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1.
Prog Chem Org Nat Prod ; 115: 177-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33797643

RESUMO

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.


Assuntos
Alcaloides , Quinolinas , Alcaloides/farmacologia , Cryptolepis , Alcaloides Indólicos/farmacologia
2.
Front Cell Infect Microbiol ; 11: 624745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763384

RESUMO

Human babesiosis is a CDC reportable disease in the United States and is recognized as an emerging health risk in multiple parts of the world. The current treatment for human babesiosis is suboptimal due to treatment failures and unwanted side effects. Although Babesia duncani was first described almost 30 years ago, further research is needed to elucidate its pathogenesis and clarify optimal treatment regimens. Here, we screened a panel of herbal medicines and identified Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Alchornea cordifolia, and Polygonum cuspidatum to have good in vitro inhibitory activity against B. duncani in the hamster erythrocyte model. Furthermore, we found their potential bioactive compounds, cryptolepine, artemisinin, artesunate, artemether, and baicalein, to have good activity against B. duncani, with IC50 values of 3.4 µM, 14 µM, 7.4 µM, 7.8 µM, and 12 µM, respectively, which are comparable or lower than that of the currently used drugs quinine (10 µM) and clindamycin (37 µM). B. duncani treated with cryptolepine and quinine at their respective 1×, 2×, 4× and 8× IC50 values, and by artemether at 8× IC50 for three days could not regrow in subculture. Additionally, Cryptolepis sanguinolenta 90% ethanol extract also exhibited no regrowth after 6 days of subculture at doses of 2×, 4×, and 8× IC50 values. Our results indicate that some botanical medicines and their active constituents have potent activity against B. duncani in vitro and may be further explored for more effective treatment of babesiosis.


Assuntos
Artemisia annua , Babesia , Euphorbiaceae , Fallopia japonica , Animais , Cricetinae , Cryptolepis , Humanos , Extratos Vegetais , Scutellaria baicalensis
3.
Biomed Pharmacother ; 137: 111354, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561642

RESUMO

Following the high treatment gap and massive impact of epilepsy on global health particularly in low- and middle-income countries, our study aims to investigate cryptolepine, the major alkaloid of Cryptolepis sanguinolenta as well as its solid-lipid nanoparticle formulation for potential antiseizure activity. Cryptolepine was isolated and a solid-lipid formulation was prepared. Antiseizure activity of Solid-Lipid Nanoparticle formulation of cryptolepine (SLN-CRYP) was investigated using Pentylenetetrazole (PTZ)-induced model of seizure-like behaviors in Zebrafish with 2.5 and 5 mg/kg each of cryptolepine and SLN-CRYP. Drug receptor binding and permeability of the compound across the Blood Brain Barrier (BBB) were also assessed. SLN formulation of cryptolepine increased its permeability to the BBB from 0.32 × 10-6 cm/s to 10.81 × 10-6 cm/s. 2.5 and 5 mg/kg of SLN-CRYP significantly reduced mean seizure score (P = 0.0018; F(6, 63) = 23.52) and significantly increased (P < 0.0001; F(6, 63) = 65.41) latency to onset of seizures. The total distance swam by fish administered with 2.5 and 5 mg/kg of SLN-CRYP was significantly (P < 0.000; F(6, 63) = 161.9) decreased. 5 mg/kg of cryptolepine also significantly decreased swimming distance. Cryptolepine exhibited inhibitory modulation of human voltage-gated calcium channels (Cav1.2), H1-receptor, Peripheral Benzodiazepine Receptor and Sigma 2 receptor with a high Ki values of 6133.38 nM and 2945.0 nM, indicating less potent antagonism on Cav1.2 and Sigma 2 receptors compared to Nifedipine and Haloperidol respectively. This study reveals that the solid-lipid nanoparticle formulation of cryptolepine improves its BBB permeability and hence antiseizure activity.


Assuntos
Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Nanopartículas , Quinolinas/química , Quinolinas/farmacologia , Animais , Anticonvulsivantes/administração & dosagem , Barreira Hematoencefálica , Convulsivantes , Cryptolepis/química , Composição de Medicamentos , Alcaloides Indólicos/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , Pentilenotetrazol , Quinolinas/administração & dosagem , Receptores de Droga/metabolismo , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Natação , Peixe-Zebra
4.
Biomed Res Int ; 2020: 5324560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029513

RESUMO

The ongoing global pandemic caused by the human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions of people and claimed hundreds of thousands of lives. The absence of approved therapeutics to combat this disease threatens the health of all persons on earth and could cause catastrophic damage to society. New drugs are therefore urgently required to bring relief to people everywhere. In addition to repurposing existing drugs, natural products provide an interesting alternative due to their widespread use in all cultures of the world. In this study, alkaloids from Cryptolepis sanguinolenta have been investigated for their ability to inhibit two of the main proteins in SARS-CoV-2, the main protease and the RNA-dependent RNA polymerase, using in silico methods. Molecular docking was used to assess binding potential of the alkaloids to the viral proteins whereas molecular dynamics was used to evaluate stability of the binding event. The results of the study indicate that all 13 alkaloids bind strongly to the main protease and RNA-dependent RNA polymerase with binding energies ranging from -6.7 to -10.6 kcal/mol. In particular, cryptomisrine, cryptospirolepine, cryptoquindoline, and biscryptolepine exhibited very strong inhibitory potential towards both proteins. Results from the molecular dynamics study revealed that a stable protein-ligand complex is formed upon binding. Alkaloids from Cryptolepis sanguinolenta therefore represent a promising class of compounds that could serve as lead compounds in the search for a cure for the corona virus disease.


Assuntos
Alcaloides/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Cryptolepis/química , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/antagonistas & inibidores , Alcaloides/química , Antivirais/química , Antivirais/farmacologia , Betacoronavirus/enzimologia , COVID-19 , Simulação por Computador , Proteases 3C de Coronavírus , Infecções por Coronavirus/virologia , RNA-Polimerase RNA-Dependente de Coronavírus , Cisteína Endopeptidases , Avaliação Pré-Clínica de Medicamentos , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Pneumonia Viral/virologia , Relação Quantitativa Estrutura-Atividade , Quinolinas/química , Quinolinas/farmacologia , RNA Polimerase Dependente de RNA/antagonistas & inibidores , SARS-CoV-2 , Proteínas não Estruturais Virais/antagonistas & inibidores
5.
Tuberculosis (Edinb) ; 124: 101987, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32841928

RESUMO

Regimens of current drugs for tuberculosis are lengthy and are associated with many adverse effects. Currently, the emergence of different resistant strains has been observed. This urges a need for the discovery and development of novel drugs. The main sources of drug lead candidates are based on natural products. Zanthoxylum leprieurii, Lantana camara, and Cryptolepis Sanguinolenta are among the plants that have antimycobacterial activity. Recent technological methods, such as metabolomics, can rapidly detect and identify active compounds from medicinal plants. In this review, we aim to provide an overview and discussion of the antimycobacterial activity, phytochemical analysis and toxicity profile of these plants and their products as well as the potential of metabolomic fingerprinting of medicinal plants with a given activity on microbes, in the search for the potential drug hit molecules. The information for this review was extracted from databases such as Excerpta Medica Database, Google Scholar, Springer, and PubMed Central. Primary studies, using a combination of the keywords antimycobacterial medicinal plant, multidrug-resistant tuberculosis, phytochemistry, toxicity, Zanthoxylum leprieurii, Lantana camara, Cryptolepis sanguinolenta, and plant metabolomics/metabolic fingerprinting of plant extracts, have been considered. The above-mentioned plant species showed antimycobacterial activity against drug-resistant strains of M. tuberculosis. They may provide potential candidates for novel drugs against multidrug-resistant tuberculosis. However, extensive work is still needed. To our knowledge, there is no or limited literature that reports the metabolic fingerprints of these plants. The analysis of the metabolite fingerprints of medicinal plants with similar antimicrobial activity could be important to determine whether the activity results from common metabolites within different plant species. This review shows that these plants are potential candidates to provide drug hits against multidrug-resistant tuberculosis strains. Future studies of compound optimization, in vivo safety and efficacy, as well as of the specific mechanisms of action are however required.


Assuntos
Antituberculosos/farmacologia , Metaboloma , Mycobacterium tuberculosis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/metabolismo , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Animais , Antituberculosos/isolamento & purificação , Cryptolepis/metabolismo , Humanos , Lantana/metabolismo , Metabolômica , Mycobacterium tuberculosis/patogenicidade , Extratos Vegetais/isolamento & purificação , Metabolismo Secundário , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Zanthoxylum/metabolismo
6.
Phytother Res ; 34(7): 1556-1569, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32022345

RESUMO

Malaria is one of the life-threatening parasitic diseases that is endemic in tropical areas. The increased prevalence of malaria due to drug resistance leads to a high incidence of mortality. Drug discovery based on natural products and secondary metabolites is considered as alternative approaches for antimalarial therapy. Herbal medicines have advantages over modern medicines, including fewer side effects, cost-effectiveness, and affordability encouraging the herbal-based drug discovery. Several naturally occurring, semisynthetic, and synthetic antimalarial medications are on the market. For example, chloroquine is a synthetic medication for antimalarial therapy derived from quinine. Moreover, artemisinin, and its derivative, artesunate with sesquiterpene lactone backbone, is an antimalarial agent originated from Artemisia annua L. A. annua traditionally has been used to detoxify blood and eliminate fever in China. Although the artemisinin-based combination therapy against malaria has shown exceptional responses, the limited medicinal options demand novel therapeutics. Furthermore, drug resistance is the cause in most cases, and new medications are proposed to overcome the resistance. In addition to conventional therapeutics, this review covers some important genera in this area, including Artemisia, Cinchona, Cryptolepis, and Tabebuia, whose antimalarial activities are finely verified.


Assuntos
Antimaláricos/uso terapêutico , Artemisia/química , Cinchona/química , Cryptolepis/química , Malária/tratamento farmacológico , Plantas Medicinais/química , Tabebuia/química , Antimaláricos/farmacologia , Humanos
7.
J Ethnopharmacol ; 254: 112683, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32087321

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthosicyos naudininus, Gomphocarpus fruticosus, and Cryptolepis decidua are, according to the knowledge of traditional healers, used in Namibia to treat inflammatory disorders such as pain, fever and skin rashes. AIM OF THE STUDY: The present study was conducted to evaluate the immunomodulatory effects and the possible underlying mechanisms of action of the plant extracts on peripheral blood mononuclear cells (PBMCs) such as T-lymphocytes. MATERIALS AND METHODS: Methanolic and EtOAc extracts of A. naudinianus, G. fruticosus and C. decidua were analysed for their immunomodulatory potential. PBMCs were isolated from the blood of healthy donors and incubated with the plant extracts at concentrations 100, 30, 10, 3, 1 and 0.3 µg/mL. Effects on proliferation and viability of activated human lymphocytes were assessed in comparison to ciclosporin A by flow cytometry using carboxyfluorescein succinimidyl ester (CFSE) and WST-1 assay. Flow cytometry by annexin V/propidium iodide (PI) staining was performed to investigate the necrotic/apoptotic effect of the plant extracts on mitogen-activated human lymphocytes. In addition, analysis of the influence of plant extracts on the regulatory mechanisms of T-lymphocytes was performed using activation marker and cytokine production assays. An HPLC-PDA-ELSD-ESIMS profile was recorded for each of the extracts. RESULTS: T-lymphocyte proliferation was inhibited in a dose-dependent manner by the extracts of A. naudinianus, G. fruticosus, and C. decidua in concentrations not causing apoptosis or necrosis. This effect was mediated by inhibition of lymphocyte activation, specifically the suppression of CD25 and CD69 surface receptor expression. Moreover, the extracts suppressed effector functions, as indicated by reduced production of IFN-γ and IL-2. Based on the HPLC profile, possible responsible compound classes could be identified for the extracts of A. naudinianus (cucurbitacins) and C. decidua (indole alkaloids), but not for G. fruticosus. CONCLUSIONS: The data show that the extracts of A. naudinianus, G. fruticosus and C. decidua have in vitro immunomodulatory activity and they interfere with the function of immunocompetent cells, suggesting an anti-inflammatory mode-of-action. The present chemical determination and pattern recognition results explain the therapeutic potency. However, further studies to investigate the therapeutic potential of the plants in inflammatory disorders should be done.


Assuntos
Anti-Inflamatórios/farmacologia , Apocynaceae/química , Cryptolepis/química , Imunomodulação/efeitos dos fármacos , Magnoliopsida/química , Extratos Vegetais/farmacologia , Anti-Inflamatórios/química , Apoptose/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Ciclosporina/farmacologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Namíbia , Extratos Vegetais/química , Linfócitos T/metabolismo , Linfócitos T/fisiologia
8.
Drug Res (Stuttg) ; 68(12): 717-724, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29945275

RESUMO

BACKGROUND: The effects of methanol extract of Parquetina nigrescens were studied on histomorphometry and protein expression (SDS-PAGE) from the ovaries and uteri of wistar rats. METHODS: 30 sexually matured rats were used for the study with 10 each in the control and treatment 100 mgkg-1 and 400 mgkg-1 groups. The extract was orally administered for 14 days. Histological sections of tissues collected presented no abnormalities. RESULTS: An increase in the number of developing and matured follicles were observed during the study in the treated groups compared to the control in the follicular and the luteal phases. The corpora lutea in the treated groups were fewer in number to that of the control in the follicular phase and in the luteal phase. Sections of the uterine horns showed significant narrowing in the lumen diameter and increases in epithelial height with increased laydown of the lamina propria in the treated groups. The expression of protein bands fractionated during the study, confirm the presence of proteins expressed repeatedly from the ovary and uterine horns in the follicular and luteal phases at the 70 kDa and 63 kDa regions. CONCLUSIONS: The study concluded that the methanol extract of the plant increased folliculogenesis on the ovary, secretory activity in the nuclei of the epithelium and the fibroplasia of the lamina propria while narrowing the lumen of the uterine horns which are similar to the effects of oestrogen or oestrogen-like substances on these reproductive organs and may have an effect on the abundance of protein expressed in the follicular phase.


Assuntos
Cryptolepis/química , Ovário/efeitos dos fármacos , Extratos Vegetais/farmacologia , Útero/efeitos dos fármacos , Administração Oral , Animais , Feminino , Fase Luteal/efeitos dos fármacos , Metanol/química , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Ovário/anatomia & histologia , Ovário/metabolismo , Folhas de Planta/química , Ratos , Ratos Wistar , Útero/anatomia & histologia , Útero/metabolismo
9.
Malar J ; 17(1): 153, 2018 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618354

RESUMO

BACKGROUND: Increasing resistance to current anti-malarial therapies requires a renewed effort in searching for alternative therapies to combat this challenge, and combination therapy is the preferred approach to address this. The present study confirms the anti-plasmodial effects of two compounds, cryptolepine and xylopic acid and the relationship that exists in their combined administration determined. METHODS: Anti-plasmodial effect of cryptolepine (CYP) (3, 10, 30 mg kg-1) and xylopic acid (XA) (3, 10, 30 mg kg-1) was evaluated in Plasmodium berghei-infected male mice after a 6-day drug treatment. The respective doses which produced 50% chemosuppression (ED50) was determined by iterative fitting of the log-dose responses of both drugs. CYP and XA were then co-administered in a fixed dose combination of their ED50s (1:1) as well as different fractions of these combinations (1/2, 1/4, 1/8, 1/16 and 1/32) to find the experimental ED50 (Zexp). The nature of interaction between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Zexp with the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs associated with malarial parasiticidal action was assessed. RESULTS: The Zadd and Zexp were determined to be 12.75 ± 0.33 and 2.60 ± 0.41, respectively, with an interaction index of 0.2041. The Zexp was significantly (P < 0.001) below the additive isobole indicating that co-administration of cryptolepine and xylopic acid yielded a synergistic anti-plasmodial effect. This observed synergistic antiplasmodial effect did not have any significant deleterious effect on the kidney, liver and spleen. However, the testis were affected at high doses. CONCLUSION: The co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with minimal toxicity.


Assuntos
Antimaláricos/administração & dosagem , Diterpenos do Tipo Caurano/administração & dosagem , Alcaloides Indólicos/administração & dosagem , Plasmodium berghei/efeitos dos fármacos , Quinolinas/administração & dosagem , Animais , Cryptolepis/química , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Camundongos/parasitologia , Camundongos Endogâmicos ICR/parasitologia , Extratos Vegetais/farmacologia , Xylopia/química
10.
BMC Complement Altern Med ; 18(1): 86, 2018 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-29530027

RESUMO

BACKGROUND: Khaya grandifoliola (C.D.C.) stem bark, Cymbopogon citratus (Stapf) and Cryptolepis sanguinolenta (Lindl.) Schltr leaves are used in Cameroonian traditional medicine for the treatment of inflammatory diseases. Several studies have been performed on the biological activities of secondary metabolites extracted from these plants. However, to the best of our knowledge, the anti-neuro inflammatory and protective roles of the polysaccharides of these three plants have not yet been elucidated. This study aimed at investigating potential use of K. grandifoliola, C. sanguinolenta and C. citratus polysaccharides in the prevention of chronic inflammation. METHODS: Firstly, the composition of polysaccharide fractions isolated from K. grandifoliola stem bark (KGF), C. sanguinolenta (CSF) and C. citratus (CCF) leaves was assessed. Secondly, the cytotoxicity was evaluated on Raw 264.7 macrophages and U87-MG glioblastoma cell lines by the MTT assay. This was followed by the in vitro evaluation of the ability of KGF, CSF and CCF to inhibit lipopolysaccharides (LPS) induced overproduction of various pro-inflammatory mediators (NO, ROS and IL1ß, TNFα, IL6, NF-kB cytokines). This was done in Raw 264.7 and U87-MG cells. Finally, the in vitro protective effect of KGF, CSF and CCF against LPS-induced toxicity in the U87-MG cells was evaluated. RESULTS: CCF was shown to mostly contain sugar and no polyphenol while KGP and CSP contained very few amounts of these metabolites (≤ 2%). The three polysaccharide fractions were non-toxic up to 100 µg.mL- 1. All the polysaccharides at 10 µg/mL inhibited NO production, but only KGF and CCF at 12.5 µg/mL down-regulated LPS-induced ROS overproduction. Finally, 100 µg/mL LPS reduced 50% of U87 cell viability, and pre-treatment with the three polysaccharides significantly increased the proliferation. CONCLUSION: These results suggest that the polysaccharides of K. grandifoliola, C. citratus and C. sanguinolenta could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.


Assuntos
Cryptolepis/química , Cymbopogon/química , Glioblastoma/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Meliaceae/química , Doenças Neurodegenerativas/tratamento farmacológico , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/imunologia , Glioblastoma/fisiopatologia , Humanos , Lipopolissacarídeos/efeitos adversos , Macrófagos/imunologia , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia , Folhas de Planta/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
11.
J Diet Suppl ; 15(3): 269-284, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-28800275

RESUMO

Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined. Dichlorvos exposure caused a significant decrease in L-glutathione (reduced glutathione) and other antioxidant enzymes with increases in malondialdehyde, myeloperoxidase, advanced oxidation protein products, and protein carbonyl levels. It also brought about alterations in microanatomy of the heart and kidneys accompanied by increases in serum creatinine and urea levels. Exposure to dichlorvos induced prolonged QRS interval and shortened QT durations in rats. Immunohistochemistry revealed lower expressions of cardiac nitrotyrosine and renal p38 (mitogen-activated protein kinase; MAPK) in rats treated with prf of P. nigrescens. Combining all, prf of P. nigrescens demonstrated antioxidant as well as protective properties in the heart and kidneys of rats exposed to dichlorvos. It ameliorated dichlorvos-induced cardio- and nephrotoxicity giving credence to its use in ethnomedicine.


Assuntos
Cryptolepis/química , Suplementos Nutricionais , Intoxicação por Organofosfatos/prevenção & controle , Componentes Aéreos da Planta/química , Extratos Vegetais/uso terapêutico , Polifenóis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Administração Oral , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Cryptolepis/crescimento & desenvolvimento , Diclorvós/administração & dosagem , Diclorvós/antagonistas & inibidores , Diclorvós/toxicidade , Suplementos Nutricionais/análise , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Inseticidas/administração & dosagem , Inseticidas/antagonistas & inibidores , Inseticidas/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Masculino , Nigéria , Intoxicação por Organofosfatos/metabolismo , Intoxicação por Organofosfatos/patologia , Intoxicação por Organofosfatos/fisiopatologia , Componentes Aéreos da Planta/crescimento & desenvolvimento , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polifenóis/administração & dosagem , Polifenóis/análise , Polifenóis/isolamento & purificação , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Distribuição Aleatória , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Tirosina/agonistas , Tirosina/análogos & derivados , Tirosina/antagonistas & inibidores , Tirosina/metabolismo , Disfunção Ventricular/etiologia , Disfunção Ventricular/prevenção & controle , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Malar J ; 15: 89, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26879905

RESUMO

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.


Assuntos
Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Animais , Antimaláricos/farmacologia , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Cryptolepis/química , Sinergismo Farmacológico , Quimioterapia Combinada , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/fisiologia , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Ratos , Ratos Sprague-Dawley
13.
J Diet Suppl ; 13(4): 420-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26634775

RESUMO

Parquetina nigrescens is a medicinal herb with recognized antioxidant properties and potential to alleviate conditions associated with oxidative stress, including gastric ulcers. We investigated the protective potential of methanol extract of Parquetina nigrescens (MEPN) against ischemia-reperfusion injury in the intestine of rats. Thirty (30) male Wistar albino rats were randomly assigned into five groups with Group I made up of control rats and Group II consisting of rats experimentally subjected to ischemia and reperfusion (IR) by clamping of the superior mesenteric artery (SMA) for 30 minutes and 45 minutes, respectively. Groups III and IV rats also had IR, but were initially pre-treated with MEPN at 500 mg/kg and 1000 mg/kg respectively, for seven days. Rats in Group V were also pre-treated with Vitamin C, for seven days, before induction of IR. The results showed marked reduction in intestinal epithelial lesions in groups treated with MEPN, compared to the IR group which had severe villi erosion, inflammatory cell infiltration and hemorrhages. There were significant increases in Malondialdehyde (MDA) and significant reductions in reduced glutathione (GSH) and Glutathione S-transferase (GST) activity with IR injury, while pre-treatment with either MEPN or Vitamin C prevented these effects. Increases in Glutathione peroxidase (GPX), Catalase (CAT) and Superoxide dismutase (SOD) with IR provided evidence for adaptive responses to oxidative injury during IR and preservation of enzyme activity by MEPN and Vitamin C. Taken together, Parquetina nigrescens provided considerable alleviation of intestinal injury produced by IR, at values much as effective as that offered by Vitamin C.


Assuntos
Antioxidantes/farmacologia , Cryptolepis/química , Extratos Vegetais/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Ácido Ascórbico/farmacologia , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Enteropatias/induzido quimicamente , Enteropatias/tratamento farmacológico , Masculino , Malondialdeído/metabolismo , Metanol/química , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
14.
Angew Chem Int Ed Engl ; 54(35): 10160-4, 2015 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-26178441

RESUMO

Cryptospirolepine is the most structurally complex alkaloid discovered and characterized thus far from any Cryptolepis specie. Characterization of several degradants of the original, sealed NMR sample a decade after the initial report called the validity of the originally proposed structure in question. We now report the development of improved, homodecoupled variants of the 1,1- and 1,n-ADEQUATE (HD-ADEQUATE) NMR experiments; utilization of these techniques was critical to successfully resolving long-standing structural questions associated with crytospirolepine.


Assuntos
Alcaloides/química , Cryptolepis/química , Espectroscopia de Ressonância Magnética/métodos , Extratos Vegetais/química , Alcaloides Indólicos/química , Estrutura Molecular , Quinolinas/química
15.
Bioorg Med Chem ; 23(7): 1530-9, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25725608

RESUMO

We recently reported that potent N10,O11-bis-alkylamine indolo[3,2-b]quinoline antimalarials act as hemozoin (Hz) growth inhibitors. To improve access and binding to the target we have now designed novel N10,N11-di-alkylamine bioisosteres. 3-Chloro derivatives (10a-f) showed selectivity for malaria parasite compared to human cells, high activity against Plasmodium falciparum chloroquine (CQ)-resistant strain W2 (IC50s between 20 and 158nM), good correlation with ß-hematin inhibition and improved vacuolar accumulation ratios, thus suggesting inhibition of Hz growth as one possible mechanism of action for these compounds. Moreover, our studies show that Hz is a valid target for the development of new antimalarials able to overcome CQ resistance.


Assuntos
Antimaláricos/síntese química , Desenho de Fármacos , Hemeproteínas/antagonistas & inibidores , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/síntese química , Antimaláricos/farmacologia , Cryptolepis , Hemeproteínas/metabolismo , Humanos , Quinolinas/farmacologia
16.
Biomed Res Int ; 2014: 978582, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247198

RESUMO

Cryptolepis buchanani Roem. & Schult. is widely used in folk medicine in Southeast Asia for treating muscle tension and arthritis. This study aimed to investigate an analgesic activity of the methanol extract of C. buchanani (CBE) in acetic acid-induced writhing response in mice, and to examine its anti-inflammatory activity in ethyl phenylpropiolate- (EPP-) induced ear edema and carrageenan-induced paw edema in rats. Its effects on cartilage degradation induced by interleukin-1ß (IL-1ß) in porcine cartilage explant culture were also determined. This study demonstrated that CBE significantly reduced acetic acid-induced writhing response. It also inhibited edema formation in both EPP-induced ear edema and carrageenan-induced paw edema models. In cartilage explant culture, CBE significantly reduced the sulfated glycosaminoglycan and hyaluronan released into culture media while it reserved the uronic acid and collagen within the cartilage tissues. It also suppressed the matrix metalloproteinase-2 activity with no effect on cell viability. In conclusion, CBE shows analgesic, anti-inflammatory, and chondroprotective effects in this preliminary study. Therefore, CBE may be useful as an alternative treatment for osteoarthritis.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Cryptolepis/química , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Inflamação/diagnóstico , Masculino , Camundongos , Dor/diagnóstico , Ratos , Ratos Sprague-Dawley , Suínos
17.
Eur J Med Chem ; 63: 333-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23507189

RESUMO

Cryptolepis sanguinolenta and its bioactive alkaloid, cryptolepine have shown anti-inflammatory activity. However, the underlying mechanism of anti-inflammatory action in neuronal cells has not been investigated. In the present study we evaluated an extract of C. sanguinolenta (CSE) and cryptolepine (CAS) on neuroinflammation induced with IL-1ß in SK-N-SH neuroblastoma cells. We then attempted to elucidate the mechanisms underlying the anti-neuroinflammatory effects of CAS in SK-N-SH cells. Cells were stimulated with 10 U/ml of IL-1ß in the presence or absence of different concentrations of CSE (25-200 µg/ml) and CAS (2.5-20 µM). After 24 h incubation, culture media were collected to measure the production of PGE2 and the pro-inflammatory cytokines (TNFα and IL-6). Protein and gene expressions of cyclooxygenase (COX-2) and microsomal prostaglandin synthase-1 (mPGES-1) were studied by immunoblotting and qPCR, respectively. CSE produced significant (p < 0.05) inhibition of TNFα, IL-6 and PGE2 production in SK-N-SH cells. Studies on CAS showed significant and dose-dependent inhibition of TNFα, IL-6 and PGE2 production in IL-1ß-stimulated cells without affecting viability. Pre-treatment with CAS (10 and 20 µM) was also found to inhibit IL-1ß-induced protein and gene expressions of COX-2 and mPGES-1. Further studies to determine the mechanism of action of CAS showed inhibition of NF-κBp65 nuclear translocation, but not IκB phosphorylation. At 10 and 20 µM, CAS inhibited IL-1ß-induced phosphorylation of p38 MAPK. Studies on the downstream substrate of p38, MAPK-activated protein kinase 2 (MAPKAPK2) showed that CAS produced significant (p < 0.05) and dose dependent inhibition of MAPKAPK2 phosphorylation in IL-1ß-stimulated SK-N-SH cells. This study clearly shows that cryptolepine (CAS) inhibits neuroinflammation through mechanisms involving inhibition of COX-2 and mPGES-1. It is suggested that these actions are probably mediated through NF-κB and p38 signalling.


Assuntos
Anti-Inflamatórios/farmacologia , Alcaloides Indólicos/farmacologia , Quinolinas/farmacologia , Fator de Transcrição RelA/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Linhagem Celular Tumoral , Cryptolepis/química , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Immunoblotting , Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Interleucina-1beta/farmacologia , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Estrutura Molecular , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prostaglandina-E Sintases , Quinolinas/síntese química , Quinolinas/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos
18.
Ghana Med J ; 47(3): 137-47, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24391229

RESUMO

Cryptolepis sanguinolenta (Lindl.) Schltr (Periplocaceae), has a longstanding traditional use in the treatment of malaria in the West African region. Recent evidence suggests that the aqueous extract from the roots and the major alkaloid from the plant, cryptolepine, have prospects as cancer chemotherapeutic agents on account of their potent cytotoxicity to mammalian cells. Several mechanisms have been proposed to explain the cytotoxic activities of the agents. However, emerging evidence from their anti-inflammatory actions suggest that the mechanism of the cytotoxicity may be closely related to its anti-inflammatory activity. This review looks at the mechanisms of cryptolepis-induced cytotoxicity, its link with inflammation and its potential as anticancer agent. The elucidation of these interwoven mechanisms may be useful in the development of cryptolepine or other analogues as new anticancer agents.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cryptolepis , Alcaloides Indólicos/uso terapêutico , Fitoterapia , Neoplasias da Próstata/tratamento farmacológico , Quinolinas/uso terapêutico , Animais , Antimaláricos/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Feminino , Humanos , Alcaloides Indólicos/efeitos adversos , Inflamação/tratamento farmacológico , Masculino , NF-kappa B/antagonistas & inibidores , Preparações de Plantas/efeitos adversos , Preparações de Plantas/uso terapêutico , Quinolinas/efeitos adversos
19.
Biol Pharm Bull ; 35(9): 1432-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22975492

RESUMO

Indoloquinoline alkaloids represent an important class of antimalarial, antibacterial and antiviral compounds. Indolo[2,3-b]quinolines are a family of DNA intercalators and inhibitors of topoisomerase II, synthetic analogs of neocryptolepine, an alkaloid traditionally used in African folk medicine. These cytotoxic substances are promising anticancer agents. Active representatives of indolo[2,3-b]quinolines affect model and natural membranes. The distinct structure and hydrophobicity of the compounds leads to marked differences in the disturbing effects on membrane organization and function. Our results also indicated a strong relationship between the presence of the chain and the Poct of the molecule as well as the capacity for incorporation into carboxyfluorescein-trapped liposomes in the 0.02-0.06 mM range. Moreover, a correlation between binding to neutral dimyristoylphosphatidylcholine (DMPC) or negative charged dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DMPC:DMPG, 9:1 w/w) liposomes, as well as to erythrocyte ghosts and pKa, was also found. All the compounds cause hemolysis in isotonic conditions with concentration causing 50% hemolysis (HC50) in the 0.12-0.88 mM range. The concentration-dependent inhibitory effect of the tested agents on erythrocyte ghosts' acetylcholinesterase activity was also studied.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Membrana Celular/efeitos dos fármacos , Cryptolepis/química , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Quinolinas/farmacologia , Acetilcolinesterase/metabolismo , Alcaloides/química , Animais , Antineoplásicos Fitogênicos/química , Membrana Celular/metabolismo , Dimiristoilfosfatidilcolina/química , Relação Dose-Resposta a Droga , Eritrócitos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Lipossomos , Medicina Tradicional Africana , Fosfatidilgliceróis/química , Extratos Vegetais/química , Quinolinas/química , Ovinos , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia
20.
Ann Clin Microbiol Antimicrob ; 11: 16, 2012 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-22709723

RESUMO

BACKGROUND: Following claims that some plants have antimicrobial activities against infectious microbes, the in vitro antimicrobial activities of different solvent fractions of ethanolic extract of Cryptolepis sanguinolenta were evaluated against eight standard bacteria and clinical isolates. METHODS: The solvent partitioning protocol involving ethanol, petroleum ether, chloroform, ethyl acetate and water, was used to extract various fractions of dried pulverized Cryptolepis sanguinolenta roots. Qualitative phyto-constituents screening was performed on the ethanol extract, chloroform fraction and the water fraction. The Kirby Bauer disk diffusion method was employed to ascertain the antibiogram of the test organisms while the agar diffusion method was used to investigate the antimicrobial properties of the crude plant extracts. The microplate dilution method aided in finding the MICs while the MBCs were obtained by the method of Nester and friends. The SPSS 16.0 version was used to analyze the percentages of inhibitions and bactericidal activities. RESULTS: The phytochemical screening revealed the presence of alkaloids, reducing sugars, polyuronides, anthocyanosides and triterpenes. The ethanol extract inhibited 5 out of 8 (62.5%) of the standard organisms and 6 out of 8 (75%) clinical isolates. The petroleum ether fraction inhibited 4 out of 8 (50%) of the standard microbes and 1 out of 8 (12.5%) clinical isolates. It was also observed that the chloroform fraction inhibited the growth of all the organisms (100%). Average inhibition zones of 14.0 ± 1.0 mm to 24.67 ± 0.58 mm was seen in the ethyl acetate fraction which halted the growth of 3 (37.5%) of the standard organisms. Inhibition of 7 (87.5%) of standard strains and 6 (75%) of clinical isolates were observed in the water fraction. The chloroform fraction exhibited bactericidal activity against all the test organisms while the remaining fractions showed varying degrees of bacteriostatic activity. CONCLUSION: The study confirmed that fractions of Cryptolepis sanguinolenta have antimicrobial activity. The chloroform fraction had the highest activity, followed by water, ethanol, petroleum ether and ethyl acetate respectively. Only the chloroform fraction exhibited bactericidal activity and further investigations are needed to ascertain its safety and prospects of drug development.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cryptolepis/química , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
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