The brown algae: Sargassum binderi sonder bears potential nephroprotective activity in in-vivo experimental model.

OBJECTIVES: This study aimed to investigate the protective activity of brown seaweed, the ethanolic and water extracts of Sargassum binderi (S. binderi) were examined. Anticancer drug, cisplatin is normally used for the treatment of solid tumors that cause acute kidney damage after assemblage in the renal tubules. MATERIAL AND METHODS: It was an acute nephrotoxicity study, animals were divided into several groups randomly, cisplatin (7mg/kg i.p.) and normal saline were used as positive and negative control respectively. The S. bindari ethanolic and water extract were given orally in a dose of 200mg/kg for 5days. Various biomarkers were assessed to observe the nephroprotective potential, while antioxidant activities were investigated using reduced glutathione, catalase and malondialdehyde as oxidative stress. GCMS was performed to validate the presence of important therapeutic moieties. RESULTS: The current result justified that pretreatment with S. binderi inhibited the elevation of antioxidant parameters and also showed protection against lipid peroxidation, induced by cisplatin challenge. The overall impact was the nephroprotection, which has been revealed from the results. GCMS evaluation of hexanes fraction revealed the presence of therapeutically important compounds including heptasiloxane, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, hexadecamethyl, cyclooctasiloxane, and hexadecamethyl. These compounds have been reported for their antioxidant, antibacterial, anticancer, and antifungal activities. CONCLUSION: S. binderi showed reno-protective effect by checking their well-known biochemical parameters probably due to the antioxidant activity as confirmed by the presence of compounds.

Ulva fasciata, a green alga, attenuates the kidney and liver dysfunctions in rats induced by acetaminophen.

Acetaminophen (AAP) is an analgesic-antipyretic drug which is considered safe at recommended dose, but its overuse may induce renal and hepatic injuries. Marine macro algae have great potential against drug-induced renal and hepatic dysfunctions. The present study described the reno-protective and hepato-protective effects of the ethanol extract of an edible green alga Ulva fasciata and its fractions (n-hexane, chloroform and methanol) against AAP toxicity. In the 1st set of experiment, rats were divided into five groups. Of which two were treatment groups beside three controls, the first treatment group was given ethanol extract of U. fasciata alone and the second group was given the same extract with AAP. In the 2nd set of experiment, rats were divided into nine groups, of which three treatment groups administered n-hexane, chloroform and methanol fractions of ethanol extract of U. fasciata respectively while other three treatment groups received the same fractions individually with AAP. On the 11th day, rats were decapitated after 12 h of fasting from both sets, blood samples were collected for assessment of biochemical parameters and kidney tissues were used for determination of oxidants and antioxidants. Histopathological assessment was also done in kidney tissues. A single dose of AAP (600 mg/kg) affected kidney markers including creatinine, urea and blood urea nitrogen (BUN) and hepatic enzymes. Ethanolic extract of U. fasciata normalized kidney and liver markers in AAP intoxicated rats. AAP also reduced glutathione (GSH) in kidney tissues and altered kidney architecture, which were improved by ethanolic extract and chloroform soluble fraction of U. fasciata. A total of 14 polyunsaturated fatty acids were identified from chloroform soluble fraction of U. fasciata by GC-MS and assumed these may be involved in protective activities of U. fasciata.

Urease inhibition and DPPH radical scavenging potential of phytoconstituent from Alstonia scholaris and molecular docking interactions of bioactive luteolin with target proteins.

A polyphenolic flavone Luteolin (3',4',5,7-tetrahydroxyflavone) is found in various plants and is traditionally used in Chinese medicine. It is obtained from Alstonia scholaris (L.) R.Br Flower belonging to the family Apocynaceae while investigation. Various studies have been demonstrated the antioxidant or antiulcer potential of luteolin from different plant sources. In the present investigation the antioxidant or antiulcer effect of the Luteolin has been carried out using molecular docking simulations. The objective of this study was to analyze the antioxidant and antiulcer potential of luteolin obtained during isolation. The in vitro biological evaluation has been supported by the in silico studies using Autodock vina 4 shows the ligand-protein interaction of lute olin with 1HD2, 4GY7 and 3O1Q. Luteolin showed significant DPPH scavenging and urease inhibition activity i.e., 23.4 ± 0.87, 6.21±0.45 IC50 (uM) respectively as compared to the standard BHA and thiourea 44.2±0.45, 22.4±0.29 IC50 (uM) respectively. The docking simulations showed significant binding pocket sites with the respective proteins1HD2, 4GY7 and 3O1Q with the least binding energy -6.8, -8.0 and -8.2 kcal/mol respectively. Thus, Strong evidence has been presented with their confirmation structural interaction via molecular docking with proteins that serve as binding sites for available Luteolin molecule. The findings justify the application of the compound as a novel antioxidant and antiulcer agent.

Constituents from Nauclea latifolia with Anti-Haemophilus influenzae Type b Inhibitory Activities.

Three previously undescribed indole alkaloids, named latifolianine A (1) and latifoliaindoles A and B (2 and 3), along with 10 known compounds (4-13), were isolated from the heartwood of Nauclea latifolia. Their structures were elucidated based on the analysis of their NMR and MS data. Latifolianine A (1) represents an unusual and unprecedented monoterpene indole alkaloid unit condensed with an ursane-type pentacyclic triterpenoid moiety. Plausible biogenetic routes toward latifolianine A (1) and latifoliaindoles A and B (2 and 3) were proposed. All the isolates were assessed in vitro for their inhibitory effects on Haemophilus influenzae. Naucleidinal (7) exhibited potent antibacterial activity (MIC value of 3.1 µg/mL) as compared to a reference drug, ciprofloxacin (MIC value of 1.6 µg/mL).

Flavonoids and triterpenes from Combretum fragrans with anti-inflammatory, antioxidant and antidiabetic potential.

Despite the well-documented benefits of Combretum fragrans in Cameroon, only few scientific works have been done on it. In this study we isolated eight compounds from the leaves extract of C. fragrans: velutin (1), belamcanidin (2), cirsilineol (3), cirsimaritin (4), 3ß-acetoxy-20,24-epoxy-11,25-hydroxy-dammarane (5), combretin A (6), combretin B (7) and a mixture of arjunolic acid (8a) and asiatic acid (8b). Compounds 6 and 7 presented potent anti-inflammatory, antioxidant and antidiabetic activities. Compounds 1, 3, 5 and the mixture of 8a and 8b were significantly active, and compounds 2 and 4 presented moderate activity for reactive oxygen species inhibitory and free-radical scavenging. All compounds were isolated using chromatographic techniques; their structures were elucidated by spectroscopic techniques and their spectroscopic data compared with those of the literature. Anti-inflammatory activity was evaluated via the oxidative burst assay using a luminol-amplified chemiluminescence technique, antioxidant activity by free-radical scavenging activity (DPPH) and antidiabetic activity via α-glucosidase inhibition. All of the isolated compounds (1-8) were reported to exhibit significant antioxidant activity. Compounds 1, 3, and 5-8 exhibited potent chemiluminescence inhibition effect, and only compounds 6 and 7 inhibited α-glucosidase. Thus, C. fragrans can be used as an effective natural source of anti-inflammatory, antioxidant and antidiabetic compounds.

Immunomodulatory activities of isolated compounds from the root-bark of Cussonia arborea.

CONTEXT: Cussonia arborea Hochst. ex A. Rich (Araliaceae) is a folk medicine used to treat various diseases. However, there is no report of the root phytochemistry. OBJECTIVE: This study isolates and identifies the immunomodulatory compounds from root-bark of C. arborea. MATERIALS AND METHODS: The methanol extract (18 g) was subjected to repeated column chromatography resulting in isolation of five compounds (1-5). Structure determination was achieved by analysis of their 1 D and 2 D NMR, and mass spectroscopy. The compounds (100-1.0 µg/mL) were examined immunomodulatory for effect on production of reactive oxygen species (ROS) from whole blood phagocytes and on proliferation of T-cells. The compounds cytotoxicity (100-1.0 µg/mL) was evaluated on NIH-3T3 normal fibroblast cells. RESULTS: Three pentacyclic triterpenoids [3, 23-dihydroxy-12-oleanen-28-oic acid (1), 3ß-hydroxylolean-12-en-28-oic (2) and 23-hydoxy-oxo-urs-12-en-28-oic acid (5)], two phytosterols: [stigmasterol (3)] and [3-O-ß-d-glucopyranosyl stigmasterol (4)] were all isolated from the methanol soluble extract. All the tested compounds (1-4) were found to be nontoxic on NIH-3T3 cells. Compound 1 and 2 moderately inhibited the production of ROS (IC50 = 24.4 ± 4.3 and 37.5 ± 0.1 µg/mL, respectively) whereas compound 2 exhibited the highest inhibitory effect (IC50 = 12.6 ± 0.4 µg/mL) on proliferation of phytoheamagglutinin (PHA) activated T-cells. CONCLUSIONS: The isolated compounds (1-5) are reported for the first time from this species. In addition, compound 2 with suppressive potential on production of intracellular ROS and proliferation of T-cells could be of immense value in control of autoimmune diseases as well as in immune compromised patients.

Synthesis, biological screening and molecular docking studies of some ethylated sulfonamides having 1,4-Benzodioxane moiety.

The presented study comprises the synthesis of a new series of ethylated sulfonamides in which 1,4-benzodioxane moiety has been incorporated. The reaction of 1,4-benzodioxane-6-amine (1) with ethane sulfonyl chloride (2) yielded N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethanesulfonamide (3), which further on treatment with various alkyl/aralkyl halides, 4a-r, in N,Nꞌ-dimethylformamide (DMF) and in the presence of lithium hydride (LiH) acting as a weak base and catalyst; yielded derivatives of N-alkyl/aralkyl substituted N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethanesulfonamides (5a-r). The characterization of these derivatives was carried out by different spectroscopic techniques like infra red, proton-NMR and mass spectrometry; then screened against various enzymes i.e. acetylcholinesterase, butyrylcholinesterase, lipoxygenase and α-glucosidase enzymes and five different bacterial strains. The synthesized compounds were found to be good inhibitors of lipoxygenase but moderate inhibitors of AChE, BChE and α-glucosidase; whereas compounds 3, 5a, 5f, 5n and 5r were found good antibacterial compounds. The interaction between inhibitors and target enzymes (cholinestrases and lipoxygenase) was computationally observed which correlated with the experimental results.

Evaluation of Iyengariastellata for its hypolipidemic and hepatoprotective activity.

Cholesterol is believed to be the major regulator involved in the formation and progression of atheroma plaque. Seaweeds are known to possess enormous biological activities. They contain variety of active constituents, which have pharmacological significance. The objective of this study is to explore hypolipidemic and hepatoprotective activities of the brown seaweed Iyengariastellata. Ethanolic extract of seaweed was suspended in distilled water and administered orally at 10mg/200g body weight to rabbits for 30 days and total lipid level, cholesterol, triglycerides, HDL, LDL, VLDL, alkaline phosphatase, SGPT, SGOT, Gamma GT were assessed. The results showed overall decrease in lipid profile whereas Iyengariastellata increased liver enzymes except SGPT which was decreased highly significantly, since SGPT is more specific indicator of liver injury, decreased value of SGPT indicates that Iyengariastellata toxicity is less severe and reversible with marked hypolipidemic effect, but during the course of ingestion of the seaweed the liver enzymes must be carefully monitored to ensure liver safety.

Urease inhibitory isoflavonoids from different parts of Calopogonium mucunoides (Fabaceae).

The dichloromethane-methanol (1:1) soluble part of Calopogonium mucunoides (Fabaceae) resulted in the isolation of 10 isoflavones (4'-O-methylalpinumisoflavone, 4'-O-methylderrone, alpinumisoflavone, daidzeine, Calopogonium isoflavone A, atalantoflavone, 2',4',5',7-tetramethoxyisoflavone, 7-O-methylcuneantin, cabreuvin and 7-O-methylpseudobaptigenin) and a rotenoid (6a,12a-dehydroxydegueline). Among these, daidzeine, 7-O-methylcuneantin, atalantoflavone and 6a, 12a-dehydroxydegueline have been isolated for the first time from C. mucunoides while remaining are already reported from this source. Structures of all the isolated constituents were elucidated with the aid of NMR spectroscopic and mass spectrometric techniques. Among all the isolated constituents, nine were evaluated for their urease inhibitory potential. However, six were found potent. These include 4'-O-methylderrone, daidzeine, atalantoflavone, 2',4',5',7-tetramethoxyisoflavone, 7-O-methylcuneantin and 6a, 12a-dehydroxydegueline.

Preussiate, a new urease inhibitory chalcone from Dioscorea preussii Pax.

The phytochemical investigation of the aqueous methanolic extract of the aerial parts of Dioscorea preussii, led to the isolation of a new chalcone preussiate (1) along with 10 other compounds including xanthomicrol (2), cholestan-3-one (3), arjunolic acid (4), tormentic acid (5), ursolic acid (6), betulin (7), lupeol (8), p-hydroxybenzoic acid (9), isovanillin (10) and vanillic acid (11), being reported for the first time from this plant. Their structures were established by spectroscopic techniques including 2D NMR spectroscopy. All the isolates were subjected to the biological screening but only showed antioxidant and urease inhibitory properties. The compounds 1,8 and 11 displayed the most potent urease inhibitory properties with IC50 values, 22.4, 33.3 and 35.7 µM, respectively, while 3 was moderately active. The compound 11 showed potent antioxidant activity among all the tested isolates with an IC50 value of 45.3 µM.

New secondary metabolites and volatile constituents from the leaves of Ocimum gratissimum Linn.

The phytochemical investigation on the ethanolic extract of the leaves of Ocimum gratissimum (syn. O. viride) has led to the isolation of a new alkaloid, diazovirid or 1,1'-(diazeno1,2-diyl) bis (ethane-1,2-diol) (1) and 2-hydroxy-D-glucal or (2 R, 3S, 4S)-2-(hydroxymethyl)-3,4-dihydro-2H-pyran-3,4,5-triol (2), reported for the first time as a natural product. Their structures were determined by spectroscopic analyses. The volatile constituents have also been studied by GC-FID and GC-MS leading to the characterization of compounds 3-18, respectively.

Zenkeramide: a new iso-benzofuranone propanamide and urease inhibitory constituents of Celtis zenkeri Engl stem bark (Ulmaceae).

A new iso-benzofuranone propanamide: 3-(3-oxo-1, 3-dihydroisobenzofuran-1-yl) propanamide (zenkeramide) (1) along with three known compounds: Trans-N-coumaroyltyramine (2), ß-Sitosterol (3) and ß-sitosterol-3-0-ß-D-glucopyranoside (4) were isolated from the ethyl acetate fraction of the stem-bark of Celtis zenkeri Engl (Ulmaceae). The structure of the new compound was elucidated by extensive spectroscopic analysis. The compounds were examined for Urease Inhibitory Activity. Compounds 1 and 2 showed moderate activities (IC50 values (µM) of 42.3 ± 0.19 and 45.2 ± 0.55, respectively), while compounds 3 and 4 were potent inhibitors of the Jack bean urease (IC50 values (µM) of 20.3 ± 0.37and 27.6 ± 0.52, respectively), when compared to the standard inhibitor (thiourea- IC50 21.5 ± 0.47). The isolation of all the compounds from C. zenkeri and the urease activity of compounds 1 and 2 are reported for the first time.

Partial syntheses of aromatic amides: their anti-urease potential and docking studies.

The aromatic amide: N-p-trans-coumaroyltyramine (1) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives (1a-d) and previously reported diacetylated product (1e) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product (1e) was found to be the most potent inhibitor with an IC50 value of 19.5 ± 0.23 µM compared to thiourea used as standard (21.5 ± 0.47 µM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b, 1c, 1d and 1e remained stable throughout the simulation. This study provides insight into the N-p-trans-coumaroyltyramine derivatives (1b-e) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma.

Crotofoligandrin, a new endoperoxide crotofolane-type diterpenoid from the twigs of Croton oligandrus Pierre ex. Hutch (Euphorbiaceae).

Crotofoligandrin (1), a new endoperoxide crotofolane-type diterpenoid was isolated from the dichloromethane/methanol (1:1) extract of the twigs of Croton oligandrus Pierre Ex Hutch along with thirteen known secondary metabolites including 1-nonacosanol (2), lupenone (3), friedelin (4), ß-sitosterol (5), taraxerol (6), (-)-hardwickiic acid (7), apigenin (8), acetyl aleuritolic acid (9), betulinic acid (10), fokihodgin C 3-acetate (11), D-mannitol (12), scopoletin (13) and quercetin (14). The structures of the isolated compounds were determined based on their spectroscopic data. The crude extract and the isolated compounds were assessed in vitro for their antioxidant, lipoxygenase, butyrylcholinesterase (BChE), urease and glucosidase inhibitory potentials. Compounds 1-3, and 10 displayed activities on all the performed bioassays. All the tested samples showed strong to significant antioxidant activity with compound 1 being the most potent (IC50 39.4 µM).

Lipoxygenase inhibitory sphingolipids from Launaea nudicaulis.

Four new sphingolipids: nudicaulin A [(2S,3S,4R,14E)-2-{[octadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 1], nudicaulin B [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol; 2], nudicaulin C [(2S,3S,4R,14E)-2-{[(2R)-2-hydroxyoctadecanoyl]amino}tetraeicos-14-ene-1,3,4-triol-1-O-ß-D-glucopyranoside; 3], and nudicaulin D [(2S,3S,4R)-2-{[(2R,3S,12E)-2,3-dihydroxyeicos-12-enoyl]amino}octadecane-1,3,4-triol; 4] together with 1-hexatriacontanol, ß-sitosterol, octadecyl 4-hydroxycinnamate, elaidic acid, cholesta-5,22-diene-3,7-diol, oleanolic acid, apigenin, and ß-sitosterol 3-O-ß-D-glucopyranoside were isolated from the methanolic extract of the whole plant of Launaea nudicaulis. Their structures were elucidated using ¹H and ¹³C NMR spectra and 2D NMR analyses (HMQC, HMBC, and COSY) in combination with mass spectrometry (EI-MS, HR-EI-MS, FAB-MS, and HR-FAB-MS) experiments and comparison with literature data of related compounds. Compounds 1-4 displayed moderate inhibitory potential against enzyme lipoxygenase in concentration-dependent manner with IC50 value ranges 103-193 µM.

Muricazine, a new hydrazine derivative from Ranunculus muricatus L. with antioxidant, lipoxygenase and urease inhibitory activities.

Ranunculus muricatus L., an important member of family Ranunculaceae upon submission to phytochemical studies, led to the isolation of a novel natural hydrazine derivative, muricazine (1). Chemical structure of the compound was established with the aid of advanced spectroscopic techniques. It was evaluated for in vitro antioxidant, lipoxygenase, and urease (jack-bean) inhibitory activities. Results suggested that compound 1 could scavenge the DPPH free radical (42.1 ± 0.12 µM) to a great extent as compared to the standard (40.6 ± 0.91 µM). However, it showed moderate inhibitory potential against lipoxygenase (65.2 ± 0.45 µM) and urease (54.8 ± 0.23 µM) enzymes.

Novel Plant-Based Metabolites as Disinfectants against Acanthamoeba castellanii.

Due to global warming, coupled with global water shortages and the reliance of the public on household water tanks, especially in developing countries, it is anticipated that infections caused by free-living amoebae such as Acanthamoeba will rise. Thus, the development of novel disinfectant(s) which can target pathogenic free-living amoebae effectively is warranted. Herein, we extracted and isolated several plant-based secondary metabolites as novel disinfectants for use against pathogenic Acanthamoeba. The identity of the compounds was confirmed by nuclear magnetic resonance and tested for antiamoebic activities against clinical isolate of A. castellanii, belonging to the T4 genotype. Amoebicidal assays revealed that the compounds tested showed antiamoebic properties. Betulinic acid and betulin exhibited parasite killing of more than 65%. When tested against the cyst stage, betulinic acid, betulin, and vanillic acid inhibited both encystation and excystation processes. Furthermore, the plant-based metabolites significantly inhibited the binding capability of A. castellanii to host cells. Finally, most of the tested compounds displayed minimal cytotoxic activities against human cells and noticeably perturbed amoeba-mediated host cell cytotoxicity. Notably, both alkaloid and betulinic acid showed 20% cytotoxic effects, whereas betulin and lupeol had cytotoxic effects of 24% and 30%, respectively. Overall, our findings indicate that plant-based natural compounds demonstrate anti-Acanthamoebic properties, and they have potential candidates for water disinfectants or contact lens disinfecting solutions, as well as possible therapeutic drugs against Acanthamoeba infections.

New bioactive monoterpene indole alkaloid from Rinorea yaundensis Engl.

Extraction of the aerial part of Rinorea yaundensis has led to the isolation of a new monoterpene indole alkaloid (1) along with 10 known compounds (2-11) for the first time from this plant. Their structures were determined by HRMS and NMR spectroscopic analyses as yaundentine hydrochloride (1), Nb-oxide of iso-reserpiline (2), iso-reserpiline (3), iso-carapanaubine (4), lichenxanthone (5), stigmastane-3,6-dione (6), methyl ß-orcinol carboxylate (7), ß-sitosterol-3-O-ß-D-glucoside (8), betulinic acid (9), ursolic acid (10) and benzoic acid (11) while the stereochemistry and absolute configuration of 1 was confirmed by single crystal x-ray crystallography and circular dichroism CD spectrum. Yaundentine hydrochloride (1) exhibited pronounced antioxidant, urease and lipoxygenase inhibitory activities with IC50 values of 35.6 ± 0.23, 20.3 ± 0.58 and 29.6 ± 0.77 µM, respectively. Compound 1 also showed good antimicrobial activity against some Gram positive and negative bacteria.

Echinograciolide, a new antibacterial nor-triterpenoid and other constituents from Echinops gracilis O. Hoffm. (Asteraceae).

Antibacterial resistance is a serious threat against humankind and the search for new therapeutics is needed. This study aims to investigate the antibacterial activity of extracts and compounds from Echinops gracilis O. Hoffm. Standard chromatographic and spectroscopic methods were used to isolate and characterize compounds (1-15) from the methanol extract. The extract, chromatographic fractions and compounds 1-3, 8, 11, 13 and 14 were subjected to in vitro antibacterial assays against Staphylococcus aureus ATCC25923, Salmonella Typhi ATCC6539, Klebsiella pneumoniae 22, and Salmonella Typhi 68, using broth micro-dilution method. As results, a new nor-triterpenoid (1) and fourteen known compounds (2-15) were characterized. The extract and fractions displayed moderate (128 ≤ MIC ≤ 512 µg/mL) and significant (MIC 64 µg/mL) antibacterial activities. Compounds 1 and 14 showed the best anti-staphylococcal and anti-salmonella activity (MIC 16 µg/mL), respectively. These results partially justified the antimicrobial uses of E. gracilis in traditional medicine.

bis-Sigmodiol: a new prenylflavanone dimer from Erythrina sigmoidea Hua (Fabaceae) of Nigeria.

A new prenylflavanone dimer named bis-sigmodiol was isolated from Erythrina sigmoidea, along with six known constituents isobavachin, lupiwighteone, orientanol A, ergosta-4, 6, 8 (14), 22-tetraen-3-one, lupenyl acetate, and p-hydroxybenzoic acid. These known constituents have not been reported so far from E. sigmoidea. Their structures were elucidated by spectroscopic methods.