Anti-inflammatory Quinoline Alkaloids from the Roots of Waltheria indica.

Sixteen new quinoline alkaloids (1a-7, 8a, 9, 10, 13-15, 17, and 21) and 10 known analogs (8b, 11, 12, 16, 18-20, and 22-24), along with three known cyclopeptide alkaloids (25-27), were isolated from the roots of Waltheria indica. The structures of the new compounds were elucidated by detailed NMR and circular dichroism with computational support and mass spectrometry data interpretation. Anti-inflammatory potential of isolates was evaluated based on inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa B (NF-κB) activity with cell culture models. In the absence of cell growth inhibition, compounds 6, 8a, 9-11, 13, 21, and 24 reduced TNF-α-induced NF-κB activity with IC50 values ranging from 7.1 to 12.1 µM, comparable to the positive control (BAY 11-7082, IC50 = 9.7 µM). Compounds 6, 8a, 8b, and 11 showed significant NO-inhibitory activity with IC50 values ranging from 11.0 to 12.8 µM, being more active than the positive control (l-NMMA, IC50 = 22.7 µM). Structure-activity relationships indicated that NO inhibitory activity was significantly affected by C-8 substitution. Inhibition of LPS-induced nitric oxide synthase (iNOS) by 8b [(5S)-waltherione M, IC50 11.7 ± 0.8 µM] correlated with inhibition of iNOS mRNA expression. The biological potential of W. indica metabolites supports the traditional use of this plant for the treatment of inflammatory-related disorders.

Microgrewiapine C: Asymmetric Synthesis, Spectroscopic Data, and Configuration Assignment.

The first asymmetric synthesis of microgrewiapine C, a piperidine alkaloid isolated from Microcos paniculata, is reported. This synthesis prompted correction of the 1H and 13C NMR data for the natural sample of the alkaloid, which was achieved by reanalysis of the original spectra. The corrected data for the natural product were found to be identical to those of the synthetic sample prepared herein, thus confirming the structural and relative configurational assignment of microgrewiapine C. Although comparison of specific rotation values indicates that the (1R,2S,3S,6S) absolute configuration should be assigned to the alkaloid, consideration of potential common biosynthetic origins of microgrewiapine C and congeners suggests that further phytochemical investigations are warranted.

Evidence for the Involvement of Cytokines Modulation and Prokinetic Properties in Gastric Ulcer Healing Effects of Helicteres sacarolha A. St.-Hil. A. Juss.

Preparations of Helicteres sacarolha (Malvaceae) leaves and roots are used in the form of decoction, infusion or maceration, to treat gastrointestinal disturbances, among others. Studies supporting some of its ethnomedicinal uses are still incipient. The present study aimed to investigate it potential effect on chronic ulcer, ulcerative colitis and possible prokinetic activities as part of its mechanism of action. The powdered leaves of Helicteres sacarolha (HEHs) was prepared by maceration in 70 % hydroethanolic solution. Its qualitative phytochemical constituents were investigated by direct flow injection analysis coupled to atmospheric pressure chemical ionization ion trap tandem mass spectrometry (FIA-APCI-IT-MSn ). The gastric ulcer healing effect was evaluated in acetic acid induced chronic ulcer in mice and the lesions were evaluated, including analysis of blood plasma cytokine levels. The prokinetic properties (gastric emptying and intestinal transit) were carried out in mice. Potential anti-ulcerative colitis activity was evaluated in rats using 2,4,6-trinitrobenzenesulfonic acid (5 % TNBS) -induced colitis. All animal experiments were carried out at the doses of 20, 50 and 250 mg/kg (p.o.). Eight compounds were putatively identified, specifically lariciresinol, and its derivatives, kaempferol derivatives and Tricin-O-Glc. The extract promoted increased gastric ulcer healing at all doses tested. Modulation of the cytokines involved inhibition of some key pro-inflammatory cytokines with maximum effect on IL-1ß (70 %, 50 mg/kg, p<0.05), TNF-α (79 %, 20 mg/kg, p<0.01), and in the anti-inflammatory cytokines, namely IL-10 (57 %, 50 mg/kg, p<0.05) and IL-17 (79 %, only at 50 mg/kg, p<0.05). Histological findings demonstrated a mitigated inflammatory activity, and tissues undergoing regeneration. HEHs treatment caused delayed gastric emptying, and increased intestinal transit, but had no effect in the experimentally induced ulcerative colitis. We report for the first time putatively the presence of Lariciresinol and tricin derivatives from the hydroethanolic leaves extract of H. sacarolha. Its possible mechanism of actions of gastric ulcer healing involves cytokines modulation, mitigation of inflammatory response and tissue regeneration and provoked opposing effect in the gastrointestinal system. The present study demonstrates the therapeutic potential of H. sacarolha leaves used in Brazilian ethnomedicine in the treatment of chronic gastric ulcer.

Coumarinolignans with Reactive Oxygen Species (ROS) and NF-κB Inhibitory Activities from the Roots of Waltheria indica.

Seven new coumarinolignans, walthindicins A-F (1a, 1b, 2-5, 7), along with five known analogs (6, 8-11), were isolated from the roots of Waltheria indica. The structures of the new compounds are determined by detailed nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. Compounds were tested for their antioxidant activity in Human Cervical Cancer cells (HeLa cells). Compounds 1a and 6 showed higher reactive oxygen species (ROS) inhibitory activity at 20 µg/mL when compared with other natural compound-based antioxidants such as ascorbic acid. Considering the role of ROS in nuclear-factor kappa B (NF-κB) activation, compounds 1a and 6 were evaluated for NF-κB inhibitory activity and showed a concentration-dependent inhibition in Human Embryonic Kidney 293 cells (Luc-HEK-293).

Preclinical safety assessment of the crude extract from Sida rhombifolia L. aerial parts in experimental models of acute and repeated-dose 28 days toxicity in rats.

Sida rhombifolia (Malvaceae) is popularly used as a treatment for several pathological conditions; however, there is a lack of studies that identify its compounds and that evaluate comprehensively the safety of its consumption. Therefore, the aim of this study was to determinate the phytochemical constitution of the crude extract of Sida rhombifolia (CESR), and its safety in models of acute and repeated doses (28 days) toxicity. The tested dose for the model of acute toxicity was 2000 mg/kg doses for the repeated dose model were 150, 300 e 600 mg/kg. Hematological, biochemical, histopathological and oxidative markers were investigated. HPLC-DAD-MS analysis evidenced the presence of caffeic acid, coumarin, and rutin. In the acute toxicity model the only altered parameters were tissue ROS, and AST and BUN in serum. As for the repeated dose experiment both hematological and biochemical markers remained within the values of reference for the species. Obtained results demonstrate that the CESR did not present significant toxic effects when administrated orally to male and female rats in acute and repeated doses.

Metabolic Profiling of Vasorelaxant Extract from Malvaviscus arboreus by LC/QTOF-MS.

We aimed to develop a standardized methodology to determine the metabolic profile of organic extracts from Malvaviscus arboreus Cav. (Malvaceae), a Mexican plant used in traditional medicine for the treatment of hypertension and other illnesses. Also, we determined the vasorelaxant activity of these extracts by ex vivo rat thoracic aorta assay. Organic extracts of stems and leaves were prepared by a comprehensive maceration process. The vasorelaxant activity was determined by measuring the relaxant capability of the extract to decrease a contraction induced by noradrenaline (0.1 µM). The hexane extract induced a significant vasorelaxant effect in a concentration- and endothelium-dependent manner. Secondary metabolites, such as polyunsaturated fatty acids, terpenes and one flavonoid, were annotated by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOF-MS) in positive ion mode. This exploratory study allowed us to identify bioactive secondary metabolites from Malvaviscus arboreus, as well as identify potentially-new vasorelaxant molecules and scaffolds for drug discovery.

Evaluation on Antidiabetic Properties of Medicinal Plants from Myanmar.

OBJECTIVES: To explore the effective and safe medicines for treating diabetes. METHODS: Hydroalcoholic extracts of 130 medicinal plants belonging to 66 families were evaluated using porcine pancreatic lipase (PPL) inhibition and glucose uptake methods together with a literature review. RESULTS: The extracts of 22 species showed the PPL inhibition activity; 18 extracts of 15 species stimulated glucose uptake in 3T3-L1 adipocytes. Among them, Mansonia gagei J.R. Drumm., Mesua ferrea L., and Centella asiatica (L.) Urb. exhibited both activities. The extracts of Caladium lindenii (André) Madison rhizomes and Azadirachta indica A. Juss. leaves presented the utmost lipase inhibitory activity with IC50 of 6.86 ± 0.25 and 11.46 ± 0.06 µg/mL, respectively. The extracts of Coptis teeta Wall. rhizomes and Croton tiglium L. seeds stimulated the maximum glucose uptake. Ten species are reported to have antidiabetic activity for the first time. Flavonoids and triterpenoids are the dominant antidiabetic compounds in selected medicinal plants from Myanmar. CONCLUSIONS: P. zeylanica, L. cubeba, H. crenulate, M. gagei, C. teeta, and M. ferrea are worthy to advance further study according to their strong antidiabetic activities and limited research on effects in in vivo animal studies, unclear chemical constitutes, and safety.

Activity-Guided Characterization of COX-2 Inhibitory Compounds in Waltheria indica L. Extracts.

Inflammation is the body's response to infection or tissue injury in order to restore and maintain homeostasis. Prostaglandin E2 (PGE-2) derived from arachidonic acid (AA), via up-regulation of cyclooxygenase-2 (COX-2), is a key mediator of inflammation and can also be induced by several other factors including stress, chromosomal aberration, or environmental factors. Targeting prostaglandin production by inhibiting COX-2 is hence relevant for the successful resolution of inflammation. Waltheria indica L. is a traditional medicinal plant whose extracts have demonstrated COX-2 inhibitory properties. However, the compounds responsible for the activity remained unknown. For the preparation of extracts with effective anti-inflammatory properties, characterization of these substances is vital. In this work, we aimed to address this issue by characterizing the substances responsible for the COX-2 inhibitory activity in the extracts and generating prediction models to quantify the COX-2 inhibitory activity without biological testing. For this purpose, an extract was separated into fractions by means of centrifugal partition chromatography (CPC). The inhibitory potential of the fractions and extracts against the COX-2 enzyme was determined using a fluorometric COX-2 inhibition assay. The characterizations of compounds in the fractions with the highest COX-2 inhibitory activity were conducted by high resolution mass spectrometry (HPLC-MS/MS). It was found that these fractions contain alpha-linolenic acid, linoleic acid and oleic acid, identified and reported for the first time in Waltheria indica leaf extracts. After analyzing their contents in different Waltheria indica extracts, it could be demonstrated that these fatty acids are responsible for up to 41% of the COX-2 inhibition observed with Waltheria indica extract. Additional quantification of secondary metabolites in the extract fractions revealed that substances from the group of steroidal saponins and triterpenoid saponins also contribute to the COX-2 inhibitory activity. Based on the content of compounds contributing to COX-2 inhibition, two mathematical models were successfully developed, both of which had a root mean square error (RMSE) = 1.6% COX-2 inhibitory activity, demonstrating a high correspondence between predicted versus observed values. The results of the predictive models further suggested that the compounds contribute to COX-2 inhibition in the order linoleic acid > alpha linolenic acid > steroidal saponins > triterpenoid saponins. The characterization of substances contributing to COX-2 inhibition in this study enables a more targeted development of extraction processes to obtain Waltheria indica extracts with superior anti-inflammatory properties.

Effects of Induced Exosomes from Endometrial Cancer Cells on Tumor Activity in the Presence of Aurea helianthus Extract.

Endometrial cancer (EC) cells metastasize to various regions, including the ovaries, fallopian tubes, cervix, blood, liver, bone, and brain. Various carcinogens are known to cause EC. Exosomes are released from several types of cells and contain various cellular components. In this study, flow cytometry and quantitative PCR were used to evaluate marker levels, cell migration, cell invasion, and mitochondrial membrane potential, and cellular senescence tests were used to estimate cancer activity. The microRNAs were profiled using next-generation sequencing. Although tocopherol-α and rutin content in Aurea helianthus is high, A. helianthus extract was more useful in modulating tumor activity compared to the two aforementioned substances. Notably, we established that the extract induced bioactive exosomes in EC cells, and profiling of miRNAs in the extract-inducing exosomes (EIE) indicated their potency to be developed as a biological drug. The extract and EIE contributed to the following five biological process categories for EC cells: (1) cell migration and invasion suppression, (2) cellular senescence activation by attenuating mitochondrial membrane potential and enhancing autophagy, (3) reproductive cancer activity attenuation, (4) drug susceptibility activation, and (5) EIE containing miRNAs associated with decreasing inflammation.

Ascleposide, a natural cardenolide, induces anticancer signaling in human castration-resistant prostatic cancer through Na+ /K+ -ATPase internalization and tubulin acetylation.

BACKGROUND: Cardiac glycosides, which inhibit Na+ /K+ -ATPase, display inotropic effects for the treatment of congestive heart failure and cardiac arrhythmia. Recent studies have suggested signaling downstream of Na+ /K+ -ATPase action in the regulation of cell proliferation and apoptosis and have revealed the anticancer activity of cardiac glycosides. The study aims to characterize the anticancer potential of ascleposide, a natural cardenolide, and to uncover its primary target and underlying mechanism against human castration-resistant prostate cancer (CRPC). METHODS: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay, carboxyfluorescein succinimidyl ester staining assay and clonogenic examination. Flow cytometric analysis was used to detect the distribution of cell cycle phase, mitochondrial membrane potential, intracellular Na+ and Ca2+ levels, and reactive oxygen species production. Protein expression was examined using Western blot analysis. Endocytosis of Na+ /K+ -ATPase was determined using confocal immunofluorescence microscopic examination. RESULTS: Ascleposide induced an increase of intracellular Na+ and a potent antiproliferative effect. It also induced a decrease of G1 phase distribution while an increase in both G2/M and apoptotic sub-G1 phases, and downregulated several cell cycle regulator proteins, including cyclins, Cdk, p21, and p27 Cip/Kip proteins, Rb and c-Myc. Ascleposide decreased the expression of antiapoptotic Bcl-2 members (eg, Bcl-2 and Mcl-1) but upregulated proapoptotic member (eg, Bak), leading to a significant loss of mitochondrial membrane potential and activation of both caspase-9 and caspase-3. Ascleposide also dramatically induced tubulin acetylation, leading to inhibition of the catalytic activity of Na+ /K+ -ATPase. Notably, extracellular high K+ (16 mM) significantly blunted ascleposide-mediated effects. Furthermore, ascleposide induced a p38 MAPK-dependent endocytosis of Na+ /K+ -ATPase and downregulated the protein expression of Na+ /K+ -ATPase α1 subunit. CONCLUSION: Ascleposide displays antiproliferative and apoptotic activities dependent on the inhibition of Na+ /K+ -ATPase pumping activity through p38 MAPK-mediated endocytosis of Na+ /K+ -ATPase and downregulation of α1 subunit, which in turn cause tubulin acetylation and cell cycle arrest. Cell apoptosis is ultimately triggered by the activation of caspase cascade attributed to mitochondrial damage through the downregulation of Bcl-2 and Mcl-1 protein expressions while upregulation of Bak protein levels. The data also suggest the potential of ascleposide in anti-CRPC development.

Pyridine-4(1H)-one Alkaloids from Waltheria indica as Antitrypanosomatid Agents.

Twelve new pyridine-4(1H)-one derivatives, namely, 8-demethoxywaltherione F (1), waltheriones R-V (2, 6, 7, 10, and 11), 1-methoxywaltherione O (3), (S)-15-hydroxywaltherione G (4), (8R)-8-hydroxywaltherione M (5), (9S,13S)-2-hydroxymethylwaltherione C (8), (9S,10S,13S)-10-hydroxywaltherione C (9), and (S)-13-methoxywaltherione V (12), as well as melovinone (13) and 5'-methoxywaltherione A (14) were isolated from the CH2Cl2 extract of the aerial parts of Waltheria indica. Their chemical structures were determined by means of a comprehensive analysis including 1H NMR, DEPTQ, HSQC, HMBC, 1H-1H COSY, ROESY, and HRESIMS data. The absolute configurations were assigned via comparison of the experimental and calculated ECD data. In addition, the isolated constituents as well as the known waltheriones M-Q were evaluated for their in vitro antitrypanosomal activity. Compounds 2, 5, and 7 as well as waltheriones M, P, and Q showed potent growth inhibition toward Trypanosoma cruzi with IC50 values of 2.1, 0.8, 2.1, 1.3, 0.5, and 0.1 µM, respectively, and selectivity indices of >12, >33, >13, 5, 25, and 14. These findings further demonstrate that the waltheriones are a promising class of antichagasic compounds worthy of further investigations.

Effect of Abelmoschus esculentus (okra) on metabolic syndrome: A review.

Metabolic syndrome is a disorder characterized by dyslipidemia, insulin resistance, abdominal fat, high blood pressure, hypertriglyceridemia, and diminished high density lipoprotein cholesterol. Okra (Abelmoschus esculentus L.), routinely called lady's finger, has belonged to the Malvaceae family. Okra is considered as a valuable crop due to the multiple functions of its leaves, buds, flowers, pods, stems, and seeds in traditional and modern medicines. Several bioactive components are presented in different parts of okra including polyphenolic compounds especially oligomeric catechins and flavonol derivatives such as quercetin. The antioxidant, anti-inflammatory, anticancer, immunomodulatory, gastroprotective, neuroprotective, lipid lowering, and antidiabetic effects of okra have been established. Although different in vivo and in vitro studies revealed that okra has an ability to overcome metabolic syndrome symptoms, the lack of clinical studies is notable. So, further clinical trials should be accomplished to confirm the role of okra in metabolic syndrome. The aims of this review are to gather different studies regarding the potential efficacy of okra in metabolic syndrome.

Anti-inflammatory activities of Waltheria indica extracts by modulating expression of IL-1B, TNF-α, TNFRII and NF-κB in human macrophages.

In Hawaiian traditional medicinal practices, the indigenous 'uhaloa, Waltheria indica var. Americana is one of the most recognized plants. Waltheria is also known in various cultures as a medicinal plant for the treatment of inflammatory conditions. Results in human subjects and cell and animal models supported anti-inflammatory activity for the Waltheria flavonoid quercetin, and for crude plant extracts, limited animal studies also confirmed anti-inflammatory effects. Yet no systematic studies have examined immune or inflammatory responses affected by these extracts. In order to gain insight into inflammatory cascades modulated by Waltheria extracts, and to uncover the mechanistic bases for the effective use of this medicinal plant as a natural anti-inflammatory agent, we have undertaken analyses of LPS and TNF-α/IF-γ-stimulated human macrophages treated with Waltheria extracts using targeted qRT-PCR and Inflammation Panels to test differential mRNA expression of two hundred immune-related genes, furthermore, ELISA assays and Inflammatory Protein arrays to determine extracts-modulated intracellular and secreted levels of prominent cytokines. Results demonstrate that Waltheria extracts inhibit key inflammatory cytokines and cytokine receptors including protein levels of IL-1B, IL-1ra, IL-8 and IL-6, reduce both mRNA and protein levels of TNF-α and protein levels of its receptor, TNF RII, predicting diminished TNF-α-associated inflammatory signaling that, together with significant reduction of NF-κB mRNA and protein, can effectively diminish activities of multiple pro-inflammatory signaling pathways and mitigate key processes in diseases with inflammatory components.

Insights on the Larvicidal Mechanism of Action of Fractions and Compounds from Aerial Parts of Helicteres velutina K. Schum against Aedes aegypti L.

Viral diseases transmitted by the female Aedes aegypti L. are considered a major public health problem. The aerial parts of Helicteres velutina K. Schum (Sterculiaceae) have demonstrated potential insecticidal and larvicidal activity against this vector. The objective of this research was to investigate the mechanisms of action involved in the larvicidal activity of this species. The cytotoxicity activity of H. velutina fractions and compounds of crude ethanolic extract of the aerial parts of this species was assessed by using fluorescence microscopy and propidium iodide staining. In addition, the production of nitric oxide (NO) and hemocyte recruitment were checked after different periods of exposure. The fluorescence microscopy revealed an increasing in larvae cell necrosis for the dichloromethane fraction, 7,4'-di-O-methyl-8-O-sulphate flavone and hexane fraction (15.4, 11.0, and 7.0%, respectively). The tiliroside did not show necrotic cells, which showed the same result as that seen in the negative control. The NO concentration in hemolymph after 24 h exposure was significantly greater for the dichloromethane fraction and the 7,4'-di-O-methyl-8-O-sulphate flavone (123.8 and 56.2 µM, respectively) when compared to the hexane fraction and tiliroside (10.8 and 8.3 µM, respectively). The presence of plasmocytes only in the dichloromethane fraction and 7,4'-di-O-methyl-8-O-sulphate flavone treatments suggest that these would be the hemocytes responsible for the highest NO production, acting as a defense agent. Our results showed that the larvicidal activity developed by H. velutina compounds is related to its hemocyte necrotizing activity and alteration in NO production.

Unravelling the Biological Activities of the Byttneria pilosa Leaves Using Experimental and Computational Approaches.

Byttneria pilosa is locally known as Harijora, and used by the native hill-tract people of Bangladesh for the treatment of rheumatalgia, snake bite, syphilis, fractured bones, elephantiasis and an antidote for poisoning. The present study was carried out to determine the possible anti-inflammatory, analgesic, neuropharmacological and anti-diarrhoeal activity of the methanol extract of B. pilosa leaves (MEBPL) through in vitro, in vivo and in silico approaches. In the anti-inflammatory study, evaluated by membrane stabilizing and protein denaturation methods, MEBPL showed a significant and dose dependent inhibition. The analgesic effect of MEBPL tested by inducing acetic acid and formalin revealed significant inhibition of pain in both tests. During the anxiolytic evaluation, the extract exhibited a significant and dose-dependent reduction of anxiety-like behaviour in mice. Similarly, mice treated with MEBPL demonstrated dose-dependent reduction in locomotion effect in the open field test and increased sedative effect in the thiopental sodium induced sleeping test. MEBPL also showed good anti-diarrheal activity in both castor oil induced diarrheal and intestinal motility tests. Besides, a previously isolated compound (beta-sitosterol) exhibited good binding affinity in docking and drug-likeliness properties in ADME/T studies. Overall, B. pilosa is a biologically active plant and could be a potential source of drug leads, which warrants further advanced study.

Brachychiton populneus as a novel source of bioactive ingredients with therapeutic effects: antioxidant, enzyme inhibitory, anti-inflammatory properties and LC-ESI-MS profile.

Brachychiton populneus is one of the unexploited Tunisian plants, traditionally eaten as food and used for medicinal purposes. The present study aimed to investigate the phytochemical components of the seeds, leaves and flowers from B. populneus using three different solvents and to explore their antioxidant, anti-inflammatory and neuroprotective effects. Further, this study was focused on the identification of phenolic compounds from the most active extract. In vitro, all extracts showed strong antioxidant property by DPPH, ferrous ion chelating and lipid peroxidation-inhibiting assays, noticeable anti-inflammatory activity by protein denaturation and membrane stabilization methods and important neuroprotective effects by acetylcholinesterase inhibitory test. In vivo, B. populneus (50, 100 and 200 mg/kg, i.p.) showed significant dose-response anti-inflammatory effects against carrageenan-induced paw edema. With respect to the phenolic profile, the leaf methanol extract presented eight phenolic acids, one flavone and four flavonoids, with salvianolic acid B (820.3 mg/kg), caffeic acid (224.03 mg/kg), syringic acid (100.2 mg/kg) and trans-ferulic acid (60.02 mg/kg) as the major compounds. The results of the current study suggested that B. populneus could be a precious source of health-benefitting biomolecules and may be developed as new antioxidant, anti-inflammatory and AChE inhibitors.

Response surface optimization and antioxidant activity of total proanthocyanidins fraction from Abutilon theophrasti Medic. leaves.

The extraction procedure and antioxidant activity were investigated for total proanthocyanidins extracts from Abutilon theophrasti Medic. leaves collected in August, September and October. The maximum extraction yield was achieved with 90% ethanol, 80°C of heating reflux temperature, 149.94 min of extraction time and 60(ml/g) of the ratio of solvent and material, which were optimized by Box-Behnken Design of response surface method. Spectrophotometric study displayed that total proanthocyanidins content was (0.44±0.02)% (0.52±0.01)% and (0.59±0.01)% for August, September and October samples, respectively. The proanthocyanidins extracts exhibited much stronger antioxidant activity to scavenge ABTS and DPPH free radicals, and reduce ferric power than the control synthetic antioxidant BHT. The present findings suggest that the proanthocyanidins extract from Abutilon theophrasti Medic. leaves was a very interesting candidate for the research and development of natural and healthy antioxidant for the pharmaceutical and food industries.

The Synthesis of Waltherione F and Its Analogues with Modifications at the 2- and 3-Positions as Potential Antitrypanosomal Agents.

Chagas disease also know as American Trypanosomiasis (AT) is a tropical parasitic disease endemic in South America, is caused by Trypanosoma cruzi, which is transmitted by the blood-sucking insect vectors called triatomine bugs. Quinoline alkaloids from the root extract of Waltheria indica are known to possess antitrypanosomal activity. Waltherione F, one of those alkaloids, was synthesised in 5 steps in 11 % overall yield. We report here the first X-ray crystallographic confirmation of the structure of Waltherione F 3. A key step in the sequence utilised the Conrad-Limpach synthesis for the formation of the quinolin-4(1H)-one ring system. Our synthetic strategy was designed to enable the modification of the 2- and 3-positions of the scaffold, allowing the generation of a diverse library of analogues to support our on-going medicinal chemistry program that is looking for new agents to tackle this devastating disease.

Salinity modifies heavy metals and arsenic absorption by the halophyte plant species Kosteletzkya pentacarpos and pollutant leaching from a polycontaminated substrate.

Phytomanagement of polycontaminated soils is challenging, especially in areas simultaneously affected by salinity. The wetland halophyte plant species Kosteletzkya pentacarpos was cultivated in a column device allowing leachate harvest, on a polycontaminated spiked soil containing Cd (6.5 mg kg-1 DW), As (75 mg kg-1 DW), Zn (200 mg kg-1 DW) and Pb (300 mg kg-1 DW) and irrigated with salt water (final soil electrical conductivity 5.0 ms cm-1). Salinity increased Cd bioavailability in the soil and Cd accumulation in the shoots while it had an opposite effect on As. Salinity did not modify Pb and Zn bioavailability and accumulation. Cultivating plants on the polluted soil drastically reduced the volume of leachate. In all cases, salinity reduced the total amounts of heavy metals removed by the leachate and significantly increased the proportion of Cd and Zn removed by the plants. Heavy metal contamination induced a decrease in shoot dry weight and an increase in malondialdehyde (an indicator of oxidative stress); both symptoms were alleviated by the additional presence of NaCl but this positive impact was not related to increase in protecting phytochelatins synthesis. It is concluded i) that bioavailability estimated by the 0.01M CaCl2 extraction procedure is not fully relevant from the heavy metal mobility, ii) that salinity decreased heavy metal percolation, especially in soils cultivated with K. pentacarpos and iii) that salinity improves plant tolerance to heavy metals in K. pentacarpos and that this species is a promising plant material for phytoremediation of polycontaminated soils.

Effect of Glyphaea brevis twigs extract on cell viability, apoptosis induction and mitochondrial membrane potential in TM3 Leydig cells.

Glyphaea brevis twigs (Spreng) Monach. (GBT) are used by local herb healers to manage male sexual fertility disorders. The aim of this study was to examine the effects of G. brevis twigs on TM3 Leydig cells. GBT was extracted using methanol solvent, and Leydig cells were exposed to the respective concentrations of GBT extract (0.1, 1, 10, 100 and 1,000 µg/ml) for 24 and 72 hr respectively. Parameters evaluated include cell morphology, viability (MTT assay), mitochondrial membrane potential (TMRE dye), apoptosis (Annexin V Alexa Fluor 488 binding) and RT-qPCR analyses of the mRNA expression. Results revealed that GBT had no cytotoxic effect on cell viability and the cell morphology. GBT also revealed a considerable elevation (p < 0.05) in fluorescence intensity, accompanied by intact mitochondria in TM3 Leydig cells. Furthermore, GBT resulted in the reduction of necrotic and apoptotic cells. The mRNA StAR was upregulated markedly with the effect prominent at 100 µg/ml. This study showed that GBT might be useful for managing male infertility ailments.