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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

Rapid Identification of Common Secondary Metabolites of Medicinal Herbs Using High-Performance Liquid Chromatography with Evaporative Light Scattering Detector in Extracts.

The discovery and identification of novel natural products of medicinal importance in the herbal medicine industry becomes a challenge. The complexity of this process can be reduced by dereplication strategies. The current study includes a method based on high-performance liquid chromatography (HPLC), using the evaporative light scattering detector (ELSD) to identify the 12 most common secondary metabolites in plant extracts. Twelve compounds including rutin, taxifolin, quercetin, apigenin, kaempferol, betulinic acid, oleanolic acid, betulin, lupeol, stigmasterol, and ß-sitosterol were analyzed simultaneously. The polarity of the compounds varied greatly from highly polar (flavonoids) to non-polar (triterpenes and sterols). This method was also tested for HPLC-DAD and HPLC-ESI-MS/MS analysis. Oleanolic acid and ursolic acid could not be separated in HPLC-ELSD analysis but were differentiated using LC-ESI-MS/MS analysis due to different fragment ions. The regression values (R2 > 0.996) showed good linearity in the range of 50-1000 µg/mL for all compounds. The range of LOD and LOQ values were 7.76-38.30 µg/mL and 23.52-116.06 µg/mL, respectively. %RSD and % trueness values of inter and intraday studies were mostly <10%. This method was applied on 10 species of medicinal plants. The dereplication strategy has the potential to facilitate and shorten the identification process of common secondary metabolites in complex plant extracts.

The chemistry and biological activities of Citrus clementina Hort. Ex Tanaka (Rutaceae), a vegetatively propagated species.

We report the chemistry and biological activities of a Cameroonian Citrus clementina Hort. Ex Tanaka, a vegetatively propagated species. The compounds isolated from this plant were determined to be the known 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (1), tangerine (3), nobilletin (4), 5,7,8,4'-tetramethoxyflavone (5), citracridone I (6), 5-hydroxynoracronycine (7), citracridone III (8), xanthyletin (10), suberosin (9), E-suberenol (11), E-methoxysuberenol (13), 6-formylumbelliferone (12), aurantiamide acetate (2), limonin (14), stigmasterol, ß-sitosterol and ß-sitosterol-3-O-ß-D-glucoside. The structures of the compounds were established on the basis of their NMR spectroscopic data and comparison with published data. Methanol leaf extract and compounds 1, 2, 4, 6, 7 and 10 were evaluated for their anti-inflammatory, antioxidant, urease and anti-diabetic effects. Compound 10 showed antioxidant activity, anti-inflammatory effect, urease activity and anti-diabetic activity with IC50 values of 47.3 µM, 33.5 µM, 25.2 µM and 33.9 µM respectively, values that were comparable to the respective positive standards.

Bioactive constituents from Manilkara obovata (Sabine & G.Don) J.H.Hemsl.

The phytochemical investigation of the methanolic extracts of roots, stem bark, leaves and twigs of Manilkara obovata has led to the isolation of one new friedelane triterpene, lacefriedelic acid or 3ß,23-dihydroxy D:A-friedooleanan-28-oic acid (1) and one new prenylated xanthone, lacexanthone or 4,7-dihydroxy-2,3,3,9,9-pentamethyl-2,2-dihydrofurano[2,3-a]pyrano[2,3-i]xanthen-13(9H)-one (2) alongside twenty-four known compounds. Compounds 1-11 are reported here for the first time from the genus Manilkara. The structures of all compounds were determined by spectroscopic analyses and X-ray crystallography. The methanolic extracts of twigs and leaves showed anti-oxidant activity of 93.2 and 91.1%, respectively, at 100 µg/mL when measured by DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate), while the twig extract displayed 86.3% at 100 µg/mL against the urease inhibition assay. Some isolated compounds (1-4, 15 and 20) showed significant to moderate anti-oxidant activity and urease inhibition assay. It is estimated that significantly active anti-oxidants and urease inhibitors metabolized by the plant may find future application in food industry.

A new dammarane type triterpene glucoside from the aerial parts of Gouania longipetala (Rhamnaceae).

3-O-ß-D-glucopyranosyl gouanogenin A (1), a new naturally occurring dammarane class of triterpene glucoside, has been isolated from the aerial parts of Gouania longipetala along with six known secondary metabolites 2-7. Their structure was elucidated through spectroscopic data including 1 D- and 2 D-NMR. The compounds 1 and 6 showed significant antioxidant potential in DPPH radical scavenging assay. On the other hand, the compound 4 revealed potent inhibitory potential against the enzyme urease, while 1 and 3 were significantly active.

Muriolide, a novel antioxidant lactone from Ranunculus muricatus.

Muriolide (1), a new aromatic lactone, has been isolated from the ethyl acetate fraction of Ranunculus muricatus. The compound was structurally characterized with the help of UV, IR, mass, 1D- and 2D-NMR data. It was tested in vitro for antioxidant and lipoxygenase inhibitory potential. Compound 1 showed good DPPH radical scavenging activity (IC50=56.9 µM), however it was moderately active against lipoxygenase enzyme (IC50=68.3 µM).

Crotoliganfuran, a new clerodane-type furano-diterpenoid from Croton oligandrus Pierre ex Hutch.

The phytochemical investigation of the methanol extract of the bark of Croton oligandrus Pierre ex Hutch yielded a new clerodane-type diterpenoid crotoliganfuran (1) along with ten other compounds including 12-epicrotocorylifuran (2), lupeol (3), syringic acid (4), aleuritolic acid acetate (5), aleuritolic acid (6), scopoletin (7), geddic acid (8), ß-sitosterol (9), vanilic acid (10) and stigmastane-3,6-dione (11). Their structures were established by spectroscopic means. The extract and all the isolates were screened for their inhibitory properties against butyrylcholinesterase and urease enzymes, respectively. The extract and compounds 1, 4 and 7 displayed the most potent urease inhibitory properties with IC50 values, 22.2, 26.7 and 28.5 µM, respectively. Compound 9 was the most active of all the tested compounds against butyrylcholinesterase enzyme with an IC50 value of 36.3 µM.[Formula: see text].

Nephroprotective effect of ethanol extract and fractions of a sea lettuce, Ulva fasciata against cisplatin-induced kidney injury in rats.

Cisplatin is widely used in anticancer therapy, but a substantial percentage of patients who receive the therapeutic dose of cisplatin develop nephrotoxicity. Hepatotoxicity may also develop after a single dose or low repeated doses of cisplatin. Ulva fasciata is an edible seaweed, commonly known as sea lettuces have also been shown various biological activities. In this study, ethanol extract and its solvent fractions (n-hexane and chloroform) of U. fasciata were given (orally) to different groups of rats for 10 days. Injury to the kidney was induced by administrating cisplatin, intraperitoneally (i.p.) to rats at a dose of 7 mg/kg body weight (b.w.) dissolved in 1 mL saline, at 5th day of the experiment. At 10th day rats were sacrificed and kidney parameters (creatinine, urea, and blood urea nitrogen (BUN)) and electrolyte balance (Ca++, Mg++, K+, and Na+) in serum were determined, while oxidative stress markers glutathione (GSH), catalase (CAT) and malondialdehyde (MDA), and inflammatory cytokines, tumor necrosis factor (TNF α), and interleukin (IL-6) were determined in kidney tissues. Histological examination of the kidney was also performed to examine the changes in kidney tissues. Cisplatin caused adverse effects on blood parameters, antioxidants, and inflammatory markers with severe renal tubular injury in kidney tissues. Ethanol extract of U. fasciata and its fractions effectively improved these disorders and diminished the renal dysfunction. However, ethanol extract was found more effective in attenuating the adverse effect of cisplatin than its fractions. n-Hexane-soluble fraction that was subjected to GC-FID and GC-MS analysis revealed the presence of several compounds and some of them are new from this source. It could be concluded that the U. fasciata possesses nephroprotective effect and can attenuate cisplatin-induced renal dysfunction. Since U. fasciata is an edible seaweed, it may be used as a diet supplement.

Antibacterial phloroglucinols derivatives from the leaves of Mallotus oppositifolius (Geisler) Müll. Arg. (Euphorbiaceae).

From the ethno-medicinally used leaves of Mallotus oppositifolius, four acylphloroglucinol derivatives, namely Acronyculatin SU (1-3) and Mallotojaponin D (4) were isolated along with seven known compounds (5-11). Structures were elucidated by comprehensive spectroscopic analyses and HRMS data. Absolute configurations were assigned by careful comparison of their specific optical rotation with those of closely related compounds. Compounds 1, 2, 6 and 11 demonstrated inhibitory activity against the bacterial strains E. coli, S. aureus, S. typhi, P. aeruginosa with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50 µg/ml.