Ifanosine: Olea europaea L. and Hyphaene thebaica L. combination, from traditional utilization to rational formulation: Preclinical and clinical efficacy on hypertensives patients.

ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine). AIM OF THE STUDY: The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine. MATERIALS AND METHODS: In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days. RESULTS: Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects. CONCLUSION: This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies.

Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate.

The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities.

Two new aromatic acids from Clerodendrum formicarum Gurke (Lamiaceae) of Cameroon.

The ethanolic extract of the leaves of Clerodendrum formicarum, a Lameacious plant of Cameroon, afforded two new salicylic acid derivatives named formoic acids A and B along with four known constituents which have been obtained for the first time from this source. They include flemingipanic acid, martynoside, verbascoside, and seguinoside K. Structures of all the isolated constituents have been elucidated with the aid of 1D and 2D NMR spectroscopic techniques.

Formadienoate-A and B: two new long chained feruloyl esters from Clerodendrum formicarum (Lamiaceae) of Cameroon.

The ethanol extract of the leaves of Clerodendrum formicarum Gürke, a Lameacious plant of Cameroon, afforded two new long-chained esters named formadienoate-A (1) and B (2) along with two known constituents which have been obtained for the first time from C. formicarum. They include: hexacosyl-(E)-ferulate (3) and 26-hydroxyhexacosyl-(E)-ferulate (4). Structures of all the isolated constituents have been elucidated with the aid of 1D and 2D NMR spectroscopic techniques.

Antimicrobial and immunomodulatory properties of prenylated xanthones from twigs of Garcinia staudtii.

Phytochemical investigation of the methanol extract of the twigs of Garcinia staudtii yielded four new prenylated xanthones, staudtiixanthones A-D (1-4), along with eleven known compounds. Their structures were determined by analysis of 1D and 2D NMR spectra and by comparison of spectroscopic data with those previously reported. Some of these compounds have been evaluated for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The new compounds were also screened for phagocyte chemiluminescence, neutrophil chemotaxis, T-cell proliferation, cytokine production from mononuclear cells and cytotoxicity. They were found to exhibit potent immunomodulatory activities.

Induction of neuronal differentiation in neurosphere stem cells by ellagic acid derivatives.

A bioassay-guided fractionation of methanol extracts of stem barks, combined with screening based on Epidermal Growth Factor (EGF)-responsive neural stem cells (erNSCs) differentiation assay, has been used. This study resulted in the isolation of 3,3'-di-O-methylellagic acid 1, 3,3'-di-O-methyl ellagic acid-4-O-beta-D-xylopyranoside 2, ellagic acid 3, and arjunolic acid 4. Among them, compounds 1 and 2 exhibit potent induction of neuronal differentiation in neurosphere stem cells with no cytotoxic effect. These results indicate that compounds 1 and 2 may be useful as pharmacological agents for the treatment of neurodegenerative diseases. These compounds may account, for the use of T. superba in folk medicine for nervous system and mental disorders.

Antimicrobial dihydroisocoumarins from Crassocephalum biafrae.

Bioassay-guided fractionation of the CHCl (3)-soluble extract of the stem bark of Crassocephalum biafrae (Asteraceae) resulted in the isolation of three new dihydroisocoumarins, named biafraecoumarins A ( 1), B ( 2), and C ( 3); two known triterpenes ( 4 and 5); and a known ceramide ( 6). The structures of the new compounds were established as 7-but-15-enyl-6,8-dihydroxy-3( R)-penta-9,11-dienylisochroman-1-one ( 1), 7-butyl-6,8-dihydroxy-3( R)-penta-9,11-dienylisochroman-1-one ( 2), and 7-butyl-6,8-dihydroxy-3( R)-pent-10-enylisochroman-1-one ( 3) using spectroscopic data. Compounds 1- 3 exhibit low to significant antimicrobial activities against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Pseudomonas picketti, Trichphyton longifusus, Aspergillus flavus, Microsporum canis, Fusarium solani, Candida albicans, and Candida glabrata.

Antimicrobial pentacyclic triterpenoids from Terminalia superba.

Antibacterial bioassay-guided fractionation of the methanol extract of the stem bark of Terminalia superba led to the isolation of four new triterpene glucosides (1-4) which were characterized as 2 alpha,3 beta-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (1), 2 alpha,3 beta, 21 beta-trihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (2), 2 alpha,3 beta, 29-trihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (3) and 2 alpha,3 beta,23,27-tetrahydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (4) together with the known triterpene 2 alpha,3 beta,23-trihydroxyolean-12-en-28-oic acid (5). Structures were established by spectroscopic methods including one- and two-dimensional NMR, EI-MS and HR-EI-MS. The antibacterial activity of 1-5 was also investigated against two gram-positive (Bacillus subtilis, Staphylococcus aureus), and four gram-negative (Escherichia coli, Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi) bacterial strains.

Triprenylated flavonoids from Dorstenia psilurus and their alpha-glucosidase inhibition properties.

Six new unusual C-4'-prenylated flavonols, dorsilurins F-K (1-6), together with six known compounds were isolated from the roots of Dorstenia psilurus, and their structures were elucidated on the basis of spectroscopic evidence. The isolated compounds exhibited moderate to low alpha-glucosidase inhibitory activity. Dorsilurin F (1), with three unmodified prenyl groups, was the most active, while dorsilurin K (6), with only one unmodified prenyl group, was the least active compound. Furthermore, NMR data of dorsilurin C (7), isolated some years ago from the same plant, have been revised.

alpha-glucosidase inhibitors from Garcinia brevipedicellata (Clusiaceae).

In our continuous search for alpha-glucosidase inhibitors from plants, four new depsidones named brevipsidones A-D (1-4) were isolated from stem bark of Garcinia brevipedicellata together with known damnacanthal, scopoletin and a mixture of stigmasterol and beta-sitosterol. Structural elucidations were made by spectroscopic analyses including 2D-NMR data.

Alpha-glucosidase inhibitors ellagic acid derivatives with immunoinhibitory properties from Terminalia superba.

Fractionation of stem barks of Terminalia superba yielded two new ellagic acid derivatives, 3,4'-di-O-methylellagic acid 3'-O-beta-D-xylopyranoside (1) and 4'-O-galloy-3,3'-di-O-methylellagic acid 4-O-beta-D-xylopyranoside (2) together with known 3,3'-di-O-methylellagic acid, ellagic acid and 3,3'-di-O-methylellagic acid 4'-O-beta-D-xylopyranoside. Compounds (1) and (2) showed significant alpha-glucosidase inhibition activity and possessed significant immunoinhibitory activities with no cytotoxic effects.

Bioactive aristolactams from Piper umbellatum.

Four alkaloids named piperumbellactams A-D (1-4) were isolated from branches of Piper umbellatum together with known N-hydroxyaristolam II (5), N-p-coumaroyl tyramine (6), 4-nerolidylcatechol (7), N-trans-feruloyltyramine, E-3-(3,4-dihydroxyphenyl)-N-2-[4-hydroxyphenylethyl]-2-propenamide, beta-amyrin, friedelin, apigenin 8-C-neohesperidoside, acacetin 6-C-beta-d-glucopyranoside, beta-sitosterol, its 3-O-beta-d-glucopyranoside and its 3-O-beta-d-[6'-dodecanoyl]-glucopyranoside. Glycosidase inhibition, antioxidant and antifungal activities of these compounds were evaluated. Compounds 1-3 showed moderate alpha-glucosidase enzyme inhibition with IC50 values 98.07+/-0.44, 43.80+/-0.56 and 29.64+/-0.46, respectively. In DPPH radical scavenging assay, compounds 2, 3 and 6 showed potent inhibitory activity while compounds 4, 5 and 7 showed potent antifungal activity.

Further cytotoxic sesquiterpene lactones from Elephantopus mollis KUNTH.

Three new sesquiterpene lactones, (4betaH)-5alpha-hydroxy-8alpha-(2-methylbut-2-enoyloxy)-2-oxo-1(10),11(13)-guaiadien-12,6alpha-olide (1), (4betaH)-8alpha-(2-methylbut-2-enoyloxy)-2-oxo-1(5),10(14),11(13)-guaiatrien-12,6alpha-olide (2) and 2,5-epoxy-2beta-hydroxy-4alpha-methoxy-8alpha-(2-methylbut-2-enoyloxy)-4(15),10(14),11(13)-germacratrien-12,6alpha-olide (3), have been isolated from roots and stems of Elephantopus mollis together with two known sesquiterpene lactones (4, 5). The identification of the isolates was accomplished by spectroscopic methods. Compounds (1-5) exhibited significant cytotoxic activities against mouse neuroblastoma B104 cells.

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera.

In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1) and F (4) showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 microM and 0.16 microM, respectively) comparable to that of the reference compound, miltefosine (0.46 microM). Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE) and butylcholinesterase (AChE). For AChE, the IC50 value (0.66 microM) of garcinol (2) was almost equal to that of the reference compound galanthamine (0.50 microM). Furthermore, guttiferone A (1) and guttiferone F (4) (IC50 = 2.77 and 3.50 microM, respectively) were more active than galanthamine (IC50 = 8.5) against BChE.

Antimicrobial prenylated anthracene derivatives from the leaves of Harungana madagascariensis.

Three new prenylated anthranoids, harunmadagascarins C (1) and D (2) and kenganthranol D (3), together with three known compounds (4-6) were isolated from the leaves of Harungana madagascariensis. Their structures were assigned by spectroscopic methods and by comparison with literature data. In the three new natural products 1-3, one or two prenyl groups are incorporated in furan, pyran, or cyclohexane rings in four different modes of annulation. Compounds 2, 4, and 6 were strongly active against the Gram-positive Bacillus megaterium.

Anti-plasmodial and antioxidant activities of constituents of the seed shells of Symphonia globulifera Linn f.

A xanthone derivative, named gaboxanthone (1), has been isolated from the seed shells of Symphonia globulifera, together with known compounds, symphonin (2), globuliferin (3), guttiferone A (4), sistosterol, oleanolic acid and methyl citrate. The structure of the compound was assigned as 5,10-dihydroxy-8,9-dimethoxy-2,2-dimethyl-12-(3-methylbut-2-enyl) pyrano [3,2-b]xanthen-6(2H)-one, by means of spectroscopic analysis. The anti-plasmodial and antioxidant activities of the phenolic compounds were evaluated, respectively, in culture against W2 strain of Plasmodium falciparum and using the free radical scavenging activity of the DPPH radical, respectively. Compounds 1-4 were found to be active against the Plasmodium parasites (IC(50) of 3.53, 1.29, 3.86 and 3.17 microM, respectively). Guttiferone A (4) showed a potent free radical scavenging activity compared to the well-known antioxidant caffeic acid.