Search

Two previously undescribed naphthazarins named hermansones A (1) and B (2), were isolated from the wood-decaying basidiomycete Hermanssonia centrifuga. The study presents the first report of natural products from the species. The structures of the secondary metabolites were elucidated through NMR spectroscopy and mass spectrometry. The absolute configuration of compound 1 was elucidated using TDDFT-ECD calculations. Hermansone B (2) demonstrated moderate inhibitory effects against Chikungunya virus at IC 50 of 55.97 μM, without inducing notable cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sherif S. Ebada reports financial support was provided by Alexander von Humboldt Foundation. Winnie C. Sum reports financial support was provided by German Academic Exchange Service. Tibor Kurtan reports financial support was provided by National Research Development and Innovation Office. Jackson M. Muema reports financial support was provided by Alexander von Humboldt Foundation. Marc Stadler is a member of the Editorial Board of Fitoterapia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nematode-associated fungi revealed the potential to produce a broad spectrum of chemical scaffolds. In this study, a mycelial extract of Laburnicola nematophila , a fungal strain derived from the cereal cyst nematode Heterodera filipjevi , was chemically explored and afforded six unprecedentedly reported acylic N -acetyl oligopeptides, laburnicotides A-F ( 1 - 6 ). Structure elucidation of the isolated compounds was established based on comprehensive 1D and 2D NMR spectroscopic analyses together with the acquired HR-ESI-MS spectrometric data. The absolute configuration of amino acid residues in 1 - 6 was established by performing advanced Marfey's derivatization method. All isolated compounds were assessed for their cytotoxic, antimicrobial, antiviral, and nematicidal activities with no potential activity observed., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Visceral and cutaneous leishmaniasis are endemic to specific regions due to the ecological preferences of phlebotomine sand flies and Leishmania spp. transmission. Sand fly entomological data in northern Kenya are scarce due to limited studies and neglect of leishmaniasis. The aim of this study was to investigate: (i) sand fly diversity and distribution; (ii) occurrence of Leishmania DNA within sand flies; and (iii) blood-meal sources of sand flies in Laisamis, northern Kenya. We conducted an entomological survey during February and March of 2021 in five areas of Laisamis sub-county using standard CDC light traps. A total of 1009 sand flies (394 male and 615 female) were morphologically identified, and representative samples verified by PCR amplification and sequencing of the cytochrome c oxidase subunit 1 ( cox 1) gene. Similarly, we identified blood-meal sources and Leishmania DNA in female sand flies by PCR amplicon sequencing of the vertebrate cytochrome b ( cyt b ) gene and internal transcribed spacer 1 (ITS1) of the 28S rRNA gene, respectively. Sergentomyia clydei (59.8%) was the most abundant sand fly species. Though collected mainly from one locality (Tirgamo), 14.8% of samples belonged to Phlebotomus ( Artemievus ) alexandri Sinton, 1928. We detected DNA of Leishmania major in 5.19% of Ph. alexandri , whereas Leishmania adleri DNA was detected in S. clydei (7.51%), Sergentomyia squamipleuris (8.00%), and Sergentomyia africanus (8.33%). Nine of 13 blood-fed sand flies had obtained blood from humans, of which 33.3% had L. major DNA. Both Ph. alexandri and S. clydei primarily fed on humans and could potentially be involved in the transmission of cutaneous leishmaniasis. The findings of this study contribute to the understanding of sand fly vector populations and their potential to transmit leishmaniasis in the area., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: The unmet demand for effective malaria transmission-blocking agents targeting the transmissible stages of Plasmodium necessitates intensive discovery efforts. In this study, a bioactive bisbenzylisoquinoline (BBIQ), isoliensinine, from Cissampelos pariera (Menispermaceae) rhizomes was identified and characterized for its anti-malarial activity., Methods: Malaria SYBR Green I fluorescence assay was performed to evaluate the in vitro antimalarial activity against D6, Dd2, and F32-ART5 clones, and immediate ex vivo (IEV) susceptibility for 10 freshly collected P. falciparum isolates. To determine the speed- and stage-of-action of isoliensinine, an IC 50 speed assay and morphological analyses were performed using synchronized Dd2 asexuals. Gametocytocidal activity against two culture-adapted gametocyte-producing clinical isolates was determined using microscopy readouts, with possible molecular targets and their binding affinities deduced in silico., Results: Isoliensinine displayed a potent in vitro gametocytocidal activity at mean IC 50 gam values ranging between 0.41 and 0.69 µM for Plasmodium falciparum clinical isolates. The BBIQ compound also inhibited asexual replication at mean IC 50 Asexual of 2.17 µM, 2.22 µM, and 2.39 µM for D6, Dd2 and F32-ART5 respectively, targeting the late-trophozoite to schizont transition. Further characterization demonstrated a considerable immediate ex vivo potency against human clinical isolates at a geometric mean IC 50 IEV  = 1.433 µM (95% CI 0.917-2.242). In silico analyses postulated a probable anti-malarial mechanism of action by high binding affinities for four mitotic division protein kinases; Pfnek1, Pfmap2, Pfclk1, and Pfclk4. Additionally, isoliensinine was predicted to possess an optimal pharmacokinetics profile and drug-likeness properties., Conclusion: These findings highlight considerable grounds for further exploration of isoliensinine as an amenable scaffold for malaria transmission-blocking chemistry and target validation., (© 2023. The Author(s).)

An integrated approach to innovatively counter the transmission of various arthropod-borne diseases to humans would benefit from strategies that sustainably limit onward passage of infective life cycle stages of pathogens and parasites to the insect vectors and vice versa. Aiming to accelerate the impetus towards a disease-free world amid the challenges posed by climate change, discovery, mindful exploitation and integration of active natural products in design of pathogen transmission-blocking interventions is of high priority. Herein, we provide a review of natural compounds endowed with blockade potential against transmissible forms of human pathogens reported in the last 2 decades from 2000 to 2021. Finally, we propose various translational strategies that can exploit these pathogen transmission-blocking natural products into design of novel and sustainable disease control interventions. In summary, tapping these compounds will potentially aid in integrated combat mission to reduce disease transmission trends., (© 2022. The Author(s).)

Studies have looked into how environmental and climate covariates affect under-and over-nutrition, but little is known about the spatial distribution of different forms of malnutrition in Kenya and whether there are locations that suffer from double-burden of malnutrition. This research quantifies spatial variations and estimates how climatic and environmental factors affect under-and over-nutrition among women in Kenya. This enables us to determine if the patterns in which these factors affect the malnutrition indicators are similar and whether there are overlaps in the spatial distributions. The study used data from the Demographic and Health Survey, which included cross-sectional data on malnutrition indicators as well as some climate and environmental variables. A multicategorical response variable that classified the women into one of four nutritional classes was generated from the body mass index (BMI) of the women, and a Bayesian geoadditive regression model with an estimate based on the Markov chain Monte Carlo simulation technique was adopted. Findings show that women in Turkana, Samburu, Isiolo, Baringo, Garissa, and West Pokot counties are more likely to be underweight than women in other counties while being overweight is prevalent in Kirinyag'a and Kitui counties. Obesity is prevalent in Kirinyag'a, Lamu, Kiambu, Murang'a, and Taita Taveta counties. The study further shows that as mean temperature and precipitation increase, the likelihood of being underweight reduces. The chances of being underweight are lower among literate women [OR: 0.614; 95% CrI: 0.513,0.739], married women [OR: 0.702; 95% CrI: 0.608,0.819] and those from rich households [OR: 0.617; 95% CrI: 0.489,0.772], which is not the case for overweight and obesity. The generated spatial maps identify hot spots of the double burden of malnutrition that can assist the government and donor agencies in channeling resources efficiently., Competing Interests: The authors have conflicts of interest to declare., (© 2021 The Authors. Published by Elsevier Ltd.)

Intracellular effects exerted by phytochemicals eliciting insect growth-retarding responses during vector control intervention remain largely underexplored. We studied the effects of Zanthoxylum chalybeum Engl. (Rutaceae) (ZCE) root derivatives against malaria (Anopheles gambiae) and arbovirus vector (Aedes aegypti) larvae to decipher possible molecular targets. We report dose-dependent biphasic effects on larval response, with transient exposure to ZCE and its bioactive fraction (ZCFr.5) inhibiting acetylcholinesterase (AChE) activity, inducing larval lethality and growth retardation at sublethal doses. Half-maximal lethal concentrations (LC 50 ) for ZCE against An. gambiae and Ae. aegypti larvae after 24-h exposure were 9.00 ppm and 12.26 ppm, respectively. The active fraction ZCFr.5 exerted LC 50 of 1.58 ppm and 3.21 ppm for An. gambiae and Ae. aegypti larvae, respectively. Inhibition of AChE was potentially linked to larval toxicity afforded by 2-tridecanone, palmitic acid (hexadecanoic acid), linoleic acid ((Z,Z)-9,12-octadecadienoic acid), sesamin, β-caryophyllene among other compounds identified in the bioactive fraction. In addition, the phenotypic larval retardation induced by ZCE root constituents was exerted through transcriptional modulation of ecdysteroidogenic CYP450 genes. Collectively, these findings provide an explorative avenue for developing potential mosquito control agents from Z. chalybeum root constituents., (Copyright © 2021. Published by Elsevier Inc.)

Anaplasmosis, caused by infection with bacteria of the genus Anaplasma, is an important veterinary and zoonotic disease. Transmission by ticks has been characterized but little is known about non-tick vectors of livestock anaplasmosis. This study investigated the presence of Anaplasma spp. in camels in northern Kenya and whether the hematophagous camel ked, Hippobosca camelina, acts as a vector. Camels (n = 976) and > 10,000 keds were sampled over a three-year study period and the presence of Anaplasma species was determined by PCR-based assays targeting the Anaplasmataceae 16S rRNA gene. Camels were infected by a single species of Anaplasma, 'Candidatus Anaplasma camelii', with infection rates ranging from 63-78% during the dry (September 2017), wet (June-July 2018), and late wet seasons (July-August 2019). 10-29% of camel keds harbored 'Ca. Anaplasma camelii' acquired from infected camels during blood feeding. We determined that Anaplasma-positive camel keds could transmit 'Ca. Anaplasma camelii' to mice and rabbits via blood-feeding. We show competence in pathogen transmission and subsequent infection in mice and rabbits by microscopic observation in blood smears and by PCR. Transmission of 'Ca. Anaplasma camelii' to mice (8-47%) and rabbits (25%) occurred readily after ked bites. Hence, we demonstrate, for the first time, the potential of H. camelina as a vector of anaplasmosis. This key finding provides the rationale for establishing ked control programmes for improvement of livestock and human health., Competing Interests: The authors have declared that no competing interests exist.

Olfaction is orchestrated at different stages and involves various proteins at each step. For example, odorant-binding proteins (OBPs) are soluble proteins found in sensillum lymph that might encounter odorants before reaching the odorant receptors. In tsetse flies, the function of OBPs in olfaction is less understood. Here, we investigated the role of OBPs in Glossina fuscipes fuscipes olfaction, the main vector of sleeping sickness, using multidisciplinary approaches. Our tissue expression study demonstrated that GffLush was conserved in legs and antenna in both sexes, whereas GffObp44 and GffObp69 were expressed in the legs but absent in the antenna. GffObp99 was absent in the female antenna but expressed in the male antenna. Short odorant exposure induced a fast alteration in the transcription of OBP genes. Furthermore, we successfully silenced a specific OBP expressed in the antenna via dsRNAi feeding to decipher its function. We found that silencing OBPs that interact with 1-octen-3-ol significantly abolished flies' attraction to 1-octen-3-ol, a known attractant for tsetse fly. However, OBPs that demonstrated a weak interaction with 1-octen-3-ol did not affect the behavioral response, even though it was successfully silenced. Thus, OBPs' selective interaction with ligands, their expression in the antenna and their significant impact on behavior when silenced demonstrated their direct involvement in olfaction.

Objectives: We and others have shown that Aspilia pluriseta is associated with various biological activities. However, there is a lack of information on its cytotoxicity. This has created an information gap about the safety of A. pluriseta extracts. As an extension to our recent publication on the antimicrobial activity and the phytochemical characterization of A. pluriseta root extracts, here we report on cytotoxicity of tested solvent fractions. We evaluated the potential cytotoxicity of these root extract fractions on Vero cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay., Results: We show that all solvent extract fractions (except methanolic solvent fractions) had cytotoxic concentration values that killed 50% of the Vero cells (CC 50 ) greater than 20 µg/mL and selectivity index (SI) greater than 1.0. Taken together, we demonstrate that, A. pluriseta extract fractions' earlier reported bioactivities are within the acceptable cytotoxicity and selective index limits. This finding scientifically validates the potential use of A. pluriseta in the discovery of safe therapeutics agents.

Aspilia pluriseta is associated with various bioactivities, although with limited scientific justification. In this study, we evaluated the antimicrobial activity, and characterized the phytochemicals of root extracts of A. pluriseta aimed at validating its therapeutic potential. We used BACTEC MGIT™ 960 system to test for antitubercular activity, disc-diffusion together with the microdilution method to evaluate antimicrobial activities and qualitative phytochemical tests together with gas chromatography-mass spectrometry (GC-MS) analysis to determine the phytochemicals that associated with A. pluriseta extracts activity. We show that methanolic crude extract (at 1 g/mL) had high Mycobacterium tuberculosis (MTB) inhibitory activity (0 growth unit) and considerable potency against Escherichia coli (11.7 mm), Staphylococcus aureus (9.0 mm), and Candida albicans (7.7 mm). All the extract fractions exerted remarkable antimycobacterial activities with minimum inhibitory activity of between 6.26 - 25 μg/mL. The highest antimicrobial activity of petroleum ether and dichloromethane fraction was against E. coli at inhibition zone diameters of 8.3 mm, and 8.0 mm, respectively, while ethyl acetate fraction was against S. aureus with an inhibition zone of 8.7 mm. Methanolic fraction exhibited broad-spectrum activity against 87.5% of the tested microbes (inhibition zones 6.3-8.3 mm). Furthermore, we qualitatively detected terpenoids, alkaloids, and phenolics such as flavonoids, and anthraquinones in extract fractions. GC-MS analysis detected an abundance of fatty acid esters, 2-hydroxy-1-(hydroxymethyl) ethyl ester-hexadecanoic acid, and 2,3-dihydroxy propyl ester-octadecanoic acid and four alkanes. Taken together, we show that A. pluriseta extract fractions (especially ethyl acetate and methanolic fractions) have strong selective antitubercular activity, and thus, we scientifically validate the use of A. pluriseta as a potential source for the discovery of novel antitubercular agents., (© 2020 The Author(s).)

Malaria presents an overwhelming public health challenge, particularly in sub-Saharan Africa where vector favourable conditions and poverty prevail, potentiating the disease burden. Behavioural variability of malaria vectors poses a great challenge to existing vector control programmes with insecticide resistance already acquired to nearly all available chemical compounds. Thus, approaches incorporating plant-derived compounds to manipulate semiochemical-mediated behaviours through disruption of mosquito olfactory sensory system have considerably gained interests to interrupt malaria transmission cycle. The combination of push-pull methods and larval control have the potential to reduce malaria vector populations, thus minimising the risk of contracting malaria especially in resource-constrained communities where access to synthetic insecticides is a challenge. In this review, we have compiled information regarding the current status of knowledge on manipulation of larval ecology and chemical-mediated behaviour of adult mosquitoes with plant-derived compounds for controlling mosquito populations. Further, an update on the current advancements in technologies to improve longevity and efficiency of these compounds for field applications has been provided.

Successful optimization of plant-derived compounds into control of nuisance insects would benefit from scientifically validated targets. However, the close association between the genotypic responses and physiological toxicity effects mediated by these compounds remains underexplored. In this study, we evaluated the sublethal dose effects of proanthocyanidins (PAs) sourced from green tea (Camellia sinensis) on life history traits of Anopheles gambiae (sensu stricto) mosquitoes with an aim to unravel the probable molecular targets. Based on the induced phenotypic effects, genes selected for study targeted juvenile hormone (JH) biosynthesis, signal transduction, oxidative stress response and xenobiotic detoxification in addition to vitellogenesis in females. Our findings suggest that chronic exposure of larval stages (L3/L4) to sublethal dose of 5 ppm dramatically extended larval developmental period for up to 12 days, slowed down pupation rates, induced abnormal larval-pupal intermediates and caused 100% inhibition of adult emergence. Further, females exhibited significant interference of fecundity and egg hatchability relative to controls (p < 0.001). Using reverse transcription quantitative polymerase chain reaction (RT-qPCR), our findings show that PA-treated larvae exhibited significant repression of AgamJHAMT (p < 0.001), AgamILP1 (p < 0.001) and AgamCYP6M2 (p < 0.001) with up-regulation of Hsp70 (p < 0.001). Females exposed as larvae demonstrated down-regulation of AgamVg (p = 0.03), AgamILP1 (p = 0.009), AgamCYP6M2 (p = 0.05) and AgamJHAMT (p = 0.02). Our findings support that C. sinensis proanthocyanidins affect important vectorial capacity components such as mosquito survival rates and reproductive fitness thus could be potentially used for controlling populations of malaria vectors.

Background: Vector control remains the mainstay to effective malaria management. The negative implications following persistent application of synthetic insecticides geared towards regulation of mosquito populations have necessitated prospection for ecofriendly effective chemistries. Plant-derived compounds have the potential to control malaria-transmitting mosquito populations. Previously, Agerantum conyzoides extracts have demonstrated toxicity effects on disease-transmitting mosquitoes. However, their efficacy in controlling Afrotropical malaria vectors remains unclear. Herein, the toxicity and growth disruption activities of crude methanolic leaf extract of A. conyzoides on Anopheles gambiae sensu stricto and An. arabiensis larvae were assessed., Methods: Late third (L3) instars of An. gambiae s.s and An. arabiensis larvae were challenged with increasing doses of crude methanolic extract of A. conyzoides. The larval mortality rates were recorded every 24 h and the LC 50 values determined at their associated 95% confidence levels. ANOVA followed by Post-hoc Student-Newman-Keuls (SNK) test was used to compare results between treatment and control groups. Phytochemical profiling of the extract was performed using standard chemical procedures., Results: Treatment of larvae with the methanolic extract depicted dose-dependent effects with highest mortality percentages of ≥ 69% observed when exposed with 250 ppm and 500 ppm for 48 h while growth disruption effects were induced by sublethal doses of between 50-100 ppm for both species. Relative to experimental controls, the extract significantly reduced larval survival in both mosquito species (ANOVA, F (8,126)  = 43.16776, P < 0.001). The LC 50 values of the extract against An. gambiae s.s ranged between 84.71-232.70 ppm (95% CI 81.17-239.20), while against An. arabiensis the values ranged between 133.46-406.35 ppm (95% CI 131.51-411.25). The development of the juvenile stages was arrested at pupal-larval intermediates and adult emergence. The presence of alkaloids, aglycone flavonoids, triterpenoids, tannins and coumarins can partly be associated with the observed effects., Conclusion: The extract displayed considerable larvicidal activity and inhibited emergence of adult mosquitoes relative to experimental controls, a phenomenon probably associated with induced developmental hormone imbalance. Optimization of the bioactive compounds could open pathways into vector control programmes for improved mosquito control and reduced malaria transmission rates.

Background: Anopheles arabiensis and A. gambiae (sensu stricto) are the most prolific Afrotropical malaria vectors. Population control efforts of these two vectors have been hampered by extremely diverse larval breeding sites and widespread resistance to currently available insecticides. Control of mosquito larval stages using bioactive compounds of plant origin has the potential to suppress vector populations leading to concomitant reduction in disease transmission rates. In this study, we evaluated the efficacy of Camellia sinensis crude leaf extract and its fraction against the larvae of A. arabiensis and A. gambiae (s.s.)., Methods: Late third/early fourth instar larvae (L3/L4) of A. arabiensis and A. gambiae (s.s.) were exposed to increasing doses of C. sinensis leaf extract and its active fraction for 72 h, with mortality rates recorded every 24 h in both control and test groups. Ultra performance liquid chromatography electron spray ionization quadruple time of flight coupled with mass spectrometry (UPLC/ESI-Qtof/MS) was used to determine the main active constituents in the fraction., Results: The major bioactive chemical constituents in the C. sinensis leaf extract were identified to be proanthocyanidins. The extract significantly interfered with larval survival and adult emergence in both species (ANOVA, F (5,24) = 1435.92, P < 0.001). Additionally, larval exposure to crude extract at 250 ppm and 500 ppm for 24 h resulted in larval mortality rates of over 90 % in A. gambiae (s.s.) and 75 % in A. arabiensis. A relatively lower concentration of 100 ppm resulted in moderate mortality rates of < 50 % in both species, but induced growth disruption effects evident as abnormal larval-pupal intermediates and disrupted adult emergence. The estimated LC 50 concentrations of the crude leaf extract against A. arabiensis and A. gambiae (s.s.) larvae at 24 h were 154.58 ppm (95 % CI: 152.37-158.22) and 117.15 ppm (95 % CI: 112.86-127.04), respectively. The bioactive polar fraction caused 100 % larval mortality in both vector species at 25 ppm., Conclusions: Our findings demonstrate the potential of green tea extract and its active constituents in disrupting mosquito larval development. This could contribute to the control of mosquito populations and improved management of malaria.