Aktivitas Antimalaria Daun Gempol (Nauclea orientalis (L.) L) terhadap Plasmodium falciparum

Abstract The use of gempol (Nauclea orientalis (L.) L) stem as a malaria medicine has been empirically and scientifically proven. This condition encourages exploitation which can lead to scarcity of raw materials. Substitution of plant parts as raw material for medicine is one of the innovations that can be done for the sustainability of the plant species. Leaves are one part of the plant that is often used as a raw material for medicine. The selection of leaves as the main ingredient has many advantages over other parts. Until now, research related to the antimalarial bioactive potential of N. orientalis (L.) L leaves has not been published. Therefore, this study aimed to explore the potential for leaf antimalarial activity as an alternative to substitution of stem parts. The leaf extract of N. orientalis (L.) L was prepared by maceration method with 96% ethanol then fractionation was carried out in stage using hexane, ethyl acetate and methanol as solvents. Antimalarial activity testing was carried out in vitro against Plasmodium falciparum 3D7 and Thin Layer Chromatography (TLC) for screening phytochemical compounds in each sample. The hexane solvent was known to produce the most optimum extract by with a yield of 20%. The antimalarial activity of the hexane (IC 50 1.93 μg/mL) and methanol (IC 3.91 μg/ mL) fractions were classified as ‘very active’ and had a tendency to be able to compete with chloroquine phosphate activity. The potential for antimalarial activity in both samples was influenced by the content of alkaloids, steroids, flavonoids and terpenoids which had been developed as active ingredients for malaria drugs. The results of this study indicate that the leaves of Nauclea orientalis (L.) L have the potential to be developed as an alternative to malaria medicine. Abstrak Pemanfaatan batang gempol (Nauclea orientalis (L.) L) sebagai obat malaria telah terbukti secara empiris dan ilmiah. Kondisi tersebut mendorong terjadinya eksploitasi hingga dapat berujung pada kelangkaan bahan baku. Substitusi bagian tumbuhan sebagai bahan baku obat merupakan salah satu inovasi yang dapat dilakukan untuk keberlanjutan hidup spesies tumbuhan tersebut. Daun merupakan salah satu bagian tumbuhan yang sering digunakan sebagai bahan baku obat. Pemilihan daun sebagai bahan utama memiliki banyak kelebihan dibandingkan bagian lainnya. Penelitian terkait potensi bioaktif antimalaria daun Nauclea orientalis (L.) L hingga saat ini belum dipublikasikan. Oleh karena itu, penelitian ini bertujuan untuk menggali potensi aktivitas antimalaria daun sebagai alternatif subtitusi bagian batang. Ekstrak daun Nauclea orientalis (L.) L disiapkan dengan metode maserasi dengan etanol 96%, kemudian dilakukan fraksinasi cair-cair bertingkat menggunakan pelarut heksana, etil asetat, dan metanol. Pengujian aktivitas antimalaria dilakukan secara in vitro terhadap Plasmodium falciparum 3D7 dan Kromatografi Lapis Tipis (KLT) untuk penapisan senyawa fitokimia pada masingmasing sampel. Pelarut heksana diketahui menghasilkan ekstrak paling optimum dengan rendemen 20%. Aktivitas antimalaria fraksi heksana (IC 50 1,93 µg/mL) dan metanol (IC 3,91 µg/mL) yang tergolong dalam kategori ‘sangat aktif, serta memiliki kecenderungan mampu bersaing dengan aktivitas klorokuin fosfat. Potensi aktivitas antimalaria pada kedua sampel tersebut dipengaruhi oleh kandungan senyawa alkaloid, steroid, flavonoid dan terpenoid yang telah banyak dikembangkan sebagai bahan aktif obat malaria. Hasil penelitian ini menunjukkan bahwa daun Nauclea orientalis (L.) L berpotensi untuk dikembangkan sebagai alternatif obat malaria.

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In vitro antimalarial activity of six Aspidosperma species from the state of Minas Gerais (Brazil)

Anais da Academia Brasileira de Ciências ◽

10.1590/s0001-37652012000400005 ◽

2012 ◽

Vol 84 (4) ◽

pp. 899-910 ◽

Cited By ~ 15

Author(s):

Maria Fâni Dolabela ◽

Salma G. Oliveira ◽

José M. Peres ◽

José M.S. Nascimento ◽

Marinete M. Póvoa ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Minas Gerais ◽

The State ◽

Active Compounds ◽

Human Malaria ◽

Plant Parts ◽

Ic50 Values

Ethnomedicinal informations point to some Aspidosperma species (Apocynaceae) as antimalarial plants in Brazil and have motivated the evaluation of six species which were collected in the state of Minas Gerais: A. cylindrocarpon Müll. Arg., A. parvifolium A. DC., A. olivaceum Müll. Arg., A. ramiflorum Müll. Arg., A. spruceanum Benth. ex Müll. Arg. and A. tomentosum Mart.. A total of 23 extracts of different plant parts in different solvents were assayed in vitro against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. All the extracts were shown to be active with IC50 values in the range of 5.0 ± 0 2.8 µg/mL to 65.0 ± 4.2 µg/mL. TLC profile of the extracts revealed the presence of alkaloids in the six species assayed. These results seem to confirm the popular use of Aspidosperma species to treat human malaria in Brazil and seem point to alkaloids as the putative active compounds of the assayed species.

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Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

Author(s):

S Whitehead ◽

TE Peto

Keyword(s):

Plasmodium Falciparum ◽

Growth Inhibition ◽

Antimalarial Activity ◽

Clinical Malaria ◽

Inhibitory Effect ◽

Parasite Development ◽

And Control ◽

Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2094 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2094-2098 ◽

Cited By ~ 13

Author(s):

B Pradines ◽

F Ramiandrasoa ◽

L K Basco ◽

L Bricard ◽

G Kunesch ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Mechanism Of Action ◽

Ribonucleotide Reductase ◽

Antimalarial Activity ◽

Iron Chelators ◽

Resistant Clone ◽

Iron Deprivation ◽

Level Of Activity ◽

Susceptible Clone

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.

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In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP)

Scientific Reports ◽

10.1038/s41598-021-84622-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Merricka C. Livingstone ◽

Alexis A. Bitzer ◽

Alish Giri ◽

Kun Luo ◽

Rajeshwer S. Sankhala ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Monoclonal Antibodies ◽

Disease Burden ◽

Vaccine Candidate ◽

Specific Binding ◽

Circumsporozoite Protein ◽

Target Epitope ◽

Selection Of

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

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Synthesis and in Vitro Antimalarial Activity of Alkyl Esters Gallate as a Growth Inhibitors of Plasmodium Falciparum

Oriental Journal Of Chemistry ◽

10.13005/ojc/340207 ◽

2018 ◽

Vol 34 (2) ◽

pp. 655-662 ◽

Cited By ~ 2

Author(s):

Ade Arsianti ◽

Hendry Astuti ◽

Fadilah Fadilah ◽

Daniel Martin Simadibrata ◽

Zoya Marie Adyasa ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Growth Inhibitors ◽

Alkyl Esters

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Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i4.24532 ◽

2015 ◽

Vol 10 (4) ◽

pp. 917 ◽

Cited By ~ 1

Author(s):

Mukesh Kumar Kumawat ◽

Dipak Chetia

Keyword(s):

Plasmodium Falciparum ◽

Molecular Docking ◽

Resistant Strain ◽

Antimalarial Activity ◽

Binding Pocket ◽

Docking Studies ◽

Spectroscopic Techniques ◽

Molecular Docking Studies ◽

Activity Screening

Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of Plasmodium falciparum (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.

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Overexpression of Plasmodium falciparum M1 Aminopeptidase Promotes an Increase in Intracellular Proteolysis and Modifies the Asexual Erythrocytic Cycle Development

Pathogens ◽

10.3390/pathogens10111452 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1452

Author(s):

Carolina C. Hoff ◽

Mauro F. Azevedo ◽

Adriana B. Thurler ◽

Sarah El Chamy Maluf ◽

Pollyana M. S. Melo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Fold Increase ◽

Cysteine Proteases ◽

Aminopeptidase Activity ◽

Lower Sensitivity ◽

Wild Type ◽

Erythrocytic Cycle ◽

Transgenic Parasite

Plasmodium falciparum, the most virulent of the human malaria parasite, is responsible for high mortality rates worldwide. We studied the M1 alanyl-aminopeptidase of this protozoan (PfA-M1), which is involved in the final stages of hemoglobin cleavage, an essential process for parasite survival. Aiming to help in the rational development of drugs against this target, we developed a new strain of P. falciparum overexpressing PfA-M1 without the signal peptide (overPfA-M1). The overPfA-M1 parasites showed a 2.5-fold increase in proteolytic activity toward the fluorogenic substrate alanyl-7-amido-4-methylcoumarin, in relation to the wild-type group. Inhibition studies showed that overPfA-M1 presented a lower sensitivity against the metalloaminopeptidase inhibitor bestatin and to other recombinant PfA-M1 inhibitors, in comparison with the wild-type strain, indicating that PfA-M1 is a target for the in vitro antimalarial activity of these compounds. Moreover, overPfA-M1 parasites present a decreased in vitro growth, showing a reduced number of merozoites per schizont, and also a decrease in the iRBC area occupied by the parasite in trophozoite and schizont forms when compared to the controls. Interestingly, the transgenic parasite displays an increase in the aminopeptidase activity toward Met-, Ala-, Leu- and Arg-7-amido-4-methylcoumarin. We also investigated the potential role of calmodulin and cysteine proteases in PfA-M1 activity. Taken together, our data show that the overexpression of PfA-M1 in the parasite cytosol can be a suitable tool for the screening of antimalarials in specific high-throughput assays and may be used for the identification of intracellular molecular partners that modulate their activity in P. falciparum.

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Selection of Fish Raw Material Suppliers by Integrating ANP and Topsis Methods in CV. Riki Utama Mandiri

Procedia of Engineering and Life Science ◽

10.21070/pels.v1i2.923 ◽

2021 ◽

Vol 1 (2) ◽

Author(s):

Aula Fajar Iman Sakti ◽

Wiwik Sulistiyowati

Keyword(s):

Supplier Selection ◽

Raw Materials ◽

Rank Order ◽

Raw Material ◽

Network Process ◽

The Common ◽

Common Problems ◽

Frozen Fish ◽

A Company ◽

Selection Of

CV. Riki Utama Mandiri is a company in distributing an economic fish frozen product. This company distributed any kind of retail and wholesaler, both domestic and export. They distributing many frozen fish products variant such as Patin Fillet and Shark Fin. The all raw materials of those frozen seafood was obtained by three different suppliers. The common problems found in CV. Riki Utama Mandiri mostly about raw patin fish supplier which often committed delivery delays. The purpose of this research is to fixing the supply chain management in deciding the more accurate selections of raw materials supplier. To overcome the common problems that happen. Analytical network process (ANP) will simplify the criteria weight values and sub criteria of each supplier. Meanwhile, technique for others reference by similarity to ideal solution (TOPSIS) method is used for giving a rank order of the alternative supplier. This research is expected for being a consideration for the company in obtaining a good and more effective kind of raw supplier. We also expecting the company for tighten supplier selection more effective way so that it can fullfilled the existing standard. Also to overcome the common problems such as delivery delays, competing raw materials with uncertain quality, and difficulty in sort out the raw materials due to size issues.

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HPTLC METHOD FOR ESTIMATION AND QUANTIFICATION OF β-SITOSTEROL FROM IN-VIVO AND IN-VITRO SAMPLES OF MERREMIA AEGYPTIA AND MERREMIA DISSECTA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i10.38983 ◽

2020 ◽

pp. 162-165

Author(s):

RIDHI JOSHI ◽

RISHIKESH MEENA ◽

PREETI MISHRA ◽

VIDYA PATNI

Keyword(s):

High Performance ◽

Normal Phase ◽

Leaf Sample ◽

Plant Parts ◽

Methanolic Extracts ◽

Aluminum Plates ◽

Layer Chromatography ◽

Hptlc Method

Objective: A normal-phase high-performance thin-layer chromatography (HPTLC) method has been developed and validated for estimation and quantitation of beta-sitosterol from the methanolic fraction of different plant parts of two medicinally important plants viz. Merremia aegyptia and Merremia dissecta. These plants have been reported to possess antimicrobial, antioxidant, and anti-inflammatory activities. Methods: Chromatographic separation of beta-sitosterol from the methanolic extracts of plant parts of M. aegyptia and M. dissecta was performed on TLC aluminum plates pre-coated with silica gel 60F254 using a suitable mobile phase. The densitometric scanning was done after derivatization at ????-580 nm for ????-sitosterol. Result: Only M. dissecta leaf sample was reported to contain ????-sitosterol (4.6 ng/μl), whereas other samples such as seed, stem, and callus extracts of M. aegyptia and M. dissecta did not showed its presence. Conclusion: The developed HPTLC method is simple, rapid, and precise and can be used for routine analysis and quantification of ????-sitosterol and other useful plant bioactives that are phytopharmaceutically important.

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