In vivo Antimalarial, Antioxidant Activities and Safety of Carapa procera DC. (Meliaceae).

Background and Objectives: Carapa procera is a popular herb used by traditional healers in the western part of Burkina Faso. In a previous study, Carapa procera showed interesting antiplasmodial activity in vitro against P. falciparum. The present study aimed to evaluate its in vivo potential against malaria parasites and its safety in mice. Materials and Methods: The antimalarial activity of the ethanolic extract was evaluated on Plasmodium berghei Anka in the Naval Medical Research Institute (NMRI) mice using the Peters 4-day suppressive test. The acute toxicity was performed according to the Lorke method and sub-acute toxicity following the Seewaboon method. The polyphenols and flavonoids were determined by colorimetric methods. The antioxidant activity of the extract was evaluated in vitro by Ferric Reducing Antioxidant Power (FRAPP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. Results: Carapa procera had a good antiplasmodial activity at a dose of 250 mg kg¹ b.wt. Phytochemical screening revealed the presence of polyphenols and flavonoids in the extracts. Soxhlet ethanolic extracts had the highest content in polyphenols and flavonoids. The antioxidant activity of Soxhlet ethanolic extracts was better than macerated extract by DPPH method and FRAP method. Besides, no mortality in mice was recorded with the soxhlet ethanolic extract. No toxic signs were observed in animals in the sub-acute toxicity test. Conclusion: Carapa procera soxhlet ethanolic stem bark extract had a good in vivo antimalarial activity against Plasmodium berghei infection in mice and the extract was relatively safe when administered orally in mice.

Experimental warming across a tropical forest canopy height gradient reveals minimal photosynthetic and respiratory acclimation.

Tropical forest canopies cycle vast amounts of carbon, yet we still have a limited understanding of how these critical ecosystems will respond to climate warming. We implemented in situ leaf-level + 3°C experimental warming from the understory to the upper canopy of two Puerto Rican tropical tree species, Guarea guidonia and Ocotea sintenisii. After approximately 1 month of continuous warming, we assessed adjustments in photosynthesis, chlorophyll fluorescence, stomatal conductance, leaf traits and foliar respiration. Warming did not alter net photosynthetic temperature response for either species; however, the optimum temperature of Ocotea understory leaf photosynthetic electron transport shifted upward. There was no Ocotea respiratory treatment effect, while Guarea respiratory temperature sensitivity (Q10 ) was down-regulated in heated leaves. The optimum temperatures for photosynthesis (Topt ) decreased 3-5°C from understory to the highest canopy position, perhaps due to upper canopy stomatal conductance limitations. Guarea upper canopy Topt was similar to the mean daytime temperatures, while Ocotea canopy leaves often operated above Topt . With minimal acclimation to warmer temperatures in the upper canopy, further warming could put these forests at risk of reduced CO2 uptake, which could weaken the overall carbon sink strength of this tropical forest.

Biological Activities of Gedunin-A Limonoid from the Meliaceae Family.

Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.

Acetylation of cedrelone increases its cytotoxic activity and reverts the malignant phenotype of breast cancer cells in 3D culture.

Cedrelone is a limonoid isolated from the plant Trichilia catigua (Meliaceae). Previous studies have demonstrated that cedrelone (1) has several damaging effects on triple negative breast tumor (TNBC) cell line MDA-MB-231. In this work we investigated two new derivatives of cedrelone, the acetate (1a) and the mesylate (1b), to examine whether their effects are improved in comparison to the lead molecule. Cedrelone acetate (1a) was the most cytotoxic compound on TNBC cells and was chosen for additional analyses in traditional two-dimensional (2D) monolayer cultures and three-dimensional (3D) assays. In 2D, 1a induced cell cycle arrest, apoptosis and inhibited essential steps of the metastasis process of the MDA-MB-231 cells, in vitro. Moreover, 1a was able to revert the malignant phenotype of the T4-2 cells in 3D. These effects were concomitant with the downregulation of EGFR, ß1-integrin and phospho-Akt, which could have resulted in a decrease of NFκB levels and MMP9 activity. These results suggest that 1a could be used as an important model for the design of a new drug to be applied in cancer treatment and be further studied in vivo for its antitumor and antimetastatic effects.

Characterization of typical potent odorants in raw and cooked Toona sinensis (A. Juss.) M. Roem. by instrumental-sensory analysis techniques.

Toona sinensis (A. Juss.) M. Roem. (TS) possesses a unique and pleasant flavor and is consumed as a popular seasonal vegetable in certain parts of eastern and southeastern Asia. The potent odorants in raw and cooked TS were identified by combined sensory and instrumental analysis techniques, including sensory descriptive aroma profiling and two complimentary volatile isolation methods combined with gas chromatography-olfactometry (GC-O) techniques. Highly volatile odorants were determined by static headspace dilution analysis (SHDA)-GC-O, while those of intermediate- and semi-volatility were determined by solvent-assisted flavor evaporation-aroma extract dilution analysis (SAFE-AEDA). Among the numerous odorants identified by SHDA and SAFE-AEDA, (E,E)-bis-(1-propenyl) disulfide was found to be predominant in both raw and cooked TS. In agreement with results of sensory descriptive analysis, hexanal, (Z)-3-hexenal, (E)-2-hexenal and (Z)-3-hexen-1-ol contributed green, grassy and leafy aroma notes; while hydrogen sulfide, methyl thiirane, (E,E)-bis-(1-propenyl) disulfide and (E,Z)-bis-(1-propenyl) disulfide contributed pungent, sulfurous and alliaceous notes in TS.

Xylomolones A-D from the Thai Mangrove Xylocarpus moluccensis: Assignment of Absolute Stereostructures and Unveiling a Convergent Strategy for Limonoid Biosynthesis.

Two new 9,10- seco limonoids with a central 3,4-dihydro-2 H-pyran motif, named xylomolones A and B (1 and 2, respectively), possessing identical absolute configurations but reversed alignments of ring A, compared to the tricyclic core of rings B-D, were obtained from seeds of the Thai mangrove Xylocarpus moluccensis, together with a highly modified 1,2- seco limonoid, named xylomolone C (3), containing a novel 3-oxabicyclo[3.2.1]octane-2,7-dione motif, and a new C11-terpenic acid methyl ester (4). The relative and absolute configurations of 1-4 were evidenced by extensive nuclear magnetic resonance (NMR) investigations combined with density functional theory and time-dependent density functional theory calculations of electronic circular dichroism, specific optical rotation, and 13C NMR data. The co-isolation of 1-4 allowed us to propose a novel convergent strategy for limonoid biosynthesis for the first time. This study demonstrates that mangroves of the genus Xylocarpus harbor new limonoid biosynthetic routes.

Sentulic acid isolated from Sandoricum koetjape Merr attenuates lipopolysaccharide and interferon gamma co-stimulated nitric oxide production in murine macrophage RAW264 cells.

A seco-triterpenoid, sentulic acid (SA) isolated from Sandoricum koetjape Merr attenuated nitric oxide (NO) production following co-stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFNγ) in RAW264.7 macrophage cells. The mRNA expression levels of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), IFNγ, interleukin (IL)-6, and IL-12 in LPS/IFNγ co-stimulated RAW264.7 cells also decreased upon SA treatment. To determine the molecular mechanisms underlying the inhibitory effect of SA on LPS/IFNγ-induced NO production in RAW264.7 cells, we further analyzed Toll-like receptor (TLR) signaling by western blotting. The expression of TLR4 and IFN signaling molecules in cells treated with SA was significantly suppressed compared to that in cells not treated with SA. Additionally, SA inhibited the binding of LPS to the TLR4 receptor in RAW264.7 cells stimulated with Alexa Fluor 488-conjugated LPS. These results demonstrate that SA attenuates NO production after LPS/IFNγ co-stimulation in RAW264.7 cells by inhibiting the binding of LPS to TLR4. Our findings suggest that SA is beneficial for the treatment of inflammatory diseases.

Renal toxicological evaluations of sulphonated nanocellulose from Khaya sengalensis seed in Wistar rats.

Nanocellulose is currently gaining attention due to its unique properties. This attention includes its application as building blocks for developing novel functional materials, plant drug and also in drug delivery systems. However, its safety remains largely untested or less understood. Thus, sulphonated nanocellulose (KSS) was prepared from cellulose (KSC) isolated from Khaya senegalensis seed (KS). KS, KSC and KSS were characterized using Fourier transformed infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), particle size distribution (PSD), zeta potential and scanning electron microscopy (SEM). The impact of KSS on selected renal markers of oxidative stress, inflammation and apoptosis in Wistar rats was also investigated. Thus, male rats were randomly assigned to four groups of five animals each and were treated with KSS (0, 50, 75 and 100 mg/kg BW) for 14 days. Thereafter, biomarkers of renal oxidative damage, inflammation and immunohistochemical expressions of iNOS, COX-2, Bcl-2 and p53 were evaluated. The results revealed KSS to have crystallinity of 70.40%, it was monomodal and has a flaky surface with agglomerations. KSS had no effect on markers of kidney function and oxidative damage, although there was a generalized hypernatremia after 14 days of exposure. Lastly, KSS enhanced the antioxidant status and immunohistochemical expressions of iNOS and COX-2 in the kidney of the rats. While the biomedical applications of KSS may appear plausible, our data suggests that it could induce renal toxicity via the combined impacts of electrolyte imbalance and inflammation.

HPLC-PDA-MS/MS Characterization of Bioactive Secondary Metabolites from Turraea fischeri Bark Extract and Its Antioxidant and Hepatoprotective Activities In Vivo.

Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications.

Isolation of the New Antiplasmodial Butanolide, Malleastrumolide A, from Malleastrum sp. (Meliaceae) from Madagascar.

An extract of Malleastrum sp. (Meliaceae) collected in Madagascar by the Madagascar International Cooperative Biodiversity Group was found to have antimalarial activity, with an IC50 value between 2.5 and 5 µg ml-1 . After purification by liquid-liquid partition, chromatography on a Diaion open column, C18 SPE and C18 reversed phase HPLC, the new butanolide, malleastrumolide A, was isolated. The structure of malleastrumolide A was determined by mass spectrometry, NMR, and ECD. The double bond position was determined by cross-metathesis and mass spectrometry. The compound has antiproliferative activity against the A2780 ovarian cancer cell line with an IC50 value of 17.4 µm and antiplasmodial activity against the drug-resistant Dd2 strain of Plasmodium falciparum with an IC50 value of 2.74 µm.

Triconoids A-D, Four Limonoids Possess Two Rearranged Carbon Skeletons from Trichilia connaroides.

Four limonoids, triconoids A-C (1-3) possessing a new rearranged mexicanolide skeleton and triconoid D (4) furnishing a new rearranged 1,2-seco-phragmalin skeleton, were isolated from the Nepalese plant Trichilia connaroides. Two rearranged limonoid skeletons sharing an F ring of methyl 5-oxotetrahydrofuran-2-carboxylate were postulated to be formed biosynthetically via a very unique chemical cascade. Their structures were fully accomplished by spectroscopic data, single-crystal X-ray diffraction, and electrostatic circular dichroism analysis.

Treatment of urea manufacturing facility effluent by Hopea odorata and Khaya ivorensis.

Phytoremediation is an environmentally friendly and sustainable alternative for treatment of nitrogen-enriched wastewaters. In this study, Ta-khian (Hopea odorata) and Lagos mahogany (Khaya ivorensis), two tropical timber plants, were investigated for their performances in treatment of urea manufacturing factory effluent with high nitrogen (N) content. Plant seedlings received four concentrations of N (190, 240, 290 and 340 mg/L N) in laboratory-scale constructed wetlands every 4 days for a duration of 8 weeks. The solution volumes supplied to each container, amount of N recovered by plants and plant growth characteristics were measured throughout the experiment. Results showed that Ta-khian plants were highly effective at reducing N concentration and volume of water. A maximum of 63.05% N recovery was obtained by Ta-khian plants grown in 290 mg/L N, which was assimilated in the chlorophyll molecule structure and shoot biomass. Significant positive correlations have been shown between N recovery percentages and plant growth parameters. Ta-Khian plants can be applied as suitable phytoremediators for mitigating N pollution in water sources.

Insights into the equilibrium, kinetic and thermodynamics of nickel removal by environmental friendly Lansium domesticum peel biosorbent.

Lansium domesticum peel (LDP), a waste material generated from the fruit consumption, was evaluated as a biosorbent for nickel removal from aqueous media. The effects of dosage, contact time, initial pH, initial concentration and temperature on the biosorption process were investigated in batch experiments. Equilibrium data were fitted by the Langmuir, Freundlich, Temkin and Dubinin-Radushkevich models using nonlinear regression method with the best-fit model evaluated based on coefficient of determination (R(2)) and Chi-square (χ(2)). The best-fit isotherm was found to be the Langmuir model exhibiting R(2) very close to unity (0.997-0.999), smallest χ(2) (0.0138-0.0562) and largest biosorption capacity (10.1mg/g) at 30°C. Kinetic studies showed that the initial nickel removal was rapid with the equilibrium state established within 30min. Pseudo-second-order model was the best-fit kinetic model indicating the chemisorption nature of the biosorption process. Further data analysis by the intraparticle diffusion model revealed the involvement of several rate-controlling steps such as boundary layer and intraparticle diffusion. Thermodynamically, the process was exothermic, spontaneous and feasible. Regeneration studies indicated that LDP biosorbent could be regenerated using hydrochloric acid solution with up to 85% efficiency. The present investigation proved that LDP having no economic value can be used as an alternative eco-friendly biosorbent for remediation of nickel contaminated water.

UPLC/Tandem mass and antimicrobial activity of Khaya senegalensis (A. Juss.) / UPLC/Tándem masa y la actividad antimicrobiana de Khaya senegalensis

Characterization of flavonoids and limonoids in the defatted acetone extract of Khaya senegalensis flowers (A. Juss.) contents was performed using ultra performance liquid chromatography (UPLC) coupled with ultraviolet (UV) and electrospray ionization (ESI) mass spectrometry, furthermore, tandem mass spectrometry (MS/MS) was performed to assist in the structural elucidation. The antimicrobial effect was tested against representative gram positive and negative bacteria and candida. Cytotoxicity of extract was evaluated using the mitochondrial- dependent reduction of MTT. The method used enabled identification of five flavonoid glycosides (di and mono- sugar) and twelve limonoids of different types viz: mexicanolides, phragmalins and angolensate were tentatively identified. The extract was effective against tested microorganism revealing potent growth inhibitory effect on Salmonella typhimurium ATCC 25566, Escherichia coli NRRN 3008 , Pseudomonas aeruginosa ATCC 10145 and fungus Candida albicans EMCC105, MIC ≤ 25µg/µl while MIC ≤ 50 µg/µl for Bacillus cereus, staphylococcus aureus ATCC 6538. Extract showed cytotoxicity against MCF7 (Breast carcinoma cell line) compared to doxorubicin, IC50=88.1(µg/mL) but no activity on HCT 116 (Colon carcinoma cell line) and HepG2 (liver cell carcinoma) was observed. Bioactive compounds in K senegalensis flowers acetone extract possesses promising antimicrobial activity with low cytotoxic effect warrants further investigation for their therapeutic and prophylactic roles

Se ha procedido a la caracterización de los flavonoides y limonoides del extracto acetónico de las flores de la especie Khaya senegalensis (A. Juss.) El análisis de sus componentes se realizó mediante cromatografía líquida de ultra resolución (UPLC) con detección ultravioleta (UV) y de espectrometría de masas de ionización por electrospray (ESI), así como espectrometría de masas (MS / MS) para ayudar en la elucidación estructural de los compuestos. Se comprobó el efecto antimicrobiano en bacterias gram positivas y negativas y levaduras como el género Candida. La citotoxicidad del extracto se evaluó mediante la reducción mitocondrial dependiente de MTT. El método de análisis permitió la identificación de cinco glucósidos flavonoides (di y mono-azúcar) y doce limonoides de diferentes tipos:se identificaron tentativamente mexicanolidos, phragmalinas y angolensato. El extracto fue efectivo contra microorganismos (≤ MIC 25µg / l ), revelando potente efecto inhibidor del crecimiento de Salmonella typhimurium (ATCC 25566), Escherichia coli (NRRN 3008), Pseudomonas aeruginosa (ATCC 10145) y el hongo Candida albicans (EMCC105). Igualmente fue eficaz a MIC ≤ 50 mg / l sobre Bacillus cereus, Staphylococcus aureus (ATCC 6538). Igualmente, el extracto mostró citotoxicidad contra línea celular de carcinoma de mama (MCF7) en comparación con la doxorrubicina, (IC50 = 88.1 (µg/ mL), pero no modificó la actividad en una línea celular de carcinoma colon (HCT 116) y en células de carcinoma del hígado (HepG2). Los compuestos bioactivos en extracto acetónico de flores de K. senegalensis poseen una actividad antimicrobiana prometedora con bajos efectos citotóxicos que garantizan la necesidad de una mayor investigación para conocer completamente sus papeles terapéuticos y profilácticos

Production of rohitukine in leaves and seeds of Dysoxylum binectariferum: an alternate renewable resource.

CONTEXT: Rohitukine is an important precursor for the synthesis of potential anticancer drugs flavopiridol (Sanofi-Aventis) and P-276-00 (Piramal Healthcare Limited, Mumbai, India). Trunk bark of Dysoxylum binectariferum (Roxb.) Hook. f. ex Bedd. (Meliaceae) is the widely used source for isolation of rohitukine. However, removal of trunk bark threatens the survival of the tree. OBJECTIVE: To investigate the amount of rohitukine accumulated in other tissues of D. binectariferum. MATERIALS AND METHODS: Rohitukine standard was isolated from leaves of D. binectariferum. Its purity was ascertained using HR-MS and NMR. Crude extracts were prepared from different tissues of D. binectariferum. Rohitukine content in all the tissues was quantified by HPLC. RESULTS: Rohitukine accumulates in a significant amount in seeds, trunk bark, leaves, twigs, and fruits of D. binectariferum. Seeds have the highest rohitukine content (2.42%, dry weight) followed by trunk bark (1.34%, dry weight), leaves (1.064%, dry weight), twigs (0.844% dry weight), and fruits (0.4559% dry weight). DISCUSSION AND CONCLUSION: Seeds and leaves of D. binectariferum could be used as alternate renewable sources for isolation of rohitukine.

Rubescins A, B and C: new havanensin type limonoids from root bark of Trichilia rubescens (Meliaceae).

Three new limonoids, rubescins A-C (1-3), and three known compounds including, havanensin type limonoid TS3 (4), ß-sitosterol, and stigmasterol were isolated from the root bark of Trichilia rubescens. Their structures were elucidated by means of extensive spectroscopic analyses, particularly one dimensional (1D)- and 2D-NMR techniques in conjunction with mass spectrometry. Rubescins A-C (1-3) and limonoid TS3 (4) were evaluated for their protective effects against oxidative stress induced in HC-04 cells by H2O2. Compound (1) showed strong inhibitory effects on lactase dehydrogenase (LDH) leakage, being as active (IC50 value of 0.0026 µM) as the positive control quercetin (IC50 value of 0.0030 µM).

Inhibitory effect of four triterpenoids from trichilia connaroides on nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells.

Two new highly rearranged trichiliton-type limonoids (trichilitons G-H, 1-2), and two new cycloartane-type triterpenoids, 21-(E)-coumaroyloxy-5α-cycloart-24-ene-3,23-dione (3) and 21-(E)-feruloyloxy-5α-cycloart-24-ene-3,23-dione (4), were isolated from the stem and bark of Trichilia connaroides. These isolates were elucidated on the basis of detailed spectroscopic analysis, and inhibitory effect of these compounds on lipopolysaccharide-induced nitric oxide production in mouse macrophage RAW264.7 cells was evaluated.

Chrotacumines E and F, two new chromone-alkaloid analogs from Dysoxylum acutangulum (Meliaceae) leaves.

A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum leaves led to the isolation and characterization of two new chromone alkaloid analogs named chrotacumines E and F (1 and 2, resp.). Structure elucidation of 1 and 2 was achieved by spectroscopic analyses, including 2D-NMR. Both of these alkaloids exhibited modest activities as tyrosinase inhibitors with 29.2 and 25.8% inhibition at 100 µg/ml, respectively.

Identification of (S,S)-γ-glutamyl-(cis-S-1-propenyl)thioglycine, a naturally occurring norcysteine derivative, from the Chinese vegetable Toona sinensis.

Extracts of Toona sinensis shoots were studied to identify the precursors of volatile sulfur-containing flavor molecules. T. sinensis was found to contain new compounds (S,S)-γ-glutamyl-(cis-S-1-propenyl)thioglycine, 1, (S,S)-γ-glutamyl-(trans-S-1-propenyl)thioglycine, 2, and γ-glutamyl-(cis-S-1-propenyl)-cysteine, 3. The structures of these compounds were determined by interpretation of multistage mass spectrometric (MS(n)), 1D, and 2D NMR data. The absolute configuration of 1 was established by comparison of experimental with computed infrared and vibrational circular dichroism spectra. Because of the flexibility of the molecule and the novelty of the structure, the configuration was further confirmed by X-ray crystallography. Compounds 1 and 2 are the first examples of norcysteine-containing metabolites reported from nature. They may release thiols via cleavage of the amide bond by proteases, followed by spontaneous decomposition of the resulting unstable alk(en)yl norcysteine moiety.

Temperature and saline stress on seedlings of Swietenia macrophylla: a comparative study.

Physical responses of plants to change in climatic factors like temperature, precipitation and abiotic factors like salinity intrusion may lead positive or negative effects. Some factor may promulgate growth while other may stunts their vigour. Present study seeks growth of a plantation species at its early stage of life towards elevated temperature and saline water stresses. Growth records of Swietenia macrophylla seedlings were enumerated by measuring height, collar diameter and leaf number development of the replicates growing at an environment-controlled plant growth chamber. One experimented with merely elevated temperature while other tries to find results of combined effect of elevated temperature (30, 32 and 34 degrees C) and saline (0.5, 1.5 and 2.5 g L(-1) NaCl) to said species seedlings. Seedling replicates showed diverse response to elevated temperature and saline irrigation at height, collar diameter and leaf number development. Results depict that elevated temperature alone might be positive for S. macrophylla seedlings, rather most favourable for its growth in height, however, collar diameter and leaf number may remain unaffected. Saline treatment along with higher temperature stresses may lead seedlings toward stunted or very low growth. As saline intensity increases, species growth tends to decrease proportionally. Elevated temperature aided with higher salinity may direct further under development of S. macrophylla seedlings which is distressing to plantation establishment of this species in sites which are vulnerable to salinity intrusion due to climate change. However, S. macrophylla may be a promising plantation species in drier part of the globe in near future.