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Background: 3-caffeoylquinic acid (3-CQA), a member of the chlorogenic acid family, possesses diverse pharmacological properties, such as scavenging, antioxidant, and antiapoptotic activity, rendering substantial value to alimentary consumables and therapeutic substances. However, the pervasiveness of non-standard practices, notably the misuse and abuse of indigenous botanicals, coupled with the inherent susceptibility of 3-CQA to degradation under light and heat exposure, engenders discernible disparateness in the quality profiles of the same kinds of herbs. Consequently, precise quantification of 3-CQA becomes imperative. Methods: In this context, an artificial antigen was synthesized as a specific conjugate of 3-CQA and bovine serum albumin (3-CQA-BSA), followed by the generation of a monoclonal antibody (mAb) against the conjugate. Through optimization, a mAb-based indirect competitive chemiluminescence enzyme immunoassay (ic-CLEIA) was developed. Results: It demonstrated an IC50 and the calibration range of 2.97 ng/mL and 0.64-13.75 ng/mL, respectively, outperforming the conventional enzyme-linked immunosorbent assay (ELISA). Notably, the ic-CLEIA displayed 10.71% cross-reactivity with 3,5-dicaffeoylquinic acid, alongside minimal cross-reactivity toward other isomeric counterparts and analogs. Validation experiments on herbs and Chinese patent medicines using ic-CLEIA, confirmed by high-performance liquid chromatography (HPLC) analysis, revealed a robust correlation coefficient of 0.9667 between the two modalities. Conclusion: These findings unequivocally demonstrated that the proposed ic-CLEIA represents a viable and reliable analytical method for 3-CQA determination. This method holds significant potential for ensuring the quality control and therapeutic efficacy germane to herbs and patent medicines, spanning diverse therapeutic milieus and applications.
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N-acetylneuraminic acid is an active ingredient in tonic foods and an important additive in foods and biopharmaceuticals. To address the limitations of existing methods of N-acetylneuraminic acid quantification, we developed an immunoassay based on antibodies induced in hens using artificial antigen, showing high sensitivity and specificity with no cross-reactivity with eight N-acetylneuraminic acid analogues. An IgY-based indirect competitive enzyme-linked immunosorbent assay showed a detection range of 1.14 to 70.08 ng/mL and a limit of detection of 0.57 ng/mL. In spiked samples, recoveries by the indirect competitive enzyme-linked immunosorbent assay ranged from 74.05% to 110.87% compared with HPLC (73.01% to 108.8%). Consistency between the indirect competitive enzyme-linked immunosorbent assay and HPLC was satisfactory (R2 = 0.9736), demonstrating this established immunoassay as a rapid and reliable approach for N-acetylneuraminic acid analysis. The assay described in this study provides an important method for the screening of N-acetylneuraminic acid in biological samples and foodstuffs.
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Background: Type 1 (T1D) and type 2 (T2D) diabetes lead to an aberrant metabolism of sialoglycoconjugates and elevated free serum sialic acid (FSSA) level. The present study evaluated sialidase and sialyltranferase activities in serum and some organs relevant to diabetes at early and late stages of T1D and T2D. Methods: Sialic acid level with sialidase and sialyltransferase activities were monitored in the serum, liver, pancreas, skeletal muscle and kidney of diabetic animals at early and late stages of the diseases. Results: The FSSA and activity of sialidase in the serum were significantly increased at late stage of both T1D and T2D while sialic acid level in the liver was significantly decreased in the early and late stages of T1D and T2D, respectively. Furthermore, the activity of sialidase was significantly elevated in most of the diabetes-relevant organs while the activity of sialyltransferase remained largely unchanged. A multiple regression analysis revealed the contribution of the liver to the FSSA while pancreas and kidney contributed to the activity of sialidase in the serum. Conclusions: We concluded that the release of hepatic sialic acid in addition to pancreatic and renal sialidase might (in)directly contribute to the increased FSSA during both types of diabetes mellitus.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Ácido N-Acetilneuramínico , Neuraminidasa , Sialiltransferasas , Animales , Neuraminidasa/metabolismo , Sialiltransferasas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ratas , Masculino , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/sangre , Hígado/metabolismo , Hígado/enzimología , Ratas Wistar , Páncreas/metabolismo , Páncreas/enzimología , Riñón/metabolismo , Músculo Esquelético/metabolismoRESUMEN
Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.
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Ácidos Siálicos , Humanos , Ácidos Siálicos/metabolismo , Animales , Diabetes Mellitus/metabolismo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/diagnósticoRESUMEN
African science has substantial potential, yet it grapples with significant challenges. Here we describe the establishment of the Biomedical Science Research and Training Centre (BioRTC) in Yobe State, Northeast Nigeria, as a case study of a hub fostering on-continent research and describe strategies to overcome current barriers. We detail the steps taken to establish BioRTC, emphasising the critical importance of stakeholder engagement, community involvement, resource optimisation and collaborations. With its state-of-the-art facilities and commitment to training African scientists, BioRTC is poised to significantly advance neuroscience research and training in the region. Although we are in the early stages of our journey, our model, emphasizing open access and inclusivity, offers a replicable blueprint for neuroscience research development in similar resource-limited settings, promising to enrich the global neuroscience community. We invite the support and collaboration of those who share our vision and believe in our potential.
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Investigación Biomédica , Neurociencias , Nigeria , Neurociencias/educaciónRESUMEN
The 2023 Nobel Prize in Chemistry honors the groundbreaking contributions of Alexei Ekimov, Louis Brus, and Moungi Bawendi to the field of quantum dots (QDs). In this spirit, we developed a direct competitive QD fluorescence immunoassay (dc-QD-FLISA) to detect aristolochic acid type I (AAI), a potent carcinogen found in herbal remedies. Unexpectedly, the dc-QD-FLISA exhibited lower sensitivity than that of an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA), contrary to our initial expectations. This discrepancy in the sensitivity prompted a comprehensive analysis of the entire experimental process. We propose that steric hindrance between QDs and antigen-binding sites on antibodies may significantly diminish the binding efficiency, reducing sensitivity within the dc-QD-FLISA method. Furthermore, issues such as buffer conditions, antibody handling, and separation methods are also contributing factors. We recommend site-directed QD modification and stringent consideration of the experimental conditions. This study not only provides insights into QD-based immunoassays but also highlights the need for future advancements in immunoassay technology in terms of augmenting sensitivity and specificity, potentially revolutionizing disease diagnosis, biomarker discovery, and biomedical research.
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Puntos Cuánticos , Puntos Cuánticos/química , Inmunoensayo/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Anticuerpos/química , Sensibilidad y EspecificidadRESUMEN
Apocynum venetum L. is an important medicinal perennial rhizome plant with good ecological and economic value. Its leaves have many pharmacological effects such as anti-inflammatory, anti-depression, anti-anxiolytic, etc., while its fibers have the title of "king of wild fibers". Furthermore, it was suitable for the restoration of degraded saline soil in arid areas. An increasing studies have been published in the past years. A scientometric analysis was used to analyze the publications of Apocynum venetum L. to clearly review the pharmacology, fiber application of Apocynum venetum L. and the potential value with its similar species (Apocynum pictum Schrenk) to the environment.
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Apocynum , Hojas de la Planta , RizomaRESUMEN
As a famous tonic herb, Cistanches Herba is known for its broad medicinal functions, especially its hormone balancing, anti-aging, anti-dementia, anti-tumor, anti-oxidative, neuroprotective, and hepatoprotective effects. This study aims to provide a comprehensive bibliometric analysis of studies on Cistanche and to identify research hotspots and frontier topics on the genus. Based on the metrological analysis software CiteSpace, 443 Cistanche related papers were quantitatively reviewed. The results indicate that 330 institutions from 46 countries have publications in this field. China was the leading country in terms of research importance and number of publication (335 articles). In the past decades, studies on Cistanche have mainly focused on its rich active substances and pharmacological effects. Although the research trend shows that Cistanche has grown from an endangered species to an important industrial plant, its breeding and cultivation continue to be important areas for research. In the future, the application of Cistanche species as functional foods may be a new research trend. In addition, active collaborations among researchers, institutions, and countries are expected.
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Diterpenes are a diverse group of structurally complex natural products with a wide spectrum of biological activities, including antidiabetic potential. In the last 25 years, numerous diterpenes have been investigated for antidiabetic activity, with some of them reaching the stage of clinical trials. However, these studies have not been comprehensively reviewed in any previous publication. Herein, we critically discussed the literature on the potential of diterpenes as antidiabetic agents, published from 1995 to September, 2021. In the period under review, 427 diterpenes were reported to have varying degrees of antidiabetic activity. Steviol glycosides, stevioside (1) and rebaudioside A (2), were the most investigated diterpenes with promising antidiabetic property using in vitro and in vivo models, as well as human subjects. All the tested pimaranes consistently showed good activity in preclinical evaluations against diabetes. Inhibitions of α-glucosidase and protein tyrosine phosphatase 1B (PTP 1B) activities and peroxisome proliferator-activated receptors gamma (PPAR-γ) agonistic property, were the most frequently used models for studying the antidiabetic activity of diterpenes. The molecular mechanisms of action of the diterpenes include increased GLUT4 translocation, and activation of phosphoinositide 3-kinase (PI3K) and AMP-activated protein kinase (AMPK)-dependent signaling pathways. This review revealed that diterpenes hold promising antidiabetic potential while stevioside (1) and rebaudioside A (2) are the only diterpenes that were advanced to the clinical trial stage of the drug discovery pipeline. Diterpenes belonging to the abietane, labdane, pimarane and kaurane classes have shown promising activity in in vitro and in vivo models of diabetes and should be further investigated.
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Diabetes Mellitus , Diterpenos de Tipo Kaurano , Diterpenos , Proteínas Quinasas Activadas por AMP , Diabetes Mellitus/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/uso terapéutico , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Fosfatidilinositol 3-QuinasasRESUMEN
Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A2 (PLA2) were investigated. Treatment with phloroglucinol for 14 days significantly (p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense-associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of -4.9 and -5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (-67.84 ± 0.50 kJ/mol) than PLA2-phloroglucinol complex (-77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA2-phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA2.
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Floroglucinol/farmacología , Tripanocidas/farmacología , Trypanosoma congolense/efectos de los fármacos , Tripanosomiasis Africana/tratamiento farmacológico , Anemia/complicaciones , Anemia/tratamiento farmacológico , Animales , Femenino , Riñón/efectos de los fármacos , Riñón/parasitología , Riñón/patología , Hígado/efectos de los fármacos , Hígado/parasitología , Hígado/patología , Masculino , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/química , Tamaño de los Órganos/efectos de los fármacos , Floroglucinol/química , Floroglucinol/uso terapéutico , Fosfolipasas A2/química , Fosfolipasas A2/metabolismo , Ratas Wistar , Análisis de Supervivencia , Tripanocidas/química , Tripanocidas/uso terapéutico , Trypanosoma congolense/parasitología , Tripanosomiasis Africana/sangre , Tripanosomiasis Africana/complicaciones , Tripanosomiasis Africana/parasitologíaRESUMEN
PURPOSE: Understanding some variations in specialized molecules during malaria could facilitate adequate monitoring of patients and reduce the fatalities caused by the disease. The present study reports changes in the levels of free serum sialic acid (FSSA) among Plasmodium-infected individuals in Zaria, Nigeria, in a cross-sectional study with 170 individuals. METHODS: The FSSA and total sialic acid (TSA) in the blood were determined using the thiobarbituric acid method and the white blood cells (WBC) count, haemoglobin concentration and packed cell volumes were assessed using an automated haematological analyser. RESULTS: The results showed that, in the patients aged > 5 years the level of TSA was significantly elevated (P < 0.05) compared to apparently healthy age-matched controls whereas TSA was slightly lower in patients aged < 5 years compared to controls. The ratio of FSSA to TSA was not different between patients aged > 5 years compared to their age-matched controls whereas FSSA/TSA was significantly elevated (P < 0.05) in patients aged < 5 years compared to their aged-matched controls. The level of FSSA/TSA in the patients aged < 5 years was not correlated with parasite density, white blood cell count, haemoglobin concentration or packed cell volume. CONCLUSION: We concluded that, metabolism and/or physiology of serum sialo-glycoconjugates is affected by malaria and FSSA is mainly elevated in children < 5 years of age but not among older patients suggesting the possible usefulness of FSSA in the analysis of uncomplicated malaria in under five children.
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Malaria Falciparum , Malaria , Niño , Preescolar , Estudios Transversales , Hemoglobinas , Humanos , Malaria Falciparum/parasitología , Ácido N-Acetilneuramínico , Nigeria , Plasmodium falciparumRESUMEN
Sialic acid and its associated metabolic enzymes have emerged as important components of the pathophysiology of type 2 diabetes (T2D). There is an elevation in the serum concentration of sialic acid in humans and animals with T2D. The present study investigated the modulation of mRNA expression level of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and neuraminidase 1 (NEU1) genes in some organs of type 2 diabetic rats. T2D was induced using fructose-streptozotocin model and eight weeks after the induction of diabetes, sialic acid was assayed in the blood and organs (adipose tissue, brain, colon, kidney, liver, pancreas, skeletal muscle and spleen) followed by quantification of mRNA expression level of GNE and NEU1 genes by qPCR. The results showed a significant (P < 0.05) increase in sialic acid level in the serum and all the afore-mentioned organs investigated except in the adipose tissue and skeletal muscle of the diabetic rats compared the normal control. The expression GNE gene was only increased in the pancreas (1.8-fold) of the diabetic rats while there was a decrease in the expression of the gene in the colon. In contrast, the expression of NEU1 gene was increased in the spleen (3.5-fold), brain (2.2-fold), liver (1.9-fold), colon (1.5-fold) and kidney of the diabetic rats. It was concluded that the elevated level of sialic acid in the organs of diabetic rats, except the pancreas, might not be due to increased endogenous synthesis of sialic acid.
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Diabetes Mellitus Tipo 2/enzimología , Complejos Multienzimáticos/genética , Animales , Encéfalo/enzimología , Colon/enzimología , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Regulación Enzimológica de la Expresión Génica , Hígado/enzimología , Ácido N-Acetilneuramínico/sangre , Ácido N-Acetilneuramínico/metabolismo , Neuraminidasa/genética , Páncreas/enzimología , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Bazo/enzimologíaRESUMEN
The present study was designed to review the antidiabetic potential of anthraquinones (AQs) with emphasis on the extent of blood glucose reduction, the half maximal inhibitory concentration values (in vitro studies), the proposed mechanisms of action, and the structure activity relationship studies. We sourced relevant data from the major scientific databases (Pubmed, Science Direct, Medline, and Google Scholar). According to our search, 25 AQs have shown variable antidiabetic potential, whereas one AQ (morindone-6-O-ß-D-primeveroside) showed no blood glucose-lowering ability. Emodin and rhein showed the most promising antidiabetic potential in various models. The proposed mechanisms of antidiabetic action include upregulation of insulin receptor substrates-1, phosphoinositide-3-kinase, and Akt-ser473 expression and elevation of glucagon-like peptide-1 level in diabetic animal models linked to the potent protein tyrosine phosphatase 1B and dipeptidyl peptidase-4 inhibitions. In addition, activation of peroxisome proliferator-activated receptors gamma and inhibition of α-glucosidase activity are other possible targets proposed as the mechanism of AQs antidiabetic action. The position and the number of hydroxyl group showed great influence on the overall antidiabetic potential of AQs. AQs hold promising antidiabetic activity despite scanty information. We hope that the present study will serve as a template to further explore the antidiabetic potential of AQs and subsequent antidiabetic drug development.
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Antraquinonas/farmacología , Diabetes Mellitus/tratamiento farmacológico , Emodina/farmacología , Hipoglucemiantes/farmacología , Animales , Antraquinonas/química , Glucemia/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Emodina/química , Humanos , Hipoglucemiantes/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidoresRESUMEN
Copper is an essential component of cuproproteins but can be toxic to cells, therefore copper metabolism is very carefully regulated within cells. To gain insight into trypanosome copper metabolism, Trypanosoma spp. genomic databases were screened for the presence of copper-containing and -transporting proteins. Among other genes encoding copper-binding proteins, a copper-transporting P-type ATPase (CuATPase) gene was identified. Sequence and phylogenetic analyses suggest that the gene codes for a Cu+ transporter belonging to the P1B-1 ATPase subfamily that has an N-terminal domain with copper binding motifs. The N-terminal cytosolic domains of the proteins from Trypanosoma congolense and Trypanosoma brucei brucei were recombinantly expressed in Escherichia coli as maltose binding protein (MBP) fusion proteins. These N-terminal domains bound copper in vitro and within E. coli cells, more than the control MBP fusion partner alone. The copper binding properties of the recombinant proteins were further confirmed when they inhibited copper catalysed ascorbate oxidation. Native CuATPases were detected in a western blot of lysates of T. congolense IL3000 and T. b. brucei ILTat1.1 bloodstream form parasites using affinity purified IgY antibodies against N-terminal domain peptides. The CuATPase was also detected by immunofluorescence in T. b. brucei bloodstream form parasites where it was associated with subcellular vesicles. In conclusion, Trypanosoma species express a copper-transporting P1B-1-type ATPase and together with other copper-binding proteins identified in the genomes of kinetoplastid parasites may constitute potential targets for anti-trypanosomal drug discovery.
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ATPasas Transportadoras de Cobre , Cobre/metabolismo , Trypanosoma , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Proteínas Portadoras/metabolismo , ATPasas Transportadoras de Cobre/química , ATPasas Transportadoras de Cobre/genética , ATPasas Transportadoras de Cobre/inmunología , ATPasas Transportadoras de Cobre/metabolismo , Vesículas Citoplasmáticas , Escherichia coli/genética , Transporte de Proteínas , Proteínas Recombinantes/genética , Trypanosoma/genética , Trypanosoma/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Trypanosoma congolense/genética , Trypanosoma congolense/metabolismoRESUMEN
BACKGROUND: Katsina State Government in Northern Nigeria introduced integrated supportive supervision (ISS) in primary health centers. The study was guided by the Primary Health Care Performance Initiative Conceptual Framework. The goal of the study was to measure the impact of ISS on the quality of primary health-care delivery. The outcome variables measured include infrastructure, basic equipment, human resources for health, essential drugs, the number of pregnant women screened for HIV, and the number of children receiving immunization. METHODS: The study was a cross-sectional survey of 34 health facilities. Kruskal-Wallis nonparametric test followed by Dunn post hoc test and analysis of variance followed by Tukey post hoc test were both employed to compare the mean values of various indicators obtained over 6 visits of the ISS program from July 2018 to December 2018. FINDINGS: The study shows the positive effect of the ISS on infrastructure, human resources for health, essential drugs, and the number of pregnant women screened for HIV (P < .05). Human resources for health and the number of children receiving immunization were both not affected by ISS (P > .05). CONCLUSION: Integrated supportive supervision need to be embedded into the 3 levels (primary, secondary, and tertiary) of health-care service delivery. IMPLICATIONS: Integrated supportive supervision will strengthen the Katsina State health system, ensure efficient use of the health facility assets and resources utilization, and improve patient/client satisfaction.
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Leishmaniases are endemic diseases in tropical and sub-tropical regions of the world and are considered by the World Health Organization (WHO) to be among the six most important neglected tropical diseases. The current therapeutic arsenal against the disease is associated with a series of chemotherapeutic setbacks. However, since the early 1990s, naturally occurring chalcones with promising antileishmanial effects have been reported, and several other synthetic chalcones and chalcone-hybrid molecules have been confirmed to possess potent activity against various Leishmania species. This paper is a comprehensive review covering the antileishmanial activity of 34 naturally occurring chalcones, 224 synthetic/semisynthetic chalcones and 54 chalcone-hybrid molecules. Several chalcones in the synthetic/semisynthetic category had IC50 values < 5 µM, with very good selectivity against parasites, and the structure-activity relationships as well as the proposed mechanism of action are discussed. We identified knowledge-gaps with the hope of providing future direction for the discovery of novel antileishmanial drugs from chalcones.
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Antiprotozoarios/farmacología , Productos Biológicos/farmacología , Chalconas/farmacología , Leishmania/efectos de los fármacos , Leishmaniasis/tratamiento farmacológico , Antiprotozoarios/química , Antiprotozoarios/uso terapéutico , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Chalconas/química , Chalconas/uso terapéutico , Humanos , Concentración 50 Inhibidora , Relación Estructura-ActividadRESUMEN
The small intestine (SI) is the main site for food absorption and glutamine utilization hence critical in metabolic disorders that involve energy balance such as diabetes. This study investigates the effects of oleanolic acid (OA) on SI morphology and some enzymes of glutamine metabolism in male Sprague-Dawley diabetic rats. High dose STZ-induced diabetes (HDD) and low dose STZ-induced diabetes (LDD) were induced by intraperitoneal injection of 60 and 40 mg streptozotocin/kg body weight respectively. Non-diabetic and diabetic rats were treated for two weeks with OA, insulin or OA + insulin in HDD study while animals in the in LDD study were treated with OA. There was significant (P<0.05) increase in the weight of the SI of diabetic animals and of villus height (VH) in the jejunum and duodenum of HDD animals. OA and insulin treatment significantly decreased VH in duodenum of HDD animals while OA treatment profoundly increased VH in normal rats. Jejunal of phosphate-dependent glutaminase (PDG) activity was unaffected by diabetes however alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were significantly (P<0.05) elevated by diabetes and treatments decreased these elevated aminotransferase activities. It is suggested that the intestine meets the energy demand in diabetes by modulating the activities of aminotransferases without change in PDG activity.
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Parasitic infections are among the leading global public health problems with very high economic and mortality burdens. Unfortunately, the available treatment drugs are beset with side effects and continuous parasite drug resistance is being reported. However, new findings reveal more promising compounds especially of plant origin. Among the promising leads are the pentacyclic triterpenes (PTs) made up of the oleanane, ursane, taraxastane, lupane and hopane types. This paper reviews the literature published from 1985 to date on the in vitro and in vivo anti-parasitic potency of this class of phytochemicals. Of the 191 natural and synthetic PT reported, 85 have shown high anti-parasitic activity against various species belonging to the genera of Plasmodium, Leishmania, Trypanosoma, as well as various genera of Nematoda. Moreover, structural modification especially at carbon 3 (C3) and C27 of the parent backbone of PT has led to improved anti-parasitic activity in some cases and loss of activity in others. The potential of this group of compounds as future alternatives in the treatment of parasitic diseases is discussed. It is hoped that the information presented herein will contribute to the full exploration of this promising group of compounds as possible drugs for parasitic diseases.
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Enfermedades Parasitarias/tratamiento farmacológico , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/uso terapéutico , Animales , Humanos , Leishmania/efectos de los fármacos , Leishmaniasis/tratamiento farmacológico , Malaria/tratamiento farmacológico , Ratones , Infecciones por Nematodos/tratamiento farmacológico , Enfermedades Parasitarias/parasitología , Triterpenos Pentacíclicos/efectos adversos , Triterpenos Pentacíclicos/química , Plasmodium/efectos de los fármacos , Clima Tropical , Trypanosoma/efectos de los fármacos , Tripanosomiasis/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: African trypanosomiasis is one of the neglected tropical diseases caused by different species of trypanosomes that affect both human and livestock with devastating consequences in the continent. Most of the affected populations commonly use traditional medicinal plants for the treatment of the disease. Consequently, this prompted ethnopharmacological research activities on the anti-trypanosomal activity of a number of these African medicinal plants in order to validate their ethnomedicinal use. Furthermore, such studies could lead to the identification of chemical leads for the development of newer anti-trypanosomal agents from those plants. This review aims to provide updated information on the ethnopharmacological evidence of African medicinal plants with anti-trypanosomal activity. METHODS: Literature was collected via electronic search (PubMed, Sciencedirect, Medline and Google Scholar) from published articles that report on the in vitro or in vivo anti-trypanosomal activity of plants that were collected from different parts of Africa. RESULTS: African medicinal plants investigated for in vitro and in vivo anti-trypanosomal activity from January 1993 to October 2013 are systematically compiled and all the in vivo studies are critically discussed. A total of 264 plant species belonging to 79 families were investigated for anti-trypanosomal activity. However, only 48 bioactive anti-trypanosomal compounds were successfully isolated in pure forms. Furthermore, some of the plants were investigated for possible ameliorative effects on the trypanosome-induced pathological changes out of which 18 plants were reported to be effective while a few others were not. In spite of interesting preclinical ethnopharmacological evidence for anti-trypanosomal activity, not a single African medicinal plant was investigated in a clinical study. CONCLUSION: Several African medicinal plants have demonstrated promising anti-trypanosomal effects but the studies on the anti-trypanosomal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.