Cordycepin (3′-deoxyadenosine) pentostatin (deoxycoformycin) combination treatment of mice experimentally infected withTrypanosoma evansi

SUMMARYThe aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3′-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase)in vitroby using mice experimentally infected withTrypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In thein vivotrials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg−1) and pentostatin (2 mg kg−1) was 100% effective in theT. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3′-deoxyadenosine with deoxycoformycin has a curative effect on mice infected withT. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.

Download Full-text

Evaluation of in vitro and in vivo Antiplasmodial Activity of the Leaf Latex of Aloe Weloensis (Aloaceae)

10.21203/rs.3.rs-37849/v1 ◽

2020 ◽

Author(s):

Gedefaw Getnet Amare ◽

Tadesse Awgichew ◽

Solomon Ahmed ◽

Zemene Demelash Kifle

Keyword(s):

Antioxidant Activity ◽

Antioxidant Activities ◽

Antimalarial Activity ◽

Potential Effect ◽

Pack Cell Volume ◽

Curative Effect ◽

Parasitemia Level ◽

Dose Dependent

Abstract Background: Nature has gifted a variety of plants having potential effect against plasmodium parasites. The present study was aimed to determine in vitro and in vivo antimalarial activity of the leaf latex of Aloe weloensis.Methods: In vitro antimalarial activity of the leaf latex of A. weloensis was determined against 3D7 strain of P. falciparum. Antimalarial activity of the three doses the latex was evaluated in 4 day-suppressive and curative models against P. berghei infected mice. Antioxidant activity of the leaf latex of A. weloensis was assessed in 2,2- diphenyl 1- picrylhydrazine assay model. Results: Antioxidant activity of the latex was concentration dependent; the strongest inhibition was measured at 400 μg/mL (73.54%). The leaf latex of A. weloensis was demonstrated inhibitory activity against 3D7 malarial strain (IC50 = 9.14 μg/ml). Suppressive and curative effect of the latex was found to be dose dependent. Parasitemia reduction was significant (200 mg/kg, p<0.01, 400 and ,600 mg/kg, p<0.001) in 4-day suppressive test compared to vehicle control. Parasitemia level of the mice treated with 200, 400 and 600 mg/kg doses of the latex significantly (p<0.001) reduced with suppression of 36%, 58% and 64% respectively in curative test. Administration of the leaf latex of A. weloensis significantly (p<0.01) improved mean survival time, pack cell volume, rectal temperature and body weight of P. berghei infected mice. Conclusion: The finding showed that the leaf latex of Aloe weloensis endowed prominent antimalarial and antioxidant activities. The result can serve as a step towards the development of safe and effective herbal therapy against plasmodium parasites.

Download Full-text

EFFICACY OF AN ACTIVE COMPOUND OF THE HERB, ASHWAGANDHA IN PREVENTION OF STRESS INDUCED HYPERGLYCEMIA

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i10.28717 ◽

2018 ◽

Vol 10 (10) ◽

pp. 44 ◽

Cited By ~ 1

Author(s):

Sarjan H. N. ◽

Yajurvedi H. N.

Keyword(s):

Phosphoenolpyruvate Carboxykinase ◽

Ethanolic Extract ◽

Dependent Manner ◽

Stress Exposure ◽

In Vitro Experiment ◽

Isolated Compound ◽

Dose Dependent ◽

Different Doses

Objective: To find out whether an isolated compound (IC) from the ethanolic extract of roots of ashwagandha prevents stress-induced hyperglycemia by direct interference with the action of increased concentration of corticosterone on hepatocytes or by preventing hyper-secretion of corticosterone or both.Methods: A group of rats served as controls, and those in another group were subjected to restraint (1 h) and forced swimming exercise (15 min), after a gap of 4 h daily for 4 w. The third group of rats received orally IC (5 mg/kg bw/rat) 1 h prior to exposure to stressors. After the last treatment period, a blood sample was collected and serum was separated for the estimation of corticosterone and glucose. In in vitro experiment, hepatocytes were treated with different concentrations of corticosterone (100, 200, 300, 400 and 500 ng/ml). In another set of experiment, hepatocytes were treated with different doses of IC (1, 10, 100, 1000 and 10 000 μg/ml of medium) along with corticosterone (400ng/ml). The concentration of glucose and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined after the treatment.Results: Stress exposure caused a significant increase in serum concentration of corticosterone and glucose whereas, administration of IC did not result in similar changes. Further, treatment of corticosterone in in vitro significantly increased the activities of PEPCK and G6Pase and concentration of glucose in a dose-dependent manner in hepatocytes. However, treatment with IC did not interfere with the corticosterone-induced an increase in the activities of PEPCK and G6Pase as well as the concentration of glucose in hepatocytes.Conclusion: The in vivo and in vitro results put together reveal that IC does not directly interfere with the action of corticosterone on hepatocytes. However, it prevents stress-induced hyperglycemia by suppressing hyper-secretion of corticosterone.

Download Full-text

Liposomes produced by reverse phase evaporation: in vitro and in vivo efficacy of diminazene aceturate against Trypanosoma evansi

Parasitology ◽

10.1017/s0031182013002114 ◽

2014 ◽

Vol 141 (6) ◽

pp. 761-769 ◽

Cited By ~ 11

Author(s):

CAMILA BELMONTE OLIVEIRA ◽

LUCAS ALMEIDA RIGO ◽

LUCIANA DALLA ROSA ◽

LUCAS TREVISAN GRESSLER ◽

CARINE ELOISE PRESTES ZIMMERMANN ◽

...

Keyword(s):

Culture Medium ◽

Similar Efficacy ◽

Trypanosoma Evansi ◽

Diminazene Aceturate ◽

Reverse Phase ◽

Dependent Effect ◽

Dose Dependent ◽

Dose Dependent Effect

SUMMARYThis study aimed to develop and test the in vitro and in vivo effectiveness of diminazene aceturate encapsulated into liposomes (L-DMZ) on Trypanosoma evansi. To validate the in vitro tests with L-DMZ, the efficacy of a commercial formulation of diminazene aceturate (C-DMZ) was also assessed. The tests were carried out in culture medium for T. evansi, at concentrations of 0·25, 0·5, 1, 2 and 3 μg mL−1 of L-DMZ and C-DMZ. A dose-dependent effect was observed for both formulations (L-DMZ and C-DMZ), with the highest dose-dependent mortality of trypomastigotes being observed at 1 and 3 h after the onset of tests with L-DMZ. The results of in vivo tests showed the same effects in the animals treated with L-DMZ and C-DMZ in single doses of 3·5 mg kg−1 and for 5 consecutive days (3·5 mg kg−1 day−1). It was possible to conclude that T. evansi showed greater in vitro susceptibility to L-DMZ when compared with C-DMZ. In vivo tests suggest that treatment with the L-DMZ and C-DMZ showed similar efficacy in vivo. The potential of the formulation developed in this study was clearly demonstrated, as it increased the efficacy of the treatment against trypanosomosis, but more studies are needed to increase the effectiveness in vivo.

Download Full-text

Anti-malarial activity of the leaf latex of Aloe weloensis (Aloaceae) against plasmodium parasites

10.21203/rs.3.rs-37849/v2 ◽

2021 ◽

Author(s):

Gedefaw Getnet Amare ◽

Amsalu Degu ◽

Zemene Demelash Kifle

Keyword(s):

Antioxidant Activity ◽

Folk Medicine ◽

Inhibition Activity ◽

Survival Times ◽

Dpph Assay ◽

Curative Effect ◽

Parasitemia Level ◽

Dose Dependent

Abstract Background: Lack of available vaccines and emerging resistance on the anti-malarial drug have provided the necessity to find noble plant--based anti-malarial drugs. The leaf latex Aloe weloensis has been used in folk medicine against malarial and other human ailments in Ethiopia. Hence, the present study aimed to investigate the anti-malarial activity of the leaf latex of A. weloensis against Plasmodium parasites to validate its traditional claim.Methods: The leaf latex of A. weloensis was evaluated in vitro anti-malarial activity against 3D7 strain of Plasmodium falciparum. The prophylactic and curative models were employed to determine in vivo anti-malarial activity of the latex against P. berghei infected mice, and antioxidant activity of the leaf latex of A. weloensis was assessed in DPPH assay.Results: The leaf latex of Aloe weloensis endowed with free radical inhibition activity (IC50 = 10.25 μg/ml). The latex of A. weloensis leaf was demonstrated inhibitory activity against 3D7 strain of P. falciparum (IC50 = 9.14 μg/ml). The prophylactic and curative effect of the latex was found to be dose-dependent. Parasitemia reduction was significant (200 mg/kg, p<0.01, 400 and ,600 mg/kg, p<0.001) in prophylactic test compared to the control. Parasitemia level of the mice treated with 200, 400, and 600 mg/kg doses of the latex significantly (p<0.001) reduced with suppression of 36%, 58%, and 74% respectively in the curative test. The leaf latex significantly (p<0.01) improved mean survival times, packed cell volume , rectal temperature, and bodyweight of P. berghei infected mice.Conclusion: The result was confirmed the anti-malarial activity of the leaf latex of Aloe weloensis at various doses which corroborates the traditional uses of the plant.

Download Full-text

Anti-malarial activity of the leaf latex of Aloe weloensis (Aloaceae) against plasmodium parasites

10.21203/rs.3.rs-37849/v3 ◽

2021 ◽

Author(s):

Gedefaw Getnet Amare ◽

Amsalu Degu ◽

Zemene Demelash Kifle

Keyword(s):

Antioxidant Activity ◽

Folk Medicine ◽

Inhibition Activity ◽

Survival Times ◽

Dpph Assay ◽

Curative Effect ◽

Parasitemia Level ◽

Dose Dependent

Abstract Lack of available vaccines and emerging resistance on the anti-malarial drug have provided the necessity to find noble plant--based anti-malarial drugs. The leaf latex Aloe weloensis has been used in folk medicine against malarial and other human ailments in Ethiopia. Hence, the present study aimed to investigate the anti-malarial activity of the leaf latex of A. weloensis against Plasmodium parasites to validate its traditional claim. Methods: The leaf latex of A. weloensis was evaluated in vitro anti-malarial activity against 3D7 strain of Plasmodium falciparum. The prophylactic and curative models were employed to determine in vivo anti-malarial activity of the latex against P. berghei infected mice, and antioxidant activity of the leaf latex of A. weloensis was assessed in DPPH assay. Results: The leaf latex of Aloe weloensis endowed with free radical inhibition activity (IC50 = 10.25 μg/ml). The latex of A. weloensis leaf was demonstrated inhibitory activity against 3D7 strain of P. falciparum (IC50 = 9.14 μg/ml). The prophylactic and curative effect of the latex was found to be dose-dependent. Parasitemia reduction was significant (200 mg/kg, p<0.01, 400 and ,600 mg/kg, p<0.001) in prophylactic test compared to the control. Parasitemia level of the mice treated with 200, 400, and 600 mg/kg doses of the latex significantly (p<0.001) reduced with suppression of 36%, 58%, and 74% respectively in the curative test. The leaf latex significantly (p<0.01) improved mean survival times, packed cell volume , rectal temperature, and bodyweight of P. berghei infected mice. Conclusion: The result was confirmed the anti-malarial activity of the leaf latex of Aloe weloensis at various doses which corroborates the traditional uses of the plant.

Download Full-text

In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes

Veterinary Research ◽

10.1186/s13567-019-0710-7 ◽

2019 ◽

Vol 50 (1) ◽

Cited By ~ 2

Author(s):

Qi Xin ◽

Miaomiao Yuan ◽

Huanping Li ◽

Xiaoxia Song ◽

Jun Lu ◽

...

Keyword(s):

Energy Production ◽

Alveolar Echinococcosis ◽

Weekly Treatment ◽

Significant Toxicity ◽

Liver And Kidney ◽

In Vitro Effects ◽

In Vivo Effects ◽

Dose Dependent

AbstractWhile searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).

Download Full-text

Antimalarial Activity of Hydromethanolic Crude Extract and Chloroform Fraction of Brucea antidysenterica Leaves in Plasmodium berghei-Infected Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2089114 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Tezera Jemere Aragaw ◽

Kefyalew Ayalew Getahun

Keyword(s):

Crude Extract ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Negative Control ◽

Chloroform Fraction ◽

Curative Effect ◽

Antimalarial Agents ◽

Different Doses

Background. Different parts of Brucea antidysenterica are used in traditional and alternative medicine in Ethiopia for the treatment of different health problems including malaria and have good in vitro antimalarial activity. However, no in vivo study was conducted to substantiate the claim. Our study planned to determine the antimalarial effect of B. antidysenterica extract. Methods. Swiss albino mice (6–8 weeks old, 20–28 g) were inoculated with Plasmodium berghei. Different doses of both hydromethanolic extract and chloroform fraction were orally given at 100, 200, and 400 mg/kg/day. Results. The parasitemia suppression percent of hydromethanolic crude extract and chloroform fraction in chemosuppressive tests ranged between 33.48 and 75.93% and 38.32 and 76.64%, respectively. The hydromethanolic crude extract and chloroform fraction exhibited the curative effect of 46.75–70.91% and 50.30–80.06% parasitemia suppression, respectively ( p < 0.001), compared with negative control. Conclusion. From our study, it is concluded that the hydromethanolic crude extract and chloroform fraction of B. antidysenterica leaves showed promising antiplasmodial effects against Plasmodium berghei. This upholds the folkloric use of B. antidysenterica leaves and the thought of as a possible source to develop new antimalarial agents.

Download Full-text

Trypanocidal activity of free and nanoencapsulated curcumin on Trypanosoma evansi

Parasitology ◽

10.1017/s0031182014001292 ◽

2014 ◽

Vol 142 (3) ◽

pp. 439-448 ◽

Cited By ~ 16

Author(s):

L. T. GRESSLER ◽

C. B. OLIVEIRA ◽

K. CORADINI ◽

L. DALLA ROSA ◽

T. H. GRANDO ◽

...

Keyword(s):

Lethal Effect ◽

Positive Control ◽

Trypanosoma Evansi ◽

Control Group ◽

Trypanocidal Activity ◽

Male Wistar Rats ◽

Protein Peroxidation ◽

Liver And Kidney

SUMMARYThis study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg−1, intraperitoneally [i.p.]) and C-LNCs (10 mg kg−1, i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0·05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.

Download Full-text

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653872 ◽

1995 ◽

Vol 73 (05) ◽

pp. 805-811 ◽

Cited By ~ 12

Author(s):

Yasuo Takahashi ◽

Yoshitaka Hosaka ◽

Hiromi Niina ◽

Katsuaki Nagasawa ◽

Masaaki Naotsuka ◽

...

Keyword(s):

Human Urine ◽

Specific Activity ◽

Anticoagulant Activity ◽

Rabbit Lung ◽

Soluble Thrombomodulin ◽

Molecular Weights ◽

Dose Dependent Fashion ◽

Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Download Full-text

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

INTERNATIONAL JOURNAL OF TOXICOLOGICAL AND PHARMACOLOGICAL RESEARCH ◽

10.25258/ijtpr.v9i03.9068 ◽

2017 ◽

Vol 9 (03) ◽

Author(s):

Nurgozhin T. ◽

Sergazy S. H. ◽

Adilgozhina G. ◽

Gulyayev A. ◽

Shulgau Z. ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Experimental Model ◽

Lethal Dose ◽

Radical Scavenging ◽

Cabernet Sauvignon ◽

Intragastric Administration ◽

Liver And Kidney ◽

Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

Download Full-text