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Hepatoprotective effect of extracts from Pergularia daemia Forsk.

Pergularia daemia (Asclepiadaceae) is a perennial herb growing widely along the road sides of India. It has been used in folk medicine for the treatment of liver disorders. The aim of this work is to study the hepatoprotective effect of crude ethanolic and aqueous extracts from the aerial parts of Pergularia daemia. The aqueous and ethanolic extracts obtained from aerial parts of Pergularia daemia were evaluated for hepatoprotective activity in rats by inducing liver damage by carbon tetrachloride. The ethanolic extract at an oral dose of 200 mg/kg exhibited a significant (P<0.05) protective effect by lowering serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin and total cholesterol and increasing the levels of total protein and albumin levels as compared to silymarin used as a positive control. These biochemical observations were supplemented by histopathological examination of liver sections. The activity may be a result of the presence of flavonoid compounds. Furthermore, the acute toxicity of the extracts showed no signs of toxicity up to a dose level of 2000 mg/kg. Thus it could be concluded that ethanolic extract of Pergularia daemia possesses significant hepatoprotective properties.

Administration, Oral↗

Gastroprotective effect of a traditional Chinese herbal drug "Baishouwu" on experimental gastric lesions in rats.

"Baishouwu" is an appellative name of dried root tubers from three Asclepiadaceae plants: Cynanchum auriculatum Royle ex Wight, Cynanchum bungei Decne and Cynoctonum wilfordii Maxim. In order to establish the pharmacological basis for the ethnomedicinal use of Baishouwu in gastric disorders, this study examined the effects of ethanol extracts and fractions from root tubers of Cynanchum auriculatum, Cynanchum bungei and Cynoctonum wilfordii on ethanol-, indomethacin-induced gastric lesions and histamine-induced gastric acid secretion in rats. Plant materials were collected from various areas of China. Oral administration of ethanol extract and chloroform fraction of Cynoctonum wilfordii collected from Changbai Cordillera at doses of 150 and 68 mg/kg, respectively, significantly inhibited the development of ethanol- and indomethacin-induced gastric lesions and also caused significant decrease of gastric acid secretion after histamine-induced gastric lesion. Oral administrations of ethanol extract and chloroform fraction of Cynanchum auriculatum collected from Binhai at the doses of 300 and 69 mg/kg, respectively, significantly inhibited ethanol- and indomethacin-induced gastric lesions. This study demonstrates the gastroprotective property of Baishouwu for the first time.

Animals↗

Nitric oxide-dependent vasodilatation by ethanolic extract of Hancornia speciosa via phosphatidyl-inositol 3-kinase.

The vasodilator effect of the ethanolic extract of leaves from Hancornia speciosa Gomes (HSE) was studied in rat aortic rings. HSE produced a concentration-dependent vasodilatation (pIC(50)=5.6+/-0.1), which was completely abolished in endothelium-denuded vessels. The endothelium-dependent vasodilatation induced by HSE was abolished by l-NAME (100 microM), a nitric oxide (NO) synthase inhibitor, but not atropine (1 microM; pIC(50)=5.6+/-0.2), a muscarinic receptor antagonist, nor indomethacin (10 microM; pIC(50)=5.4+/-0.2), a cyclooxygenase inhibitor. The concentration-response curve of HSE was significantly shifted to the left by superoxide dismutase (SOD; 300U/mL). In addition, while SOD displaced the 3-morpholino-sidnonimine (SIN-1; P<0.05) concentration-effect curve to the left, HSE (50 microg/mL) had no effect. Finally, wortmannin (0.3 microM), an inhibitor of phosphatidyl-inositol 3-kinase (PI3K), dramatically reduced the vasodilator effect of HSE. Together, these findings lead us to conclude that HSE induces a NO- and endothelium-dependent vasodilatation in rat aortic preparations, likely by a mechanism dependent on the activation of PI3K.

Animals↗

In vitro antiprotozoal activities and cytotoxicity of some selected Cameroonian medicinal plants.

Eight extracts from seven selected Cameroonian medicinal plants, traditionally used to treat malaria and other protozoal diseases, were tested in vitro for their antiprotozoal activities against Plasmodium falciparum K1 chloroquine-resistant strain, Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei rhodesiense, protozoa responsible for malaria, visceral leishmaniasis, Chagas disease and African trypanosomiasis, respectively. The most active extract against Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense was the methanolic extract of Albizia zygia (Fabaceae) stem bark with IC(50) values of 1.0 microg/ml and 0.2 microg/ml, respectively. Five extracts showed IC(50) values below 5mug/ml against Leishmania donovani, with the methanolic seed extract of Harungana madagascarensis showing the highest activity, but only the methanolic extract of Albizia zygia showed activity against Trypanosoma cruzi. Cytotoxicity and selectivity indexes were estimated for the most active extracts. The best ratio of cytotoxicity to antiplasmodial activity (SI(a)=14) was established for the methanolic leaf extract of Symphonia globulifera (Clusiaceae), while the methanolic stem bark extract of Albizia zygia showed the best ratio of cytotoxicity to antitrypanosomal activity (SI(b)=22.5).

Albizzia↗

A new lignan from the Jian-er syrup and its content determination by RP-HPLC.

The Jian-er syrup is a commonly used traditional Chinese medicinal preparation refined from two herbs, Metaplexis japonica (Thunb.) Makino and Justicia procumbens L. A new lignan, named 6'-hydroxy-Justicidin B, was isolated from the ethyl acetate extract of the Jian-er syrup and its structure was established on the basis of spectral analysis. The content of 6'-hydroxy-Justicidin B in the Jian-er syrup was determined by RP-HPLC for the first time. Chromatographic separation was achieved on an Agilent Zorbax SB-C18 column (150 mmx4.6 mm i.d., 5 microm) at 25 degrees C and the mobile phase was a mixture of acetonitrile and water (31:69 v/v) detected at 256 nm at a flow rate of 1.0 ml/min. This method was validated in terms of selectivity, linearity, precision, accuracy, limit of detection, limit of quantitation and solution stability. It can be used to control the quality of this preparation effectively.

Apocynaceae↗

Long range dispersal and spatial pattern formation in biological invasions.

In this paper we explore the consequences of long distance dispersal in biological invasion processes through simulations using a recently developed cellular automaton model. We show that long distance dispersal generate characteristic spatial patterns with several stationary scale-invariant properties. In particular, the patterns display a main patch around the focus of spread, with a fractal border structure whose fractal dimension contains information about the main statistical properties of the dispersal mechanism. Our results are in agreement with field data of spread of invaders with long distance dispersal mechanisms.

Apocynaceae↗

Antinociceptive properties produced by the pregnane compound velutinol A isolated from Mandevilla velutina.

Velutinol A is a pregnane compound isolated from the rhizomes of the Brazilian plant Mandevilla velutina that interferes with kinin actions and possesses anti-inflammatory action. Here, we investigate the effect produced by velutinol A in different models of inflammatory nociception. The nociceptive effect caused by the intraplantar injection of phorbol myristate acetate (PMA, 50 pmol/paw) in mice was practically abolished by coadministration of velutinol A (1-10 nmol/paw). In contrast, the coadministration of velutinol A (10 nmol/paw) failed to affect the nociceptive response elicited by either bradykinin (BK, 10 nmol/paw) or prostaglandin E(2) (PGE(2), 10 nmol/paw). Of note, velutinol A (10 nmol/paw) partially inhibited the nociceptive response caused by capsaicin (1 nmol/paw). However, velutinol A (10 microM) did not significantly interfere with the specific binding sites of [(3)H]resiniferatoxin or [(3)H]BK in vitro. Our data also suggest that these effects are related with its ability to interact with kinin B(1) receptor-mediated mechanisms, as the cotreatment of mice with velutinol A (10 nmol/paw) consistently blocked the nociceptive response induced by the selective B(1) receptor agonist des-Arg(9)-BK. Finally, the persistent hyperalgesia produced by intraplantar injection of carrageenan (300 microg/paw) was completely reversed by the coadministration of velutinol A (10 nmol/paw). Collectively, the present results show that the pregnane compound velutinol A produces peripheral antinociceptive action in some models of acute and persistent inflammatory pain by interacting with kinin B(1)-receptor mediated effects. Thus, velutinol A or its derivatives could constitute an attractive molecule of interest for the development of new analgesic drugs. Additional studies are now in progress in order to further explore its precise mechanism of action on B(1) receptor pathways.

Analgesics↗

Endothelium-dependent vasodilation induced by Hancornia speciosa in rat superior mesenteric artery.

The vasodilator effect of the ethanolic extract of leaves from Hancornia speciosa Gomes (HSE) was evaluated in superior mesenteric artery rings. HSE produced a concentration-dependent vasodilation (IC50 = 10.8 +/- 4.0 microg/mL) in arterial rings pre-contracted with phenylephrine, which was completely abolished in endothelium-denuded vessels. Endothelium-dependent vasodilation induced by HSE was strongly reduced by L-NAME (100 microM), a nitric oxide (NO) synthase inhibitor, but neither by atropine, a muscarinic receptor antagonist (1 microM), nor by indomethacin (10 microM), a cyclooxygenase inhibitor. In rings pre-contracted with 80 mM KCl, the vasodilator effect of HSE was shifted to the right and was completely abolished in the presence of L-NAME (100 microM). Similar effects were obtained in mesenteric rings pre-contracted with phenylephrine in the presence of KCl 25 mM alone or in addition to 100 microM L-NAME. In addition, BaCl2 (1 mM) dramatically reduced the vasodilation induced by HSE. Together, these findings led us to conclude that HSE induces an endothelium-dependent vasodilation in rat mesenteric artery, by a mechanism dependent on NO, on the activation of potassium channels and endothelium-derived hyperpolarizing factor release. Rutin, identified as a major peak in the HPLC fingerprint obtained for HSE, might contribute for the observed vasodilator effect, since it was able to induce an endothelium-dependent vasodilation in rat superior mesenteric arteries.

Animals↗

Cytotoxic cardenolide glycoside from the seeds of Cerbera odollam.

A cardenolide glycoside, 3 beta-O-(2'-O-acetyl-l- thevetosyl)-15(14-->8)-abeo-5 beta-(8R)-14-oxo-card-20(22)-enolide (2'-O-acetyl cerleaside A), was isolated from a methylene chloride extract of the seeds of Cerbera odollam, together with four known compounds: cerleaside A, 17 alpha-neriifolin, 17 beta- neriifolin and cerberin. Their structures were elucidated by spectroscopic methods. All compounds except cerleaside A exhibited cytotoxic activities against oral human epidermoid carcinoma (KB), human breast cancer cell (BC) and human small cell lung cancer (NCI-H187).

Antineoplastic Agents, Phytogenic↗

Acetylated glucuronide triterpene bidesmosidic saponins from Symplocos glomerata.

Nine new bidesmosidic 3-O-glucuronide oleanane triterpenoid saponins were isolated from the stem bark of Symplocos glomerata King along with two known saponins, salsoloside C and copteroside E, and two major lignans, (-)-pinoresinol and (-)-pinoresinol-4'-O-beta-D-glucopyranoside. The structures of the new saponins were established using one- and two-dimensional NMR spectroscopy and mass spectrometry as, 3-O-[beta-D-xylopyranosyl(1-->4)-[2-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[beta-D-xylopyranosyl(1-->4)-[3-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[beta-D-xylopyranosyl (1-->4)-[2,3-O-diacetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[alpha-L-arabinopyranosyl(1-->4)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[alpha-L-arabinopyranosyl (1-->4)-[2-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[[beta-D-xylopyranosyl (1-->2)]-[beta-D-xylopyranosyl (1-->4)]-[3-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[[beta-D-glucopyranosyl (1-->2)]-[beta-D-xylopyranosyl (1-->4)]-[3-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, 3-O-[[beta-D-glucopyranosyl (1-->2)]-[alpha-L-arabinofuranosyl (1-->4)]-[3-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-oleanolic acid, and 3beta-O-[beta-D-xylopyranosyl(1-->4)-[2-O-acetyl]-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl]-morolic acid. The EtOH and EtOAc extracts of the stem bark showed no cytotoxic activity. At a concentration of 370 microg/ml, the saponin mixture showed haemolytic activity and caused 50% haemolysis of a 10% suspension of sheep erythrocytes.

Acetylation↗

Polyhydroxypregnane glycosides from Oxystelma esculentum var. alpini.

Three new polyhydroxypregnane glycosides named alpinoside A [kidjolanin 3-O-beta-d-glucopyranosyl-(1-->4)-beta-d-glucopyranosyl-(1-->4)-beta-d-thevetopyranosyl-(1-->4)-beta-d-cymaropyranosyl-(1-->4)-beta-d-cymaropyranoside], alpinoside B [kidjolanin 3-O-beta-d-glucopyranosyl-(1-->4)-beta-d-thevetopyranosyl-(1-->4)-beta-d-cymaropyranosyl-(1-->4)-beta-d-cymaropyranoside], and alpinoside C [kidjolanin 3-O-beta-d-glucopyranosyl-(1-->4)-beta-d-glucopyranosyl-(1-->4)-beta-d-oleandropyranosyl-(1-->4)-beta-d-cymaropyranosyl-(1-->4)-beta-d-cymaropyranoside] were isolated from the leaves of Oxystelma esculentum var. alpini. The structure elucidation was accomplished by extensive spectroscopic analysis and acid-catalyzed hydrolysis.

Apocynaceae↗

Chemical constituents of leaves and stem bark of Plumeria obtusa.

The continued studies on the constituents of the fresh leaves and stem bark of Plumeria obtusa Linn. have led to the isolation and characterization of four new triterpenoids, dammara-12,20(22)Z-dien-3-one (1), dammara-12,20(22)Z-dien-3beta-ol (2), olean-12-en-3beta,27-diol (3), and 27-hydroxyolean-12-en-3-one (4) and 12 known compounds, which included eight triterpenoids; dammara-3beta,20(S),25-triol (5), urs-12-en-3beta-hydroxy-27-Z-feruloyloxy-28-oic acid (6), 3beta-hydroxyolean-12-en-28-oic acid (7), 3beta,27-dihydroxylupan-29-ene (8), 3beta-hydroxylupan-29-en-28-oic acid (9), 3beta-hydroxyursan-12-en-28-oic acid (11), 3beta-hydroxy-27-p-coumaroyloxy-olea-12-en-28-oic acid (12) and urs-12-en-3-one (15); an iridoid 1alpha-plumieride (10); a cardenolide 3alpha,14beta-dihydroxy-17beta-card-20(22)-enolide (13); a fatty acid ester methyl n-octadecanoate (14) and a steroid 3beta-hydroxy-delta5-stigmastane (16). The new constituents were characterized through spectroscopic studies including 1D (1H and 31C NMR) and 2D (COSY-45, NOESY, J-resolved, HMQC and HMBC) NMR and chemical transformations. This is the first report on the isolation of dammarane triterpenoids from P. obtusa. Compounds 5 and 6 are hitherto unreported from P. obtusa. The known compounds were identified by comparison of their spectral data with those reported in the literature.

Apocynaceae↗

New unusual pregnane glycosides with antiproliferative activity from Solenostemma argel.

Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated from Solenostemma argel. Stemmosides E--J are characterized by the occurrence of an uncommon 14 beta proton configuration while stemmosides E and F possess in addition a rare enolic function in C-16. On the other hand, stemmosides G-J display an unusual C-17 alpha side chain. Their structures were established by ESI-MS and NMR experiments. Moreover, the effect of these compounds on the VEGF-induced in Kaposi's sarcoma cell proliferation was tested. Results indicated that all the compounds reduced the cell proliferation in a dose dependent manner.

Antineoplastic Agents, Phytogenic↗

New pregnane glycosides from Caralluma dalzielii.

Twenty-seven new pregnane glycosides were isolated from the whole plant of Caralluma dalzielii, and their structures elucidated from extensive 2D NMR analysis as well as ESI-MS experiments. All isolated compounds were tested for their antiproliferative activity on J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high potency of cytotoxicities were found in almost all tested compounds, confirming the significant cytotoxic activity of pregnane glycosides.

Animals↗

Four new C-21 steroidal glycosides from the roots of Stephanotis mucronata and their immunological activities.

Four new C-21 steroidal glycoside, stemucronatosides D (1), E (2), F (3), and G (4) were isolated from the roots of Stephanotis mucronata. Their structures were determined on the basis of chemical evidence and extensive spectroscopic methods including one-dimensional and two-dimensional NMR. These isolated compounds were assayed for their immunological activities in vitro against concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced proliferation of mice splenocytes. Compounds 1, 2, and 4 showed immunosuppressive activities in a dose-dependent manner, while compound 3 showed immunomodulating activities.

Animals↗

Steroidal glycosides from Cynanchum forrestii Schlechter.

Nine new steroidal glycosides, cynaforrosides B, C, D, E, and F, based on a 13, 14: 14, 15-disecopregnane-type skeleton, cynaforrosides G, H, and I with a new aglycone named cynaforrogenin A, and cynaforroside J together with three known C21 steroidal glycosides cynatratoside A, hancoside and komaroside C were isolated from the ethanol extract of the roots of Cynanchum forrestii Schlechter. The structures of new compounds were determined on the basis of spectral and chemical evidence. Steroidal glycosides with three kinds of skeletons were isolated from this plant simultaneously. The sugar units of cynaforrosides B-I contained two moieties of glucoses and especially cynaforrosides E-I contained two glucoses with the mode of 1-->6 linkage, which were rare among steroidal glycosides of the genus Cynanchum.

Apocynaceae↗

Four new immunomodulating steroidal glycosides from the stems of Stephanotis mucronata.

Four new C-21 steroidal glycosides, mucronatosides E (1), F (2), G (3), and H (4), were isolated from the stems of Stephanotis mucronata. Two of them had the rare aglycone with a double bond between C-6 and C-7. Their structures were elucidated on the basis of spectroscopic data and chemical evidence. These isolated compounds were assayed for their immunological activities in vitro against concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced proliferation of mice splenocytes. Compounds 2 and 4 showed immunosuppressive activities in a dose-dependent manner, while compounds 1 and 3 possessed immunoenhancing activities.

Animals↗