scholarly journals In Vivo Antimalarial Activity of Leaf Latex of Aloe melanacantha against Plasmodium berghei Infected Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Gebrehiwot Kiros Gebremariam ◽  
Haile Kassahun Desta ◽  
Tekleab Teka Teklehaimanot ◽  
Tsgab Gebrecherkos Girmay
Keyword(s):  
Weight Loss ◽  
Survival Time ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Health Concern ◽  
Dependent Manner ◽  
Loss Reduction ◽  
Oral Toxicity

Background. Malaria is a major health concern in the world in general and developing countries in particular. Nowadays, the control of malaria has ended up steadily more complex due to the spread of drug-resistant parasites. Medicinal plants are the verifiable source of compelling antimalarial drugs. The present study was aimed to assess the in vivo antimalarial activity of leaf latex of A. melanacantha against Plasmodium berghei in mice. Methods. Acute oral toxicity study of the leaf latex was assessed in mice up to a dose of 2,000 mg/kg. A four-day suppressive model was utilized to investigate the antimalarial activity of the plant. Three extract doses, 100, 200, and 400 mg/kg/day, doses of the plant leaf latex, chloroquine, 10 mg/kg (positive control) and distilled water, and 10 mL/kg (negative control) were administered to mice. Percent parasitemia suppression, packed cell volume, mean survival time, body weight, and rectal body temperature were used to determine antimalarial activity. Results. Test groups treated with 100, 200, and 400 mg/kg of the latex showed a significant parasitemia suppression in dose dependent manner compared to the negative control with an IC50 of 22.63 mg/ml. Mice treated with 100, 200, and 400 mg/kg have shown parasitemia suppression of 14.86%, 29%, and 43.2%, respectively. The chemosuppression was significant ( P < 0.05 ) at all doses compared to the negative control. Similarly, mice treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg have shown a significant survival time compared to the negative control. At the same time, weight loss reduction was observed within the test groups treated with 100 mg/kg and 200 mg/kg of the latex while the test groups treated with 400 mg/kg had showed almost no weight loss reduction. The latex also reversed the PCV reduction significantly ( P < 0.05 ) at 200 mg/kg and 400 mg/kg doses and prevented rectal temperature dropping significantly ( P < 0.05 ) at all doses. Conclusion. The leaf latex of A. melanacantha has shown significant antimalarial activity against P. berghei in mice supporting the genuine traditional antimalarial usage of the plant.

scholarly journals Antimalarial activity of hydromethanolic extract and its solvent fractions of Vernonia amygdalina leaves in mice infected with Plasmodium berghei

2019 ◽  
Vol 7 ◽  
pp. 205031211984976 ◽  
Author(s):  
Temesgen Bihonegn ◽  
Mirutse Giday ◽  
Getnet Yimer ◽  
Abebe Animut ◽  
Mekonnen Sisay
Keyword(s):  
Weight Loss ◽  
Survival Time ◽  
Rectal Temperature ◽  
Crude Extract ◽  
Plasmodium Berghei ◽  
Methanol Extract ◽  
Antimalarial Activity ◽  
Vernonia Amygdalina ◽  
Oral Toxicity

Background: Vernonia amygdalina Del. (Asteraceae) is reported to be traditionally used for the treatment of malaria. Based on folkloric repute of this plant in Ethiopian traditional medicine and crude extract-based ethnopharmacological studies conducted in few countries, this study was undertaken to evaluate the in vivo antimalarial activity of 80% methanol extract and its solvent fractions of the leaves of V. amygdalina in mice infected with Plasmodium berghei. Methods: A 4-day suppressive test was conducted on mice infected with P. berghei to find out antimalarial effect of chloroform, butanol and aqueous fractions obtained from the 80% methanol crude extract. In all the activity tests, mice were randomly assigned in five groups (three tests and two controls) of six animals in each and received respective treatments. Data were analyzed using one way analysis of variance followed by Tukey’s post hoc test for multiple comparisons. Results: Acute oral toxicity test showed that all solvent fractions of the leaves of V. amygdalina revealed neither mortality nor overt signs of toxicity up to 2000 mg/kg. This study indicated that the percentage parasitemia suppression of 80% methanol extract was 32.47% (±2.65), 35.40% (±3.14) and 37.67% (±2.50) at 200, 400 and 600 mg/kg, respectively. All doses of the 80% methanol extract of V. amygdalina prolonged survival time and prevented weight loss and packed cell volume reduction in infected mice. All doses of chloroform and butanol fractions significantly suppressed parasitemia (p < 0.05), increased survival time (p < 0.05) compared to negative control and exhibited a significant reduction in rectal temperature (p < 0.05). All solvent fractions significantly prevented weight loss (p < 0.05) at all tested doses. The 80% methanol extract and chloroform and butanol fractions significantly (p < 0.05) prevented further reduction in rectal temperature of P. berghei-infected mice at all doses. Conclusion: The results of this study indicated that 80% methanol extract and solvent fractions of the leaves of V. amygdalina demonstrated promising antimalarial activity. The study corroborated the folklore use of this plant for the treatment of malaria in ethnomedicine in Ethiopia.

scholarly journals Sequestration of erythrocytes infected with Plasmodium berghei ANKA in BALB/c mice treated with goat bile

2020 ◽  
Vol 4 (2) ◽  
pp. 179
Author(s):  
Kartika Arum Wardani ◽  
Kholida Nur Aini ◽  
Heny Arwati ◽  
Willy Sandhika
Keyword(s):  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Control Group ◽  
Dependent Manner ◽  
Plasmodium Berghei Anka ◽  
Concentration Dependent Manner ◽  
Control Group Design ◽  
Bile Concentration

Abstract Sequestration of Plasmodium berghei ANKA-infected erythrocytes occurs in BALB/c mice as characteristic of  Plasmodium falciparum infection in humans. Animals’ bile has been widely used for centuries in Traditional Chinese Medicine. Goat bile has been used in healing infectious and non-infectious diseases; however, no report on the use of goat bile against malaria infection and sequestration. The purpose of this study was to analyze the correlation between parasitemia and sequestration in the liver of P.berghei ANKA-infected BALB/c mice treated with goat bile. This research was an in vivo experimental study using the post-test control group design. The male BALB/c mice aged ± 6 weeks, body weight 20-25 g were used. The mice were divided into five groups where Group 1-3 were mice treated with goat bile 25%, 50%, and 100%, respectively. Group 4-5 were negative (sterile water) and positive controls (DHP). Parasitemia was observed daily from each mouse and the number of sequestered infected erythrocytes on the endothelium of sinusoids. The data were analyzed using t independent test. Antimalarial activity of goat bile was shown by the lower parasitemia in goat bile-treated mice compared with the negative control. The average number of sequestration was goat bile concentration-dependent manner. The higher the concentration, the lower the number of sequestration. Sequestration was correlated with parasitemia (p=0,0001). Sequestration of P.berghei ANKA-infected erythrocytes correlated with parasitemia, and was goat bile concentration-dependent manner. Keywords: Malaria, parasitemia, sequestration, goat bileCorrespondence: [email protected]

scholarly journals Antimalarial Activity of Meriandra dianthera Leaf Extracts in Plasmodium berghei-Infected Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Kalay Hagazy ◽  
Gereziher G. Sibhat ◽  
Aman Karim ◽  
Gebretsadkan H. Tekulu ◽  
Gomathi Periasamy ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Leaf Extract ◽  
Antimalarial Activity ◽  
Negative Control ◽  
Mice Model ◽  
Oral Toxicity ◽  
Leaf Extracts ◽  
Traditional Use ◽  
Crude Leaf Extract

Objective. To evaluate the antimalarial effect of aqueous methanolic extract and solvent fractions of Meriandra dianthera leaves against Plasmodium berghei in mice model. Method. M. dianthera leaves were extracted with 80% methanol and dried. The dried crude extract was then defatted and further fractionated with chloroform, ethyl acetate, and butanol. Acute oral toxicity test was performed as per the Organization for Economic Cooperation and Development guideline 425. Peter’s 4-day suppressive test was used to determine the in vivo antimalarial activity of the extract and fractions. Result. The crude leaf extract of Meriandra dianthera showed parasite inhibition of 42.28% and 45.52% at doses of 400 and 600 mg/kg, respectively, as compared to the negative control. Moreover, the mice which received chloroform and aqueous fractions at the dose of 400 mg/kg/day showed significant (P<0.001) chemosuppression compared to the negative control. Both the extract and fractions were able to prevent P. berghei induced body weight loss and body temperature reduction and also increased the survival time of the mice as compared to the negative control. The aqueous methanolic leaf extract of M. dianthera showed no gross signs of toxicity or mortality in mice until a single oral dose of 2000 mg/kg. Conclusion. The extracts of M. dianthera leaves showed promising antimalarial activity, with no sign of toxicity and therefore may support its traditional use for the treatment of malaria.

scholarly journals In Vivo Antimalarial Activity of 80% Methanol and Aqueous Bark Extracts of Terminalia brownii Fresen. (Combretaceae) against Plasmodium berghei in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Hana Biruk ◽  
Biruk Sentayehu ◽  
Yonatan Alebachew ◽  
Wondmagegn Tamiru ◽  
Abebe Ejigu ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Methanol Extract ◽  
Antimalarial Activity ◽  
Scientific Progress ◽  
Negative Control ◽  
Significant Inhibition ◽  
New Drugs ◽  
Dependent Manner ◽  
Promising Source

Background. Despite a substantial scientific progress over the past two decades, malaria continues to be a worldwide burden. Evergrowing resistance towards the currently available antimalarial drugs is a challenge to combat malaria. Medicinal plants are a promising source of new drugs to tackle this problem. Thus, the present study aimed at evaluating the antiplasmodial activity of Terminalia brownii in Plasmodium berghei infected mice. Methods. A 4-day suppressive test was employed to evaluate the antimalarial effect of 80% methanol and aqueous bark extracts of T. brownii against P. berghei in Swiss albino mice. Results. The in vivo acute toxicity test indicated that both extracts of T. brownii did not cause mortality. The 4-day early infection test revealed that the 80% methanol and aqueous extracts exhibited a significant inhibition of parasitemia p<0.001 compared to negative control. The maximum level of chemosuppression (60.2%) was exhibited at 400 mg/kg dose of 80% methanol extract. Moreover, the 80% methanol extract showed a significant p<0.001 attenuation of anemia associated with infection in a dose-dependent manner. The aqueous extract, on the other hand, exhibited a percent inhibition of 51.1% at the highest dose (400 mg/kg/day). Conclusion. The present study indicated that hydromethanolic and aqueous bark extracts of T. brownii possess a promising antimalarial activity, with higher effect exhibited by the hydromethanolic extract.

scholarly journals In Vivo Antimalarial Activity of Crude Fruit Extract of Capsicum frutescens Var. Minima (Solanaceae) against Plasmodium berghei-Infected Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Getu Habte ◽  
Solomon Assefa
Keyword(s):  
Survival Time ◽  
Antimalarial Activity ◽  
Antimalarial Drugs ◽  
Negative Control ◽  
Antiplasmodial Activity ◽  
Capsicum Frutescens ◽  
Oral Toxicity ◽  
Fruit Extract ◽  
Dose Levels

Background. The alarming spread of parasite resistance to current antimalarial agents is threatening malaria controlling efforts. This, consequently, urged the scientific community to discover novel antimalarial drugs. Successful and most potent antimalarial drugs were obtained from medicinal plants. Capsicum frutescens is claimed to possess an antiplasmodial activity in Ethiopian and Ugandan folkloric medicine. However, there is a lack of pharmacological evidence for its antiplasmodial activity. This study, hence, was aimed at evaluating the in vivo antiplasmodial activity of C. frutescens in a mouse model. Methods. The dried fruits of the plant were extracted with 80% methanol using cold maceration. A 4-day suppressive test was employed to ascertain the claimed antiplasmodial effect of the plant. Following inoculation with P. berghei, mice in treatment groups were provided with three dose levels (100, 200, and 400 mg/kg) of the extract, while 2% Tween 80 and chloroquine served as the negative and positive controls, respectively. Weight, temperature, packed cell volume, parasitemia, and survival time were then monitored. Results. The acute oral toxicity study revealed that the crude extract caused no mortality and revealed no overt sign of toxicity. In the 4-day suppressive test, all dose levels of the extract were found to exhibit a significant (p<0.05) inhibition of parasitemia compared to those of the negative control. Maximum parasite suppression (93.28%) was exerted by the highest dose (400 mg/kg/day) of extract. Also, the extract significantly (p<0.05) prolonged survival time and prevented body weight loss and reduction in temperature and anemia compared to the vehicle-treated group. Conclusion. This investigation found strong evidence that the fruit extract of C. frutescens is endowed with promising antiplasmodial activity. Hence, the plant could serve as a potential source of a newer antimalarial agent.

scholarly journals Antimalarial Activity of the Leaf Latex of Aloe weloensis (Aloaceae) against Plasmodium berghei in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Tekleab Teka ◽  
Tadesse Awgichew ◽  
Haile Kassahun
Keyword(s):  
Survival Time ◽  
Cell Volume ◽  
Plasmodium Berghei ◽  
Packed Cell Volume ◽  
Antimalarial Activity ◽  
Signs And Symptoms ◽  
Negative Control ◽  
Dependent Manner ◽  
Traditional Use ◽  
Lead Compounds

Background. Emergence of drug resistance and lack of therapeutic efficacy of modern antimalarial drugs are the most triggering factors for the searching of new lead compounds with different mechanisms of action. Medicinal plants with documented traditional uses are a viable option for treatment of malaria. Traditionally, the leaf latex of Aloe weloensis has been used in the treatment of malaria in Ethiopia. Hence, this study was undertaken to investigate the antimalarial activity of the leaf latex of Aloe weloensis in Plasmodium berghei-infected mice. Methods. A four-day suppressive test was employed to evaluate the antimalarial effect of the leaf latex of the plant against P. berghei in Swiss albino mice. Mice were randomly assigned in five groups of five animals in each and given 100, 200, and 400 mg/kg of the leaf latex, chloroquine 25 mg/kg, and distilled water. The level of parasitemia, packed cell volume, survival time, temperature, and body weight was used to determine the antimalarial activity. Results. The acute toxicity study indicated that the leaf latex of A. weloensis caused neither mortality nor signs and symptoms of toxicity at a dose of 2000 mg/kg. Furthermore, the 4-day suppressive test indicated that the latex of the plant exhibited a significant parasitemia reduction in a dose-dependent manner as compared to negative control. The leaf latex of the plant exhibited a percent inhibition of 13.05%, 41.87%, and 66.84% at doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively. The chemosuppression of the antimalarial activity was statistically significant at 100 mg/kg (p<0.05), 200 mg/kg (p<0.01), and 400 mg/kg (p<0.01) as compared to negative control. All doses of the leaf latex prevented weight loss and reduction in temperature and packed cell volume and increased the survival time of infected mice. Conclusion. The results of this study demonstrated that the leaf latex of Aloe weloensis possessed antiplasmodial activity confirming the genuine traditional use of the plant as an antimalarial agent.

scholarly journals Evaluation of the Antimalarial Activity of the Hydroalcoholic Extract of Leaf of Leonotis ocymifolia (Burm. f.) Iwarsson (Lamiaceae) against Plasmodium berghei in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Tewolde Teklu ◽  
Ephrem Engidawork ◽  
Teshome Nedi ◽  
Tilahun Teklehaymanot ◽  
Leake Gebremeskel
Keyword(s):  
Survival Time ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Tween 80 ◽  
Parasite Load ◽  
Antimalarial Drugs ◽  
Negative Control ◽  
Isolation And Identification ◽  
Hydroalcoholic Extract ◽  
Test Models

Malaria’s global impact, fueled by resistance to several antimalarial drugs, has necessitated a quest to new antimalarial drugs from several sources with traditional medicinal plants being one of them. This study was conducted to assess the antimalarial activity of a traditionally used medicinal plant, Leonotis ocymifolia, against Plasmodium berghei. The plant has been extracted using maceration technique, and doses ranging from 100–800 mg/kg of Leonotis ocymifolia were used to test its antimalarial activity. Tween 80 (2% in water) and chloroquine 25 mg/kg were used as negative and positive controls, respectively. The antimalarial activities of the plant were determined by measuring parasitemia, survival time, packed cell volume, temperature, and weight. The plant’s hydroalcoholic extract, as compared to negative control, maximally decreased parasite load by 41.4% at 800 mg/kg (p < 0.001). This parasite suppression was followed by longer survival time in the groups taking 400 mg/kg (p < 0.05) and 800 mg/kg (p < 0.05) in a four-day suppressive test and in those taking 800 mg/kg (p < 0.05) in Rane’s test. The plant did not prevent weight and PCV reduction but prevented temperature reduction at 400 mg/kg (p < 0.05) and 800 mg/kg (p < 0.05) in a four-day suppressive model, and at 800 mg/kg (p < 0.05) in Rane’s model. The average but consistent antimalarial activity of the plant across the test models corroborates the folkloric antimalarial use of the plant. The study recommends further pharmacological screenings, isolation, and identification of active compound(s) of the plant Leonotis ocymifolia.

scholarly journals Antimalarial Activity of Hydroalcoholic Root Extract of Acanthus polystachyus Delile (Acanthaceae) Against Plasmodium berghei–Infected Mice

2019 ◽  
Vol 24 ◽  
pp. 2515690X1988532 ◽  
Author(s):  
Dagninet Derebe ◽  
Muluken Wubetu
Keyword(s):  
Crude Extract ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Negative Control ◽  
New Drugs ◽  
Root Extract ◽  
Root Extracts ◽  
Antimalarial Agents ◽  
Mean Survival Time

Failure of the efficacy of antimalarial drugs is recognized in different classes of medicines for treating malaria, which urges the need for new drugs. This study tried to check the in vivo antimalarial activity of the root extracts of Acanthus polystachyus Delile against Plasmodium berghei–infected mice. The study revealed that the methanolic crude extract of the root of Acanthus polystachyus Delile showed significant ( P < .01) parasitemia suppressive activities in both models compared with the negative control. Parasitemia suppressive activities were 25.26%, 33.46%, and 51.48% in a 4-day suppressive test and 23.31%, 31.20%, and 43.54% in prophylaxis test at 100, 200, and 400 mg/kg of the extract, respectively, as compared to the negative control. Besides, the extract increases mean survival time significantly in all tested doses in a 4-day suppressive test, but in the prophylaxis model, only mice treated with 200 and 400 mg/kg significantly lived longer. Based on this finding, the root of Acanthus polystachyus Delile has strong antimalarial activity, which may be a good candidate for new antimalarial agents.

scholarly journals Combination of Calotropis gigantea Radix Extract and Artemisin as an Antimalarial Agent Against Plasmodium berghei

2016 ◽  
Vol 1 (1) ◽  
pp. 12
Author(s):  
Roihatul Muti’ah ◽  
Elok Kamilah Hayati ◽  
Asnal Fatati
Keyword(s):  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Negative Control ◽  
Calotropis Gigantea ◽  
Treatment Groups ◽  
Tukey Test ◽  
Bioactive Component ◽  
Phytochemical Compounds

<p><em>Calotropis gigantea</em> radix is one of plant which has bioactive component as antimalarial.The purpose of this research are to know antimalarial activity from combination of <em>Calotropis gigantea</em> radix extract and artemisin. The research consist of extraction of <em>Calotropis gigantea</em> radix was done with extraction maseration method. Extraction was performed by maseration with  80% ethanol solvent. Concentrated extract was <em>in vivo </em>antimalarial tested to animal model. Mice were peritoneal infected with 10<sup>6</sup><em>Plasmodium berghei</em> ANKA and divided into 5 treatment groups: negative control; positive control (artemisin of dose 4 mg/kgBW); combination of artemisin(1/4 dose of artemisin standar) and <em>Calotropis gigantea</em>in 3 doses: 0,1 mg/KgBW; 1 mg/KgBWand 10 mg/KgBW. Data of inhibition was analyzed using SPSS program with <em>Two Way </em>ANOVA Test dan continued with Tukey Test.</p><p class="DefaultCxSpFirst">The result shows that combination of <em>Calotropis gigantea</em> radix extract and artemisin with dose 10 mg/KgBB has higher antimalarial activity than control positive (artemisin). The value of parasite inhibition is 55,2% for dose 0.1 mg/KgBW ; 72,8% for dose 1 mg/KgBW ; 87,3% for dose 10 mg/KgBW and 56,06 mg/KgBW for control positive (artemisin). The phytochemical compounds in 80%  ethanol solvent extract are tannins and steroids.</p><div><p class="DefaultCxSpMiddle"> </p><p class="DefaultCxSpLast"><strong>Keywords</strong>: <em>Calotropis gigantea,</em><em>antimalaria, combination, artemisin, </em><em>Plasmodium berghei</em><strong></strong></p></div>

scholarly journals Evaluation of Antimalarial Potential of Extracts from Alstonia boonei and Carica papaya in Plasmodium berghei-Infected Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Francis O. Atanu ◽  
Favour M. Idih ◽  
Charles O. Nwonuma ◽  
Helal F. Hetta ◽  
Salman Alamery ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Survival Time ◽  
Plasmodium Berghei ◽  
Carica Papaya ◽  
Negative Control ◽  
Control Group ◽  
Dependent Manner ◽  
Antioxidant Power ◽  
Mean Survival Time

Extracts of Alstonia boonei and Carica papaya are used in herbal medicine for the treatment of malaria. This work investigated the phytochemical, antioxidant, and antimalarial effects of hydromethanolic extracts of Alstonia boonei and Carica papaya. A four-day chemosuppressive test was conducted to assess the ability of the extracts to prevent establishment of infection. Three doses of the extracts were administered—100, 200, and 400 mg/kg bw—prior to Plasmodium berghei challenge. Change in body weight, parasitemia, packed cell volume (PCV), and mean survival time was determined. A three-day curative test was also carried out on Plasmodium berghei-infected mice to determine the effects of the plant extracts (200 mg/kg bw) on parasitemia and biochemical indices of liver and kidney functions, lipid metabolism, and oxidative stress. The study revealed that the extracts possessed phenolic compounds (34.13 ± 1.90 mg GAE/g for Alstonia boonei and 27.99 ± 1.46 mg GAE/g for Carica papaya) and flavonoids (19.47 ± 1.89 mg QE/g for Alstonia boonei and 18.24 ± 1.36 mg QE/g for Carica papaya). In vitro antioxidant activity measured as total antioxidant power, total reducing power, and DPPH radical scavenging activity showed that the extracts possessed higher antioxidant activity than the reference compounds. The outcome of the chemosuppressive test revealed that whereas Plasmodium berghei-infected mice had high parasitemia, decreased mean survival time, exhibited loss of weight, and had low PCV, treatment with the extracts reversed the effects in a concentration-dependent manner. Similarly, the curative test revealed that the extracts significantly suppressed parasitemia compared with the malaria negative control group. This was mirrored by reversal of indices of hepatic toxicity (AST, ALT, and ALP levels), nephropathy (urea and creatinine levels), oxidative stress (SOD, CAT, GPx, GSH, and lipid peroxides), and dyslipidemia (TC, HDL, and TG levels and HMG-CoA reductase activity) in infected but treated mice compared with negative control. Put together, the results of this study demonstrate that the extracts of Alstonia boonei and Carica papaya possess antimalarial properties and are able to ameliorate metabolic dysregulations that characterize Plasmodium berghei infection. The phytoconstituents in these extracts are believed to be responsible for the pharmacological activity reported in this study.

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