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Colin W. Wright - One of the best experts on this subject based on the ideXlab platform.
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recent advances in the chemistry and pharmacology of cryptolepine
Progress in the chemistry of organic natural products, 2021Co-Authors: Steven D Shnyder, Colin W. WrightAbstract:Cryptolepine, the principal constituent of the West African climbing shrub Cryptolepis sanguinolenta, continues to be of interest as a lead to new therapeutic agents, especially for the treatment of protozoal infections and cancer. This contribution reviews the research published in the last decade, highlighting new synthesis routes to cryptolepine and to analogs of this alkaloid, as well as their pharmacology. Studies relating to the use of C. sanguinolenta as an herbal medicine for the treatment of malaria are discussed, as well as the development of analogs of cryptolepine as leads to new agents for the treatment of malaria, trypanosomiasis, and cancer with an emphasis on the pharmacological mechanisms involved. Other potential therapeutic applications include antimicrobial, antidiabetic, and anti-inflammatory activities; the pharmacokinetics and toxicity of cryptolepine are also reviewed.
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in vitro anti malarial interaction and gametocytocidal activity of cryptolepine
Malaria Journal, 2017Co-Authors: Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W. WrightAbstract:Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations.
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In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine
'Springer Science and Business Media LLC', 2017Co-Authors: Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W. WrightAbstract:Abstract Background Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. Methods The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Results Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. Conclusions The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations
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Research Article Inhibition of Neuroinflammation in LPS-Activated
2016Co-Authors: Microglia Cryptolepine, Colin W. Wright, Olumayokun A. Olajide, Harsharan S. Bhatia, Antonio C. P. De Oliveira, Bernd L. FiebichAbstract:Copyright © 2013 Olumayokun A. Olajide et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited. Cryptolepine, an indoloquinoline alkaloid in Cryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS)- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment onmicroglial activation and production of proinflammatory mediators, PGE 2 /COX-2, microsomal prostaglandin
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Inhibition of Neuroinflammation in LPS-Activated Microglia by Cryptolepine
Hindawi Limited, 2013Co-Authors: Olumayokun A. Olajide, Colin W. Wright, Harsharan S. Bhatia, Antonio C. P. De Oliveira, Bernd L. FiebichAbstract:Cryptolepine, an indoloquinoline alkaloid in Cryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS)- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment on microglial activation and production of proinflammatory mediators, PGE2/COX-2, microsomal prostaglandin E2 synthase and nitric oxide/iNOS were investigated. We further elucidated the role of Nuclear Factor-kappa B (NF-κB) and the mitogen-activated protein kinases in the antiinflammatory actions of cryptolepine in LPS-stimulated microglia. Our results showed that cryptolepine significantly inhibited LPS-induced production of tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), nitric oxide, and PGE2. Protein and mRNA levels of COX-2 and iNOS were also attenuated by cryptolepine. Further experiments on intracellular signalling mechanisms show that IκB-independent inhibition of NF-κB nuclear translocation contributes to the anti-neuroinflammatory actions of cryptolepine. Results also show that cryptolepine inhibited LPS-induced p38 and MAPKAPK2 phosphorylation in the microglia. Cell viability experiments revealed that cryptolepine (2.5 and 5 μM) did not produce cytotoxicity in microglia. Taken together, our results suggest that cryptolepine inhibits LPS-induced microglial inflammation by partial targeting of NF-κB signalling and attenuation of p38/MAPKAPK2
Charles Ansah - One of the best experts on this subject based on the ideXlab platform.
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cryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin 6 stat3 signalling
BMC Complementary Medicine and Therapies, 2021Co-Authors: Seth A Domfeh, Charles Ansah, Patrick Williams Narkwa, Osbourne Quaye, Kwadwo A Kusi, Gordon A Awandare, Alimatu Salam, Mohamed MutocheluhAbstract:Diverse signalling pathways are involved in carcinogenesis and one of such pathways implicated in many cancers is the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signalling pathway. Therefore, inhibition of this pathway is targeted as an anti-cancer intervention. This study aimed to establish the effect of cryptolepine, which is the main bioactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, on the IL-6/STAT3 signalling pathway. First, the effect of cryptolepine on the IL-6/STAT3 pathway in human hepatoma cells (HepG2 cells) was screened using the Cignal Finder Multi-Pathway Reporter Array. Next, to confirm the effect of cryptolepine on the IL-6/STAT3 signalling pathway, the pathway was activated using 200 ng/mL IL-6 in the presence of 0.5–2 μM cryptolepine. The levels of total STAT3, p-STAT3 and IL-23 were assessed by ELISA. Cryptolepine downregulated 12 signalling pathways including the IL-6/STAT3 signalling pathway and upregulated 17 signalling pathways. Cryptolepine, in the presence of IL-6, decreased the levels of p-STAT3 and IL-23 in a dose-dependent fashion. Our results demonstrated that cryptolepine inhibits the IL-6/STAT3 signalling pathway, and therefore cryptolepine-based remedies such as Cryptolepis sanguinolenta could potentially be used as an effective immunotherapeutic agent for hepatocellular carcinoma and other cancers.
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cryptolepine the major alkaloid of Cryptolepis sanguinolenta lindl schlechter apocynaceae attenuates early and late phase symptoms of asthma
Scientific African, 2020Co-Authors: Paapa Mensahkane, Kwesi Boadu Mensah, Aaron Opoku Antwi, Arnold Donkor Forkuo, Charles AnsahAbstract:Abstract Aqueous root extract of Cryptolepis sanguinolenta has been used traditionally to treat many upper respiratory tract disorders. Besides its well-known broad spectrum antimicrobial activity, we had reasoned that cryptolepine can directly attenuate the symptoms of asthma. Therefore, this study evaluates cryptolepine, the main compound of the aqueous extract of Cryptolepis sanguinolenta, on early and late-phase symptoms of asthma attack. In the early phase study, isolated cryptolepine was evaluated on its ability to reverse histamine-induced bronchoconstriction and reduce histamine release from mast cells and bronchial mucus secretion. In the late phase study, cryptolepine was evaluated on its ability to affect airway inflammation and hypersensitivity as well as its ability to attenuate airway remodeling induced by ovalbumin. In the early asthma phase study, Cryptolepine (10–100 mg/kg) significantly and dose dependently inhibited Histamine-induced bronchoconstriction in guinea pigs. The protection lasted beyond 24 h. It also decreased the volume and optical density of bronchial secretions in mice. Cryptolepine (10–100 µg /mL) stabilized mesentery mast cells in vitro against Compound 48/80 -induced degranulation. In the late phase study, cryptolepine (10–100 mg/kg) prevented ovalbumin-induced airway obstruction and basal membrane smooth muscle hypertrophy. It significantly reduced systemic leukocytosis and inflammatory cell infiltration into airways in antigen-sensitized animals. Using the skin prick test, cryptolepine reduced the hypersensitivity to allergen challenge in antigen-sensitized animals. Cryptolepine's effects in the late phase was similar to dexamethasone (1 mg/kg) used as standard drug. Cryptolepine attenuates both early and late phase symptoms of asthma. It reduces bronchospasms, bronchial secretions, airway remodeling and hypersensitivity. This gives scientific credence to the traditional usage of Cryptolepis extracts in upper respiratory tract disorders.
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cryptolepine the main alkaloid of the antimalarial Cryptolepis sanguinolenta lindl schlechter induces malformations in zebrafish embryos
Biochemistry Research International, 2019Co-Authors: Kwesi Boadu Mensah, Arnold Donkor Forkuo, Charles Kwaku Benneh, Charles AnsahAbstract:Background. Previous studies on cryptolepine, the antimalarial and cytotoxic alkaloid of Cryptolepis sanguinolenta, showed that it preferentially accumulates in rapidly proliferating cells and melanin-containing tissues. Subsequently, we demonstrated that cryptolepine was toxic to murine embryos in vivo but no signs of teratogenicity. in vivo developmental studies can be confounded by maternal effects. Here, we hypothesized that cryptolepine-induced embryo toxicity occurs at least partly through direct inhibition of embryogenesis rather than indirectly through the induction of maternal toxicity. Aim. To determine the effects of cryptolepine on developing zebrafish embryos ex vivo. Methods. Healthy synchronized zebrafish eggs were treated with cryptolepine (10−1 − 5 × 102 μM), benzyl penicillin (6 − 6 × 102 μM), or mercury chloride (3.7 × 10−1 − 3.7 × 101 nM) from 6 to 72 hours postfertilization. Developing embryos were assessed at 24, 48, 72, and 96 hours under microscope for lethality, hatching rate, and malformation. Results. LC50 for cryptolepine in the study was found to be 260 ± 0.174 μM. Cryptolepine induced dose- and time-dependent mortality from the 24 to 96 hours postfertilization. Lower cryptolepine concentration (<100 μM) caused mortality, approximately 15–18%, only after the 48 hours postfertilization. The most sensitive period of embryo lethality corresponded well with the pharyngula (24 to 48 hours) and hatching (48 to 72 hours) stages of embryonic development. Cryptolepine (10−1 − 5 × 102 μM) dose dependently inhibited the hatching rate. At doses above 500 μM, hatching was completely inhibited. Mercury chloride (3.7 × 10−1 − 3.7 × 101 nM), used as positive control, induced a consistent pattern of embryo lethality at all stages of development, whereas benzyl penicillin (6 − 6 × 102 μM), used as negative control, did not induce any significant embryo lethality. Morphological examination of (postfertilization day 5) of eleutheroembryos treated during embryonic development with cryptolepine showed decreased body length (growth inhibition), decreased eye diameter and bulginess, enlarged pericardia, and enlarged yolk sac and muscle malformations. Conclusion. Cryptolepine induces malformations, growth retardation, and mortalities in rapidly dividing zebrafish embryos ex vivo.
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in vitro anti malarial interaction and gametocytocidal activity of cryptolepine
Malaria Journal, 2017Co-Authors: Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W. WrightAbstract:Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations.
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In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine
'Springer Science and Business Media LLC', 2017Co-Authors: Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W. WrightAbstract:Abstract Background Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. Methods The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Results Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. Conclusions The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations
Kwesi Boadu Mensah - One of the best experts on this subject based on the ideXlab platform.
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cryptolepine the major alkaloid of Cryptolepis sanguinolenta lindl schlechter apocynaceae attenuates early and late phase symptoms of asthma
Scientific African, 2020Co-Authors: Paapa Mensahkane, Kwesi Boadu Mensah, Aaron Opoku Antwi, Arnold Donkor Forkuo, Charles AnsahAbstract:Abstract Aqueous root extract of Cryptolepis sanguinolenta has been used traditionally to treat many upper respiratory tract disorders. Besides its well-known broad spectrum antimicrobial activity, we had reasoned that cryptolepine can directly attenuate the symptoms of asthma. Therefore, this study evaluates cryptolepine, the main compound of the aqueous extract of Cryptolepis sanguinolenta, on early and late-phase symptoms of asthma attack. In the early phase study, isolated cryptolepine was evaluated on its ability to reverse histamine-induced bronchoconstriction and reduce histamine release from mast cells and bronchial mucus secretion. In the late phase study, cryptolepine was evaluated on its ability to affect airway inflammation and hypersensitivity as well as its ability to attenuate airway remodeling induced by ovalbumin. In the early asthma phase study, Cryptolepine (10–100 mg/kg) significantly and dose dependently inhibited Histamine-induced bronchoconstriction in guinea pigs. The protection lasted beyond 24 h. It also decreased the volume and optical density of bronchial secretions in mice. Cryptolepine (10–100 µg /mL) stabilized mesentery mast cells in vitro against Compound 48/80 -induced degranulation. In the late phase study, cryptolepine (10–100 mg/kg) prevented ovalbumin-induced airway obstruction and basal membrane smooth muscle hypertrophy. It significantly reduced systemic leukocytosis and inflammatory cell infiltration into airways in antigen-sensitized animals. Using the skin prick test, cryptolepine reduced the hypersensitivity to allergen challenge in antigen-sensitized animals. Cryptolepine's effects in the late phase was similar to dexamethasone (1 mg/kg) used as standard drug. Cryptolepine attenuates both early and late phase symptoms of asthma. It reduces bronchospasms, bronchial secretions, airway remodeling and hypersensitivity. This gives scientific credence to the traditional usage of Cryptolepis extracts in upper respiratory tract disorders.
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cryptolepine the main alkaloid of the antimalarial Cryptolepis sanguinolenta lindl schlechter induces malformations in zebrafish embryos
Biochemistry Research International, 2019Co-Authors: Kwesi Boadu Mensah, Arnold Donkor Forkuo, Charles Kwaku Benneh, Charles AnsahAbstract:Background. Previous studies on cryptolepine, the antimalarial and cytotoxic alkaloid of Cryptolepis sanguinolenta, showed that it preferentially accumulates in rapidly proliferating cells and melanin-containing tissues. Subsequently, we demonstrated that cryptolepine was toxic to murine embryos in vivo but no signs of teratogenicity. in vivo developmental studies can be confounded by maternal effects. Here, we hypothesized that cryptolepine-induced embryo toxicity occurs at least partly through direct inhibition of embryogenesis rather than indirectly through the induction of maternal toxicity. Aim. To determine the effects of cryptolepine on developing zebrafish embryos ex vivo. Methods. Healthy synchronized zebrafish eggs were treated with cryptolepine (10−1 − 5 × 102 μM), benzyl penicillin (6 − 6 × 102 μM), or mercury chloride (3.7 × 10−1 − 3.7 × 101 nM) from 6 to 72 hours postfertilization. Developing embryos were assessed at 24, 48, 72, and 96 hours under microscope for lethality, hatching rate, and malformation. Results. LC50 for cryptolepine in the study was found to be 260 ± 0.174 μM. Cryptolepine induced dose- and time-dependent mortality from the 24 to 96 hours postfertilization. Lower cryptolepine concentration (<100 μM) caused mortality, approximately 15–18%, only after the 48 hours postfertilization. The most sensitive period of embryo lethality corresponded well with the pharyngula (24 to 48 hours) and hatching (48 to 72 hours) stages of embryonic development. Cryptolepine (10−1 − 5 × 102 μM) dose dependently inhibited the hatching rate. At doses above 500 μM, hatching was completely inhibited. Mercury chloride (3.7 × 10−1 − 3.7 × 101 nM), used as positive control, induced a consistent pattern of embryo lethality at all stages of development, whereas benzyl penicillin (6 − 6 × 102 μM), used as negative control, did not induce any significant embryo lethality. Morphological examination of (postfertilization day 5) of eleutheroembryos treated during embryonic development with cryptolepine showed decreased body length (growth inhibition), decreased eye diameter and bulginess, enlarged pericardia, and enlarged yolk sac and muscle malformations. Conclusion. Cryptolepine induces malformations, growth retardation, and mortalities in rapidly dividing zebrafish embryos ex vivo.
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in vitro anti malarial interaction and gametocytocidal activity of cryptolepine
Malaria Journal, 2017Co-Authors: Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W. WrightAbstract:Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations.
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phytochemical and pharmacological review of Cryptolepis sanguinolenta lindl schlechter
Advances in Pharmacological Sciences, 2017Co-Authors: Newman Osafo, Kwesi Boadu Mensah, Oduro Kofi YeboahAbstract:Ethnopharmacological Relevance. Cryptolepis sanguinolenta is a scrambling thin-stemmed shrub found in Africa. Traditionally in West Africa, it is employed in the treatment of malaria, diarrhea, and respiratory conditions. This review discusses the traditional importance as well as the phytochemical, ethnomedical, pharmacological, and toxicological importance of this plant. Materials and Methods. Excerpta Medica Database, Google Scholar, Springer, and PubMed Central were the electronic databases used to search for and filter primary studies on Cryptolepis sanguinolenta. Results. The detailed review of various studies conducted on C. sanguinolenta and some of its constituents gives an important body of proof of its potential therapeutic benefits and also of its use as a source of lead compounds with therapeutic potentials. Conclusion. The review on C. sanguinolenta is important in identifying grey areas in the research on this medicinal plant and also provides comprehensive data thus far to continue research on this plant.
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In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine
'Springer Science and Business Media LLC', 2017Co-Authors: Arnold Donkor Forkuo, Charles Ansah, Kwesi Boadu Mensah, Kofi Annan, Ben Gyan, Anjo Theron, Dalu Mancama, Colin W. WrightAbstract:Abstract Background Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. Methods The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Results Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. Conclusions The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations
A J Vlietinck - One of the best experts on this subject based on the ideXlab platform.
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antibacterial and antifungal activities of neocryptolepine biscryptolepine and cryptoquindoline alkaloids isolated from Cryptolepis sanguinolenta
Phytomedicine, 1998Co-Authors: T. De Bruyne, Luc Pieters, J. Totté, D Vanden Berghe, A J VlietinckAbstract:From the 80% EtOH extract of Cryptolepis sanguinolenta (Lindl.) Schlechter (Periplocaeae) root bark, a cryptolepine isomer named neocryptolepine, and two dimeric alkaloids named biscryptolepine and cryptoquindoline were isolated. These compounds were tested for their putative antibacterial and antifungal activities. Results have indicated that neocryptolepine showed an antibacterial activity against Gram-positive bacteria (MIC < 100 μg/ml), but was less acive against Gram-negative bacteria. It also inhibited the growth of the yeast C. albicans. Biscryptolepine exhibited only an activity against some Gram-positive bacteria (MIC = 62.5 or 31 μg/ml) while cryptoquindoline did not shown an activity against all selected microorganisms. The antibacterial activity of neocryptolepine and biscryptolepine is bacteriostatic rather than bactericidal. No antifungal activity could be observed for all alkaloids in our test system at the highest test concentration of 100 μg/ml.
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in vitro and in vivo antiplasmodial activity of cryptolepine and related alkaloids from Cryptolepis sanguinolenta
Journal of Natural Products, 1997Co-Authors: T. De Bruyne, Luc Pieters, A J Vlietinck, C A TurgerAbstract:Three different extracts and four alkaloids from the root bark of Cryptolepis sanguinolenta have been assessed in vitro against Plasmodium falciparum D-6 (chloroquine-sensitive strain), K-1, and W-2 (chloroquine-resistant strains). Cryptolepine (1) and its hydrochloride (2), 11-hydroxycryptolepine (3), and neocryptolepine (5) showed a strong antiplasmodial activity against P. falciparum chloroquine-resistant strains. Quindoline (4) was less active. The highest activity was obtained with compound 1. In vivo tests on infected mice showed that crytpolepine (1), when tested as its hydrochloride (2), exhibited a significant chemosuppressive effect against Plasmodium berghei yoelii and Plasmodium berghei berghei, while 1 had the same effect against P. berghei yoelii only. Compounds 3 and 4 did not show activity in this in vivo test system.
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new alkaloids from Cryptolepis sanguinolenta
Tetrahedron Letters, 1996Co-Authors: T. De Bruyne, Luc Pieters, M Claeys, A J VlietinckAbstract:Neocryptolepine and biscryptolepine, two new alkaloids, were isolated from the root bark extract of the African medicinal plant, Cryptolepis sanguinolenta (Lindl.) Schlechter (Periplocaceae), and their structures elucidated on the basis of spectral evidence. The 1H and 13C NMR assignments of cryptoquindoline, a known artefact, were revised.
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in vitro biological activities of alkaloids from Cryptolepis sanguinolenta
Planta Medica, 1996Co-Authors: T. De Bruyne, Luc Pieters, M Claeys, A Lasure, Bart Van Poel, Dirk Vanden Berghe, A J VlietinckAbstract:In our biological screening of higher plants, an aqueous and an 80% EtOH extract from the root bark of Cryptolepis sanguinolenta showed potent antibacterial, anticomplementary, and moderate antiviral activities, but no antifungal effect could be detected. Bioassay-guided fractionation of the 80% EtOH extract led to the isolation of three alkaloids: quindoline (1), hydroxycryptolepine (2), cryptolepine.HCl (3), and the corresponding base cryptolepine (4). All compounds strongly inhibited the growth of Gram-positive bacteria (MIC 500 micrograms/ml) against selected Gram-negative bacteria. They also possessed a bactericidal effect depending on the bacterial strain. Compounds 1, 2 and 3 displayed a dose-dependent inhibitory effect on the classical pathway of the complement system while compounds 2 and 3 activated the alternative pathway, except for compound 1. Compound 3 was found to possess an antiherpetic activity. Compounds 1 and 4 showed no antiviral effect, but were quite cytotoxic in the antiviral test system down to a concentration of 1 microgram/ml.
Luc Pieters - One of the best experts on this subject based on the ideXlab platform.
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interactions of cryptolepine and neocryptolepine with unusual dna structures
Biochimie, 2003Co-Authors: Lionel Guittat, Luc Pieters, Patrizia Alberti, Frederic Rosu, Sabine Van Miert, Emilie Thetiot, Valerie Gabelica, Edwin De Pauw, Alexandre Ottaviani, Jeanfrancois RiouAbstract:Cryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures among duplexes, triplexes, quadruplexes and single strands. Our data confirm that cryptolepine and neocryptolepine prefer GC over AT-rich duplex sequences, but also recognize triplex and quadruplex structures. These compounds are weak telomerase inhibitors and exhibit a significant preference for triplexes over quadruplexes or duplexes.
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inhibitors of xanthine oxidase and scavengers of superoxide anions from Cryptolepis sanguinolenta lindl schlechter periplocaceae
Pharmacy and Pharmacology Communications, 2000Co-Authors: T. De Bruyne, Sandra Apers, Luc Pieters, Paul Cos, P Bakana, D Vanden BergheAbstract:Cryptolepis sanguinolenta (Lindl.) Schlechter (Periplocaceae) is a medicinal plant used in some African countries against infectious and parasitic diseases. Six of its constituent alkaloids have been isolated from the root bark, identified spectroscopically as cryptoquindolinine (1), quindoline (2), neocryptolepine (3), cryptolepine (4), 11-hydroxycryptolepine (5) and biscryptolepine (6), and their interaction with the xanthine-xanthine oxidase enzyme system has been tested. Compound 5 has been shown to inhibit xanthine oxidase and act as a scavenger of superoxide anions. Alkaloids 1–4 and 6 were devoid of effect in both assays at the highest test concentration of 100 mM. These findings suggest the importance, in the manifestation of both activities, of the hydroxyl group present in 5 but not in the other alkaloids.
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Antimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa, Congo.
Journal of Ethnopharmacology, 1999Co-Authors: L. Tona, N.p. Ngimbi, M. Tsakala, K. Mesia, K. Cimanga, Sandra Apers, T. De Bruyne, Luc Pieters, J. Totté, Arnold J. VlietinckAbstract:Twenty extracts including ten EtOH and ten CH2Cl2 from different parts of nine African medicinal plants used in Congolese traditional medicine for the treatment of malaria, were submitted to a pharmacological test in order to evaluate their effect on P. falciparum growth in vitro. Of these plant species, 14 (70%) extracts including EtOH and CH2Cl2 from Cassia occidentalis leaves, Cryptolepis sanguinolenta root bark, Euphorbia hirta whole plant, Garcinia kola stem bark and seeds, Morinda lucida leaves and Phyllanthus niruri whole plant produced more than 60% inhibition of the parasite growth in vitro at a test concentration of 6 microg/ml. Extracts from E. hirta, C. sanguinolenta and M. morindoides showed a significant chemosuppression of parasitaemia in mice infected with P. berghei berghei at orally given doses of 100-400 mg/kg per day.
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antibacterial and antifungal activities of neocryptolepine biscryptolepine and cryptoquindoline alkaloids isolated from Cryptolepis sanguinolenta
Phytomedicine, 1998Co-Authors: T. De Bruyne, Luc Pieters, J. Totté, D Vanden Berghe, A J VlietinckAbstract:From the 80% EtOH extract of Cryptolepis sanguinolenta (Lindl.) Schlechter (Periplocaeae) root bark, a cryptolepine isomer named neocryptolepine, and two dimeric alkaloids named biscryptolepine and cryptoquindoline were isolated. These compounds were tested for their putative antibacterial and antifungal activities. Results have indicated that neocryptolepine showed an antibacterial activity against Gram-positive bacteria (MIC < 100 μg/ml), but was less acive against Gram-negative bacteria. It also inhibited the growth of the yeast C. albicans. Biscryptolepine exhibited only an activity against some Gram-positive bacteria (MIC = 62.5 or 31 μg/ml) while cryptoquindoline did not shown an activity against all selected microorganisms. The antibacterial activity of neocryptolepine and biscryptolepine is bacteriostatic rather than bactericidal. No antifungal activity could be observed for all alkaloids in our test system at the highest test concentration of 100 μg/ml.
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in vitro and in vivo antiplasmodial activity of cryptolepine and related alkaloids from Cryptolepis sanguinolenta
Journal of Natural Products, 1997Co-Authors: T. De Bruyne, Luc Pieters, A J Vlietinck, C A TurgerAbstract:Three different extracts and four alkaloids from the root bark of Cryptolepis sanguinolenta have been assessed in vitro against Plasmodium falciparum D-6 (chloroquine-sensitive strain), K-1, and W-2 (chloroquine-resistant strains). Cryptolepine (1) and its hydrochloride (2), 11-hydroxycryptolepine (3), and neocryptolepine (5) showed a strong antiplasmodial activity against P. falciparum chloroquine-resistant strains. Quindoline (4) was less active. The highest activity was obtained with compound 1. In vivo tests on infected mice showed that crytpolepine (1), when tested as its hydrochloride (2), exhibited a significant chemosuppressive effect against Plasmodium berghei yoelii and Plasmodium berghei berghei, while 1 had the same effect against P. berghei yoelii only. Compounds 3 and 4 did not show activity in this in vivo test system.