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

Kwame Nkrumah University of Science and Technology
University of Cape Coast Ghana
University of Ghana

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

32 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
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Anti-malarial drug combinations
Artemisinins
Cryptolepine
Cryptolepis sanguinolenta
Malaria
Synergy

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10.1186/s12936-016-1137-5

Cite this

@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",

issn = "1475-2875",

publisher = "BioMed Central Ltd.",

number = "1",

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TY - JOUR

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

KW - Synergy

UR - https://www.scopus.com/pages/publications/84958151535

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DO - 10.1186/s12936-016-1137-5

M3 - Article

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AN - SCOPUS:84958151535

SN - 1475-2875

VL - 15

JO - Malaria Journal

JF - Malaria Journal

IS - 1

M1 - 89

ER -

Synergistic anti-malarial action of cryptolepine and artemisinins

Abstract

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Keywords

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