Differential Expression of Platelet Activation Markers, CD62P and CD63, after Exposure to Breast Cancer Cells Treated with Kigelia Africana, Ximenia Caffra and Mimusops Zeyheri Seed Oils In Vitro.

Cancer patients, including breast cancer patients, live in a hypercoagulable state. Chemo- and hormone- therapy used in the treatment of breast cancer increases the risk of thrombosis. Due to differences in health care services between developed and developing countries, the survival rate of women with breast cancer in developing countries is low. Consequently, ethnomedicines are used and their efficacy as potential alternatives are being scientifically explored. The seed oils of Kigelia africana, Ximenia caffra and Mimusops zeyheri have anti-proliferative effects on hormone-dependent (MCF-7) and cytotoxic effects on hormone-independent (MDA-MB-231) breast cancer cells. In this study, we determined if these seed oils reduce the thrombogenic ability of breast cancer cells by measuring the platelet surface expression of the activation-specific antigens CD62P and CD63. MDA-MB-231 and MCF-7 cells were pretreated with the seed oils before being exposed to whole blood of human female volunteers. An increase in CD62P and CD63 expression following whole blood exposure to untreated breast cancer cells was observed. Treated MDA-MB-231 cells reduced CD62P and CD63 expression while treated MCF-7 cells increased CD62P and decreased CD63 expression. Kigelia africana, Ximenia caffra and Mimusops zeyheri seed oils are able to reduce the thrombogenic ability of MDA-MB-231 breast cancer cells.

Ximenia americana: Economic Importance, Medicinal Value, and Current Status in Ethiopia.

Ximenia americana is one of the most valuable wild edible plants in the world. In different countries, it is utilized as food, medicine, an essential oil source, and the industrial component to other products. In Ethiopia, it was one of the most known and very important plants for a long period of time. It was utilized as food, a medicinal plant, and animal feed. It was also one of the most economically important and culturally valuable plants. But nowadays, it is not adequately available in the country due to deforestation problem in the years. In addition, its economic importance, current status, and medicinal roles are not well documented and understood. As for research studies, it is concluded that unless a collective effort is taken, the existence of this plant is under severe threat and needs to have some measures. This review article is aimed at addressing the abovelined topics in detail and to pinpoint and explain the importance and status of Ximenia americana.

Eglerisine, a Novel Sesquiterpenoid Tropolone from Dulacia egleri with Antiproliferative Effect against an Acute Myeloid Leukemia Lineage.

Chemical investigation of the stems of Dulacia egleri resulted in the isolation of eglerisine (1: ), a compound with a rare sesquiterpenoid tropolone skeleton. Its structure was determined by analysis of spectrometric and spectroscopic data, including HRESIMS, 1D, and 2D NMR. The antiproliferative effects of eglerisine were tested in human leukemia lineages. In the Kasumi-1 lineage, an acute myeloid leukemia cell line, eglerisine reduced cell metabolism, as determined by the resazurin assay. Eglerisine did not induce cell death by either apoptotic or necrotic mechanisms. However, a reduction of the absolute number of cells was observed. Eglerisine induced cell cycle arrest after 72 h of treatment by phosphorylation of H2AX histone, reducing the S phase and increasing the G2 phase of the cell cycle.

Transcriptome analysis reveals crucial genes involved in the biosynthesis of nervonic acid in woody Malania oleifera oilseeds.

BACKGROUND: Malania oleifera Chun et Lee (Olacaceae), an evergreen broad-leaved woody tree native to southwest China, is an important oilseed tree. Its seed oil has a high level of nervonic acid (cis-tetracos-15-enoic acid, over 60%), which is essential for human health. M. oleifera seed oil is a promising source of nervonic acid, but little is known about the physiological and molecular mechanisms underlying its biosynthesis. RESULTS: In this study, we recorded oil accumulation at four stages of seed development. Using a high-throughput RNA-sequencing technique, we obtained 55,843 unigenes, of which 29,176 unigenes were functionally annotated. By comparison, 22,833 unigenes had a two-fold or greater expression at the fast oil accumulation stage than at the initial stage. Of these, 198 unigenes were identified as being functionally involved in diverse lipid metabolism processes (including de novo fatty acid synthesis, carbon chain elongation and modification, and triacylglycerol assembly). Key genes (encoding KCS, KCR, HCD and ECR), putatively responsible for nervonic acid biosynthesis, were isolated and their expression profiles during seed development were confirmed by quantitative real-time PCR analysis. Also, we isolated regulatory factors (such as WRI1, ABI3 and FUS3) that are putatively involved in the regulation of oil biosynthesis and seed development. CONCLUSION: Our results provide novel data on the physiological and molecular mechanisms of nervonic acid biosynthesis and oil accumulation in M. oleifera seeds, and will also serve as a starting point for biotechnological genetic engineering for the production of nervonic acid resources.

Effect of ginger, Paullinia cupana, muira puama and l- citrulline, singly or in combination, on modulation of the inducible nitric oxide- NO-cGMP pathway in rat penile smooth muscle cells.

INTRODUCTION: COMP-4 is a natural compound-based dietary supplement consisting of the combination of ginger, Paullinia cupana, muira puama and l-citrulline, which when given long-term has been shown in the aged rat to a) upregulate iNOS in the penile smooth muscle cells (SMC), b) reverse the corporal SMC apoptosis and fibrosis associated with corporal veno-occlusive dysfunction (CVOD), and c) improve resulting erectile function. To elucidate the mechanism of how COMP-4 and its individual components modulate the iNOS-cGMP pathway, an in vitro study was conducted using a rat corporal primary SMC culture to determine its effect on NOS, soluble guanylate cyclase (sGC), cGMP and the phosphodiesterase 5 enzyme (PDE5). MATERIALS AND METHODS: Primary SMC cultures using the explant technique were initiated by cutting small pieces of corporal tissue from 8 week old Sprague-Dawley rats. The SMC were grown in Dulbecco media with 20% fetal calf serum. The SMC were then incubated with or without COMP-4 (0.69 mg/ml) or its ingredients alone (ginger: 0.225 mg/ml; muira puama, Paullinia cupana and l-citrulline each at 0.9 mg/ml) for up to 24 h mRNA and protein were extracted and used for the determination of NOS, sGC and PDE5 content. cGMP content was determined by ELISA. L-NIL (4 µM) was used as an inhibitor of iNOS activity. RESULTS: Compared to the control values, COMP-4 upregulated expression of cGMP by 85%, induced a 42 fold increase in sGC as well as a 15 fold increase in both iNOS protein and mRNA content while it decreased both PDE5 mRNA and protein content each by about 50%. L-NIL completely inhibited the effect of COMP-4 on cGMP production. When compared with each of the individual four components of COMP-4, it appears that COMP-4 itself had the most profound effect in modulating each one the specific steps within the iNOS-cGMP pathway. CONCLUSIONS: This in vitro study demonstrates that COMP-4 is capable of activating the endogenous cellular iNOS-cGMP pathway within the CSM cells, which is theorized to be responsible for reducing the fibrosis and apoptosis as well as the CVOD observed in the aging rat penis. Further studies will be necessary in order to determine whether supplementation of COMP-4 on a daily basis may be beneficial in halting or reversing this aging related erectile dysfunction in the clinical setting.

HPLC-DAD finger printing, antioxidant, cholinesterase, and α-glucosidase inhibitory potentials of a novel plant Olax nana.

BACKGROUND: The medicinal importance of a novel plant Olax nana Wall. ex Benth. (family: Olacaceae) was revealed for the first time via HPLC-DAD finger printing, qualitative phytochemical analysis, antioxidant, cholinesterase, and α-glucosidase inhibitory assays. METHODS: The crude methanolic extract of O. nana (ON-Cr) was subjected to qualitative phytochemical analysis and HPLC-DAD finger printing. The antioxidant potential of ON-Cr was assessed via 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) and hydrogen peroxide (H2O2) free radical scavenging assays. Furthermore, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay, while α- glucosidase inhibitory assay was carried out using a standard protocol. RESULTS: The qualitative phytochemical analysis of ON-Cr revealed the presence of secondary metabolites like alkaloids, flavonoids, tannins, sterols, saponins and terpenoids. The HPLC-DAD finger printing revealed the presence of 40 potential compounds in ON-Cr. Considerable anti-radical activities was revealed by ON-Cr in the DPPH, ABTS and H2O2 free radical scavenging assays with IC50 values of 71.46, 72.55 and 92.33 µg/mL, respectively. Furthermore, ON-Cr showed potent AChE and BChE inhibitory potentials as indicated by their IC50 values of 33.2 and 55.36 µg/mL, respectively. In the α-glucosidase inhibition assay, ON-Cr exhibited moderate inhibitory propensity with an IC50 value of 639.89 µg/mL. CONCLUSIONS: This study investigated Olax nana for the first time for detailed qualitative phytochemical tests, HPLC-DAD finger printing analysis, antioxidant, anticholinesterase and α-glucosidase inhibition assays. The antioxidant and cholinesterase inhibitory results were considerable and can provide scientific basis for further studies on the neuroprotective and anti-Alzheimer's potentials of this plant. ON-Cr may further be subjected to fractionation and polarity guided fractionation to narrow down the search for isolation of bioactive compounds.

Efficacy of plants extracts from the Cerrado against adult female of Dermacentor nitens (Acari: Ixodidae).

Dermacentor nitens tick is commonly found in the equine auditory canal, where it causes economic losses due to its direct damage, causing blood spoliation, stress, transmission of pathogens, and predisposition to myasis and secondary bacterial infection in its hosts. In this study we evaluated the effect of ethanolic extracts of Cerrado plants on biological parameters of engorged females of D. nitens. Ethanolic extracts were prepared from the leaves of Schinopsis brasiliensis, Piptadenia viridiflora, Ximenia americana, and Serjania lethalis at 25-150 mg mL-1. Groups of 10 engorged adult females were treated with these extracts and compared with a control containing distilled water and another control with organophosphate, using five replicates for each group. Compared with the control with water, S. lethalis and X. americana extracts at 100 and 150 mg mL-1 significantly inhibited the posture ability. Differently, extracts of S. brasiliensis and P. viridiflora were the most effective in inhibiting larval hatching. Extracts of X. americana and P. viridiflora showed effective inhibition of reproductive parameters of the tick, presenting dose-dependent effect with IC90 78.86 and 78.94 mg mL-1, respectively. Theses effective extracts contained low condensed tannin levels and their HPLC chromatograms revealed the presence of flavonoids. The efficacies of P. viridiflora and X. americana extracts were higher than 90% indicating that these extracts are promising as alternative agents for D. nitens control.

Contribution of Secondary Metabolites to the Gastroprotective Effect of Aqueous Extract of Ximenia americana L. (Olacaceae) Stem Bark in Rats.

Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid chromatography-mass spectrometry (LC-MS) and its antiulcerogenic effect was evaluated in acute gastric lesions induced by ethanol, acidified ethanol, and indomethacin. Antisecretory action, mucus production and the participation of sulfhydryl groups (-SH) and nitric oxide (NO) were also investigated. The chromatographic analysis identified procyanidins B and C and catechin/epicatechin as major compounds. Oral administration of XaAE (100, 200 and 400 mg/kg) inhibited the gastric lesions induced by ethanol (76.1%, 77.5% and 100%, respectively), acidified ethanol (44.9%, 80.6% and 94.9%, respectively) and indomethacin (56.4%, 52.7% and 64.9%, respectively). XaAE reduced gastric contents and acidity (51.4% and 67.7%, respectively) but did not alter the production of gastric mucus. The reduction of the -SH and NO groups promoted by N-ethylmaleimide (NEM) and Nω-nitro-l-arginine-methyl-ester (L-NAME) respectively, reduced the gastroprotective effect of XaAE. In conclusion, XaAE has gastroprotective activity mediated in part by -SH, NO and antisecretory activity. This antiulcer action was initially correlated to its major constituents, procyanidins B and C and catechin/epicatechin.

Aqueous extract of Securidaca longipendunculata Oliv. and Olax subscropioidea inhibits key enzymes (acetylcholinesterase and butyrylcholinesterase) linked with Alzheimer's disease in vitro.

CONTEXT: Plants have historically been used to treat neurodegerative diseases which include Alzheimer's disease. OBJECTIVE: This study investigated the antioxidant properties and inhibitory effect of aqueous extracts of Securidaca longipendunculata root and Olax subscropioidea leaf on the cholinergic system in rat brain in vitro. MATERIALS AND METHODS: Aqueous extracts (1:20 w/v) of S. longipendunculata root and O. subscropioidea leaf was prepared and the ability of the extract to inhibit the activities of acetylcholinesterase and butyrylcholinesterase was evaluated as well as antioxidants as typified by 2,2-azino-bis-(3-ethylbenthiazoline-6-sulphonic acid (ABTS•) radical scavenging ability and Fe chelation spectophotometrically. RESULTS: ABTS• radical scavenging ability showed that S. longipendunculata (0.075 Mmol TEAC/100 g) had a higher scavenging ability than O. subscropioidea (0.07 Mmol TEAC/100 g). Also, the Fe2+ chelating ability of both extracts revealed that S. longipendunculata (IC50 = 105.57 g/mL) had a significantly (p < 0.05) higher Fe2+ chelating ability than O. subscropioidea (IC50 = 255.84 g/mL). Extracts of S. longipendunculata and O. subscropioidea inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. However, S. longipendunculata (IC50 = 108.02 g/mL) has the higher AChE inhibitory activity than O. subscropioidea (IC50 = 110.35 g/mL). Also, both extracts inhibit BChE activity in vitro but S. longipendunculata (IC50 = 82.55 g/mL) had a higher BChE inhibitory activity than O. subscropioidea (IC50 = 108.44 g/mL). DISCUSSION AND CONCLUSIONS: The mechanism by which S. longipendunculata root and O. subscropioidea leaf perform their anti-Alzheimer's disease activity may be by their inhibition on the key enzymes linked to this disease.

Antioxidant activity and peroxidase inhibition of Amazonian plants extracts traditionally used as anti-inflammatory.

BACKGROUND: The Amazon is the largest rainforest in the world and is home to a rich biodiversity of medicinal plants. Several of these plants are used by the local population for the treatment of diseases, many of those with probable anti-inflammatory effect. The aim of the present investigation was to evaluate the in vitro antioxidant and anti-peroxidases potential of the ethanol extracts of five plants from the Brazilian Amazon (Byrsonima japurensis, Calycophyllum spruceanum, Maytenus guyanensis, Passiflora nitida and Ptychopetalum olacoides). METHODS: DPPH, ABTS, superoxide anion radical, singlet oxygen and the ß-carotene bleaching methods were employed for characterization of free radical scavenging activity. Also, total polyphenols were determined. Antioxidant activities were evaluated using murine fibroblast NIH3T3 cell. Inhibition of HRP and MPO were evaluated using amplex red® as susbtract. RESULTS: The stem bark extracts of C. spruceanum and M. guyanensis provided the highest free radical scavenging activities. C. spruceanum exhibited IC50 = 7.5 ± 0.9, 5.0 ± 0.1, 18.2 ± 3.0 and 92.4 ± 24.8 µg/mL for DPPH(•), ABTS(+•), O2 (-•) and (1)O2 assays, respectively. P. olacoides and C. spruceanum extracts also inhibited free radicals formation in the cell-based assay. At a concentration of 100 µg/mL, the extracts of C. spruceanum, B. japurensis inhibited horseradish peroxidase by 62 and 50 %, respectively. C. spruceanum, M. guyanensis, B. japurensis also inhibited myeloperoxidase in 72, 67 and 56 %, respectively. CONCLUSIONS: This work supports the folk use these species that inhibited peroxidases and exhibited significant free radical scavenging and antioxidant activities what can be related to treatment of inflammation.

Effect of dietary Ximenia caffra kernel meal on blood and liver metabolic substrate content and the general clinical biochemistry of Sprague Dawley rats.

We investigated (at the University of the Witwatersrand: GPS coordinates 26°10' 52.96″S; 28°2' 33.61″E) the effects of substituting soya bean meal (SBM) with Ximenia caffra kernel meal (XCKM) as a dietary protein source on blood and liver metabolic substrates content, serum markers of liver and kidney function and the general clinical biochemistry of Sprague Dawley (SD) rats. Five diets with similar energy and protein content were formulated (D1-D5) where XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. Forty weanling male SD rats were randomly assigned to diets D1-D5, fed for 37 days and weighed twice weekly. The rats were then fasted overnight, and fasting blood glucose and triglyceride concentrations were determined from tail-vein-drawn blood. Immediately thereafter, the rats were euthanised and blood was collected via cardiac puncture. Serum was used to assay for markers of the general health profile. Livers were removed and weighed, and samples were used to determine lipid and glycogen content. Rats fed D4 (75% substitution level) had significantly lower (p < 0.05) blood triglyceride content compared with rats fed D2 (25% level of substitution). The substitution of SBM with XCKM did not affect (p > 0.05) fasting blood glucose and cholesterol concentrations, liver glycogen and lipid content. Additionally, it had no effect (p > 0.05) on serum activity/concentration of surrogate markers of liver (alanine aminotransferase and alkaline phosphatase activity and urea, total bilirubin, globulin and albumin concentrations) and kidney (phosphorus, calcium and creatinine concentrations) function and the general clinical biochemistry of the rats. Defatted XCKM could substitute SBM in rat diets without compromising blood glucose and cholesterol homeostasis, liver and kidney function and the general clinical biochemistry of growing male Sprague Dawley rats.

Sesquiterpenoid tropolone glycosides from Liriosma ovata.

Two new sesquiterpenoid tropolone glycosides, liriosmasides A (1) and B (2), along with two known compounds, secoxyloganin and oplopanpheside C, were isolated from a methanol extract of the roots of Liriosma ovata. The structures of 1 and 2 were elucidated by spectroscopic methods including 1D and 2D NMR and by high-resolution mass spectrometry involving an ultra-high-performance liquid chromatography-quadrupole-orbital ion trap mass spectrometric (UHPLC-Q-Orbitrap MS) method. Compound 1 showed weak inhibitory activity against HIV RNase H.

Evaluation of riproximin binding properties reveals a novel mechanism for cellular targeting.

Riproximin is a cytotoxic type II ribosome-inactivating protein showing high selectivity for tumor cell lines. Its binding to cell surface glycans is crucial for subsequent internalization and cytotoxicity. In this paper, we describe a unique mechanism of interaction and discuss its implications for the cellular targeting and cytotoxicity of riproximin. On a carbohydrate microarray, riproximin specifically bound to two types of asialo-glycans, namely to bi- and triantennary complex N-glycan structures (NA2/NA3) and to repetitive N-acetyl-D-galactosamine (GalNAc), the so-called clustered Tn antigen, a cancer-specific O-glycan on mucins. Two glycoproteins showing high riproximin binding, the NA3-presenting asialofetuin and the clustered Tn-rich asialo-bovine submaxillary mucin, were subsequently chosen as model glycoproteins to mimic the binding interactions of riproximin with the two types of glycans. ELISA analyses were used to relate the two binding specificities of riproximin to its two sugar binding sites. The ability of riproximin to cross-link the two model proteins revealed that binding of the two types of glycoconjugates occurs within different binding sites. The biological implications of these binding properties were analyzed in cellular assays. The cytotoxicity of riproximin was found to depend on its specific and concomitant interaction with the two glycoconjugates as well as on dynamic avidity effects typical for lectins binding to multivalent glycoproteins. The presence of definite, cancer-related structures on the cells to be targeted determines the therapeutic potency of riproximin. Due to its cross-linking ability, riproximin is expected to show a high degree of specificity for cells exposing both NA2/NA3 and clustered Tn structures.

Schoepfiajasmins A-H: C-glycosyl dihydrochalcones, dihydrochalcone glycoside, C-glucosyl flavanones, flavanone glycoside and flavone glycoside from the branches of Schoepfia jasminodora.

From the branches of Schoepfia jasminodora collected in Okinawa, three new dihydrochalcone C-glycosides, one dihydrochalcone di-O-glucopyranoside, two flavanone C-glycosides, one flavanone O-glycoside and one flavone O-glycoside were isolated. Their structures were elucidated by extensive study of one- and two-dimensional NMR spectroscopic data.

Purification and characterization of riproximin from Ximenia americana fruit kernels.

Highly pure riproximin was isolated from the fruit kernels of Ximenia americana, a defined, seasonally available and potentially unlimited herbal source. The newly established purification procedure included an initial aqueous extraction, removal of lipids with chloroform and subsequent chromatographic purification steps on a strong anion exchange resin and lactosyl-Sepharose. Consistent purity and stable biological properties were shown over several purification batches. The purified, kernel-derived riproximin was characterized in comparison to the African plant material riproximin and revealed highly similar biochemical and biological properties but differences in the electrophoresis pattern and mass spectrometry peptide profile. Our results suggest that although the purified fruit kernel riproximin consists of a mixture of closely related isoforms, it provides a reliable basis for further research and development of this type II ribosome inactivating protein (RIP).

Fruiting character variability in wild individuals of Malania oleifera, a highly valued endemic species.

Malania oleifera (Olacaceae), a tree species endemic to Southwest China, has seed oils enriched with nervonic acid and is therefore good source of this chemical. Because of this, there are promising industrial perspective in the artificial cultivation and use of this species. Understanding the variability in the fruit characters among individuals forms the basis or resource prospection. In the current investigation, fifty-three mature fruiting trees were sampled from two locations with divergent climates (Guangnan and Funing). Morphological characterization of fruits (fruit and stone weight, fruit transverse and longitudinal diameter, stone transverse and longitudinal diameter) was conducted, and the concentration of seed oil and its fatty acid composition were also analyzed in all individuals. Differences in all the morphological characters studied were more significant among individual trees than between different geographic localities, even though these had different climates. Eleven fatty acids were identified contributing between 91.39 and 96.34% of the lipids, and the major components were nervonic acid (38.93-47.24%), octadecenoic acid (26.79-32.08%), docosenoic acid (10.94-17.24%). The seed oil content (proportion of oil in seed kernel) and the proportion of nervonic acid were both higher in Funing, which has a higher average climatic temperature than Guangnan. The concentrations of nervonic acid and octadecenoic acid with the low coefficients of variation in the seed oil of M. oleifera were relatively stable in contrast to the other fatty acids. There were significant positive correlations between fruit morphological characters, but the amount of seed oil and the concentrations of its components were not correlated with any morphological character. This study provides an understanding of morphological variation in wild M. oleifera individuals. Wild individuals with excellent fruit traits could be selected and would make promising candidates for commercial cultivation.

Studies on Ethanol Extracts of Olax subscorpioidea Against Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

<b>Background and Objective:</b> Liver disease orchestrated by noxious chemicals are serious health problems the world over. Traditionally, there are claims that ethanol extracts of leaves and stem barks of <i>Olax subscorpioidea</i> are used in the treatment of hepatic disorders. Thus, it investigated the impacts of ethanol extract of leaves and stem bark of <i>Olax subscorpioidea</i> against carbon tetrachloride (CCl₄)-induced liver damage in rats. <b>Materials and Methods:</b> Liver toxicity was induced by intraperitoneal injection of 2.5 mg kg¹ b.wt., of CCl₄ in experimental rats. Rats were treated with 200, 400 and 800 mg kg¹ dose ethanol leaves and stem bark of <i>Olax subscorpioidea</i>, respectively after induction of liver damage. <b>Results:</b> Obtained results showed a significant rise in the serum levels of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Malondialdehyde (MDA) and bilirubin as well as decreased Albumin (ALB), Superoxide Dismutase (SOD), Catalase (CAT), reduced Glutathione (GSH) in CCl₄-challenged rats. Treatment with the extracts attenuated serum levels of AST, ALT, ALP, MDA and bilirubin in addition to increased activities of SOD, CAT and the levels of ALB and GSH when compared to the CCl₄ group. Histopathological studies demonstrated that the extracts ameliorated liver necrosis and inflammation due to CCl₄ insult. <b>Conclusion:</b> These results concluded that ethanol extract of leaves and stem bark of <i>Olax subscorpioidea </i>may reduce hepatic oxidative injury caused by CCl₄ by its antioxidant potentials.

Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea.

BACKGROUND: Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. METHODS: Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). RESULTS: Extracts up to 100 µg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 µg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. CONCLUSION: As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.

Phytochemical study, molecular docking, genotoxicity and therapeutic efficacy of the aqueous extract of the stem bark of Ximenia americana L. in the treatment of experimental COPD in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ximenia americana L. is popularly known as yellow plum, brave plum or tallow wood. All the parts of this plant are used in popular medicine. Its reddish and smooth bark are used to treat skin infections, inflammation of the mucous membranes and in the wound healing process. OBJECTIVE: Verification of phytochemical profile, the molecular interaction between flavonoid, (-) epi-catechin and 5-LOX enzyme, by means of in silico study, the genotoxic effect and to investigate the pharmacological action of the aqueous extract of the stem bark of X. americana in pulmonary alterations caused by experimental COPD in Rattus norvegicus. MATERIALS AND METHODS: The identification of secondary metabolites was carried out by TLC and HPLC chromatographic methods, molecular anchoring tests were applied to analyze the interaction of flavonoid present in the extract with the enzyme involved in pulmonary inflammation process and the genotoxic effect was assessed by comet assay and micronucleus test. For induction of COPD, male rats were distributed in seven groups. The control group was exposed only to ambient air and six were subjected to passive smoke inhalations for 20 min/day for 60 days. One of the groups exposed to cigarette smoke did not receive treatment. The others were treated by inhalation with beclomethasone dipropionate (400 mcg/kg) and aqueous and lyophilized extracts of X. americana (500 mg/kg) separately or in combination for a period of 15 days. The structural and inflammatory pulmonary alterations were evaluated by histological examination. Additional morphometric analyses were performed, including the alveolar diameter and the thickness of the right ventricle wall. RESULTS: The results showed that the aqueous extract of the bark of X. americana possesses (-) epi -catechin, in silico studies with 5-LOX indicate that the EpiC ligand showed better affinity parameters than the AracA ligand, which is in accordance with the results obtained in vivo studies. Genotoxity was not observed at the dose tested and the extract was able to stagnate the alveolar enlargement caused by the destruction of the interalveolar septa, attenuation of mucus production and decrease the presence of collagen fibers in the bronchi of animals submitted to cigarette smoke. CONCLUSION: Altogether, the results proved that the aqueous extract of X. americana presents itself as a new option of therapeutic approach in the treatment of COPD.

Antidepressant profile of Ptychopetalum olacoides Bentham (Marapuama) in mice.

Depression has become of universal major importance, and it is therefore vital to expand the armamentarium for treating the condition. Lack of motivation and lassitude are major symptoms treated with the use of Marapuama (Ptychopetalum olacoides, PO) remedies by communities in the Brazilian Amazon. Considering the prominence of such symptoms in depression, the present study was designed to verify the effects of a standardized PO ethanol extract (POEE) on the forced swimming (FST) and tail suspension tests (TST). POEE i.p. (15-100 mg/kg) and oral (300 mg/kg) resulted in a significant and dose-related anti-immobility effect. We further examined the involvement of dopamine, noradrenaline and serotonin in these antidepressant-like effects. POEE effects were prevented when catecholamine synthesis was inhibited by -alpha-methyl-rho-tyrosine (AMPT) (100 mg/kg, i.p.), while inhibition of serotonin synthesis with rho-chlorophenylalanine methyl ester hydrochloride (PCPA) (100 mg/kg, i.p.) was devoid of effect. The blockade of beta-adrenergic (propranolol 2 mg/kg, i.p.) and D(1) dopamine (SCH 23390 0.5 mg/kg, i.p.) receptors prevented POEE anti-immobility effects; by contrast, blockade of D(2) dopamine (sulpiride 2 and 50 mg/kg, i.p.) receptors was ineffective. Consistent with traditional use, the results indicate that POEE possesses antidepressant-like effects, possibly mediated by beta-adrenergic and D(1) dopamine receptors.