Synergistic anti-malarial action of cryptolepine and artemisinins

Arnold D. Forkuo; Charles Ansah; Kwesi M. Boadu; Johnson N. Boampong; Elvis O. Ameyaw; Ben A. Gyan; Andrea T. Arku; Michael F. Ofori

doi:10.1186/s12936-016-1137-5

Synergistic anti-malarial action of cryptolepine and artemisinins

Arnold D. Forkuo, Charles Ansah, Kwesi M. Boadu, Johnson N. Boampong, Elvis O. Ameyaw, Ben A. Gyan, Andrea T. Arku, Michael F. Ofori

Department of Immunology

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Background: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. Methods: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED₅₀s in order to determine the experimental ED₅₀ (Z_exp) of the co-administered compounds. Isobolograms were constructed to compare the Z_exp to the Z_add. Results: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Z_add of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg^-1 po) and in combination with ART (4 mg kg^-1) showed no significant difference compared to the control group. Conclusion: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.

Original language	English
Article number	89
Journal	Malaria Journal
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12936-016-1137-5
Publication status	Published - 16 Feb 2016

Keywords

Anti-malarial drug combinations
Artemisinins
Cryptolepine
Cryptolepis sanguinolenta
Malaria
Synergy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12936-016-1137-5

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@article{8d736c08ec624655bad1a11ddaaadbdf,

title = "Synergistic anti-malarial action of cryptolepine and artemisinins",

abstract = "Background: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. Methods: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. Results: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg-1 po) and in combination with ART (4 mg kg-1) showed no significant difference compared to the control group. Conclusion: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.",

keywords = "Anti-malarial drug combinations, Artemisinins, Cryptolepine, Cryptolepis sanguinolenta, Malaria, Synergy",

author = "Forkuo, {Arnold D.} and Charles Ansah and Boadu, {Kwesi M.} and Boampong, {Johnson N.} and Ameyaw, {Elvis O.} and Gyan, {Ben A.} and Arku, {Andrea T.} and Ofori, {Michael F.}",

note = "Publisher Copyright: {\textcopyright} 2016 Forkuo et al.",

year = "2016",

month = feb,

day = "16",

doi = "10.1186/s12936-016-1137-5",

language = "English",

volume = "15",

journal = "Malaria Journal",

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T1 - Synergistic anti-malarial action of cryptolepine and artemisinins

AU - Forkuo, Arnold D.

AU - Ansah, Charles

AU - Boadu, Kwesi M.

AU - Boampong, Johnson N.

AU - Ameyaw, Elvis O.

AU - Gyan, Ben A.

AU - Arku, Andrea T.

AU - Ofori, Michael F.

PY - 2016/2/16

Y1 - 2016/2/16

N2 - Background: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. Methods: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. Results: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg-1 po) and in combination with ART (4 mg kg-1) showed no significant difference compared to the control group. Conclusion: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.

AB - Background: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. Methods: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. Results: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg-1 po) and in combination with ART (4 mg kg-1) showed no significant difference compared to the control group. Conclusion: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.

KW - Anti-malarial drug combinations

KW - Artemisinins

KW - Cryptolepine

KW - Cryptolepis sanguinolenta

KW - Malaria

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Synergistic anti-malarial action of cryptolepine and artemisinins

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Keywords

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