The Effects of Transdermally Delivered Oleanolic Acid on Malaria Parasites and Blood Glucose Homeostasis in P. berghei-Infected Male Sprague-Dawley Rats

Sibiya, Happiness; Mabandla, Musa V.; Musabayane, C T

doi:10.1371/journal.pone.0167132

Cited by 8 publications

(3 citation statements)

References 39 publications

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“…either CQ-sensitive or CQ-resistant clones of P. falciparum [29]. Experiment of S. aromaticum-derived oleanolic acid on P. berghei-infected rats revealed its ability to clear and reduce malaria parasites [30]. These findings support our results (Table 1) since the plant investigated in this study belongs to the same genus Syzygium.…”

Section: Discussionsupporting

confidence: 90%

Investigation of antimalarial activity and cytotoxicity profiling of a Bangladeshi plant Syzygium cymosum

Hossainey

Sazed

Nima

et al. 2020

J Infect Dev Ctries

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Introduction: The persistent increase of resistance to existing antimalarials underscores the needs for new drugs. Historically, most of the successful antimalarial are derived from plants. The leaves of the S. cymosum is one of the plant materials used by traditional healers in malaria-endemic areas in Bangladesh for treatment of malaria. Here, we investigated the crude extract and its fractions against chloroquine (CQ)-sensitive 3D7, CQ-resistant Dd2, and artemisinin (ART)-resistant IPC 4912 Mondulkiri strains of Plasmodium falciparum. Methodology: The antimalarial activities were tested using HRP II based in-vitro antimalarial drug sensitivity ELISA described by WWARN and half inhibitory concentrations (IC50) were calculated by non-linear regression analysis using GraphaPad Prism. The cytotoxicity of the crude methanolic extract was assessed using the MTT assay on Vero cell line. Results: The methanolic crude extract revealed promising activity against 3D7 (IC50 6.28 µg/mL), Dd2 (IC50 13.42 µg/mL), and moderate activity against IPC 4912 Mondulkiri (IC50 17.47 µg/mL). Among the fractionated portions, the chloroform fraction revealed highest activity against IPC 4912 Mondulkiri (IC50 1.65 µg/mL) followed by Dd2 (1.73 µg/mL) and 3D7 (2.39 µg/mL). The crude methanolic extract also demonstrated good selectivity with the selectivity indices of > 15.92, > 7.45, and > 6.91 against 3D7, Dd2, and IPC 4912, respectively when tested against Vero cell line. Conclusions: This is the first report on S. cymosum for its putative antimalarial activity, and is imperative to go for further phytochemical analyses in order to investigate possible novel antimalarial drug compound(s).

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Section: Discussionsupporting

confidence: 90%

Investigation of antimalarial activity and cytotoxicity profiling of a Bangladeshi plant Syzygium cymosum

Hossainey

Sazed

Nima

et al. 2020

J Infect Dev Ctries

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“…We changed the drug form from oral administration to a transdermal type (td) with the goal of easy application to malaria patients, especially children. Td delivery may avoid the shortcomings associated with oral delivery and parenteral injections [ 12 , 13 , 14 , 15 ]. The aim of this study was to evaluate the effect of transdermal combination therapy (tdct) of N-89 with other known antimalarials for malaria treatment.…”

Section: Introductionmentioning

confidence: 99%

Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model

et al. 2023

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We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children.

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“…Treatment of P. berghei infection in rats, using transdermally delivered oleanolic acid (OA) from an amidated pectin hydrogel patch that contained 34 mg OA/kg, completely reduced detectable parasitemia. Noteworthy is the fact that the treatment started late, seven days post infection, when the parasitemias were extremely high, at about 40 percent ( Sibiya et al, 2016 ). A novel sublingual spray formulation of the antimalarial drug artemether was superior in pharmacokinetics to the drug in tablets ( Salman et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Transdermal delivery of artemisinins for treatment of pre-clinical cerebral malaria

Zech

Dzikowski

Simantov

et al. 2021

International Journal for Parasitology: Drugs and Drug Resistan

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Transdermal drug delivery avoids complications related to oral or parenteral delivery - the need for sterility, contamination, gastrointestinal side effects, patient unconsciousness or nausea and compliance. For malaria treatment, we demonstrate successful novel transdermal delivery of artemisone (ART) and artesunate. The incorporation of ART into a microemulsion (ME) overcomes the limitations of the lipophilic drug and provides high transcutaneous bioavailability. ART delivery to the blood (above 500 ng/ml) was proved by examining the sera from treated mice, using a bioassay in cultured Plasmodium falciparum. Skin spraying of ART-ME eliminated P. berghei ANKA in an infected mouse model of cerebral malaria (CM) and prevented CM, even after a late treatment with a relatively small amount of ART (13.3 mg/kg). For comparison, the artesunate (the most used commercial artemisinin) formulation was prepared as ART. However, ART-ME was about three times more efficient than artesunate-ME. The solubility and stability of ART in the ME, taken together with the successful transdermal delivery leading to animal recovery, suggest this formulation as a potential candidate for transdermal treatment of malaria.

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The Effects of Transdermally Delivered Oleanolic Acid on Malaria Parasites and Blood Glucose Homeostasis in P. berghei-Infected Male Sprague-Dawley Rats

Cited by 8 publications

References 39 publications

Investigation of antimalarial activity and cytotoxicity profiling of a Bangladeshi plant Syzygium cymosum

Investigation of antimalarial activity and cytotoxicity profiling of a Bangladeshi plant Syzygium cymosum

Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model

Transdermal delivery of artemisinins for treatment of pre-clinical cerebral malaria

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