Anti-Inflammatory Principles from Tamarix aphylla L.: A Bioassay-Guided Fractionation Study.

Natural products have served as primary remedies since ancient times due to their cultural acceptance and outstanding biodiversity. To investigate whether Tamarix aphylla L. modulates an inflammatory process, we carried out bioassay-guided isolation where the extracts and isolated compounds were tested for their modulatory effects on several inflammatory indicators, such as nitric oxide (NO), reactive oxygen species (ROS), proinflammatory cytokine; tumour necrosis factor (TNF-α), as well as the proliferation of the lymphocyte T-cells. The aqueous ethanolic extract of the plant inhibited the intracellular ROS production, NO generation, and T-cell proliferation. The aqueous ethanolic crude extract was partitioned by liquid-liquid fractionation using n-hexane (n-C6H6), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and water (H2O). The DCM and n-BuOH extracts showed the highest activity against most inflammatory indicators and were further purified to obtain compounds 1-4. The structures of 3,5-dihydroxy-4',7-dimethoxyflavone (1) and 3,5-dihydroxy-4-methoxybenzoic acid methyl ester (2) from the DCM extracts; and kaempferol (3), and 3-hydroxy-4-methoxy-(E)-cinnamic acid (4) from the n-BuOH extract were elucidated by different spectroscopic tools, including MS, NMR, UV, and IR. Compound 2 inhibited the production of ROS and TNF-α, whereas compound 3 showed inhibitory activity against all the tested mediators. A better understanding of the potential aspect of Tamarix aphylla L. derivatives as anti-inflammatory agents could open the door for the development of advanced anti-inflammatory entities.

Crystal structure and Hirshfeld surface analysis of the methanol solvate of sclareol, a labdane-type diterpenoid.

The title compound, C20H36O2·CH3OH [systematic name: (3S)-4-[(S)-3-hy-droxy-3-methyl-pent-4-en-1-yl]-3,4a,8,8-tetra-methyl-deca-hydro-naphthalen-3-ol methanol monosolvate], is a methanol solvate of sclareol, a diterpene oil isolated from the medicinally important medicinal herb Salvia sclarea, commonly known as clary sage. It crystallizes in space group P1 (No. 1) with Z' = 2. The sclareol mol-ecule comprises two trans-fused cyclo-hexane rings, each having an equatorially oriented hydroxyl group, and a 3-methyl-pent-1-en-3-ol side chain. In the crystal, Os-H⋯Os, Os-H⋯Om, Om-H⋯Os and Om-H⋯Om (s = sclareol, m = methanol) hydrogen bonds connect neighboring mol-ecules into infinite [010] chains. The title compound exhibits weak anti-leishmanial activity (IC50 = 66.4 ± 1.0 µM ml-1) against standard miltefosine (IC50 = 25.8 ± 0.2 µM ml-1).

Anti-glycating and anti-oxidant compounds from traditionally used anti-diabetic plant Geigeria alata(DC) Oliv. & Hiern.

A new sesquiterpene lactone geigerianoloide (1) and four known flavonoids axillarin (2), quercetin (3), 3-methoxy-5,7,3',4'-tetrahydroxy-flavone (4) and hispidulin (5) were isolated from Geigeria alata (DC) Oliv. & Hiern. (Asteraceae). Structures were deduced using 1H- and 13C- NMR spectroscopy, mass spectrometry, while the structure of compound 1 was also deduced using X-ray crystallography technique.Geigeria alata is traditionally used for diabetes, therefore compounds were tested for anti-glycation activity, in which compounds 2 and 3 showed potent activities (IC50 values of 246.97 ± 0.83 and 262.37 ± 0.22 µM, respectively) compared to IC50 value 294.50 ± 1.5 µM of rutin. Moreover, compound 4 exhibited a comparable activity to rutin (IC50 = 293.28 ± 1.34 µM). Compound 5 showed a weak activity.Compounds 2, 3, and 4 exhibited potent DPPH radical scavenging activity (IC50 = 0.1 ± 0.00, 0.13 ± 0.00 and 0.15 ± 0.01 µM, respectively). Compounds 2, 3, and 4 demonstrated significant superoxide anion scavenging activity with IC50 values of 0.14 ± 0.001, 0.17 ± 0.00, and 0.11 ± 0.006 µM, respectively.

Acute and sub-acute toxicity of the aqueous extract from the stem bark of Tetrapleura tetrapteura Taub. (Fabaceae) in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetrapteura Taub. is a leguminous multipurpose tree (Fabaceae) indigenous to tropical Africa. Fruits, seeds and stem bark infusions or decoctions of Tetrapleura tetrapteura Taub. are used to treat many diseases, such as gastric ulcer, rheumatism, malaria, hypertension and hyperlipidemia. AIM OF THE STUDY: This work was conducted to evaluate the acute and sub-acute toxicity of the aqueous extract of Tetrapleura tetrapteura Taub. (AETT) stem barks. MATERIALS AND METHODS: For the study of acute toxicity, single oral doses of 2000 mg/kg and 5000 mg/kg of AETT were administrated to male and female Balb/c mice, followed by observation of mice for 14 days. In the study of sub-acute toxicity, 48 albino wistar rats of both genders were randomly divided into six groups of 8 animals and they were daily and orally administrated for twenty eight days. The animal's test groups and satellite test group were administrated with the extract (AETT) at the doses of 100, 200 and 400 mg/kg and 400 mg/kg respectively. On the 29th day, the satellite group (control 2 and satellite 400 mg/kg) were observed during two more weeks. General behavior changes, mortality, body weight of animal, water and food intake were recorded during the study period. At the end of each treatment period, biochemical and hematological parameters were measured and histological examinations of liver and kidneys sections performed. RESULTS: Up to 5000 mg/kg single dose administration of AETT for fourteen days registered no death animal. In sub-acute study, no mortality was recorded in various experimental groups. Significant reductions in body weight, water and food intake were recorded in all treated animals. Relative weights of liver, kidneys, stomach, spleen, lungs, and heart of treated animals remained unchanged. Significant increases in the number of platelets as well as in serum ALAT level were recorded in rats, treated with 400 mg/kg of AETT. Female rat liver histology showed, at a higher dose of AETT, a slight congestion of portal vein. CONCLUSION: AETT is safe after therapeutic (200 mg/kg) or acute administration. Higher dose (400 mg/kg) administered for longer period showed signs of liver toxicity.

New iridoids from Lyonia ovalifolia and their anti-hyperglycemic effects in mice pancreatic islets.

Phytochemical investigation on the aerial parts of Lyonia ovalifolia (Wall.) Drude led to the isolation of three new iridoids, lyonofolin A (1), lyonofolin B (2), and lyonofolin C (3), and a known iridoid, gelsemiol (4). Structures of compounds 1-4 were determined by extensive spectroscopic analyses, including EI-MS, HREI-MS, UV, IR, and 1D- and 2D-NMR (HMBC, HSQC, COSY, NOESY) spectroscopic methods. The effect of insulin secretion of compounds 1, 2, and 4 were evaluated in mice pancreatic islets cellular model. This insulin secretory assay demonstrated that compound 2 potentiates glucose-induced insulin secretion, and thus can serve as a new insulin secretagogue for the treatment of diabetes. The newly isolated compounds were further evaluated against normal 3 T3 cell lines for cytotoxicity, where they did not show any cytotoxicity.

Crystal structure and Hirshfeld surface analysis of 3-oxours-12-ene-27a,28-dioic acid (quafrinoic acid).

The title compound, C30H44O5, is a penta-cyclic triterpene isolated from the Cameroonian medicinal plant Nauclea Pobeguinii and known as quafrinoic acid. The mol-ecule is composed of five fused six-membered rings, four of which adopt a chair conformation and one a half-chair conformation. Intra-molecular C-H⋯O hydrogen-bond inter-actions exist, which generate S6 and S8 rings. In the crystal, mol-ecules are linked by pairs of O-H⋯O hydrogen bonds, linking R22(8) rings into chains running parallel to the a axis; these chains are further connected into layers parallel to the ab plane by C-H⋯O hydrogen bonds. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (79.4%) and O⋯H (20.4%) inter-actions.

Substituted thieno[2,3-b]thiophenes and related congeners: Synthesis, ß-glucuronidase inhibition activity, crystal structure, and POM analyses.

A series of 15 novel compounds incorporating the thieno[2,3-b]thiophene moiety were synthesized. The chemical structures of these compounds were deduced from elemental analyses, (1)H NMR, (13)C NMR, and ESI-mass spectral data. The enzyme inhibition potential of these compounds was evaluated, in vitro, against ß-glucuronidase, xanthine oxidase, and α-chymotrypsin enzymes. The cytotoxicity was evaluated by a cell viability assay utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Among the compounds tested, compound 3 was the most potent ß-glucuronidase inhibitor with an IC50 value of 0.9 ± 0.0138 µM; it was much more active than the standard, d-saccharic acid 1,4-lactone (IC50=45.75 ± 2.16 µM). Compound 12, on the other hand, was the most potent as a xanthine oxidase inhibitor with an IC50 of 14.4 ± 1.2 µM. With the characterization of their mechanism of action and with further testing, these compounds could be useful candidates as anticancer drugs. In addition, the newly synthesized compounds were subjected to POM analyses to get insights about their degree of their toxicity.

Analysis and development of structure-fragmentation relationships in withanolides using an electrospray ionization quadropole time-of-flight tandem mass spectrometry hybrid instrument.

Structural elucidation and gas-phase fragmentation of ten withanolides (steroidal lactones) were studied using a positive ion electrospray ionization quadropole time-of-flight mass spectrometry (ESI-QqTOF-MS/MS) hybrid instrument. Withanolides form an important class of plant secondary metabolites, known to possess a variety of biological activities. Withanolides which possess hydroxyl groups at C-4, C-5, C-17, C-20, and C-27, and an epoxy group at C-5/C-6, were evaluated to determine the characteristic fragments and their possible pathways. ESI-QqTOF-MS (positive ion mode) showed the presence of the protonated molecules [M + H](+) . Low-energy collision-induced dissociation tandem mass spectrometric (CID-MS/MS) analysis of the protonated molecule [M + H](+) indicated multiple losses of water and the removal of the C-17-substituted lactone moiety affording the [M + H-Lac](+) product ion as the predominant pathways. However, withanolides containing a hydroxyl group at C-24 of the lactone moiety showed a different fragmentation pathway, which include the loss of steroidal part as a neutral molecule, with highly diagnostic ions at m/z 95 and 67 being generated from the cleavage of lactone moiety. Our results also determined the influence of the presence and positions of hydroxyl and epoxy groups on product ion formation and stability. Moreover, the knowledge of the fragmentation pattern was utilized in rapid identification of withanolides by the LC/MS/MS analysis of a Withania somnifera extract.

Separation of phenylpropanoids and evaluation of their antioxidant activity.

Phenylpropanoids are a group of natural products with a wide range of biological and pharmacological importance. They have been isolated from a large number of plants by utilizing a diverse range of chromatographic techniques. We describe here the utilization of normal, reverse phase, and high pressure liquid column chromatographic techniques for the purification of phenylpropanoids from the crude plant extracts. Most important of them is the recycling reverse phase HPLC effectively utilized to purify the highly oxygenated phenylpropanoids glycosides from the butanolic and water extracts. The antioxidant activity of the different phenylpropanoids is also reported on the basis of DPPH, superoxide anion scavenging and Fe(2+)-chelating assays, along with electron spin resonance (ESR) method.

New leishmanicidal physalins from Physalis minima.

Two new physalins, 16,24-cyclo-13,14-secoergosta-2-ene-18,26-dioic acid-14 : 17,14 : 27-diepoxy-11beta,13,20,22-tetrahydroxy-5alpha-methoxy-1,15-dioxo-gamma-lactone delta-lactone (1), and 16,24-cyclo-13,14-secoergosta-2-ene-18,26-dioic acid-14 : 17,14 : 27-diepoxy-5alpha,11beta,13,20,22-pentahydroxy-1,6,15-trioxo-gamma-lactone delta-lactone (2), have been isolated from the whole plant of Physalis minima Linn. (var. indica). Their structures were deduced on the basis of spectroscopic analysis. Both of these compounds have shown potent leishmanicidal activity against the promastigotes of Leishmania major.

Cholinesterase inhibiting withanolides from Withania somnifera.

A total of two new (1, 2) and four known (3-6) withanolides were isolated from the whole plant of Withania somnifera. Their structures were elucidated on the basis of spectroscopic techniques and were characterized as 6alpha,7alpha-epoxy-3beta,5alpha,20beta-trihydroxy-1-oxowitha-24-enolide (1), 5beta,6beta-epoxy-4beta,17alpha,27-trihydroxy-1-oxowitha-2,24-dienolide (2), withaferin-A (3), 2,3-dihydrowithaferin-A (4), 6alpha,7alpha-epoxy-5alpha,20beta-dihydroxy-1-oxowitha-2,24-dienolide (5), and 5beta,6beta-epoxy-4beta-hydroxy-1-oxowitha-2,14,24-trienolide (6), respectively. Compounds 2, 3, 5, and 6 displayed inhibitory potential against butyrylcholinesterase, but only compounds 3, 4, and 6 were found to be active against acetylcholinesterase.