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.

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.

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.

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.

An Overview on the Properties of Ximenia Oil Used as Cosmetic in Angola.

Ximenia (Ximeniaamericana L.) is a shrub, or small tree, native from Africa and spread across different continents. In Angola, the seeds oil is used by local populations, to prevent sunburn, to smooth and hydrate the skin, and to give it a pleasant color and elasticity, to prevent stretch marks, in pregnant woman, and also as hair conditioner. Herein, an oil sold in the region (LPO), and two others extracted in laboratory, from seeds collected in the same region, were investigated in terms of their composition, chemical properties, UV transmission. The three oils are similar although the LPO is more acidic, 0.48 mg KOH/g. GC-MS analysis indicated that the major components are the fatty acids, oleic (31.82%), nervonic (11.09%), ximenic (10.22%), and hexacosa-17,20,23-trienoic acids (14.59%). Long chain fatty acids, n ≥ 20, accounted for 51.1% of the total fatty acids. A thin film of the oil showed a reduction in transmittance from 200 to 300 nm. Viscosity studies of the LPO indicated that at normal temperature of skin, the oil can be spread over the skin as a thin film. At concentrations up to 10 µg/mL, the LPO is not toxic to human keratinocytes, suggesting the safety of this oil.

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia.

Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in Côte d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.

Análise de antocianinas e carotenoides em marapuama (Ptychopetalum olacoides) liofilizada / Analysis of anthocyanins and carotenoids in lyophilized marapuama (Ptychopetalum olacoides)

A marapuama é uma planta medicinal com propriedades de interesse em pesquisa. Liofilizar está planta auxilia na preservação de seus compostos. Este trabalho objetivou determinar o conteúdo de antocianinas monoméricas totais e carotenoides totais presentes no liofilizado de marapuama e otimizar a extração. Aplicou-se um DCCR para antocianinas e um para carotenoides. A maior quantidade de antocianina obtida foi de 0,107 mg/100g, e ajustou-se a um modelo onde os termos quadráticos para concentração de etanol e pH foram significativos (p<0,05). Para carotenoides nenhuma das variáveis foi significativa, podendo-se, portanto, usar os menores níveis do planejamento para reduzir custos. A maior quantidade carotenoide foi de 44,21 µg/mL. Conclui-se que quantidades relevantes de compostos antioxidantes foram encontradas em marapuama liofilizada.

Ointment of Ximenes americana promotes acceleration of wound healing in rats1.

PURPOSE: To evaluate the healing potential of the Ximenia americana hydroalcoholic extract in 10% cream in excisional wound models in rats. METHODS: Sixty male adults Wistar rats were submitted to skin and subcutaneous tissue surgery in the right and left thoracic regions, divided into three experimental groups: Standard submitted to treatment with only the base vehicle, Treated wounds treated with hydroalcoholic extract of X. americana applied on 10%, Lanette base and Control, untreated wounds. The treatment was performed daily and the wounds evaluated microscopically by the quantification of fibroblasts, collagen fibers and blood vessels. RESULTS: The histomorphometric analysis showed a significant increase in the number of fibroblasts, collagen fibers and blood vessels in the treated group. CONCLUSION: The topical action of the cream based on Ximenia americana shows angiogenic effects and improves the replacement of collagen, suggesting its use for the development of herbal remedy in the treatment of cutaneous wound healing.

4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L.

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88 ±â€¯0.18 µM and 3.19 ±â€¯0.07 µM, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Ki = 12.8 ±â€¯0.6 µM and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with Ki = 322 ±â€¯33 µM, αKi = 133 ±â€¯15 µM, ßKi = 5.14 ±â€¯0.41 µM and γKi = 13.2 ±â€¯13 µM.

A sesquiterpenoid tropolone and 1,2,3,4-tetrahydronaphthalene derivatives from Olax imbricata roots.

The methanol extract of Olax imbricata roots afforded one new sesquiterpenoid tropolone and three new 1,2,3,4-tetrahydronaphthalene derivatives, olaximbrisides A-D (1-4). Their structures were determined by 1D and 2D NMR experiments in combination of HRESIMS. The relative configurations were assigned by the NOESY experiments. The absolute configurations were established by a combination of X-ray diffraction analysis and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for their cytotoxic effects against some cancer cell lines. Among them, compound 1 exhibited the cytotoxicities against MCF-7, HepG2 and LU cell lines with IC50 values of 16.3, 34.3 and 8.0 µM, respectively.

Ointment of Ximenes americana promotes acceleration of wound healing in rats

Abstract Purpose: To evaluate the healing potential of the Ximenia americana hydroalcoholic extract in 10% cream in excisional wound models in rats. Methods: Sixty male adults Wistar rats were submitted to skin and subcutaneous tissue surgery in the right and left thoracic regions, divided into three experimental groups: Standard submitted to treatment with only the base vehicle, Treated wounds treated with hydroalcoholic extract of X. americana applied on 10%, Lanette base and Control, untreated wounds. The treatment was performed daily and the wounds evaluated microscopically by the quantification of fibroblasts, collagen fibers and blood vessels. Results: The histomorphometric analysis showed a significant increase in the number of fibroblasts, collagen fibers and blood vessels in the treated group. Conclusion: The topical action of the cream based on Ximenia americana shows angiogenic effects and improves the replacement of collagen, suggesting its use for the development of herbal remedy in the treatment of cutaneous wound healing.

Hepatoprotective and hypoglycemic effects of a tannin rich extract from Ximenia americana var. caffra root.

BACKGROUND: Liver diseases and diabetes are serious health disorders associated with oxidative stress and ageing. Some plant polyphenols can lower the risk of these diseases. PURPOSE: We investigated the phytochemical profiling of a root extract from Ximenia americana var. caffra using HPLC-PDA-ESI-MS/MS. The antioxidant activities in vitro were investigated. The hepatoprotective activities were studied in rat models with d-galactosamine (d-GaIN)-induced hepatotoxicity and the antidiabetic activities in STZ-diabetic rats were also investigated. MATERIALS AND METHODS: HPLC-PDA-ESI-MS/MS was used to identify plant phenolics. The antioxidant activities in vitro were determined using DPPH and FRAP assays. The in vivo hepatoprotective activities were determined for d-GaIN-induced hepatotoxicity in rats. We determined the liver markers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), liver peroxidation product malondialdehyde (MDA), glutathione content (GSH), albumin and total bilirubin concentration. The histopathological changes in rat liver were also studied. The antidiabetic activities were also investigated in STZ-diabetic rats and serum glucose, serum insulin hormone, and lipid peroxides were determined. RESULTS: The root extract is rich in tannins with 20 compounds including a series of stereoisomers of (epi)catechin, (epi)catechin-(epi)catechin, (epi)catechin-(epi)catechin-(epi)catechin, and their galloyl esters. Promising antioxidant potential was observed in vitro in DPPH assay with EC50 of 6.5 µg extract / 26 µg raw material and in FRAP assay with 19.54 mM FeSO4 compared with ascorbic acid (EC50 of 2.92 µg/ml) and quercetin (FeSO4 24.04 mM/mg), respectively. Significant reduction of serologic enzymatic markers and hepatic oxidative stress markers such as ALT, AST, MDA, GGT, and total bilirubin, as well as elevation of GSH and albumin were observed in rats with d-galactosamine-induced liver damage treated with the extract. These findings agree with a histopathological examination suggesting a hepatoprotective potential for the root extract. The root extract can mediate an antidiabetic effect by reducing elevated blood glucose and serum lipid peroxides levels and by increasing insulin in STZ-diabetic rats by -107, -31.1, +11.3%, respectively. CONCLUSIONS: The results of this study suggest that the tannin-rich extract from Ximenia americana var. caffra could be an interesting candidate for the treatment of several health disorders associated with oxidative stress such as hepatocellular injury and diabetes.

Mast cell concentration and skin wound contraction in rats treated with Ximenia americana L

Abstract Purpose: To evaluate wound contraction and the concentration of mast cells in skin wounds treated with wild plum (Ximenia americana) essential oil-based ointment in rats. Methods: Sixty rats were submitted to two cutaneous wounds in the thoracic region, on the right and left antimeres. Thereon, they were divided into three groups: GX (wounds treated once a day with hydro alcoholic branch extract of Ximenia americana), GP (wounds that received vehicle), and GC (wounds without product application). Wounds were measured immediately after the injury as well as 4, 7, 14 and 21 days post-topical application of the extract. At these days, five rats from each group were euthanatized. Thereafter, samples were fixed in 10% formaldehyde and processed for paraffin embedding. Sections were stained with H.E, Masson's Trichrome and toluidine blue for morphological, morphometrical and histopathological analysis, under light microscopy. The degree of epithelial contraction was measured and mast cell concentrations were also evaluated with an image analyzer (Image Pro-plus®software) . Results: The extract treated group showed lower mast cell concentrations in the 4th day of lesion, as compared to GP (GX<GP=GC, p=0.029), as well as with increased contraction at 7th and 14th days, respectively (7th and 14th days, GX > GP = GC; p<0.05) . Conclusion: Ointment containing 10% X. americana induces a decrease in mast cell concentration, at the beginning of the healing process, and promotes early skin wound contraction in rats.

Three indigenous plants used in anti-cancer remedies, Garcinia kola Heckel (stem bark), Uvaria chamae P. Beauv. (root) and Olax subscorpioidea Oliv. (root) show analgesic and anti-inflammatory activities in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytochemicals with anti-oxidative and anti-inflammatory properties are known to inhibit tumour initiation, promotion and progression. Hence, there is an increasingly-convincing rationale for employing remedies containing those phytochemicals in the treatment of cancers and also as analgesic and anti-inflammatory adjuvants in therapy. The plants Garcinia kola Heckel (Clusiaceae), stem bark; Uvaria chamae P. Beauv. (Annonaceae), root; and Olax subscorpioidea Oliv. (Olacaceae), root, have been documented to be part of various indigenous anti-cancer regimens. AIM OF THE STUDY: To determine if the three plants exhibit significant anti-oxidative and anti-inflammatory properties. MATERIALS AND METHODS: Using established models, the analgesic and anti-inflammatory activities of the three plants were investigated. RESULTS: Pre-treatment with the plant extracts at 100, 200 and 400mg/kg produced inhibition of writhes; G. kola and U. chamae showed no significant effect on formalin-induced pain, but O. subscorpioidea produced inhibition in both phases of the formalin test. Similarly, while G. kola and U. chamae did not produce any significant inhibitory effect in the xylene-induced ear oedema model, the oedema was significantly reduced by O. subscorpioidea pre-treatment. However, all the three plants significantly inhibited the time-dependent increase in paw circumference in the carrageenan- and formaldehyde-induced rat paw oedema tests, with peak effects observed at 400mg/kg, 6h after the induction of oedema, comparable in some cases to the effects of two standard drugs, the non-steroidal anti-inflammatory drug diclofenac and the anti-inflammatory antibiotic doxycycline. CONCLUSION: We conclude that the three plant extracts possess analgesic and anti-inflammatory properties, thus providing a scientific rationale for their inclusion in some traditional anti-cancer regimens.

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.

Bioactive compounds and antioxidant potential fruit of Ximenia americana L.

The caatinga ecoregion in northeast Brazil presents a wide variety in plant species. However, the potential of these species as a source of energy, carbohydrates, vitamins, minerals and bioactive properties beneficial to health is still unknown. Among these species we can find the wild plum (Ximenia americana). Due to its various phytotherapeutic properties and absence of studies on the chemical composition of the fruit this article aimed to evaluate the bioactive compounds and antioxidant potential of the X. americana in different stages of maturation. The fruits of X. americana showed considerable amounts of bioactive compounds, as well as antioxidant activity and antioxidant enzymes. The fruits at green maturity stage showed higher content of yellow flavonoids (22.07 mg/100g), anthocyanins (1.92 mg/100 g), polyphenols (3051.62 mg/100 g), starch (4.22%), antioxidant activity (489.40 g fruit/g DPPH and 198.77 µmol Trolox/g) and activity of antioxidant enzymes; the antioxidant activity allocated to the fruit was shown to be related to the contents of extractable polyphenols, yellow flavonoids, total anthocyanins and antioxidant enzymes.

Modulation of the erythromycin resistance in Staphylococcus aureus by ethanolic extracts of Ximenia americana L and Schinopsis brasiliensis Engl / Modulación de la resistencia a la eritromicina en Staphylococcus aureus por extractos etanólicos de Ximeniaamericana L y Schinopsis brasiliensis Engl

It was evaluated the in vitro efficacy of ethanolic extract of leaves and bark of Ximenia americana L and Schinopsis brasiliensis Engl. alone and in association with erythromycin as modulators of microbial resistance against six clinical isolates of Staphylococcus aureus resistant to erythromycin (SA1-SA6) and S. aureus ATCC 25923 by the microdilution method. The extracts were also subjected to bioassay with Artemia salina. The ethanolic extract of barks of X. americana showed a synergistic effect with erythromycin against SA01, SA03 and SA04. The leaf extract of S. brasiliensis exerted synergistic effect against SA03 and the bark extract showed against SA01 and S03. The results suggest that extracts from S.brasiliensis and X. americana have potential as modulator agents of bacterial resistance, which could be used as adjuvants in the treatment of infections by S. aureus resistant to erythromycin, with previous studies of toxicity.

Se evaluó la eficacia in vitro de los extractos etanólicos de hojas y corteza de Ximenia americana L y Schinopsis brasiliensis Engl solos y en asociación con eritromicina como moduladores de la resistencia microbiana frente a seis aislados clínicos de Staphylococcus aureus resistentes a Eritromicina (SA1-SA6) y S. aureus ATCC 25923, por el método de microdilución. Además se determinó la actividad tóxica de los extractos contra Artemia salina. Solo el extracto etanólico de la corteza de X. americana mostró un efecto sinérgico con la eritromicina frente a SA01, SA03 y SA04. El extracto de las hojas de S. brasiliensis ejerció efecto sinérgico contra SA03 y el extracto de corteza, contra SA01 y S03. Los resultados sugieren que S. brasiliensis y X. americana tienen potencial como agentes moduladores de la resistencia bacteriana, que podrían ser utilizados como adyuvantes en el tratamiento de infecciones por S. aureus resistentes a eritromicina, con estudios previos de toxicidad.

Evaluation of Antidepressant-like Effect of Olax Subscorpioidea Oliv. (Olacaceae) Extract in Mice.

Olax subscorpioidea is a shrub or tree found in Nigeria, and other parts of Africa. It is indicated in the management of inflammatory disorder, mental illness, convulsion, pain, and cancer.Based on the folkloric use in the management of mental illness, antidepressant activity of Olax subscorpioidea (6.25-50 mg/kg, i. p.) was investigated using forced swimming, tail suspension, yohimbine induced lethality and reserpine induced depression tests.The results showed that, Olax subscorpioidea produced significant dose dependent reduction in immobility time in forced swimming [F (5, 24) = 17.22, p < 0.0001] and tail suspension [F (5, 24) = 14.94, p < 0.0001] tests without causing changes in locomotor activity in open field test. It was also found that Olax subscorpioidea significantly reduced diarrhea in reserpine model of depression [F (5, 24) = 10, p < 0.0001]. None of the doses potentiated yohimbine induced lethality in mice. In conclusion Olax subscorpioidea possessed antidepressant action, thus justifying its use in the management of mental illness.

Antinociceptive property of Olax subscorpioidea Oliv (Olacaceae) extract in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax subscorpioidea is a shrub or tree found in Nigeria, and other parts of Africa. It is used in the management of inflammatory disorder, mental illness, convulsion, pain, and cancer. However, there is dearth of information on scientific basis for its folkloric use in the management of pain. Therefore, the study was designed to investigate the antinociceptive property of the extract of Olax subscorpioidea (EOS) leaves in mice. MATERIALS AND METHODS: Antinociceptive activity of EOS (12.5-50 mg/kg, i.p.) was investigated using acetic acid induced abdominal writhing, tail immersion, hot plate and formalin tests. RESULTS: Extract of Olax subscorpioidea produced significant dose dependent inhibition of writhing frequency [F(4,20)=155.9, p<0.0001] and significant dose dependent inhibition of neurogenic and inflammatory pains [F(4,20)=116.7, p<0.0001; F(4,20)=40.05, p<0.0001]. It also produced a significant dose dependent prolongation of the latent period and reaction times in tail immersion and hot plate tests in mice [F(4,20)=19.49, p<0.0001; F(4,20)=97.95, p<0.0001]. CONCLUSION: Olax subscorpioidea possessed potent analgesic action, mediated centrally and peripherally, thus justifying its use in the management of pain.

Riproximin's activity depends on gene expression and sensitizes PDAC cells to TRAIL.

Riproximin (Rpx) is a type II ribosome inactivating protein, which was investigated for its activity in pancreatic ductal adenocarcinoma (PDAC) in a panel of 17 human and rat PDAC cell lines and in rat pancreatic cancer liver metastasis. Cytotoxicity in response to Rpx was determined by MTT assay, apoptosis by flow cytometry and qRT-PCR for apoptosis related genes, and the modulation of the transcriptome was monitored by micro array analysis. The combination effect of Rpx and TRAIL was assessed by MTT assay. Rpx showed high but varying cytotoxicity in PDAC cells. Based on overall gene expression, the sensitivity of these cells was linked to genes involved in apoptosis. Furthermore, based on the affinity of Rpx for CEA, the expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) genes was significantly related to Rpx's cytotoxicity in cells with CEACAM gene expression. Exposure of Suit2-007 cells to Rpx induced the mRNA expression of members of signaling pathways initiating from most death receptors, and down modulation of TRAIL. Apoptosis was increased as shown by FACS analysis. Combination of Rpx with TRAIL resulted in a synergistic cytotoxic effect in human Suit2-007 and rat ASML cells, as evidenced by a 6-fold lower tumor cell survival than expected from an additive combination effect. Treatment of BDX rats bearing intra-portally implanted Suit2-007 cells showed a highly significant anticancer effect and indicated an application of Rpx against pancreatic cancer metastasis to the liver. These data favor further evaluation of Rpx as anticancer agent in PDAC.