• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.7-15
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• 2016

Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the 'apicoplast', which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle's function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug resistance.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2000.10a
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• pp.64-65
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• 2000

Cancer is a general term subjected to a series of malignant tumor diseases which may affect many different parts of the human body. These cancer diseases are characterized by a rapid and uncontrolled formation of abnormal cells in the body. Cancer chemotherapeutic agents can often provide the prolongation of life and occasionally cures. To date many kinds of compounds have been obtained from plants kingdom as anti-neoplastic and anti-cancerous agents. However, there is no special type of compounds for cancer therapy. In our laboratory, anti-tumor and cytotoxic screenings on higher plants collected in Japan, China, Korea, Southeast Asia and South America have been done by using Sarcoma 180 ascites in mice, P388 lymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells. The family, Simaroubaceae consists of about 20 genera and 120 species, mainly shrubs and trees, distributed in tropical and subtropical country. Simaroubaceae is classified as RUTALES, together with Rutaceae, Burseraceae, Meliaceae, Malpighiaceae and Polygalaceae. The members differ from the Rutaceae in not containing oil glands. Bitter principles are a characteristic of the family, Simaroubaceae. The genera include Quassia (Simarouba) (40 spp.), Picrasma (Aeschrion) (6 spp.), Brucea (10 spp.), Soulamea (10 spp.), Ailanthus (10 spp.) and Perriera (1 spp.) etc.. Surinam quassia derived from Quassia amara growing in Guianas, north Brazil and Venezuela is used in traditional medicines for stomachic, anti-amoebic, anti-malarial and anti-anaemic properties. Also, various parts of a number of plants of the family Simaroubaceae have been used in traditional medicine for the treatment of a variety oi diseases including cancer, amoebic, dysentery and malaria. Then, the research has established that it is the quassinoid content of these plants that is responsible for above activities. In this meeting, I will present on anti-tumor and anti-malarial activities and their active principles of Simaroubaceae plants, Eurycoma longifolia, Ailanthus vilmoriniana, Simaba cedron and Brucea mullis which have been studied in our laboratory.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2000.10b
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• pp.11-13
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• 2000

Cancer is a general term subjected to a series of malignant tumor diseases which may affect many different parts of the human body. These cancer diseases are characterized by a rapid and uncontrolled formation of abnormal cells in the body. Cancer chemotherapeutic agents can often provide the prolongation of life and occasionally cures. To date many kinds of compounds have been obtained from plants kingdom as anti-neoplastic and anti-cancerous agents. However, there is no special type of compounds for cancer therapy. In our laboratory, anti-tumor and cytotoxic screenings on higher plants collected in Japan, China, Korea, Southeast Asia and South America have been done by using Sarcoma 180 ascites in mice, P388 lymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells. The family, Simaroubaceae consists of about 20 genera and 120 species, mainly shrubs and trees, distributed in tropical and subtropical country. Simaroubaceae IS classified as RUTALES, together with Rutaceae, Burseraceae, Meliaceae, Malpighiaceae and Polygalaceae. The members differ from the Rutaceae in not containing oil glands. Bitter principles are a characteristic of the family, Simaroubaceae. The genera include Quassia (Simarouba) (40 spp.), Picrasma (Aeschrion) (6 spp.), Brucea (10 spp.), Soulamea (10 spp.), Ailanthus (10 spp.) and Perriera (1 spp.) etc.. Surinam quassia derived from Quassia amara growing in Guianas, north Brazil and Venezuela is used in traditional medicines for stomachic, anti-amoebic, anti-malarial and anti-anaemic properties. Also, various parts of a number of plants of the family Simaroubaceae have been used in traditional medicine for the treatment of a variety of diseases including cancer, amoebic, dysentery and malaria. Then, the research has established that it is the quassinoid content of these plants that is responsible for above activities. In this meeting, I will present on anti-tumor and anti-malarial activities and their active principles of Simaroubaceae plants, Eurycoma longifolia, Ailanthus vilmoriniana, Simaba cedron and Brucea mollis which have been studied in our laboratory.

• Korean Journal of Pharmacognosy
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• v.43 no.3
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• pp.239-242
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• 2012

This study was carried out to investigate the anti-malarial activity of Juniperus chinensis by in vitro and in vivo system using Plasmodium falciparum chloroquine-sensitive(3D7) and P. falciparum chloroquine-resistant(S20) strains. According to cytotoxicty test on NIH 3T3 cell, the ethanol extract(EtOH), ethylacetate(EtOAc) fraction and aqueous fraction possessed significant anti-malarial activity against both 3D7 and S20 strains at non-toxic concentrations(<100 /). In vitro assay, EtOAc fraction showed notable activity against 3D7 and S20 strains of P. falciparum with $IC_{50}$ values of $37{\pm}2{\mu}g/ml$ and $36{\pm}6{\mu}g/ml$. In animal test using P. falciparum infected human erythrocytes, the treatment of EtOAc fraction significantly inhibited parasitaemia in mice in a dose-dependent manner that is parasitaemia of 42%, 34% and 31% in doses of 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively. The study provides data to support the medicinal importance of the J. chinensis.

• Parasites, Hosts and Diseases
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• v.57 no.2
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• pp.117-125
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• 2019

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of $HIF1{\alpha}$ through an intracellular oxygen-sensing pathway. Activation of $HIF1{\alpha}$ may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of $2{\times}10^6$ parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and $HIF1{\alpha}$. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and $HIF1{\alpha}$ increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxiainduced angiogenesis by stimulation of $HIF1{\alpha}$ and VEGF in various tissues.

• Journal of Integrative Natural Science
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• v.10 no.1
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• pp.1-6
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• 2017

Demand for a new anti-malarial drug has been dramatically increasing in the recent years. Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) plays a vital role in fatty acid elongation process, which now emerged as a new important target for the development of anti-microbial and anti-parasitic molecules. In the present study, 19 compounds namely alginic acid, atropine, chlorogenic acid, chrotacumine A & B, coenzyme $Q_1$, 4-coumaric acid, curcumin, ellagic acid, embelin, 5-O-methyl embelin, eugenyl glucoside, glabridin, hyoscyamine, nordihydroguaiaretic acid, rohitukine, scopolamine, tlatlancuayin and ursolic acid were evaluated on their docking behaviour on P. falciparum enoyl-acyl carrier protein reductase (PfENR) using Auto dock 4.2. The docking studies and binding free energy calculations exhibited that glabridin gave the highest binding energy (-8.07 kcal/mol) and 4-coumaric acid in contrast showed the least binding energy (-4.83 kcal/mol). All ligands except alginic acid, ellagic acid, hyoscyamine and glabridin interacted with Gln409 amino acid residue. Interestingly four ligands namely coenzyme $Q_1$, 4-coumaric acid, embelin and 5-O-methyl embelin interacted with Gln409 amino acid residue present in both chains (A & B) of PfENR protein. Thus, the results of this present study exhibited the potential of these 19 ligands as P. falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitory agents and also as anti-malarial agents.

• Parasites, Hosts and Diseases
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• v.34 no.4
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• pp.239-246
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• 1996

The usefulness of malaria diagnosis by Plusmodium JaLcipawn-GDH (NADP+), obtained by affinity chromatography. is demonstrated in ELISA assays, testing IgG antibodies against GDH (NADP+) from patients with acute malaria, who have had two or more episodes of malaria. or from sera of hyperimmune patients. GDH (NADP+) thermal stability was demonstrated in a high heat resistance assay. The immunofluorescence assay demonstrated that anti-culture (P. falciporum) supernatant serum and anti-GDH (NADP+) of Proton app. recognized epitopes in Venezuelan isolates and Colombian and Brazilian malarial strains. The antigen is soluble, with high specificity is a potent imnlunogen and is thermoresistant. Key words: antigenic enzymes. glutamate dehydrogenase, malaria diagnosis, Plasmodium berghei, Plcswlodium ccthemelum, PlusmoniumJnlcipnmm, Plosmonium uiuox. soluble antigens.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5243-5248
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• 2013

Background: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. Methods: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. Results: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Conclusion: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.

• Biomedical Science Letters
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• v.25 no.2
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• pp.123-130
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• 2019

Platelet aggregation is essential for hemostatic process in case of blood vessels damages. However, excessive platelet aggregation can cause cardiovascular disorders including atherosclerosis, thrombosis and myocardial infarction. Scopoletin is usually found in the roots of genus Scopolia or Artemisia, and is known to have anticoagulant and anti-malarial effects. This study investigated the effect of scopoletin on human platelet aggregation induced by U46619, an analogue of thromboxane $A_2(TXA_2)$. Scopoletin had anti-platelet effects by down-regulating $TXA_2$ and intracellular $Ca^{2+}$ mobilization ($[Ca^{2+}]_i$), the aggregation-inducing molecules generated in activated platelets. On the other hand, scopoletin increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are known to be intracellular $Ca^{2+}$ antagonists. This resulted in inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ in U46619-induced human platelet aggregation. In addition, scopoletin inhibited the release of adenosine trisphosphate (ATP) in dose-dependent manner. This result means that the aggregation amplification activity through the granule secretion in platelets was suppressed by scopoletin. Therefore, we demonstrated that scopoletin has a potent antiplatelet effect and is highly likely to prevent platelet-derived vascular disease.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.47-53
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• 2005

Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.