Antimalarial activities and toxicities of three plants used as traditional remedies for malaria in the Democratic Republic of Congo: Croton mubango , Nauclea pobeguinii and Pyrenacantha staudtii

The antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of Croton mubango, the stem bark of Nauclea pobeguinii and the leaves of Pyrenacantha staudtii) used as antimalarial remedies in the Democratic Republic of Congo were studied both in vitro (against Plasmodium falciparum) and in mice infected with Pl. berghei berghei. The toxic effects of dried aqueous extracts of the plants were also investigated, in uninfected mice. The most active crude extracts in vitro, with median inhibitory concentrations (IC(50)) of <1 microg/ml, were found to be the methanolic and dichloromethane extracts of C. mubango, and the dichloromethane extracts of N. pobeguinii and Py. staudtii. The aqueous extract with the most antimalarial activity in vitro was that of C. mubango (IC(50) = 3.2 microg/ml), followed by that of N. probeguinii (IC(50) = 5.3 microg/ml) and then that of Py. staudii (IC(50) = 15.2 microg/ml).Results from the in-vivo tests of antimalarial activity showed that, at a daily oral dose of 200 mg/kg, all the dichloromethane extracts, the petroleum-ether, chloroformic, ethyl-acetate and residual water-soluble fractions from C. mubango, and the chloroformic, ethyl-acetate and n-butanolic fractions from Py. staudtii produced >80% chemosuppression of the parasitaemias by day 4. The aqueous extracts of C. mubango and N. probeguinii produced a slightly lower but still significant inhibition of parasitaemia (60%-80%) whereas that of Py. staudtii only suppressed the day-4 parasitaemias by 37%.The dried aqueous extract of the stem bark of C. mubango showed some signs of toxicity in mice, with median lethal doses (LD(50)) of 350 mg/kg in the female mice and 900 mg/kg in the male. The extract significantly increased the serum concentrations of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mice of both sexes, but had no effect on the blood levels of creatinine or urea. No significant toxic effect was observed for the dried aqueous extracts of N. pobeguinii and Py. staudtii (LD(50) >5 g/kg). Neither of these extracts affected the serum concentrations of GPT or the blood concentrations of creatinine and urea, although the N. pobeguinii extract did increase the serum concentration of GOT.     

The antiplasmodial and radical scavenging activities of flavonoids of Erythrina burttii

The acetone extract of the root bark of Erythrina burttii showed in vitro antiplasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC(50) values of 0.97 ± 0.2 and 1.73 ± 0.5 μg/ml respectively. The extract also had radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical with an EC(50) value of 12.0 μg/ml. The isoflav-3-enes burttinol-A and burttinol-C, and the 2-arylbenzofuran derivative burttinol-D were identified as the most active antiplasmodial (IC(50)<10 μM) and free radical scavenging (EC(50)ca. 10 μM) principles. The acetone extract of E. burttii at 800 mg/kg/day, in a 4-day Plasmodium berghei ANKA suppressive test, showed in vivo antimalarial activity with 52% chemosuppression. In the same in vivo test, marginal activities were also observed for the extracts of the root and stem bark of Erythrina abyssinica and the root bark of Erythrina sacleuxii.     

The antiplasmodial effect of the extracts and formulated capsules of Phyllanthus amarus on Plasmodium yoelii infection in mice

ObjectiveTo investigate the antiplasmodial activity of the extracts of Phyllanthus amarus (P. amarus) on Plasmodium yoelii (P. yoelii) (a resistant malaria parasite strain used in animal studies) infection in mice.MethodsThe aqueous and ethanol extracts of the whole plant of Phyllanthus amarus was administered to Swiss albino mice at doses of 200 mg/kg/day, 400 mg/kg/day, 800 mg/kg/day and 1600 mg/kg/day and the prophylactic and chemotherapeutic effect of the extracts against P. yoelii infection in mice was investigated and compared with those of standard antimalaria drugs used in the treatment of malaria parasite infection. Acute toxicity test was carried out in mice to determine the safety of the plant extract when administered orally.ResultsThe results showed that the extracts demonstrated a dose—dependent prophylactic and chemotherapeutic activity with the aqueous extracts showing slightly higher effect than the ethanol extract. The antiplasmodial effects of the extracts were comparable to the standard prophylactic and chemotherapeutic drugs used in chloroquine resistant Plasmodium infection although the activity depended on the dose of the extract administered. The extracts showed prophylactic effect by significantly delaying the onset of infection with the suppression of 79% at a dose of 1600 mg/kg/day.ConclusionsThe results obtained indicate that the extracts of the whole plant of P. amarus possess repository and chemotherapeutic effects against resistant strains of P. yoelii in Swiss albino mice. The findings justify the use of the extract of P. amarus in traditional medicine practice, for the treatment of malaria infections.     

Immunostimulating effect of pule (Alstonia scholaris L. R.Br., Apocynaceae) bark extracts

The immunostimulating effect of "Pule" (Alstonia scholaris (L.) R.Br., Apocynaceae) bark extracts was studied in BALB/c mouse. The extracts were administered orally, once a day for 7 consecutive days. The results showed that at the same doses (50, 100 and 200 mg/kg b.w.) the aqueous extract had higher phagocytic index (1.39-1.79) than the ethanolic extracts (0.81-0.93) in normal mice. The aqueous extract at 50 mg/kg b.w. also enhanced phagocytic activity of immunosuppressed mice significantly (P < 0.01). At 50 and 100 mg/kg b.w. the extract prevents the decrease of immune system induced by prednisone. The aqueous extract at 100 mg/kg b.w. increased lytic activity of peritoneal exudate cells against Escherichia coli significantly (P < 0.05). At the doses of 50 and 100 mg/kg b.w. the aqueous extract had no effect on primary antibody level. The aqueous extract at 50 mg/kg b.w. induced the cellular immune response while at 100 mg/kg b.w. inhibited the delayed type of hypersensitivity reaction.     

In vitro and in vivo antiplasmodial activity and cytotoxicity of extracts of Phyllanthus niruri L. herbs traditionally used to treat malaria in Indonesia

In endemic areas where malaria is prevalent, medicinal plants are often used to treat malaria. This study was conducted to evaluate the in vitro and in vivo antiplasmodial activity and cytotoxicity of extracts of meniran (Phyllanthus niruri L.) herb traditionally used to treat malaria in Indonesia. Three extracts viz aqueous, methanolic and chloroformic extracts were obtained by maceration of the herbs. A radioactive method was used to evaluate the in vitro antiplasmodial activity of the extracts on chloroquine-resistant (FCR-3) and chloroquine-sensitive (D-10) strains of Plasmodium falciparum. In vitro antiplasmodial activity was expressed by the concentration inhibiting 50% of parasite growth (IC50). Cytotoxicity was estimated on Hela cells and the Cytotoxicity Index (CI = IC50 on HeLa cells/IC50 on FCR-3 strain) was calculated to evaluate the safety of tested extracts. A standard 4-day test on P berghei infected mice was used to evaluate the in vivo antiplasmodial activity of the extracts showing strong in vitro antiplasmodial activity, for both the methanolic and aqueous extracts. The in vivo antiplasmodial activity was expressed by the dose inhibiting 50% of parasite growth (ED50). The IC50 values obtained for these extracts against P. falciparum ranged from 2.3 to 202.4 microg/ml. The methanolic extract was the most active in vitro extract with an IC50 that ranged from 2.3 to 3.9 microg/ml and a CI that ranged from 41.3 to 57.5. This was also the most in vivo active extract with an ED50 of 9.1 mg/kg/d. Further study will be conducted to isolate and purify active compounds presented in the methanolic extract.     

Potentiation of the bioavailability of daidzin by an extract of Radix puerariae.

The dose effect of pure daidzin on the suppression of ethanol intake in Syrian golden hamsters was compared with that of crude daidzin contained in a methanol extract of Radix puerariae (RP). EC50 values estimated from the graded dose-response curves for pure daidzin and RP extract daidzin are 23 and 2.3 mg per hamster per day, respectively. Apparently the antidipsotropic activity of the RP extract cannot be accounted for solely by its daidzin content (22 mg/g). In addition to daidzin, six other isoflavones were identified in the RP extract and quantified--namely, puerarin (160 mg per g of extract), genistin (3.7 mg/g), daidzein (2.6 mg/g), daidzein-4',7-diglucoside (1.2 mg/g), genistein (0.2 mg/g), and formononetin (0.16 mg/g). None of these, administered either alone or combined, contributes in any significant way to the antidipsotropic activity of the extract. Plasma daidzin concentration-time curves determined in hamsters administered various doses of pure daidzin or RP extract by i.p.injection indicate that the crude extract daidzin has approximately 10 times greater bioavailability than the pure compound. Reconstruction of the dose-response effects for pure and crude daidzin using bioavailable daidzin rather than administered dose gives a single curve. Synthetic daidzin added to the RP extract acquires the bioavailability of the endogenous daidzin that exists naturally in the extract. These results show that (i) daidzin is the major active principle in methanol extracts of RP, and (ii) additional constituents in the methanol extract of RP assist uptake of daidzin in golden hamsters.     

The in-vivo antimalarial activities of Uvaria chamae and Hippocratea africana

The antimalarial activities of ethanolic root extracts of two plants used traditionally as malarial remedies in southern Nigeria, Uvaria chamae (Annonaceae) and Hippocratea africana (Hippocrateaceae), were studied in vivo, in mice infected with Plasmodium berghei berghei. The extract of U. chamae, when given orally at 300-900 mg/kg.day, exhibited significant antimalarial activity against both early and established infections. When established infections were treated, the mean survival time of the mice observed with this extract at 900 mg/kg.day was similar to that seen with the positive control: chloroquine at 5 mg/kg.day. The extract of H. africana, tested at oral doses of 200-600 mg/kg.day, also demonstrated promising blood schizontocidal activity, both in early and established infections. Although the question of their toxicities has still to be fully addressed, it is clear that both U. chamae and H. africana possess considerable antimalarial activity and they, or drugs based on their antimalarial constituents, may prove useful in the treatment of human malaria.     

楮实提取物体外抗氧化活性的研究

目的 探讨楮实提取物的体外抗氧化活性.方法 先用80%乙醇,然后用蒸馏水对楮实进行提取.其中醇提取物依次用石油醚、氯仿、乙酸乙酯、正丁醇萃取,水提部分经醇沉、干燥后得到楮实粗多糖.运用羟基(·OH)自由基体系、二苯代苦味基肼(DPPH·)自由基体系和对Fe~(3+)的还原能力实验,比较楮实各提取物的抗氧化活性.结果 楮实提取物对·OH自由基和DPPH·自由基均有较好的清除作用,其中总醇提取物对·OH自由基的清除能力最强,其IC_(50)值为0.28 mg/ml;乙酸乙酯提取物对DPPH·自由基的清除效果最好,其IC_(50)值达到0.08 mg/ml;各提取物对Fe~(3+)均有较强的还原能力,乙酸乙酯提取物还原效果最为明显.结论 楮实提取物具有一定的抗氧化活性,在抗衰老方面有广泛的应用前景.     

Antimalarial activity and toxicity of Garcinia mangostana Linn.

Objective:To investigate the antimalarial activity and toxicity of the crude ethanolic extract of its pericarp both in vitro and in vim.Methods:The antimalarial activity of Gareinja mangostana(G.mangostana)Linn.extract against 3D7 and Kl Plasmodium falciparum(P.falciparum)clone were assessed using SYBR green I-based assay.A 4-day suppressive test of Plasmodium berghei{P.berghei)infected mouse was performed to investigate in vivo antimalarial activity.Results:The in vitro antimalarial activity was seleclive(SI5?and classified as weak and good lo moderate activity against both 3D7 and K1 P.falciparum,clones with median IC_(50)(range)values of 11.12(10.94-11.29)and 7.54(6.80-7.68)μg/mL,respectively.The extract was considered nontoxic to mice.The maximum tolerated doses for acute and subacute toxicity in mice were 5 000and 2 000 mg/kg,respectively.Median(range)parasite density on day 4 of the negative control group(25%Tween-80),mice treated with 250,500,1000,and 2 000 mg/kg body weight of the extract,and 10 mg/kg body weight of chloroquine for 14 d were 12.8(12.2-13.7),11.4(9.49-13.8),11.6(9.9-12.5),11.7(10.6-12.8),10.9(9.4-11.6)and 0(0-0)%respectively.Parasite density on day 4in the control group treated with Tween-80 was higher than the groups treated with chloroquine and all dose levels of the extract.Conclusions:G.mangostana linn,showed weak antimalarial activity of the extract both in vitro and in vivo could be due to limitation of absorption of the active compounds.     

In-vivo antimalarial activity of Cassia occidentalis, Morinda morindoides and Phyllanthus niruri

The ethanolic, dichloromethane and lyophilized aqueous extracts of Cassia occidentalis root bark, Morinda morindoides leaves and whole plants of Phyllanthus niruri were evaluated for their antimalarial actvity in vivo, in 4-day, suppressive assays against Plasmodium berghei ANKA in mice. No toxic effect or mortality was observed in mice treated, orally, with any of the extracts as a single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks (to give a total dose of 4 g/kg). No significant lesions were observed, by eye or during histopathological examinations, in the hearts, lungs, spleens, kidneys, livers, large intestines or brains of any mouse. At doses of 200 mg/kg, all the ethanolic and dichloromethane extracts produced significant chemosuppressions of parasitaemia (of > 60% for C. occidentalis root bark and Ph. niruri whole plant, and of 30% for M. morindoides leaves) when administered orally. The most active ethanolic extract, that of Ph. niruri, reduced parasitaemia by 73%. The dichloromethane extracts of M. morindoides and Ph. niruri produced similar reductions (74% and 72% chemosuppression, respectively), whereas that of C. occidentalis was slightly less active (60% chemosuppression). Each lyophilized aqueous extract was less active than the corresponding ethanolic extract.     

Hepatoprotective effect of the aqueous extract of the roots of Decalepis hamiltonii against ethanol-induced oxidative stress in rats.

The hepatoprotective activity of the aqueous extract of the roots of Decalepis hamiltonii was investigated against ethanol-induced oxidative stress and liver damage. Pretreatment of rats with aqueous extract of the roots of D. hamiltonii, single (50, 100 and 200mg/kg b.w.) and multiple doses (50 and 100mg/kg b.w. for 7 days) significantly prevented the ethanol (5g/kg b.w.) induced increases in the activities of the serum enzymes, aspartate and alanine transaminases, alkaline phosphatase and lactate dehydrogenase in a dose dependent manner. Parallel to these changes, the root extract inhibited the ethanol-induced oxidative stress in the liver by suppressing lipid peroxidation and protein carbonylation and maintaining the levels of antioxidant enzymes and glutathione. The biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the root extract. The protective effect of the root extract against hepatotoxicity of alcohol was more pronounced by the multiple dose pretreatment. Hepatoprotective activity of the aqueous extract of the roots of D. hamiltonii could be attributed to the antioxidant effect of the constituents and enhanced antioxidant defenses.     

In vitro antiplasmodial activity of marine sponge Clathria vulpina extract against chloroquine sensitive Plasmodium falciparum

ObjectiveTo explore the antiplasmodial potential of marine sponge Clathria vulpina (C. vulpina) against chloroquine sensitive Plasmodium falciparum (P. falciparum).MethodsThe marine sponge C. vulpina was collected from Thondi coast, authenticated and subjected for extraction by soaking in ethanol:water mixture (3:1 ratio). The percentage of extract was calculated. Filter sterilized extracts (100, 50, 25, 12.5, 6.25, 3.125 μg/mL) were screened for antiplasmodial activity against chloroquine sensitive P. falciparum. The extract was also tested for its hemolytic activity.ResultsThe percentage yield of extract of C. vulpina was found to be 4.8%. The crude extract of C. vulpina showed excellent antiplasmodial activity (IC₅₀=14.75 μg/mL) which was highly comparable to the positive control chloroquine (IC₅₀=7 μg/mL). Statistical analysis reveals that the significant antiplasmodial activity (P<0.05) was observed between the concentrations and the time of exposure. The chemical injury to erythrocytes was also carried out, which showed that there were no morphological changes in erythrocytes by the ethanolic extracts of sponges after 48 h of incubation. The extract showed slight hemolytic activity which almost equal to chloroquine at 100 μg/mL concentration (1.023%).ConclusionsThe marine sponge C. vulpina can be used as a putative antiplasmodial drug after completing successful clinical trials.     

In vitro antidiabetic activity of psidium guajava leaves extracts

ObjectiveTo evaluate the glucose uptake of (antidiabetic activity) crude n-hexane, ethanol, ethanol and aqueous leaf extracts of P. guajava.MethodsP. guajava leaf extracts were subjected to inhibitory effect of glucose utilization using specific standard in vitro procedure.ResultsResults in four different leaf extracts revealed that, the methanol extract at a concentration of 50g plant extract/l was found to be more potent than other extracts with the lowest mean glucose concentration of 201+1.69 mg/dl at the end of 27 hrs.ConclusionsThe present findings suggest that, the methanolic extract showed a significant inhibitory effect on glucose diffusion in vitro thus validating the traditional claim of the plant.     

Protective effects of Phyllanthus acidus (L.) Skeels leaf extracts on acetaminophen and thioacetamide induced hepatic injuries in Wistar rats

ObjectiveTo investigate and compare the hepatoprotective effects of crude ethanolic and aqueous extracts of Phyllanthus acidus (L.) Skeels (P. acidus) leaves on acetaminophen (APAP) and thioacetamide (TAA) induced liver toxicity in wistar rats. Silymarin was the reference hepatoprotective agent.MethodsIn two different sets of experiments, the P. acidus extracts (200 and 400 mg/kg, body weight) and silymarin (100 mg/kg, body weight) were given orally for 7 days and a single dose of APAP (2 g/kg, per oral) or TAA (100 mg/kg, subcutaneous) were given to rats. The level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin and total protein were monitored to assess hepatotoxicity and hepatoprotection.ResultsAPAP or TAA administration caused severe hepatic damage in rats as evident from significant rise in serum AST, ALT, ALP, total bilirubin and concurrent depletion in total serum protein. The P. acidus extracts and silymarin prevented the toxic effects of APAP or TAA on the above serum parameters indicating the hepatoprotective action. The aqueous extract was found to be more potent than the corresponding ethanolic extract against both toxicants. The phenolic and flavonoid content (175.02±4.35 and 74.68±1.28, respectively) and 2,2-diphenyl-1-picrylhydrazil (DPPH) [IC₅₀ = (33.2±0.31)μg/mL] scavenging potential was found maximum with aqueous extract as compared to ethanolic extract.ConclusionsThe results of present study suggests that the aqueous extract of P. acidus leaves has significant hepatoprotective activity on APAP and TAA induced hepatotoxicity, which might be associate with its high phenolic and flavonoid content and antioxidant properties.     

The effect of ethanol extract of Hypericum lysimachioides on lipid profile in hypercholesterolemic rabbits and its in vitro antioxidant activity

Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum total cholesterol and LDL cholesterol levels resulting in increased risk for development of atherosclerosis. Antioxidants play an important role in inhibiting and scavenging radicals, thus providing protection to humans against infectious and degenerative diseases. Literature shows that the antioxidant activity is high in medicinal plants. Realizing the fact that, this study was carried out to determine the effect of ethanol extract of Hypericum lysimachioides Boiss var lysimachioides (Guttifera) on serum lipid levels and serum lipid peroxidation in hypercholesterolemic rabbits. The rabbits were divided into four groups and these groups were fed with diets containing standard laboratory diet (Group I), standard laboratory diet and ethanol extracts of H. lysimachioides (HL) (50mg/kg body weight) (Group II), standard laboratory diet, ethanol extracts of HL (50mg/kg body weight) and cholesterol (100mg/kg body weight) (Group III), and finally standard laboratory diet and cholesterol (100mg/kg body weight) (Group IV), for 5 weeks. Feeding cholesterol increased serum cholesterol and LDL cholesterol levels significantly in Group IV as compared to the other groups. Ethanol extract of HL with high cholesterol diet significantly lowered LDL cholesterol and total cholesterol levels in the rabbits of Group III as compared to the Group IV. The level of serum triacylglycerol was found to be similar to all comparison groups. HDL cholesterol levels were also increased significantly in Groups II and III as compared to Group IV. Statistically significant difference was found in Group IV as compared to all other groups. The ethanol extract of HL with high cholesterol diet significantly lowered the serum MDA levels in the rabbits of Group III compared to the Group IV. The histopathological findings confirmed that the ethanol extract of HL restrained the progression of the hydropic degeneration and fatty changes in the liver and some atherosclerotic lesions in the aorta. The in vitro antioxidant activities of ethanol extract of HL was also evaluated. The free radical-scavenging properties of HL (IC(50)=28 microg/ml) were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay system. Since plant phenolic compound is one of the phytochemicals possessing radical scavenging activity, the amount of total phenolic compound was also determined in ethanol extract of HL and total phenolic content of one-milligram HL ethanol extract was equivalent to 307 microg of gallic acid. Total antioxidant activity of ethanol extract of HL was tested by using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. Antioxidative activities of ethanol extract of HL was found to be comparable with Vitamin E. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.     

Activities of pefloxacin and ciprofloxacin against Mycobacterium leprae in the mouse

Because ciprofloxacin and pefloxacin are fluoroquinolones active against many mycobacterial species, both drugs were tested against Mycobacterium leprae in the mouse foot-pad system. Preliminary pharmacokinetic studies in the mouse showed that after a single oral dose of 150 mg/kg ciprofloxacin the peak serum concentration was 3.6 micrograms/ml, and after 50 mg/kg or 150 mg/kg pefloxacin peak serum concentrations were, respectively, 9.2 micrograms/ml and 16.9 micrograms/ml, the half-lives for serum elimination being about 2 hr for both drugs. The activity of daily 50 mg/kg and 150 mg/kg ciprofloxacin and pefloxacin against M. leprae was then tested in mice infected with 5 X 10(3) M. leprae. The growth of M. leprae was not prevented in mice treated continuously with either 50 mg/kg or 150 mg/kg ciprofloxacin, indicating that this drug had no or a limited bacteriostatic effect at the dosages used. In mice treated continuously with 50 mg/kg pefloxacin, growth of M. leprae was not prevented, but at monthly harvests the number of bacilli in the foot pads remained less than those of control mice (p less than 0.05). No growth of M. leprae occurred in mice treated continuously with 150 mg/kg pefloxacin. In mice treated for only 3 months with daily 150 mg/kg pefloxacin, the growth-delay that followed the stopping of the drug was 126 days, suggesting that approximately 99% of the M. leprae were killed. The pharmacokinetics of pefloxacin being more favorable in man than in the mouse, pefloxacin appears a possible drug for the chemotherapy of leprosy.     

In vitro screening for antiplasmodial activity of isoquinoline alkaloids from Brazilian plant species

In the search for new antimalarial agents, nine Brazilian plant species were selected, from the Annonaceae (6), Menispermaceae (2) and Siparunaceae (1) families naturally occurring at the cerrado and Atlantic rainforest regions, in order to investigate their in vitro antiplasmodial activity. The ethanol and the alkaloid extracts were tested against K1, chloroquine-resistant, and Palo Alto, chloroquine-sensitive, strains of Plasmodium falciparum. The majority of the alkaloid extracts were more active than the ethanol ones, with IC(50) ranging 0.3-8.2 microg/mL. The crude Guatteria australis alkaloids were the most active against K1 with an IC(50) = 0.3 microg/mL. The most promising total alkaloid fractions for further bioguided isolation are those with the IC(50) < or = 5 microg/mL: G. australis, Cissampelos ovalifolia and Duguetia lanceolata.     

Hypericum perforatum CO2 extract and opioid receptor antagonists act synergistically to reduce ethanol intake in alcohol-preferring rats

BACKGROUND: Hypericum perforatum extracts attenuate ethanol intake in alcohol-preferring rats. The opioid receptor antagonists, naloxone and naltrexone, reduce ethanol intake in rats and humans. The combination of different agents that reduce ethanol intake has been proposed as an approach to the pharmacotherapy of alcoholism. This study evaluated the effect on ethanol intake of the combined administration of a CO2 H. perforatum extract and naloxone or naltrexone in genetically selected Marchigian Sardinian alcohol-preferring rats. METHODS: Ten percent (v/v) ethanol intake was offered 2 hr per day at the beginning of the dark phase of the reverse light-dark cycle. H. perforatum CO2 extract was given intragastrically, 1 hr before access to ethanol. Naloxone or naltrexone was given by intraperitoneal injection 10 min before the extract. RESULTS: H. perforatum CO2 extract reduced ethanol intake at 31 or 125 mg/kg, but not 7 mg/kg. These doses neither modified food or water intake during access to ethanol, nor reduce 0.2% saccharin intake. Naloxone reduced ethanol and food intake at 3 or 5 mg/kg, but not 1 mg/kg. When naloxone 1 mg/kg was combined with the three doses of H. perforatum CO2 extract, the attenuation of ethanol intake was more pronounced than that observed after the administration of the extract alone. Alcohol intake was also significantly reduced by 7 mg/kg of H. perforatum CO2 extract combined with naloxone 1 mg/kg. The combined treatments never modified the rat's locomotor activity nor the simultaneous intake of food, water or 0.2% saccharin. Naltrexone reduced ethanol intake at 1 and 3 mg/kg, but not at 0.5 mg/kg. When naltrexone 0.5 mg/kg was combined with H. perforatum CO2 extract 7 mg/kg, ethanol intake was markedly reduced. CONCLUSIONS: These findings provide evidence that H. perforatum CO2 extract and opiate receptor antagonists act synergistically to induce a pronounced and selective reduction of voluntary ethanol consumption in alcohol-preferring rats.     

Antipyretic and antimalarial activities of crude leaf extract and fractions of Enicostema littorale

ObjectiveTo evaluate the antiplasmodial and antipyretic activities of whole plant extract and fractions of Enicostemma littorale (E. littorale) for ascertaining the folkloric claim of its antimalarial and antipyretic activities.MethodsThe crude extract (260 – 780 mg/kg) and fractions (chloroform and acqeous; 520 mg/kg) of E. littorale were investigated for antiplasmodial activity against chloroquine-sensitive Plasmodium berghei (P. berghei) infections in mice and for antipyretic activity against dinitrophenol, amphetamine and yeast-induced pyrexia. The antiplasmodial activity during early and established infections as well as prophylactic were investigated. Artesunate (5 mg/kg) and pyrimethamine (1.2 mg/kg) were used as positive controls. Antipyretic activity of the crude extract was also evaluated against dinitrophenol, amphetamine and yeast-induced pyrexia.ResultsThe extract and fractions dose-dependently reduced parasitaemia induced by chloroquine-sensitive P. berghei infection in prophylactic, suppressive and curative models in mice. These reductions were statistically significant (P<0.001). They also improved the mean survival time from 11 to 27 days relative to control (P<0.01 – 0.001). The activities of extract/fractions were comparable to that of the standard drugs used (artesunate and pyrimethamine). On pyrexia induced by dinitrophenol, amphetamine and yeast, the extract caused inhibitions which were statistically significant (P<0.05 – 0.001) and in a dose-dependent fashion.ConclusionsThese plant extracts possess considerable antiplasmodial and antipyretic activities, which justify its use in ethnomedicine.     

Transforming growth factor alpha and epidermal growth factor in protection and healing of gastric mucosal injury.

Transforming growth factor alpha (TGF) and epidermal growth factor (EGF) present in the gastric mucosa are polypeptides with similar biologic activity. This study compares the activity of TGF and EGF in the protection against injury by 100% ethanol and stress and in healing of acute gastric ulcerations. TGF and EGF (12.5-100 micrograms/kg-h) infused subcutaneously 30 min before and during ethanol or stress decreased mucosal lesions dose-dependently. The ID50 for ethanol- and stress-induced lesions after TGF were 40 and 70 micrograms/kg-h and after EGF 60 and 100 micrograms/kg-h. TGF and EGF infused subcutaneously into intact rats inhibited gastric acid secretion but did not affect the gastric blood flow or mucosal generation of prostaglandin E2 (PGE2). Both TGF and EGF also significantly enhanced the healing of stress-induced lesions and the restoration of DNA synthesis. Ethanol and stress reduced blood flow in the oxyntic mucosa by 68% and 51%, respectively, and this effect was partially reversed by EGF and TGF. Pretreatment with indomethacin (5 mg/kg intraperitoneally), which reduced mucosal generation of PGE2 by 85%, decreased in part the protection by TGF and EGF against ethanol-induced damage and virtually abolished the protective action of these peptides against stress-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS)