Screening of traditional medicinal plant extracts and compounds identifies a potent anti-leishmanial diarylheptanoid from Siphonochilus aethiopicus.

Available anti-leishmanial drugs are associated with toxic side effects, necessitating the search for safe and effective alternatives. This study is focused on identifying traditional medicinal plant natural products for anti-leishmanial potential and possible mechanism of action. Compounds S and T. cordifolia residual fraction (TC-5) presented the best anti-leishmanial activity (IC50: 0.446 and 1.028 mg/ml) against promastigotes at 48 h and less cytotoxicity to THP-1 macrophages. These test agents elicited increased expression of pro-inflammatory cytokines; TNFα and IL-12. In infected untreated macrophages, NO release was suppressed but was significantly (p < 0.05) increased in infected cells treated with compound S. Importantly, Compound S was found to interact with LdTopoIIdimer in silico, resulting in a likely reduced ability of nucleic acid (dsDNA)-remodelling and, as a result, parasite proliferation in vitro. Thereby, Compound S possesses anti-leishmanial activity and this effect occurs via a Th1-mediated pro-inflammatory response. An increase in NO release and its inhibitory effect on LdTopoII may also contribute to the anti-leishmanial effect of compound S. These results show the potential of this compound as a potential starting point for the discovery of novel anti-leishmanial leads.Communicated by Ramaswamy H. Sarma.

Marmesin isolated from Celtis durandii Engl. root bioactive fraction inhibits ß-hematin formation and contributes to antiplasmodial activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a leading cause of death in many developing countries, especially in sub-Saharan Africa. Nigeria is endowed with an abundance of medicinal plants, many of which are used to treat malaria. Celtis durandii Engl. is one such plant used as a traditional antimalarial remedy in southeast Nigeria. However, its antiplasmodial potential is poorly explored. AIM OF THE STUDY: The study aimed at identifying the antiplasmodial components of C. durandii root extract through antiplasmodial activity-guided fractionation. MATERIALS AND METHODS: Dichloromethane/methanol mixture extract (1:1 v/v) of C. durandii root was prepared and partitioned against water to obtain the organic phase, which was further separated by column chromatography into nine (C1 - C9) fractions. The antiplasmodial activity was evaluated by in vitro screening of the different fractions against drug-sensitive and drug-resistant Plasmodium falciparum strains. Further purification of the active column fractions resulted in a potent anti-Plasmodial compound that was subsequently investigated for its effect on ß-hematin formation. Additionally, the isolated compound was characterized and identified as marmesin using mass spectrometry and nuclear magnetic resonance spectroscopy. RESULTS: Celtis durandii root extract exhibited promising antiplasmodial activity {IC50 (µg/ml) 5.92, 6.04, and 6.92} against PfW2mef, PfINDO, and Pf3D7 respectively. Pooled fractions with good antiplasmodial activity {IC50 (µg/ml) Pf3D7: 3.99; PfINDO: 2.24} and selectivity for the parasites (SI: 21) yielded a compound that was fourteen-fold potent in antiplasmodial activity against Pf3D7(IC50: 0.28 µg/ml). It also inhibited ß-hematin formation with an IC50 = 150 µM. Further studies using spectral data, literature, and chemical databases identified the purified compound as marmesin. CONCLUSION: This work has demonstrated that Celtis durandii root extract has good antiplasmodial activity against drug-sensitive and drug-resistant P. falciparum. The inhibition of ß-hematin formation by marmesin accounts in part for this activity.

Two New Antiprotozoal Diterpenes From the Roots of Acacia nilotica.

The powdered roots of the medicinal plant Acacia nilotica were extracted with hexane and ethyl acetate, and the extracts were subjected to column chromatography for the isolation of potentially bioactive compounds and their screening against kinetoplastid pathogens. NMR and HREI mass spectrometric analyses identified two new diterpenes, characterized as 16, 19-dihydroxycassa-12-en-15-one (Sandynone, 1) and (5S, 7R, 8R, 9R, 10S, 13Z, 17S)-7,8:7,17:16,17-triepoxy-7,8-seco-cassa-13-ene (niloticane B, 2). The previously reported (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-diene-7,17-diol (3), (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-dien-7-ol-17-al (4), and (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-dien-7-ol (5) a, mixture of stigmasterol (6a) and sitosterol (6b), and lupeol (7) were also isolated. Several column fractions displayed significant activity against a panel of Trypanosoma and Leishmania spp., and from the most active fraction, compound 4 was isolated with high purity. The compound displayed high activity, particularly against T. brucei, T. evansi, and L. mexicana (0.88-11.7 µM) but only a modest effect against human embryonic kidney cells and no cross-resistance with the commonly used melaminophenyl arsenical and diamidine classes of trypanocides. The effect of compound 4 against L. mexicana promastigotes was irreversible after a 5-h exposure, leading to the sterilization of the culture between 24 and 48 h.

A novel benzofuro-(2, 3-c)-7'-chromene from Cassia sieberiana.

The stem bark of Cassia sieberiana was extracted with methanol and the methanol extract partitioned with chloroform. Column chromatography of the chloroform fraction over silica gel yielded a novel benzofurochromene [2-(4-hydroxylphenyl)-7'-1, 2-dihydroxy-1-phenylpropyl)-4', 6'-dihydroxy [1] phenylbenzofuro (2, 3-c)-7'-chromene], lupeol and epiafzelechin. Their structures determined by Nuclear Magnetic resonance and mass spectrometry.[Figure: see text].

Antiplasmodial activity of a novel diarylheptanoid from Siphonochilus aethiopicus.

The Nigerian and South African varieties of Siphonochilus aethiopicus were examined for their phytochemical constituents. The ethyl acetate extract of the rhizomes of the South African variety yielded a novel diarylheptanoid, 2,3-diacetoxy-7-(3'',4''-dihydroxy-5''-methoxyphenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-5-heptene and the flavonoid 3,7-dimethoxyquercetin. From the hexane extract of the Nigerian variety, siphonochilone and another flavonoid, 3,4',7-trimethylkaempferol were isolated. The isolated compounds were characterised by NMR spectroscopic techniques and mass spectrometry. The diarylheptanoid was then assayed for antiplasmodial activity in vitro using a Plasmodium falciparum growth inhibition assay. At the concentrations tested, the compound inhibited parasite growth by 69 - 74%, without producing cytotoxic or significant haemolytic effects. The antiplasmodial activity of the compound is likely mediated by direct mechanism(s) in erythrocytic - stage parasites.

Antiparasitic and Cytotoxic Activity of Bokkosin, A Novel Diterpene-Substituted Chromanyl Benzoquinone From Calliandra portoricensis.

Calliandra portoricensis is a medicinal plant growing freely in Nigeria. It is used traditionally to treat tuberculosis, as an anthelmintic and an abortifacient. Phytochemical fractionation and screening of its root extracts has yielded a novel (5-hydroxy-7-methoxy-4-oxo-1-chromanyl)-4-methoxy-p-benzoquinone (breverin)-substituted cassane diterpene, which was designated bokkosin. It was obtained from column chromatography of the ethyl acetate extract of the roots. The compound was characterized using IR, NMR (1D and 2D) and mass spectral data. Promising antiparasitic activity was observed against the kinetoplastid parasite Trypanosoma brucei brucei, as well as moderate activity against Trypanosoma congolense and Leishmania mexicana and low toxicity in mammalian cells, with the best in vitro EC50 values against T. b. brucei (0.69 µg/mL against a standard laboratory strain, and its multi-drug resistant clone (0.33 µg/mL). The effect on T. b. brucei in culture was rapid and dose-dependent, leading to apparently irreversible growth arrest and cell death after an exposure of just 2 h at 2 × or 4 × EC50. The identification of bokkosin constitutes the first isolation of this class of compound from any natural source and establishes the compound as a potential trypanocide that, considering its novelty, should now be tested for activity against other microorganisms as well.

Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines.

Natural products have been successfully used to treat various ailments since ancient times and currently several anticancer agents based on natural products are used as the main therapy to treat cancer patients, or as a complimentary treatment to chemotherapy or radiation. Balanocarpol, which is a promising natural product that has been isolated from Hopea dryobalanoides, has been studied as a potential anticancer agent but its application is limited due to its high toxicity, low water solubility, and poor bioavailability. Therefore, the aim of this study is to improve the characteristics of balanocarpol and increase its anticancer activity through its encapsulation in a bilayer structure of a lipid-based nanoparticle drug delivery system where the application of nanotechnology can help improve the limitations of balanocarpol. The compound was first extracted and isolated from H. dryobalanoides. Niosome nanoparticles composed of Span 80 (SP80) and cholesterol were formulated through an innovative microfluidic mixing method for the encapsulation and delivery of balanocarpol. The prepared particles were spherical, small, and uniform with an average particles size and polydispersity index ∼175 nm and 0.088, respectively. The encapsulation of balanocarpol into the SP80 niosomes resulted in an encapsulation efficiency of ∼40%. The niosomes formulation loaded with balanocarpol showed a superior anticancer effect over the free compound when tested in vitro on human ovarian carcinoma (A2780) and human breast carcinoma (ZR-75-1). This is the first study to report the use of SP80 niosomes for the successful encapsulation and delivery of balanocarpol into cancer cells.

A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora.

The West African country Nigeria features highly diverse vegetation and climatic conditions that range from rain forest bordering the Atlantic Ocean in the South to the Desert (Sahara) at the Northern extreme. Based on data from the World Conservation Monitoring Center of the United Nations Environmental Protection, Nigeria, with ~5,000 documented vascular plants, ranks amongst the top 50 countries in terms of biodiversity. Such a rich biodiversity implies that the country is rich in diverse secondary metabolites-natural products/unique chemicals produced by the plant kingdom to confer selective advantages to them. Like many tropical countries, Nigeria is also endemic to numerous infectious diseases particularly those caused by parasitic pathogens. These phytochemicals have been exploited for the treatment of diseases and as a result, a new branch of chemistry, natural product chemistry, has evolved, to try to reproduce and improve the therapeutic qualities of particular phytochemicals. In this review, we have compiled a compendium of natural products, isolated from Nigerian flora, that have been reported to be effective against certain protozoan parasites with the aim that it will stimulate interests for further investigations, and give impetus to the development of the natural products into registered drugs. In total 93 structurally characterized natural compounds have been identified with various levels of anti-parasite activity mainly from Nigerian plants. The synthesis protocol and molecular target for some of these natural anti-parasite agents have been established. For instance, the anti-plasmodial compound fagaronine (7), a benzophenanthridine alkaloid from Fagara zanthoxyloides has been successfully synthesized in the laboratory, and the anti-trypanosomal compound azaanthraquinone (55) elicits its effect by inhibiting mitochondrial electron transfer in trypanosomes. This review also discusses the barriers to developing approved drugs from phytochemicals, and the steps that should be taken in order to accelerate the development of new antiparasitics from the highlighted compounds.

Hibiscus acid from Hibiscus sabdariffa (Malvaceae) has a vasorelaxant effect on the rat aorta.

Hibiscus sabdariffa (Malvaceae) is a plant that is widely recognised for its antihypertensive properties; however the constituent(s) responsible for this biological activity are presently unknown. The aim of this study was to identify the potential compounds that are responsible for the vasorelaxant activity of H. sabdariffa. Thereafter, the mechanisms involved in producing the vasorelaxation were investigated. The plant was extracted consecutively with hexane, ethyl acetate and methanol. The methanolic extract was subjected to bioassay-guided fractionation in order to isolate pure compounds that possessed vasorelaxant activity. The vascular effects of the pure compounds were studied on the rat aorta in vitro using myography techniques. Hibiscus acid produced a concentration-dependent relaxation of the rat aorta pre-contracted with either phenylephrine (3 µM) or KCl (60 mM), irrespective of the presence of the endothelium. When the tissue was pre-contracted with phenylephrine, the concentration required to produce 50% relaxation (IC50), was 0.09 ±â€¯0.01 mg/ml. Hibiscus acid had no effect on the phasic contraction induced by phenylephrine in Ca2+-free physiological solution; but it did affect the component of the contraction that is due to Ca2+ influx. In parallel studies, garcinia acid, a diastereoisomer of hibiscus acid, was found to have an almost identical vasorelaxant effect. The vasorelaxant action of both compounds is most likely due to the inhibition of Ca2+ influx via voltage-dependent Ca2+ channels.

Antidiarrhoeal properties of Syzygium guineense leaf extract and identification of chemical constituents in its active column fractions.

Background Syzygium guineense (Myrtaceae) has been used in traditional medicine against various ailments, including diarrhoea. This study was conducted to scientifically evaluate the antidiarrheal effects of S. guineense extract and fractions. Methods An ethanol extract of S. guineense leaves was prepared and tested for its effect on small intestinal propulsion in mice and castor oil-induced fluid accumulation in rats. The extract was also evaluated for its effect on itopride-induced small intestine propulsion in mice. Column fractions were also investigated in rats and sub-fractions were tested for activity on spontaneous contractions of isolated rabbit jejunum. Results The results showed that the extract significantly (p<0.05) inhibited intrinsic small intestinal propulsion and itopride-induced propulsive activity, similar to atropine (0.3 mg/kg) although its inhibitory effect against castor oil-induced intestinal fluid accumulation and diarrhoea was statistically insignificant (p>0.05). Column separation yielded 14 fractions, with three fractions producing significant (p<0.001) inhibition of small intestinal propulsion. Sub-fractions 1, 7 and 16 obtained from an active column fraction also exhibited relaxant effects on isolated rabbit jejunum. Spectral analysis (proton, 13C NMR) of sub-fractions 7 and 16 revealed the presence of betulinic acid, ursolic acid, oleanolic acid in 7 and a mixture of luteolin and friedelane-type triterpenes in 16. Conclusions These findings provide scientific evidence that S. guineense leaf extract possess antidiarrhoeal activity and may be potentially beneficial in treatment diarrhoeal disease. The identified compounds may also be implicated in its antidiarrhoeal effects.

Multi-target mode of action of a Clerodane-type diterpenoid from Polyalthia longifolia targeting African trypanosomes.

Natural products have made remarkable contributions to drug discovery and therapy. In this work we exploited various biochemical approaches to investigate the mode of action of 16-α-hydroxy-cleroda-3,13 (14)-Z-dien-15,16-olide (HDK-20), which we recently isolated from Polyalthia longifolia, on Trypanosoma brucei bloodstream trypomastigotes. HDK20 at concentrations ≥ EC50 (0.4 µg/ml) was trypanocidal, with its effect irreversible after only a brief exposure time (<1 h). Fluorescence microscopic assessment of DNA configuration revealed severe cell cycle defects after 8 h of incubation with the compound, the equivalent of a single generation time. This was accompanied by DNA fragmentation as shown by Terminal deoxynucleotidyl transferase dUTP Nick-End Labelling (TUNEL) assays. HDK-20 also induced a fast and profound depolarisation of the parasites' mitochondrial membrane potential and depleted intracellular ATP levels of T. brucei. Overall, HDK20 showed a multi-target mechanism of action, which provides a biochemical explanation for the promising anti-trypanosomatid activity in our previous report.

Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. AIM OF THE STUDY: To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. MATERIAL AND METHODS: Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. RESULTS: Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3ß,13ß-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC50 of 1.58µg/mL. None of the isolated compounds displayed toxicity towards Human Embryonic Kidney cells at concentrations up to 400µg/mL. In addition, the isolated compounds were active against Leishmania mexicana, as well as against T. congolense. CONCLUSION: We have isolated a clerodane compound from Polyalthia longifolia that shows low toxicity, no cross-resistance with current treatments, and promising activity against both human-infective and veterinary Trypanosoma species.

Phenolic constituents from Wissadula periplocifolia (L.) C. Presl. and anti-inflammatory activity of 7,4'-di-O-methylisoscutellarein.

This study reports the first phenolics from Wissadula genus (Malvaceae) and the anti-inflammatory activity of 7,4'-di-O-methylisoscutellarein. Using chromatographic methods, five phenolic compounds were isolated from aerial parts of Wissadula periplocifolia (L.) C. Presl. The compounds were identified as 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, trans-cinnamic acid, tamgermanetin and 7,4'-di-O-methylisoscutellarein using spectroscopic methods. The flavone 7,4'-di-O-methylisoscutellarein showed anti-inflammatory activity by inhibiting neutrophils recruitment in a mice model of pleurisy and by decreasing significantly the production of cytokines IL-1ß and TNF-α.

Antitrypanosomal Activity of a Novel Taccalonolide from the Tubers of Tacca leontopetaloides.

INTRODUCTION: Several taccalonolides with various bioactivities have been isolated from Tacca species but no studies to isolate taccalonolides with anti-trypanosomal activity from Tacca leontopetaloides have been reported. OBJECTIVES: To analyse extracts of the roots of Tacca leontopetaloides, purify the extracts by column chromatography and identify isolated compounds by spectroscopic methods. The compounds and fractions will be tested for antitrypanosomal activity in vitro against Trypanosoma brucei brucei. MATERIAL AND METHODS: Dried roots or tubers of Tacca leontopetaloides, chromatographic separation and spectroscopic identification. RESULTS: A novel taccalonolide A propanoate and some known taccalonolides were isolated and their structures were determined by NMR and mass spectrometry CONCLUSION: Several taccalonolides were isolated from Tacca leontopetaloides and were found to have in vitro antitrypanosomal activity against Trypanosoma brucei brucei and EC50 values for the isolated compounds were from 0.79 µg/mL. Copyright © 2016 John Wiley & Sons, Ltd.

New Sulphated Flavonoids from Wissadula periplocifolia (L.) C. Presl (Malvaceae).

Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five new sulphated flavonoids: 8-O-sulphate isoscutellarein (yannin) (1a); 4'-O-methyl-7-O-sulphate isoscutellarein (beltraonin) (1b); 7-O-sulphate acacetin (wissadulin) (2a); 4'-O-methyl-8-O-sulphate isoscutellarein (caicoine) (2b) and 3'-O-methyl-8-O-sulphate hypolaetin (pedroin) (3b) along with the known flavonoids 7,4'-di-O-methyl-8-O-sulphate isoscutellarein (4), acacetin, apigenin, isoscutellarein, 4'-O-methyl isoscutellarein, 7,4'-di-O-methylisoscutellarein, astragalin and tiliroside. The compounds were isolated by column chromatography and identified by NMR (¹H, (13)C, HMQC, HMBC and COSY) and LC-HRMS. A cell based assay was carried out to evaluate the preliminary cytotoxic properties of the flavonoids against UVW glioma and PC-3M prostate cancer cells as well as non-tumour cell lines. The obtained results showed that acacetin, tiliroside, a mixture of acacetin + apigenin and the sulphated flavonoids 2a + 2b exhibited inhibitory activity against at least one of the cell lines tested. Among the tested flavonoids acacetin and tiliroside showed lower IC50 values, presenting promising antitumor effects.

The isolation of antiprotozoal compounds from Libyan propolis.

Propolis is increasingly being explored as a source of biologically active compounds. Until now, there has been no study of Libyan propolis. Two samples were collected in North East Libya and tested for their activity against Trypanosoma brucei. Extracts from both samples had quite high activity. One of the samples was fractionated and yielded a number of active fractions. Three of the active fractions contained single compounds, which were found to be 13-epitorulosal, acetyl-13-epi-cupressic acid and 13-epi-cupressic acid, which have been described before in Mediterranean propolis. Two of the compounds had a minimum inhibitory concentration value of 1.56 µg/mL against T. brucei. The active fractions were also tested against macrophages infected with Leishmania donovani, and again moderate to strong activity was observed with the compounds having IC50 values in the range 5.1-21.9 µg/mL.

Phytochemical and antitrypanosomal investigation of the fractions and compounds isolated from Artemisia elegantissima.

CONTEXT: Trypanosoma brucei brucei (T.b. brucei) infection causes death in cattle, while the current treatments have serious toxicity problems. However, natural products can be used to overcome the problems associated with parasitic diseases including T.b. brucei. OBJECTIVE: Artemisia elegantissima Pamp (Asteraceae) was evaluated phytochemically for its constituents and antitrypanosomal potential against T.b. brucei for the first time. Scopoletin isolated from A. elegantissima has shown better potential then the standard drug suramin, used against T.b. brucei. MATERIALS AND METHODS: The ethanol extract of the aerial parts of A. elegantissima was fractionated by column and preparative thin-layer chromatography into six fractions (A-F) yielding 13 compounds, these were evaluated for their antitrypanosomal activity against T.b. brucei at different concentrations. RESULTS: Thirteen compounds were isolated from A. elegantissima: (Z)-p-hydroxy cinnamic acid, stigmasterol, ß-sitosterol, betulinic acid, bis-dracunculin, dracunculin, scopoletin, apigenin, dihydroluteolin, scoparol, nepetin, bonanzin, and 3',4'-dihydroxy bonanzin. The fractions D-F were found to be active at the concentration of 20 µg/ml and three compounds isolated from these fractions, scopoletin (MIC ≤0.19 µg/ml), 3',4'-dihydroxy bonanzin (MIC = 6.25 µg/ml) and bonanzin (MIC = 20 µg/ml), were found to be highly active. DISCUSSION AND CONCLUSION: Artemisia elegantissima was phytochemically and biologically explored for its antitrypanosomal potential against T.b. brucei. The number and orientation of phenolic hydroxyl groups play an important role in the antitrypanosomal potential of coumarins and flavonoids. The compounds 3',4'-dihydroxy bonanzin and scopoletin with low MIC values, hold potential for use as antitrypanosomal drug leads.

Antitrypanosomal activity & docking studies of components of Crateva adansonii DC leaves: novel multifunctional scaffolds.

Chemical investigation of Crateva adansonii DC has led to the isolation of aurantiamide acetate, a novel ethyl pyropheophorbide A, purpurin-18 ethyl ester and pyropheophorbide A. Their structures were elucidated using extensive spectral data. These metabolites were then evaluated for their in vitro bioactivity against the African trypanosome Trypanosoma brucei brucei (S427) blood stream forms. Anti-trypanosomal activity decreased with aurantiamide acetate (MIC 25µM), while it increased with the pheopytins (MIC 6.25µM), when compared to the standard drug Suramin. Using the Vlife MDS 4.3 - GRIP docking, these phytoconstituents were then tested to identify the proteins targeted and the mode of activity employed. Their affinity towards the receptor sites of trypanothione reductase, riboflavin kinase, rohedsain, glutathione synthetase & sterol-14α-demethylase (CYP51) of Trypanosoma brucei were evaluated according to the resulting docking energies.

The Inhibitory Effect of Haloxylon salicornicum on Contraction of the Mouse Uterus.

Haloxylon salicornicum (H. salicornicum) is a plant that is frequently taken as a tea by Bedouin women in Egypt who are experiencing difficulties during pregnancy, as well as to provide relief from dysmenorrhoea. Despite its medical use, there has been no detailed evaluation of the effect of this plant on uterine tissue. Therefore, the initial aim of this study was to determine whether H. salicornicum affected the contraction of the mouse uterus in vitro. The crude aqueous extract of H. salicornicum was found to inhibit the spontaneous contractions of the uterus, with the effect being rapid in onset and completely reversible upon washout. Subsequent purification of the plant extract resulted in the identification of synephrine and N-methyltyramine, both of which were found to have inhibitory effects on the spontaneous contractions of the uterus. The EC50 for the purified constituent identified as synephrine was 0.82 ± 0.24 µ g/mL. The inhibitory activity of crude H. salicornicum, as well as the isolated constituents, could be prevented by pretreatment of the uterus with the ß -adrenoceptor antagonist propranolol. In conclusion, the use of H. salicornicum during preterm labour appears to be justified, and its pharmacologic effect is consistent with it acting as a ß -adrenoceptor agonist.