Search

Diarrhea is a prevalent gastrointestinal problem associated with fatal implications. It is a huge public health concern that requires better alternatives to current drugs. This study investigated the mechanisms involved in the antidiarrheal activity of Anacardium occidentale (Ao) stem bark extract, a plant commonly used in the management of diarrhea in Nigeria. Methanolic stem bark extract of the plant was partitioned into 3 fractions; hexane fraction (AoHF), ethyl acetate fraction (AoEF) and methanol fraction (AoMF). In vitro studies on the effect of these fractions using guinea pig ileum (GPI) muscle contraction, as well as the modulatory effect of standard agonists and antagonists on such contraction, revealed AoEF as the most active fraction. In vivo studies to assess the effect of AoEF on the dopaminergic, muscarinic and serotonergic pathways were carried out using gastric emptying (GE) and gastrointestinal transit (GT) as experimental end points. AoEF was subjected to GC-MS analysis, while the identified compounds were docked with the muscarinic acetylcholinesterase receptor (M3) using AutodockVina. Results indicated that AoEF inhibited GE and GT via inhibition of M3. In addition, GC-MS analysis revealed the presence of 24 compounds in AoEF; while docking indicated that octadecanoic acid 2-(2-hydroxylethoxy) ethyl ester exhibited the highest binding affinity for M3. This study indicated that the antidiarrheal activity of Ao is through its antimotility effect via the inhibition of the muscarinic pathway. And since none of the identified compounds exhibited higher binding affinity for M3 relative to loperamide, the antimotility activity of these phytoconstituents may be via synergism.

Power supply has remained a challeng issue in developing coutries. The aim of this study was to evaluate the potentials of selected yeast species for bioelectricity generation. Different yeast species were isolated from cassava wastewater, whey wastewater, human urine, and rabbit dung using the spread plate method. These isolates were identified using analytical profile index (API). Results obtained revealed the identity of the isolated yeast species as Candida famata, Candida hellenical. Candida tropicalis and Saccharomyces cerevisia (using API method).The isolated yeast species were used singly, and as a consortium for bioelectricity generation, and yeast in continuous mode. The same wastes as used for the isolation process were evaluated as possible substrates for the generation of bioelectricity. Out of the four wastes used, cassava processing wastewater gave the highest bioelectricity potential and was subsequently used as substrate for further study. Saccharomyces cerevisiae elicited the highest electricity generation when the four yeast species were used singly (1.08V). A consortium of the four isolates elicited a synergis effect, generating 1.57V of voltage. Stacking of the Microbial Fuel Cell(MFC) components improved voltage to 2.4V due to its lower internal resistance within the stacked materials. It is apparent from the results obtained in this study that when properly harnessed, microbial fuel cells (MFCs) technology could serve as alternate source of renewable energy. Keywords: Microbial fuel cells, Waste, yeasts, Salt- Bridge, Nafion117.

Polyscias fulva (Hiern) Harms stem bark is used in traditional folk medicine in Kenya for diabetes mellitus and obesity management. This study sought to examine the antidiabetic effects of ethanolic stem bark extract of P. fulva in streptozotocin (STZ)–induced diabetic Wistar albino rats. Diabetes in rats was induced by intraperitoneal injection of STZ (50 mg/kg bwt) in experimental groups. Rats were divided into five groups (n = 5 per group): group 1, control; group 2, diabetic untreated rats; groups 3 and 4, diabetic rats on 200 and 400 mg/kg bwt/day of extract, respectively; and group 5, diabetic rats on metformin (100 mg/kg bwt/day). The rats received oral treatments daily for 21 days, and fasting blood glucose levels and body weights were determined weekly. Liver histopathological analysis and malondialdehyde (MDA) assay as well as serum analysis of lipid profile, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total proteins (TP), albumin (ALB), and globulins were performed at the end of the treatment period. Extract had significant hypoglycemic and hypolipidemic effects in the diabetic rats compared with diabetic untreated rats (p

Objectives Diarrhea, an abnormal state in which the individual has about three or more daily bowel movements, is now considered one of the most challenging global public health problems. Using plant products, such as Bridelia ferruginea is an alternative treatment option. The objective of this study was to investigate the antidiarrheal activity of B. ferruginea bark methanolic extract (BfME) and the mechanisms involved. Methods BfME antidiarrheal activity was evaluated in mice model of castor oil-induced diarrhea and enteropooling. To evaluate motility, gastrointestinal transit time was carried out using phenol red meal, while intestinal activities of selected ATPases were also evaluated. Furthermore, the active components in BfME were detected by GC-MS analysis, while molecular docking of the most abundant compounds with muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) were conducted. Results BfME at 400 and 800 mg/kg showed antidiarrheal activity by delaying onset of diarrhea, reduced gastrointestinal transit and increased intestinal activities of Na+ K+-ATPase, Ca2+ Mg2+-ATPase and Mg2+-ATPase. Molecular docking revealed that γ-sitosterol, α-amyrin, and stigmasterol have outstanding binding affinity for M3 and EP3. Conclusions In view of these results, the observed antidiarrheal activity possibly occurs via the activation of ATPases activities and inhibition of M3 and EP3.

The growing resistance to the current antimalarial drugs in the absence of a vaccine can be effectively tackled by identifying new metabolic pathways that are essential to the survival of the malaria parasite and developing new drugs against them. Triterpenes and steroids are the most abundant group of natural products with a great variety of biological activities. However, lanosterol is not known to possess any significant biological activity. In this study the binding and interactions of a dinitrophenyl hydrazine (DNP) derivative of lanosterol, LAN (a derivative that incorporates a substantially polar moiety into the steroid) with P. falciparum transketolase was studied by molecular docking and MD simulation with the view to exploit the DNP derivative as a lead in antimalarial chemotherapy development considering that the P. falciparum transketolase (PfTk) is a novel target in antimalarial chemotherapy. The enzyme catalyses the production of ribose sugars needed for nucleic acid synthesis; it lacks a three-dimensional (3D) structure necessary for docking because it is difficult to obtain a crystalline form. A homology model of PfTk was constructed using Saccharomyces cerevisiae transketolase (protein data bank ID of 1TRK) as the template. The compound was observed to have Free Energy of Binding higher than that of the cofactor of the protein (Thiamine Pyrophosphate, TPP) and a synthetic analog (SUBTPP) used as reference compounds after MD Simulation. The compound was synthesized in a two-step, one-pot reaction, utilizing a non-acidic and mild oxidant to oxidize the lanosterol in order to avoid the rearrangement that accompanies the oxidation of sterols using acidic oxidants. The LAN was characterized using IR spectroscopy and NMR experiments and tested in-vivo for its antimalarial chemo suppression using a murine model with Chloroquine as a standard. The LAN at a concentration of 25 mg/kg was found to have a comparable activity with Chloroquine at 10 mg/kg and no mortality was observed among the test animals 24 days post drug administration showing that the compound indeed has potential as an antimalarial agent and a likely inhibitor of PfTk considering that there is a strong agreement between the in-silico results and biological study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00097-8.

The chemical composition of Melanthera scandens (MS) methanol (MeOH) extract is yet to be fully comprehended. Chemical composition of a plant extract is closely related to the biological activity of the plant material, in phytomedicine. In this study, chemical analyses of MS extracts were carried out with the aim of identifying the organic chemical constituents.

Flavin-based electron bifurcation (FBEB) is a recently discovered mode of energy coupling in anaerobic microorganisms. The electron-bifurcating caffeyl-CoA reductase (CarCDE) catalyzes the reduction of caffeyl-CoA and ferredoxin by oxidizing NADH. The 3.5 A structure of the heterododecameric Car(CDE)4 complex of Acetobacterium woodii, presented here, reveals compared to other electron-transferring flavoprotein/acyl dehydrogenase family members an additional ferredoxin-like domain with two [4Fe-4S] clusters N-terminally fused to CarE. It might serve, in vivo, as specific adaptor for the physiological electron acceptor. Kinetic analysis of a CarCDE(∆Fd) complex indicates the bypassing of the ferredoxin-like domain by artificial electron acceptors. Site-directed mutagenesis studies substantiated the crucial role of the C-terminal arm of CarD and of ArgE203, hydrogen-bonded to the bifurcating FAD, for FBEB.

Medicinal plants are the richest, cheapest and most readily available source of drugs, nutraceuticals and food supplements. Pharmaceutical industries still rely largely on medicinal plants for intermediates due to their chemical diversities. This study, therefore, investigated the chemical constituents, thermal decomposition products and biological activities of extract from seeds of Cola nitida (the ‘kola nut’).

Compositae species are applied as whole or part of the feed stock for animals and poultry. However, rabbits display varied preferences in their consumption of these plants, following the order of: Melanthera scandens (MS) > Synedrella nodiflora (SN) > Aspilia africana (AA) > Ageratum conyzoides (AC). This preference profile may be due to variation in chemical composition, flavor or toxicity of the plants. The rabbits in our farm feed on 100% MS or SN with excellent performance. This study, therefore, is set to: obtain the methanol extract of these plants, screen them for their antibacterial activity, determine their toxicity and investigate the chemical composition of their n-hexane fraction (volatile constituents).

NADH-dependent reduced ferredoxin:NADP oxidoreductase (NfnAB) is found in the cytoplasm of various anaerobic bacteria and archaea. The enzyme reversibly catalyzes the endergonic reduction of ferredoxin with NADPH driven by the exergonic transhydrogenation from NADPH onto NAD(+). Coupling is most probably accomplished via the mechanism of flavin-based electron bifurcation. To understand this process on a structural basis, we heterologously produced the NfnAB complex of Thermotoga maritima in Escherichia coli, provided kinetic evidence for its bifurcating behavior, and determined its x-ray structure in the absence and presence of NADH. The structure of NfnAB reveals an electron transfer route including the FAD (a-FAD), the [2Fe-2S] cluster of NfnA and the FAD (b-FAD), and the two [4Fe-4S] clusters of NfnB. Ferredoxin is presumably docked onto NfnB close to the [4Fe-4S] cluster distal to b-FAD. NAD(H) binds to a-FAD and NADP(H) consequently to b-FAD, which is positioned in the center of the NfnAB complex and the site of electron bifurcation. Arg(187) is hydrogen-bonded to N5 and O4 of the bifurcating b-FAD and might play a key role in adjusting a low redox potential of the FADH(•)/FAD pair required for ferredoxin reduction. A mechanism of FAD-coupled electron bifurcation by NfnAB is proposed.

The electron transferring flavoprotein/butyryl-CoA dehydrogenase (EtfAB/Bcd) catalyzes the reduction of one crotonyl-CoA and two ferredoxins by two NADH within a flavin-based electron-bifurcating process. Here we report on the X-ray structure of the Clostridium difficile (EtfAB/Bcd)4 complex in the dehydrogenase-conducting D-state, α-FAD (bound to domain II of EtfA) and δ-FAD (bound to Bcd) being 8 Å apart. Superimposing Acidaminococcus fermentans EtfAB onto C. difficile EtfAB/Bcd reveals a rotation of domain II of nearly 80°. Further rotation by 10° brings EtfAB into the bifurcating B-state, α-FAD and β-FAD (bound to EtfB) being 14 Å apart. This dual binding mode of domain II, substantiated by mutational studies, resembles findings in non-bifurcating EtfAB/acyl-CoA dehydrogenase complexes. In our proposed mechanism, NADH reduces β-FAD, which bifurcates. One electron goes to ferredoxin and one to α-FAD, which swings over to reduce δ-FAD to the semiquinone. Repetition affords a second reduced ferredoxin and δ-FADH−, which reduces crotonyl-CoA., The electron-transferring flavoprotein / butyryl-CoA dehydrogenase (EtfAB/Bcd) complex catalyzes the reduction of crotonyl-CoA and ferredoxins by NADH in anaerobic microbes. Here, the authors present the crystal structure of Clostridium difficile EtfAB/Bcd and discuss the bifurcation mechanism for electron flow.

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD(+) complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH(-) is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH(-) by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH(•), immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH(-) that converts crotonyl-CoA to butyryl-CoA.

Aim This study was designed to assess the antioxidant property of crude methanolic extract of Tetracera potatoria roots (MeTp); a bioactive constituent isolated from it, betulinic acid (BA) and a combination of BA with ascorbic acid. Methods The crude extract was obtained by cold extraction. Phytochemical screening of the crude extract was carried out using standard methods. Isolation of betulinic acid (BA) was effected by Accelerated Gradient Chromatography (AGC) fractionation of MeTp. Structural elucidation of the isolated BA was done with 1 H and 13 C NMR spectroscopic technique. MeTp, isolated BA and BA plus ascorbic acid mixture (1:1) were evaluated for their antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl, (DPPH) method. Results The phytochemical analysis showed the presence of alkaloids, flavonoids, cardiac glycosides, saponins and tannins. Anthraquinones were absent. The 1 H and 13 C NMR data obtained for the isolated BA were in accordance with published data. Antioxidant activity (IC 50 ) of tested materials ranged from 18 to 148 μg/ml, with MeTp having the highest value relative to ascorbic acid, the reference standard. The radical scavenging activities of MeTp and that of BA plus ascorbic acid mixture were greater than that of ascorbic acid alone, indicating synergism between ascorbic acid and betulinic acid. Conclusion The findings established the antioxidant property of methanolic root extract of T . potatoria . The combination of betulinic acid and ascorbic acid could be useful for the development of new antioxidant drug.

Flavin-based-electron-bifurcation (FBEB) is a novel mechanism of energy coupling used by anaerobic microorganisms to optimize their energy metabolism efficiency. The first high-resolution structure of a complete FBEB enzyme complex, the NADH-dependent-reduced-ferredoxin:NADP+-oxidoreductase (NfnAB) of Thermotoga maritima, was recently solved. However, no experimental evidence for the NADPH-binding site and conformational changes during the FBEB reaction are available. Here we analysed ligand binding and the conformational dynamics of oxygen-sensitive NfnAB using Hydrogen-Deuterium-eXchange-mass-spectrometry, including a customized anaerobic workflow. We confirmed the NADH and the previously postulated NADPH-binding site. Furthermore, we observed an NfnA-NfnB rearrangement upon NADPH-binding which supports the proposed FBEB mechanism. This article is protected by copyright. All rights reserved.

Phytochemical studies on the methanolic extract of Drypetes gossweileri afforded N -β- d -glucopyranosyl- p -hydroxyphenylacetamide ( 1 ), p -hydroxyphenylacetic acid ( 2 ), p -hydroxyphenyl-acetonitrile ( 3 ), p -hydroxyacetophenone ( 4 ), 3,4,5-trimethoxyphenol ( 5 ), dolichandroside A ( 6 ), and β-amyrone ( 7 ). Compounds 1 – 7 were identified with the aid of extensive NMR and MS spectroscopic studies. Compound 1 was a new natural product and was isolated for the first time from plant containing N -glucose moiety incorporated in its structure. Compounds 1 – 7 exhibited moderate to the weak source anti-α-glucosidase inhibitory activity. Compound 7 exhibited moderate anti-acetylcholinesterase (AChE) activity while the rest of the isolates were weakly active in this bioassay. Compounds 1 – 7 also showed moderate anti-fungal activity.

A B S T R A C T Introduction: Ficus trichopoda is a ficus species growing in wet places - swamp forest, river banks and swamp grassland. It is well used in the management of inflammation - related conditions locally. This present work was undertaken to investigate anti-inflammatory and analgesic properties of aqueous ethanolic extract of Ficus trichopoda bark in rats. Methods: The anti-inflammatory effect was investigated by using the acute inflammatory model of carrageenan - induced paw oedema and its analgesic activity using formalin test and tail flick test in rats. Results: The study for preliminary phytochemical secondary metabolites revealed the presence of saponins, tannins, alkaloids and free amines/amino acids. Oral administration of the aqueous ethanolic extract of F. trichopoda in doses up to 5000 mg/kg body weight did not produce any mortality and any visible signs of toxicity. Ficus trichopoda extract at the doses (125 - 500 mg/kg) showed significant (p < 0.05) dose dependent inhibition of oedema formation in the carregeenan induced model. The extract showed significant dose dependent inhibition of the inflammatory (late) phase but not the neurogenic (early) phase of the formalin test in rats. The analgesic activity in tail flick method showed significant (p < 0.05) elevation in pain latency threshold from 30, 60, 90 and 120 minutes after pretreatment. Conclusion: The results obtained suggest marked analgesic and anti-inflammatory activity of ethanolic extract (125- 500 mg/kg). This finding supports that the stem bark is useful in inflammatory and painful conditions.

Background: The use of Carica papaya leaves for medicines and food in our rural areas is rampant, this is due to its availability and testimonies of its efficacy. Objective: This study was aimed at investigating the activities of C. papaya on the histo-architecture of some organs. Materials and Methods: About 20 Wistar rats were randomly divided into 4 groups of 5 each and received tap water, 2.5, 5, and 7.5 g/kg of ethanolic extract of C. papaya PO once a day for 14 days after which biochemical analyses was performed on the blood samples. The tissues were examined histologically. Results: Albumin was significantly increased (37.6 ± 2.70) in Group B (5 mg/kg) when compared with the control (32.4 ± 2.30). AST decreased significantly in all the treatment groups (68 ± 1.58, 87.4 ± 403, and 89 ± 1.58) when compared with the control (93.6 ± 1.14). ALT decreased in all groups but was significant in Group C (7.5 mg/kg) 22.8 ± 2.16 when compared with the control (30 ± 2.12). Urea decreased significantly in all the groups (3.34 ± 0.11, 3.78 ± 0.50, and 3.36 ± 0.28), creatinine decreased significantly in Group B (35.4 ± 2.79) when compared to their controls (4.52 ± 0.37 and 50.8 ± 6.37), respectively. Na+ and K+ significantly decreased in Groups C and B, respectively; there was no significant difference in other groups and electrolytes. There was increased level of both packed cell volume and hemoglobin significantly. Histologically, there were no tissue alterations in all the treatment groups. Conclusion: Complementary and alternative medicine is fast gaining popularity; this necessitates swift research on various dose ranges.

Studies were undertaken on the effect of a crude (TC) and an alkaloid fraction (TA) of the leaf extracts of Tylophora conspicua on indomethacin-induced gastric ulceration and gastric acid secretion in male albino rats. Both the TC and TA produced a dose-dependent inhibition of gastric ulceration. At a dose level of 40 mg/kg TC and TA were more effective (TA being more potent) than propranolol in inhibiting gastric ulceration. The highest dose of the extracts used (80 mg/kg) completely inhibited gastric ulceration. Intravenous administration of the TC and TA significantly decreased acid output at low dose (20 mg/kg), medium dose (40 mg/kg) and high dose (80 mg/kg) from the peak basal of 0.54 +/- 0.02 mEq/L/min to 0. 49 +/- 0.02 mEq/L/min, 0.35 +/- 0.01 mEq/L/min and 0.21 +/- 0.02 Meq/L/min respectively. 80 mg/kg of TC and TA significantly reduced the histamine (1 mg/kg) induced gastric acid secretion. The results suggest that the antiulcer activity of Tylophora conspicua might be produced by gastric acid inhibition.

Methyl angolensate (1), the major compound isolated from the methanol extract of the stem bark of Entandrophragma angolense produced a dose-related inhibition of gastric ulceration, 40 mg/kg body weight (B.W.) being more effective than 40 mg/kg B.W. of propranolol. The highest dose used (80 mg/kg B.W.) completely inhibited gastric ulceration and significantly reduced gastric acidity (P < 0.05). Furthermore, 1 (40 mg/kg B.W.) significantly reduced gastric acid secretion induced by histamine (1.0 mg/kg B.W.) and carbachol (1.0 mg/kg B.W.). These results suggest that 1 produces its antiulcer activity by inhibition of gastric acid secretion.

A selective high-performance liquid chromatographic (HPLC) method with ultraviolet-visible (UV-VIS) detection was developed to measure therapeutic concentrations of spectinomycin in turkey plasma. Treatment of plasma samples with 3% trifluoroacetic acid in acetonitrile facilitated spectinomycin extraction and protein precipitation. After centrifugation, the stable derivatization reagent, 2,4-dinitrophenyl-hydrazine, was added to an aliquot of the supernatant, and the mixture was incubated for 30 min at 70 degrees C. Excess reagent was quenched with acetone and additional heating. The resulting derivative, a proposed spectinomycin-hydrazone, was separated from other compounds by reversed-phase HPLC during a short gradient run. The absorbance of the effluent was monitored spectrophotometrically with the UV-VIS detector set at 205 nm. The detector response was linear through the range of interest, 2-100 micrograms/ml.

Summary1. Epinephrine subcutaneously causes a rise in calcium, citrate and glucose levels and a fall in phosphate and potassium levels. 2. Cortisone intramuscularly causes a rise in glucose and phosphate levels and a fall in calcium and citrate levels. 3. ACTH intramuscularly causes a rise in citrate and a fall in calcium levels. 4. It is suggested that the balance between ACTH, epinephrine, insulin and cortisone secretion, because of their effect on citrate, calcium and phosphate levels, play a significant role in the maintenance of the calcium ion concentration of the plasma.

SING THE DRY-ASH METHOD for PBI one has the advantage of being able to do many determinations without spending much time on each separate sample. One disadvantage is that sera containing large quantities of organic iodides, usually from patients given radiopaque compounds, will cause contamination of the other samples in the muffle furnace. Systems have been devised to detect sera so contaminated and exclude them from the run (1-3). We have observed a simple precaution that prevents cross-contamination without necessitating the removal of any sample or any pretesting. Preheat the furnace to 625#{176}-650#{176}. (It is important that the oven be hot.) Place the samples (after the overnight drying at 110#{176}-120#{176}) in the mouth of the muffle furnace with the open ends of the sample tubes slightly protruding. The tubes may be piled on each other. With the furnace door open, allow the samples to char until smoke is no longer emitted, then push the tubes completely into the furnace, close it, and continue with the incineration at 600#{176} to 625#{176}. Keeping the furnace door open allows the iodine from the decomposed organic compounds to escape and not circulate in the furnace and eventually be absorbed by the sodium carbonate ash. In 1200 determinations there was no detectable cross-contamination even though 44 specimens were subsequently found to contain organic iodides in very high concentrations.