from Clerodendrum formicarum Gürke (Lamiaceae).

Clerodendrum formicarum Gürke from the Lamiaceae family is a Cameroonian medicinal plant. The crude methanol, methanol residual and ethyl acetate extracts of leaves have been phytochemically studied using chromatography column to afford four compounds; two new flavones glycoside: clerodendronone 1a (3) and clerodendronone 1b (4) along with two known compounds: 5,7-dihydroxy-4'-methoxyflavone (1) and 5-hydroxy-7,4'-dimethoxyflavone (2). Compound structures have been elucidated on the basis of their spectroscopy data and with literature information. The anti-microbial activities of extracts and three isolated compounds were performed. The antibacterial activity was evaluated against four gram positive, five gram negative and three fungus. Clerodendronone 1b (4) showed good antibacterial activity against bacterial gram negative Shigella flexineri NR518 (MIC = 62.5 µg/ml) and moderate activity against Staphylococcus aureus NR46374 (MIC = 250 µ/ml). The ethyl acetate extract recorded good antibacterial activity against Staphylococcus aureus NR46003 (MIC = 125 µg/ml) and Staphylococcus aureus NR46374 (MIC = 125 µg/ml).

Bioactive constituents from seeds of Annona Senegalensis Persoon (Annonaceae).

Column chromatography led to the isolation and full characterization of N-cerotoyltryptamine (1) previously described in a mixture of 5 compounds, asimicin (2) and ent-19-Carbomethoxykauran-17-oic acid (3) isolated from this species for first time alongside stigmasterol glycoside (4) and lacceroic acid (5). The structures of the compounds were established by extensive EIMS, HRESIMS, 1 D and 2 D NMR studies. Compound 1 and the extract AS were more potent inhibitors of ROS with IC50 values of 2.7 ± 0.1 µg/mL and 8.7 ± 10.2 µg/mL respectively than Ibuprofen (11.2 ± 1.9 µg/mL) as a standard anti-inflammatory drug. Compound 2 showed high inhibition on nitric oxide (IC50 = 3.9 ± 0.2 µg/mL), almost 6 times more active than the standard compound L-NMMA (IC50 = 24.2 ± 0.8 µg/mL) used. Compounds showed relatively low toxicity on NIH-3T3 fibroblast cells compared to standard. The results indicate that compounds 1 and 2 are potent anti-inflammatory drug candidates.