Antimalarial Activity of Ethanol Extract of Kelakai Leaves (Stenochlaena palustris) to Parasitemia and Splenomegaly in BALB/c Mice Infected with Plasmodium berghei ANKA

Introduction: Malaria is one of global health problems. Splenomegaly is one of malaria symptoms. Antimalarial drug resistance had been reported. Alternative treatment is by using traditional medicinal plants such as kelakai (Stenochlaena palustris). Kelakai contains alkaloid and flavonoid which had been reported to have antimalarial activity. The aim of this study was to discover antimalarial activity of ethanol extract of kelakai leaves to parasitemia and splenomegaly of Plasmodium berghei ANKA in infected BALB/c mice.Methods: This study was based on a modified Peter test using BALB/c mice infected with P. berghei ANKA treated with ethanol extract of kelakai leaves, with chloroquine diphosphate as a positive control. The negative control was P. berghei ANKA infected mice without any additional treatment. Administration of ethanol extract of kelakai leaves was performed for 4 days with a serial doses of 100, 10, and 1 mg/kg body weight. The positive control was given chloroquine diphosphate 20 mg/kg body weight. Parasitemia was observed daily prior to the calculation of the percentage of parasite growth and parasite growth inhibition. At the end of the test, the mice were sacrificed and spleens were isolated to measure their sizes. Probit analysis was performed to obtain ED50 to find the effect of extract in parasite killing by 50%. Spearman test was performed to analyze the correlation of doses of extract and splenomegaly.Results: Parasitemia growth inhibition was directly proportional to the dose. Higher parasitemia inhibition was obtained at higher doses and vice versa. Result of probit analysis showed an ED50 was 77.05 mg/kg body weight. Statistical analysis resulted in insignificant correlation between doses and splenomegaly p = 1.0 (significancy < 0.05).Conclusion: Ethanol extract of kelakai leaves possessed good antimalarial activity and there was no correlation between extract doses and splenomegaly in Plasmodium berghei ANKA-infected mice.

Differential Effect of Antioxidants Glutathione and Vitamin C on the Hepatic Injuries Induced by Plasmodium berghei ANKA Infection

Malaria is a life-threatening disease caused by Plasmodium and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by Plasmodium infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by Plasmodium berghei ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during Plasmodium infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of Plasmodium-infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition.

Suppressive effect of goat bile in Plasmodium berghei ANKA infection in mice

Background and Aim: Some individuals in Indonesia consume intact goat gallbladder to prevent and treat malaria. The acute and subacute toxicity tests of goat bile (GB) have shown mild diarrhea in mice. Therefore, this study aimed to evaluate the suppressive effect of GB on parasitemia, splenomegaly, hepatomegaly, and blood biochemistry to assess liver and kidney function in BALB/c mice infected with Plasmodium berghei ANKA. Materials and Methods: Fifty healthy mice were infected with P. berghei ANKA and divided into five groups. Mice in three groups were administered 0.5 mL of 25%, 50%, or 100% of GB by gavage. Animals in Group 4 were administered 187.2 mg/kg BW of dihydroartemisinin-piperaquine phosphate as a positive control (POS Group). Mice in fifth group were administered sterile water as negative (NEG) controls. Further, 30 uninfected mice were divided into groups 6-8 and administered GB as were mice in the first three groups. Group 9 included 10 uninfected and untreated animals as healthy controls. Treatments were administered in a 4-day suppressive test followed by daily observation of Giemsa-stained blood smears. On day 7, mice were sacrificed to measure the length and weight of spleens and livers, plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine. Results: GB suppressed parasitemia but did not affect the size and weight of spleens or livers or plasma levels of AST and ALT compared to uninfected GB-treated and healthy control animals. Conversely, plasma levels of BUN and creatinine were suppressed and remained in the normal range in all groups of mice. Conclusion: GB suppresses parasitemia with no significant impact on hepatic enzymes in GB-treated infected mice. Liver dysfunction in GB-treated infected mice was due to P. berghei rather than GB treatment.

Nephroprotective effect of virgin coconut oil in Plasmodium berghei ANKA infected Balb/c mice

Malaria is a parasitic infectious disease caused by Plasmodium, which remains a world health problem with an estimated 219 million cases worldwide. In severe malaria infection, several organs of the body can be affected, including the kidneys. One of the pathophysiology associated with the worsening of this disease is oxidative stress. The use of antioxidants is expected to prevent this, and one product that has a high antioxidant content is virgin coconut oil (VCO). This study aimed to analyze the effect of VCO on the kidney in Plasmodium berghei ANKA-infected mice. This study was an in vivo laboratory experimental study with a randomized post-test only control group design using 35 BALB/c mice infected with P. berghei ANKA, weighing 20-30 grams. VCO with the Javara® brand is used with doses of 1, 5, and 10 ml/kg body weight (kgBW)/ day. The parameter assessed were levels of BUN, creatinine, and renal histopathological changes. The administration of VCO on the treated group shows minimal tubular necrosis and glomerulonephritis compared to the negative control group. The BUN and creatinine levels in the treated group were also lower than the negative control group. The results showed that VCO has a nephroprotective effect against P. berghei ANKA infection in mice.Keywords: malaria, kidney, virgin coconut oil

Antimalarial Activity of Ethanol Extract of Noni Leaves (Morinda citrifolia) towards Parasitemia, Splenomegaly, and Hepatomegaly in Plasmodium berghei ANKA Infected Mice

Introduction: Malaria is one of the infectious diseases found in tropical countries and sub-tropical countries. In 2016 there were an estimated 445,000 people died to malaria. Alternative medicine is needed, such as natural based ingredient. Morinda citrifolia or noni plant is a medicinal plant found in all parts of Indonesia which has many benefits, such as antibacterial, analgesic, anticancer, antioxidant, and anti-inflammatory. The aims of this study were to determine the antimalarial activity of ethanol extract of noni leaves and its effect on splenomegaly and hepatomegaly.Methods: Extract of noni leaves was prepared by maceration using ethanol solvent. In vivo experiments were conducted using Plasmodium berghei infected BALB/c mice treated with the doses of 100, 10, 1 mg/kg body weight(BW) orally of ethanolic extract of noni leaves. Then, the percentage of parasitemia was calculated from day 1 to day 4 after treatment and at the end of the test, mice were sacrificed then spleen and liver were collected. Results: The highest parasite growth was found in the group treated with noni leaves ethanol extract at a dose of 1 mg/kg WB and vice versa. Probit analysis resulted in ED50 was 0.882 mg/kg WB. Spearmen test showed there was no correlation between doses and the size of splenomegaly with p=0,2 and between doses and the size of hepatomegaly with p=0,6.Conclusion: Ethanol extract of noni leaves possessed antimalaria activity and there was no correlation between doses of extract and t he splenomegaly and hepatomegaly.

Tamoxifen Suppresses the Immune Response to Plasmodium berghei ANKA and Exacerbates Symptomatology

Malaria is the most lethal parasitic disease in the world. Mortality and severity in symptoms are higher in men than women, suggesting that oestrogens, which are in higher concentration in females than in males, may regulate the immune response against malaria. Tamoxifen, a selective oestrogen receptor modulator used in breast cancer treatment due to its antagonistic effect on oestrogen receptors α and β, is also studied because of its potential therapeutic use for several parasitic diseases. However, most studies, including one in malaria, have not addressed the immunomodulatory role of tamoxifen. In this work, we evaluated the effect of tamoxifen on the immune response of CBA/Ca mice against Plasmodium berghei ANKA. This study showed for the first time that tamoxifen increased parasite load, aggravated symptoms by decreasing body temperature and body weight, and worsened anaemia. Additionally, tamoxifen significantly increased the splenic index and the percentages of CD4+ and NK+ cells on day eight post-infection. By contrast, tamoxifen decreased both CD8+ and B220+ populations in the spleen and decreased the serum levels of IL-2, IL-6, and IL-17. Our findings support the notion that tamoxifen is a potent immunomodulator in malaria-infected mice and suggest caution when administering it to malaria-infected women with breast cancer.

Effect of Plasmodium berghei infection on fetuses in pregnant BALB/c mice at two periods of pregnancy

Malaria is a disease caused by a protozoan of the genus Plasmodium in humans and vertebrates. It has a high morbidity and mortality rate, especially in pregnant women living in countries with high transmission rates. Murine models have been an excellent tool to evaluate the effects of malarial infection in the mother-fetus relationship. For this reason, we evaluated the effect of malarial infection on fetal development at the beginning and middle of the gestational period in BALB/c mice infected with Plasmodium berghei ANKA. Our results show that malarial infection at the beginning of pregnancy markedly affects the development of the fetus in size, weight, and development of its limbs so that the control of the pregnant mother is relevant at the beginning of gestation