Schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from Clerodendrum umbellatum Poir leaves aqueous extract in Schistosoma mansoni infection in mice.

BACKGROUND: The intensive use of Praziquantel for the treatment of schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. As drug treatment is an important feature of schistosome control programs, the search for alternative drugs is therefore a priority. The aim of this study was to assess the schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from Clerodendrum umbellatum Poir leaves aqueous extract. METHODS: A phytochemical screening of the fraction of C. umbellatum was conducted. The fraction was administered orally and daily to Schistosoma mansoni-infected mice (BALB/c) from the 36th day post-infection for 28 days at 100, 200 and 400 mg/kg. Praziquantel (500 mg/kg) was used as reference drug. Non-infected and infected-untreated mice served as controls. All mice were sacrificed at 65th day post-infection. Body weight, liver/body and spleen/body weights, as well as worm burden, fecal egg count, liver and intestine egg load were determined. In the plasma, levels of total protein, transaminases (ALT, AST), alkaline phosphatase and total bilirubin were monitored to assess the possibility of liver damage. Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) levels were measured in the liver as biomarkers of the oxidative stress. RESULTS: The phytochemical analysis of the fraction from C. umbellatum aqueous leaves extract revealed the presence of alkaloids, flavonoids, cardiac glycosides, phenols, saponins, tannins and terpenoids. The worm burden, fecal egg count and egg load in the liver and intestine of infected mice treated with the fraction were significantly (p < 0.001) fewer than in infected-untreated mice. Only the highest-fraction dose reduced the worm and egg burdens in a similar way as praziquantel. Hepatosplenomegaly induced by S. mansoni infection was reduced by the treatment. The liver function on infected mice was ameliorate after administration of the fraction by significant reduction of ALT activity (35.43 to 45.25%) and increase of total protein level (44.79 to 70.03%). The methanolic fraction of C. umbellatum prevents the elevated MDA level induced by the infection while significant increase in catalase activity (297.09 to 438.98%) and glutathione level (58.23 to 95.88%) were observed after treatment. CONCLUSIONS: This study disclosed the schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from C. umbellatum leaves aqueous. These fraction's activities were similar to those of praziquantel. This fraction can be considered as a promising source for schistosomicidal agents.

Chemical constituents from stem bark and roots of Clausena anisata.

Phytochemical investigations on the stem bark and roots of the tropical shrub Clausena anisata led to the isolation and characterization three carbazole alkaloids: girinimbine, murrayamine-A and ekeberginine; two peptide derivatives: aurantiamide acetate and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate; and a mixture of two phytosterols: sitosterol and stigmasterol. The structures of these compounds were established by nuclear magnetic resonance (1H-NMR, 13C-NMR, COSY, HSQC, HMQC, HMBC and NOESY) spectroscopy and electrospray ionization mass spectrometry (MS).

Dorstenpictanone: a new bicyclic polyprenylated compound from Dorstenia picta.

One new bicyclic polyprenylated compound, dorstenpictanone (1), was isolated from Dorstenia picta. The structure of the new compound was elucidated by detailed spectroscopic analysis such as (1)H NMR, (13)C NMR, COSY, HMQC, HMBC, and HREIMS. The relative configuration of dorstenpictanone (1) was distinguished by comparative analysis of the NMR spectral data with known analogues together with the ROESY experiment.

Ozocardic A: a new alkylanacardic acid from Ozoroa pulcherrima.

One new alkylanacardic acid, ozocardic A (1), along with the known and related metabolites 6-tridecyl anacardic acid (2) and ß-sitosterol (3) was isolated from Ozoroa pulcherrima. The structure of the new compound was elucidated by detailed spectroscopic analysis such as (1)H, (13)C NMR, COSY, HMQC, HMBC, and HREIMS. The structures of known compounds (6-tridecyl anacardic acid (2) and ß-sitosterol (3)) were identified by the comparison of their spectral data with those published in the literature.

Antiarol cinnamate and africanoside, a cinnamoyl triterpene and a hydroperoxy-cardenolide from the stem bark of Antiaris africana.

From the methanol extract of the stem bark of the African tree Antiaris africana Engler, two new bioactive metabolites were isolated, namely, the α-amyrin derivative 1ß,11α-dihydroxy-3ß-cinnamoyl-α-amyrin (antiarol cinnamate, 1) and a cardiac glycoside, 3ß-O-(α-L-rhamnopyranosyl)-14ß-hydroperoxy-5ß-hydroxy-19-oxo-17ß-card-20(22)-enolide (africanoside, 2a), together with the known compounds ß-amyrin and its acetate, ß-sitosterol and its 3-O-ß-D-glucopyranoside, friedelin, ursolic and oleanolic acid, 19-norperiplogenin, strophanthidol, strophanthidinic acid, periplogenin (3a), 3-epiperiplogenin, strophanthidin (3b) and 3,3'-dimethoxy-4'-O-ß-D-xylopyronosyl-ellagic acid. Their structures were established on the basis of their spectroscopic data and by chemical methods, while 3a was additionally confirmed by X-ray crystal structure analysis. The aglycone moiety possessing a hydroperoxy group was found for the first time in cardenolides. Compounds 1 and 2a showed no activity against bacteria, fungi, and microalgae; however, the crude extract exhibited a high toxicity against Artemia salina and a selective antitumor activity against human tumor cell lines. Africanoside (2a) effected a concentration-dependent inhibition of tumor cell growth with a mean IC(50) value of 5.3 nM.

Cameroonemide A: a new ceramide from Helichrysum cameroonense.

From the extracts of all parts of the plant Helichrysum cameroonense, five compounds were isolated and identified. One of them, a ceramide, named cameroonemide A (1), is reported for the first time as a new natural product. Its structure was determined by comprehensive analyses of their 1D and 2D NMR and HR-EI-MS spectral data. The remaining four known compounds were identified by comparing their spectroscopic data with those reported in the literature as kaurenoic acid (2), 3-acetyloxykaurenoic acid (3), beta-sitosterol (4), and beta-sitosterol glucopyranoside (5). Preliminary studies showed that 3-acetyloxykaurenoic acid (3) inhibited the alga Chlorella fusca, while kaurenoic acid (2) showed strong antibacterial activity against Bacillus megaterium.

Acute and chronic anti-inflammatory properties of the stem bark aqueous and methanol extracts of Sclerocarya birrea (Anacardiaceae).

Sclerocarya birrea is used in folk medicine for the treatment of inflammatory disorders. The effect of the stem bark aqueous and methanol extracts of S. birrea (150 or 300 mg/kg) was evaluated on carrageenan-, histamine- or serotonin-induced paw oedema in rats. The methanol extract of S. birrea (300 mg/kg) being the most active, exhibited a maximum inhibition of 75.45 and 55.31% on carrageenan- and histamine-induced inflammation, respectively. When administered at 300 mg/kg, the methanol extract of S. birrea also exhibited 80.68% inhibition on the 10th day and 54.43% inhibition on the 21st day in formalin- or complete Freund's adjuvant (CFA)-induced paw oedema in rats. GSH level was significantly increased (75.14%), while MAD level was significantly decreased (31.22%) in the liver of CFA rats treated with S. birrea (300 mg/kg). The results suggest that the anti-inflammatory activity of the aqueous and methanol extracts of S. birrea is due to the inhibition of histamine and prostaglandin pathways and to its antioxidant activity.

Evaluation of the schistosomicidal, antioxidant and anti-inflammatory activities of the ethyl acetate fraction from Ozoroa pulcherrima Schweinf. Roots on Schistosoma mansoni-induced liver pathology in mice and its phytochemical characterization.

ETHNOPHARMACOLOGICAL RELEVANCE: Ozoroa pulcherrima Schweinf. (syn.: Heeria pulcherrrima Schweinf.) is a small shrub belonging to the family Anacardiaceae. In Africa, the stem and the leaves are used to treat dystocia, hyperthermia, and conjunctivitis, while the root is used to treat dysmenorrhea and intestinal helminthiasis. AIM OF THE STUDY: The aim of this study was to assess the schistosomicidal, antioxidant and anti-inflammatory effects of the ethyl acetate fraction from O. pulcherrima roots methanolic extract (EAOp) on S. mansoni- induced liver pathology in mice. Additionally, its phytochemical composition was elucidated. MATERIAL AND METHODS: The phytochemical characterization of EAOp was carried out by High-Performance Liquid Chromatography-Mass spectrometry (HPLC-MS). Total phenolic and flavonoid contents were also quantified in the fraction. S. mansoni-infected mice received daily and per os, for 28 days, EAOp at 200 or 400 mg/kg, starting from the 36th day post-infection. Praziquantel was used as reference drug. Uninfected-untreated, uninfected-treated and infected-untreated mice served as controls. At the 65th day post-infection mice were sacrificed and parasitological burden monitored. Transaminases, total bilirubin, and total proteins levels were determined in the plasma. Malondialdehyde (MDA), nitrites, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were measured in the liver as biomarkers of the oxidative stress. Liver histology and morphometric analysis of granulomas were also conducted. RESULTS: The HPLC-MS analysis data of EAOp revealed the presence of four triterpenes namely oleaterminaloic acid, hydroxyoleanolic acid, moronic acid, and oleanolic acid; a flavonoid dipentoxybenzoic acid and two alkaloids. Its total phenolic content was 76.46 ±â€¯0.01 mg GAE/g and total flavonoid content 6.26 ±â€¯0.31 mg rutin equivalent/g. The reductions of worm burden (48.89 and 75.56%), fecal egg count (77.76 and 69.52%) and egg load in the liver (65.33 and 77.18%) and intestine (78.06 and 84.63%) were significant after EAOp treatment. EAOp at all doses significantly (p < 0.001) reversed the increasing transaminases activities and total bilirubin level induced by the infection. A normalization of total proteins concentration was also recorded. Treatment of S. mansoni-infected mice with EAOp at 200 or 400 mg/kg resulted in a significant reduction (p < 0.001) of MDA concentration by 73.20% and 67.78% respectively. The level of nitrites which was reduced by the infection significantly increased after the treatment. EAOp significantly increased by 4.67 and 5.69-fold the CAT activity and by 126.67% the GSH level. Histologically, a significant reduction of the number (66.39 and 57.82%) and the volume (52.25 and 34.81%) of liver inflammatory granulomas was recorded after EAOp treatment at all doses. CONCLUSIONS: These results suggest that the liver pathology in S. mansoni infection is improved by EAOp which disclosed good schistosomicidal, antioxidant and anti-inflammatory activities. Its effects on the liver dysfunction and the hepatic oxidative stress were comparable to that of praziquantel. These findings justified the traditional use of O. pulcherrima for the treatment of intestinal helminthiasis. This fraction can be considered as a promising source for schistosomicidal agents.

Efficacy of Ozoroa pulcherrima Schweinf methanolic extract against Schistosoma mansoni-induced liver injury in mice.

The roots of Ozoroa pulcherrima Schweinf are used in traditional medicine to treat intestinal helminthiasis. The aim of this study was to assess the effect of Ozoroa pulcherrima roots methanolic extract (OPME) on liver injury induced by Schistosoma mansoni in mice. A preliminary phytochemical study of OPME was conducted. OPME was given daily and orally to S. mansoni-infected mice at 100, 200 or 400 mg/kg for 28 days, starting from the 36th day post-infection. Praziquantel was used as reference drug. Non-infected and infected-untreated mice served as controls. Worm burden and egg output, transaminases, total bilirubin, alkaline phosphatase and total protein; as well as malondialdehyde, catalase and reduced glutathione were evaluated. In OPME, total phenolic was 79.61 ± 0.25 mg gallic acid equivalent/g, while total flavonoid was 7.98 ± 0.04 mg rutin equivalent/g. Treatment of S. mansoni-infected mice with OPME produced significant reduction of worm burden and ova count in the faeces, liver and intestine. Significant reduction of alanine aminotransferase activity (p < 0.001) as well as significant increase of total protein content (p < 0.001) was recorded after OPME treatment at all doses. Total bilirubin level was also reduced (p < 0.01). Administration of OPME at all doses corrected the high malondialdehyde level (p < 0.001) induced by the infection. At 200 mg/kg, catalase activity and reduced glutathione concentration were significantly increased (p < 0.001). OPME at 200 mg/kg showed moderate schistosomicidal effect, but was effective as the standard drug praziquantel in restoring the liver function after S. mansoni infection.

Effects of hydroquinone-containing creams on capillary glycemia before and after serial hand washings in Africans.

BACKGROUND: Hydroquinone-containing creams cause false increases in capillary glycemia. However, the magnitude of this false increase, and the means to reverse it have not been investigated. OBJECTIVE: To evaluate the technical and clinical impact of hydroquinone-containing creams on capillary glycemia and investigate the efficacy of hand washing and other common practices, in reversing cream effects. METHODS: We included 91 participants in a quasi-experimental study in Buea, Cameroon. After determining the hydroquinone content of a cream, Caro Light, we used two glucometers with different enzymatic systems (Accu-Chek Active and OneTouch Ultra 2) to measure fasting glycemia after: initial hand washing (reference), application of 1 ml of hydroquinone-containing cream, finger swabbing with wet gauze, sanitizer application and a series of three hand washings following cream application. Reference glycemia was compared to those obtained after various interventions. Statistical significance was assessed by paired sample t-test, clinical significance by total error allowable (TEa), and clinical impact by Parke's error grid analysis. RESULTS: The mean differences in capillary glycemia (Intervention-reference) measured by Accu-Chek Active in mg/dl were 28, 27, 38, 16, 4, and -2 after cream application, finger swabbing, sanitizer application, one, two, and three hand washings respectively. Corresponding values for OneTouch Ultra2 were 41, 44, 64, 22, 5 and -5. These differences, except after two and three hand washings were both statistically (p < 0.0001) and clinically significant (TEa). After cream application, Accu-Check had 9.9% of values in Parke's Zones C-E, while OneTouch had 18.7%. CONCLUSION: Hydroquinone-containing creams cause significant false increase in capillary glycemia irrespective of the enzymatic system of the glucometer used, and can lead to potentially wrong clinical decisions. A minimum of two hand washings is required prior to capillary glucose measurement.

Effect of Sclerocarya birrea (Anacardiaceae) stem bark methylene chloride/methanol extract on streptozotocin-diabetic rats.

Sclerocarya birrea (Anacardiaceae) is used as a traditional treatment of diabetes in Cameroon. In this study, we investigated the possible antidiabetic effect of the stem bark extract in diabetic rats. Diabetes was induced by intravenous injection of streptozotocin (STZ, 55 mg/kg) to male Wistar rats. Experimental animals (six per group), were treated by oral administration of plant extract (150 and 300 mg/kg body weight) and metformin (500 mg/kg; reference drug) for comparison, during 21 days. The stem bark methanol/methylene chloride extract of Sclerocarya birrea exhibited at termination, a significant reduction in blood glucose and increased plasma insulin levels in diabetic rats. The extract also prevented body weight loss in diabetic rats. The effective dose of the plant extract (300 mg/kg) tended to reduce plasma cholesterol, triglyceride and urea levels toward the normal levels. Four days after diabetes induction, an oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The results showed a significant improvement in glucose tolerance in rats treated with Sclerocarya birrea extract. Metformin, a known antidiabetic drug (500 mg/kg), significantly decreased the integrated area under the glucose curve. These data indicate that Sclerocarya birrea treatment may improve glucose homeostasis in STZ-induced diabetes which could be associated with stimulation of insulin secretion.

Tithoniamarin and tithoniamide: a structurally unique isocoumarin dimer and a new ceramide from Tithonia diversifolia.

Tithoniamarin (1), a new isocoumarin dimer and a new ceramide, named tithoniamide (2a), have been isolated from Tithonia diversifolia, in addition to the known beta-sitosterol and beta-sitosterol glucopyranoside. The structures were elucidated on the basis of spectroscopic and chemical evidence. Preliminary studies showed that 1 has antifungal and herbicidal activities against Microbotryum violaceum and Chlorella fusca.

Chalcones and other constituents of Dorstenia prorepens and Dorstenia zenkeri.

The twigs of Dorstenia prorepens furnished the digeranylated chalcone, 5,3'-(3,7-dimethyl-2,6-octadienyl)-3,4, 2',4'-tetrahydroxychalcone while Dorstenia zenkeri yielded the 3',4'-(3-hydroxy-2,2-dimethyldihydropyrano)-4,2'-dihydroxychalcone and a bichalcone. 4-Hydroxylonchocarpin was found in both plants. D. prorepens also yielded the known compounds: psoralen, bergapten, beta-sitosterol and its D-glucopyranosyl derivative. D. zenkeri yielded p-hydroxybenzaldehyde, dorsmanin A, 4,2',4'-trihydroxychalcone and 4,2',4'-trihydroxy-3'-prenylchalcone. Structures of the new compounds were established by UV, IR, MS and 2-D NMR analysis.

Dinklagins A, B and C: three prenylated flavonoids and other constituents from the twigs of Dorstenia dinklagei.

Three prenylated flavonoids, dinklagins A, B and C identified, respectively, as (-)-6-(3,3-dimethylallyl)-7-hydroxy-6''', 6'''-dimethylchromeno-(4',3',2''',3''')-flavanone, (+)-5,4',5"xi-trihydroxy-6'',6''-dimethylchromano-(7,6,2'',3'')-flavone and (+)6-(2xi-hydroxy-3-methyl-3-butenyl)-5,7,4'-trihydroxyflavone were isolated from the twigs of Dorstenia dinklagei together with the known 6-prenylapigenin, 4-hydroxylonchocarpin, stipulin and 5,4'-dihydroxy-6'',6''-dimethylchromano-(7,6,2'',3'')-flavone. Their structures were determined on the basis of spectral data and by comparison with data reported in the literature and with authentic specimens for known compounds.

Prenylated flavonoids, monoterpenoid furanocoumarins and other constituents from the twigs of Dorstenia elliptica (Moraceae).

A monoprenylated flavan and two monoterpenoid substituted furanocoumarins were isolated from the twigs of Dorstenia elliptica along with 3-(3,3-dimethylallyl)-4,2',4'-trihydroxylchalcone, psoralen, bergapten, O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl)butyl]bergaptol, beta-sitosterol and its beta-D-glucopyranoside. The structure of the flavan was determined as 6(1,1-dimethylallyl)-7,4'-dihydroxylflavan and the monoterpenoid substituted furanocoumarins were assigned as O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl)-3-hydroxybutyl]-bergaptol and O-[2-(5-hydroxy-2,6,6-trimethyl-3-oxo-2H-pyran-2-yl)ethyl]bergaptol, respectively, using spectroscopic analysis, especially, 2D NMR spectra.

Leaf methanol extract of Bidens pilosa prevents and attenuates the hypertension induced by high-fructose diet in Wistar rats.

Chronic fructose treatment in rats has repeatedly been shown to elevate blood pressure in association with insulin resistance and hyperinsulinemia. The purpose of the current study was to investigate the effect of the leaf methanol extract of Bidens pilosa on systolic blood pressure (SBP) and plasma glucose, insulin, cholesterol, triglycerides and creatinine levels in rats with fructose-induced hypertension. Wistar rats that drank a 10% fructose solution for 3-6 weeks showed significant increase not only in plasma insulin and cholesterol levels but also in SBP. B. pilosa extract was able to prevent the establishment of hypertension and lower elevated blood pressure levels. The extract also reduced the highly elevated plasma insulin levels provoked by the high fructose diet. These results suggest that the leaf methanol extract of B. pilosa exerts its antihypertensive effect in part by improving insulin sensitivity.

Melicilamide A: a new ceramide from Milicia excelsa.

This article deals with a phytochemical investigation of Melicia excelsa from which melicilamide A (1), a new ceramide has been isolated. Its structure was determined by comprehensive analyses of its (1)H- and (13)C-NMR, COSY, HMQC and HMBC spectroscopic, EI-MS and ESI-MS data. The remaining one known compound was identified as ß-sitosterol glucopyranoside.

Cordioxime: a new dioxime gamma-lactam from Cordia platythyrsa.

Cordia platythyrsa Baker is known for its medicinal value. This paper deals with a phytochemical investigation of this species, from which cordioxime (1), a new dioxime y-lactam has been isolated. Its structure was determined by comprehensive analyses of its 1H and 13C NMR, COSY, HMQC, and HMBC spectroscopic, and HREIMS data. The remaining two known compounds were identified as beta-sitosterol, and beta-sitosterol glucopyranoside.

Two new alkylanacardic acids, ozorcardic A and B, from Ozoroa pulcherrima.

Two new alkylanacardic acids, ozorcardic A (1) and B (2), along with the known and related metabolite anacardic acid (3), were isolated from Ozoroa pulcherrima. The structures of the new compounds were elucidated by detailed spectroscopic and spectrometric analysis.

Hyloglyceride and hylodiglyceride: two new glyceride derivatives from Hylodendron gabunensis.

Phytochemical investigation of Hylodendron gabunensis resulted in the isolation of two new glyceride derivatives, hyloglyceride (1) and hylodiglyceride (2). The structures of the two new compounds were determined by comprehensive analysis of their 1D and 2D NMR spectroscopic, and HREIMS data. One known compound was also isolated and identified as beta-sitosterol.