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1 H NMR-based metabolomics of antimalarial plant species traditionally used by Vha-Venda people in Limpopo Province, South Africa and isolation of antiplasmodial compounds
Abstract
Ethnopharmacological relevance:
The Vha-Venda people living in rural areas of Limpopo Province of South Africa regularly use traditional plant-based medicines to treat malaria. In our earlier publication, twenty indigenous plant species used to treat malaria or its symptoms by Vha-Venda people were evaluated for antiplasmodial activity. The main objective of the current study was to assess the robustness of NMR-based metabolomics in discriminating classes of secondary compounds that are responsible for the observed antimalarial activity and the isolation of antiplasmodial compounds.
Materials and methods:
Twenty dichloromethane extracts were reconstituted in CDCl3, subjected to 1H NMR-based metabolomic analysis on a Varian 600MHz spectrometer and the acquired 1H NMR spectra were then evaluated collectively using multivariate data analysis (MDA). Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) were used to 'globally' discern antiplasmodial profiles. A contribution plot was then generated from the OPLS-DA scoring plot in an attempt to determine the classes of compounds that are responsible for the observed grouping. Further phytochemical analyses were conducted on the lipophilic extracts of Tabernaemontana elegans and Vangueria infausta subsp. infausta. These best candidates were fractionated, purified and their isolated compounds identified based on conventional chromatographic and spectroscopic techniques.
Results:
The PCA did not separate the acquired profiles according to the detected antiplasmodial bioactivity. Application of a supervised OPLS-DA on the 1H NMR profiles resulted in a discrimination pattern that could be correlated to the observed antimalarial bioactivity. A contribution plot generated from the OPLS-DA scoring plot illustrated the classes of compounds responsible for the observed grouping. Prominent peaks were observed in the aromatic, sugar-based/N-containing and aliphatic spectral regions of the contribution plot. Two known indole alkaloids were isolated from T. elegans, and identified as tabernaemontanine (IC50 = 12.0±0.8µM) and dregamine (IC50 = 62.0±2.4µM). Friedelin (IC50 = 7.20±0.5µM) and morindolide (IC50 = 107.1±0.6µM) were isolated from V. infausta subsp. infausta. This is the first report of the rare iridoid lactone, morindolide's antimalarial activity. While these two compounds have been previously identified, this is the first account of their occurrence in the genus Vangueria.
Conclusion:
The study illustrated the potential of NMR-based metabolomics in discriminating classes of compounds that may be attributed to antiplasmodial activity. Additionally, the study demonstrated the potential of discovering novel antiplasmodial scaffolds from medicinal plants and the rationale for the bioprospecting antimalarial plant species used by Vha-Venda people.
... The biological activities of V. infausta have been extensively investigated, relative to its phytochemistry. The reviewed literature shows that all parts of the plant have exhibited both antimalarial 60 and antifungal activities [60][61][62] . Inhibitory activities of leaf extracts against seven pathogenic fungi were observed with acetone and dichloromethane (DCM) extracts at a MIC of 0.32 mg/mL. ...
... 36 An indole alkaloid, morindolide, isolated from the leaf displayed good antimalarial activity at IC 50 = 107.1±0.6 µM. 60 The hexane, DCM, acetone, and methanol extracts of V. infausta leaves demonstrated inhibitory activities against Enterococcus faecalis at a low MIC value of 0.02 mg/mL. 60 The DCM extract of V. infausta root exhibited high inhibitory effects on the Leishmania protozoan with an IC 50 value of 4.51 µg/mL 63 , a significant antiplasmodial activity at IC 50 of 1.84 µg/mL, and a selectivity index of 25 against Plasmodium falciparum 64 . ...
... 60 The hexane, DCM, acetone, and methanol extracts of V. infausta leaves demonstrated inhibitory activities against Enterococcus faecalis at a low MIC value of 0.02 mg/mL. 60 The DCM extract of V. infausta root exhibited high inhibitory effects on the Leishmania protozoan with an IC 50 value of 4.51 µg/mL 63 , a significant antiplasmodial activity at IC 50 of 1.84 µg/mL, and a selectivity index of 25 against Plasmodium falciparum 64 . The report resonated with earlier findings, which identified chloroform extracts from the V. infausta root bark that markedly inhibited the activities of two Plasmodium falciparum strains at IC 50 s of 3.8 µg/mL and 4.50 µg/mL. ...
The coastal regions of Africa are endowed with indigenous wild fruit plants rich in nutritional and medicinal phytochemicals and micronutrients. South African wild fruit plants complement the diet and health needs of rural poor households by providing vital dietary nutrients and remedies for various health concerns, and alleviating food insecurity. Milk plum, Natal plum, wild custard apple, and wild medlar medicinal plants are found mainly in the coastal provinces of South Africa. Studies have established that these plants are good sources of vitamins, essential elements, and bioactive phytocompounds such as flavonoids, phenolic acids, and terpenoids, which demonstrate significant antioxidant, antimicrobial and anti-inflammatory activities. The plants studied possess anti-epileptic, antiplasmodial, and snake antivenom qualities. Here we highlight the views of different reports on ethnopharmacological relevance, phytochemistry, and bioactivity of the selected South African indigenous medicinal plants. We found a research gap in the phytochemical composition and phytopharmacological activity evaluation of Carissa macrocarpa and Englerophytum magalismontanum.
Significance:
• South African indigenous medicinal plants augment the dietary and other health needs of the rural populace. The phytochemistry and phytopharmacological activities of C. macrocarpa and E. magalismontanum have been only partially studied, hence the need for further studies to examine their worth and possible use in cosmetic product enrichment.
... Biological activities of C. spicata extracts and compounds isolated from the species include acetylcholinesterase [100], antibacterial [57,58,77,101,102], antiviral [101,103], anti-inflammatory [57,58], antileishmanial [104], antiplasmodial [57,58,63,64,102,[105][106][107], antiprotozoan [102], antioxidant [100], larvicidal [108,109], molluscicidal [60,110,111], spermicidal [112], and cytotoxicity [63,64,[102][103][104] activities. ...
... The extracts exhibited moderate cytotoxicity activities with IC 50 values ranging from 23.9 mg/mL to >50.0 mg/mL [102]. Bapela [64] and Bapela et al. [63,104,107] evaluated cytotoxicity activities of dichloromethane and 50% methanol root bark extracts of C. spicata against mammalian L-6 rat skeletal myoblast cells with podophyllotoxin as a control. The dichloromethane extract demonstrated IC 50 value of 47.8 µg/ml and selectivity index value of 15 and 50% methanol extract exhibited IC 50 value of 69.1 µg/ml which was considered to be non-toxic to rat skeletal myoblast L6 cells [63,104,107]. ...
... Bapela [64] and Bapela et al. [63,104,107] evaluated cytotoxicity activities of dichloromethane and 50% methanol root bark extracts of C. spicata against mammalian L-6 rat skeletal myoblast cells with podophyllotoxin as a control. The dichloromethane extract demonstrated IC 50 value of 47.8 µg/ml and selectivity index value of 15 and 50% methanol extract exhibited IC 50 value of 69.1 µg/ml which was considered to be non-toxic to rat skeletal myoblast L6 cells [63,104,107]. ...
Cussonia spicata is an evergreen tree widely used as herbal medicine throughout its distributional range in tropical Africa. The current study is aimed at providing a critical review of the phytochemistry, pharmacology, and evaluation of the medicinal potential of C. spicata. Documented information on the phytochemistry, pharmacology, and medicinal applications of C. spicata was collected from several online sources which included BMC, Scopus, SciFinder, Google Scholar, Science Direct, Elsevier, PubMed, and Web of Science. Additional information on the phytochemistry, pharmacology, and medicinal applications of C. spicata was gathered from pre-electronic sources such as book chapters, books, journal articles, and scientific publications sourced from the University library. This study showed that the bark, flowers, flower stalks, fruits, leaves, roots, root bark, and stems of C. spicata are used as antifebrile and emetic and herbal medicine for fever, nausea, vomiting, gonorrhea, venereal diseases, malaria, and mental illness. Phytochemical compounds identified from the leaves, root bark, stems, and stem bark of C. spicata include alkaloids, anthocyanins, anthracene glycosides, botulin, condensed tannins, free gallic acid, gallotannins, iridoids, pentacyclic triterpenoids, saponins, steroids, tannins, flavonoids, phenolics, triterpenoids, and volatile oils. Pharmacological research revealed that C. spicata crude extracts and compounds have acetylcholinesterase, antibacterial, antiviral, anti-inflammatory, antileishmanial, antiplasmodial, antiprotozoan, antioxidant, larvicidal, molluscicidal, spermicidal, and cytotoxicity activities. Future research should focus on evaluating the phytochemical, pharmacological, and toxicological properties of C. spicata crude extracts as well as compounds isolated from the species.
... The extract showed activities with IC50 value of 5.47 µg/ml in comparison to 0.003 µg/ml exhibited by the positive control (Bapela et al., 2014). Bapela et al. (2019) Gaichu et al. (2023a,b) evaluated the cardioprotective activities of aqueous extracts of P. capensis leaves in salbutamolinduced Wistar albino rats with myocardial infarction. The extracts exhibited dose-dependent cardioprotective activities (Gaichu et al., 2023a,b). ...
... evaluated antiplasmodial activities of dichloromethane and methanol extracts of P. capensis twigs using the [ 3 H]-hypoxanthine incorporation assay against the chloroquine sensitive (NF54) strain of Plasmodium falciparum. Both extracts exhibited activities with IC50 values of 5.47 µg/ml and 24.8 µg/ml, respectively(Bapela et al., 2019).Tajuddeen et al. (2021) evaluated the antiplasmodial activities of methanol extracts of P. capensis leaves and the compounds quercetin 3-O-arabinopyranoside, quercitrin, kaempferol 3-O-arabinopyranoside and quercitrin 3-O-β-D-glucoside isolated from the species against the chloroquine-sensitive 3D7 Plasmodium falciparum using the parasite lactate dehydrogenase assay. The methanol extract and the phytochemical compounds inhibited the viability of Plasmodium falciparum(Tajuddeen et al., 2021).Mabuza et al. (2022) evaluated the antiplasmodial activities of dichloromethane, methanol and water mixture of P. capensis twigs using the using the [ 3 H]-hypoxanthine incorporation assay against the Plasmodium falciparum (NF54) and chloroquine as the standard drug. ...
Background: Pappea capensis has potential as a fruit plant on the basis of fruit size, palatability, yield, abundance and nutritional properties. But today, P. capensis it is a well-known medicinal plant throughout its distributional range, with local communities relying on its traditional materia medica for primary healthcare needs. The present review compiles existing information on traditional uses, chemical, pharmacological properties, and further use potential and applications of P. capensis. Methods: Multiple searches on existing literature on the traditional, medicinal, phytochemistry and pharmacological properties of P. capensis were conducted in online databases such as Scopus, JSTOR, PubMed, Google Scholar and Science Direct as well as using pre-electronic literature sources obtained from the university library. Results: This study showed that P. capensis is a multipurpose species used as food plant, source of firewood, timber and herbal medicine. Pappea capensis is used as medicinal plant against human and animal diseases in 11 countries, representing 55.0% of the countries where the species is indigenous. The chemical evaluation of the plant species revealed that it contains acids, alcohols, aliphatic, alkaloids, alkyl, amino acids, anthocyanidins, cardiac glycosides, cyanidins, cyclic esters, fatty acids, flavonoids, phenolics, phytol, phytosterols, saponins, tannins and terpenoids. The pharmacological evaluations showed that the crude extracts and phytochemical compounds isolated from the species demonstrated anthelmintic, antibacterial, antimycobacterial, antigonococcal, antifungal, anti-HIV, anticancer, antidiabetic, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, cardioprotective and molluscicidal. Conclusions: Detailed ethnopharmacological evaluation of P. capensis focusing on its phytochemistry, pharmacological properties and toxicological evaluations, in vivo and clinical research are recommended. Keywords: indigenous pharmacopeia, materia medica, Pappea capensis, traditional medicine, tropical Africa
... Nowadays medicinal plants still represent an important pool for the identification of novel drug leads (Atanasov et al., 2015). However, the potential of many of them as new antimicrobial scaffolds has not sufficiently been explored (Bapela et al., 2019). Furthermore, the isolation and purification of plant compounds in an adequate yield remains a major concern (Savi et al., 2019). ...
... Friedelin has been previously isolated from several Terminalia species including T. glaucescens T. mollis and T. avicennioides (Mann et al., 2012). The activity of friedelin against P. falciparum found in our study (31.2 μM) is lower than previously reported (IC 50 7.70 and 7.20 ± 0.5 μM) (Ngouamegne et al., 2008;Bapela et al., 2019). ...
Ethnopharmacological relevance
Terminalia albida (Combretaceae), widely used in Guinean traditional medicine, showed promising activity against Plasmodium falciparum and Candida albicans in previous studies. Bioassay-guided fractionation was carried out in order to isolate the compounds responsible for these activities.
Materials and methods
Fractionation and isolation were performed by flash chromatography, followed by semi-preparative HPLC-DAD-MS. The structural elucidation of the isolated compounds was carried out by 1D and 2D NMR as well as HR-ESI-MS. Isolated compounds were evaluated against Plasmodium falciparum, Candida albicans, Staphylococcus aureus and Escherichia coli, and their cytotoxicity against MRC-5 cells was determined.
Results
Bioassay-guided fractionation of Terminalia albida root resulted in the isolation of 14 compounds (1–14), and their antimicrobial properties were evaluated. Pantolactone (1) (IC50 0.60 ± 0.03 μM) demonstrated significant activity against P. falciparum. Other compounds, including 3,4,3′-tri-O-methyl-ellagic acid (3), the triterpenes arjunolic acid (5), arjungenin (6), arjunic acid (7) and arjunglucoside II (10), and the phenol glycoside calophymembranside-B (14), were less active and showed IC50 values in the range 5–15 μM. None of the tested compound showed antibacterial or antifungal activity.
Conclusion
These results may explain at least in part the activity of the root extract of T. albida against P. falciparum.
... All of the above is entirely dependent on the ability to isolate and purify bioactive compounds from extracts. Classical bioassay-guided fractionation approaches have been expansively employed within the malaria field [134][135][136], whilst cutting-edge technologies for improved isolation of bioactive compounds have been developed and should be explored for transmission-blocking discovery [134][135][136][137][138]. ...
... All of the above is entirely dependent on the ability to isolate and purify bioactive compounds from extracts. Classical bioassay-guided fractionation approaches have been expansively employed within the malaria field [134][135][136], whilst cutting-edge technologies for improved isolation of bioactive compounds have been developed and should be explored for transmission-blocking discovery [134][135][136][137][138]. ...
The ability to block human-to-mosquito and mosquito-to-human transmission of Plasmodium parasites is fundamental to accomplish the ambitious goal of malaria elimination. The WHO currently recommends only primaquine as a transmission-blocking drug but its use is severely restricted by toxicity in some populations. New, safe and clinically effective transmission-blocking drugs therefore need to be discovered. While natural products have been extensively investigated for the development of chemotherapeutic antimalarial agents, their potential use as transmission-blocking drugs is comparatively poorly explored. Here, we provide a comprehensive summary of the activities of natural products (and their derivatives) of plant and microbial origins against sexual stages of Plasmodium parasites and the Anopheles mosquito vector. We identify the prevailing challenges and opportunities and suggest how these can be mitigated and/or exploited in an endeavor to expedite transmission-blocking drug discovery efforts from natural products.
... In particular, future studies documenting the traditional use of plants to treat malaria by ethnic groups in endemic malaria areas are required. We were only able to find limited studies reviewing the use of traditional medicines by the Venda people for the treatment of malaria (Prozesky et al., 2001;Bapela et al., 2019). Similarly, ethnobotanical studies recording the traditional methods of treating malaria for the Ndebele, northern Sotho, Tsonga, Tswana, and Pedi are lacking. ...
... Although chemical characterization of antimalarial compounds was not the main focus of this review, cognisance of the chemistry is important. In fact, more recently, NMR-based metabolomics have been used for in-depth studies into the phytochemistry of the compounds within in medicinal plants responsible for antimalarial activity (Bapela et al., 2019). Such studies hold promise for future structure elucidation studies. ...
Ethnopharmalogical relevance:
Malaria is one of the most prevalent and deadly parasitic diseases globally, with over 200 million new cases and nearly 500,000 deaths reported annually. It is estimated that approximately half of the world's population lives in malaria endemic areas. Malaria is substantially less prevalent in South Africa than in other African regions and the disease is limited to some regions of the Limpopo, Mpumalanga and KwaZulu-Natal provinces. However, it still has a significant impact on the health of the populations living in those regions. Traditional medicines have long been used in South Africa by multiple ethic groups and many people continue to rely on these natural therapies for their healthcare. The usage of South African medicinal plants in several traditional healing systems to treat malaria have been documented (particularly for Zulu and Venda traditional medicine), although ethnobotanical investigations of other ethnic groups living in endemic malaria areas remains relatively neglected.
Aim of the study:
To document the use of South African medicinal plants known to be used traditionally to treat Plasmodium spp. infections. We also critically reviewed the literature on the therapeutic properties of these and other South African plants screened against Plasmodium spp. parasites with the aim of highlighting neglected studies and fostering future research in this area.
Materials and methods:
Books and ethnobotanical reviews were examined for medicinal plants used specifically for fever. Exclusion criteria were studies not involving southern African medicinal plants. Furthermore, while fever is a common symptom of malaria, if not accompanied by the term "malaria" it was not considered. Databases including PubMed, ScienceDirect, Scopus and Google Scholar were used to source research relevant to southern African plants and malaria. Exclusion criteria were those publications where full articles could not be accessed.
Results:
Eighty South African plant species were identified as traditional therapies for malaria. The majority of these species were documented in Zulu ethnobotanical records, despite malaria occurring in only a relatively small portion of the Zulu's traditional territory. Surprisingly, far fewer species were reported to be used by Venda, Ndebele, northern Sotho, Tsonga, Tswana, and Pedi people, despite them living in endemic malaria areas. Interestingly many of the identified species have not been investigated further. This review summarises the available ethnobotanical and laboratory research in this field, with the aim of promoting and focusing research on priority areas.
Conclusion:
Although malaria remains a serious disease affecting millions of people, medicinal plants while used extensively, have not been given the attention warranted for further investigation.
... However, nuclear magnetic resonance spectroscopy (NMR) is used to identify substances in medicinal plants based on the 1 H NMR technique in metabolomics. It has also been used in the quality control of herbal parts [19,20] and to discover new substances in plants. This technique has the advantage of being non-destructive. ...
Fingerroot (Boesenbergia rotunda (L.) Mansf.) is valued for its therapeutic benefits, both in Thailand and internationally. This study optimized in vitro propagation and induced microrhizomes (MRZ) to produce cleaned plantlets to support organic farming using disease-free plantlets, which is crucial for preventing and eradicating diseased plantlets, reducing the use of chemicals, and alternative approaches to enhancing phytochemical diversity. Shoots cultured on ½-strength MS medium with 1 mg L⁻¹ of 6-benzylaminopurine (BAP) showed the highest shoot formation (69%) and shoot multiplication (3.45 ± 0.29 shoots per explant). Plantlets acclimatized in peat moss or a peat moss–coconut coir (1:1) mixture achieved a 100% survival rate. Genetic fidelity was confirmed using SSR markers, showing genetic consistency with the mother plant. The MRZ formation was the highest (98.33%) under white LED light with 30 g L⁻¹ of sucrose. Nuclear magnetic resonance (NMR) analysis in MRZ revealed aspartate, a precursor to pinocembrin and pinostrobin. Additionally, nine unique metabolites not previously identified in fingerroot were detected in the MRZ, suggesting some potential in novel therapeutic applications. These findings support the development of efficient micropropagation methods and highlight MRZ as a source of diverse bioactive compounds, contributing to the medicinal value of B. rotunda in sustainable and large-scale production.
... Vangueria infausta belongs to the Rubiaceae family, seldom browsed by cattle, but very much so by goats, and wild animals such as elephant, giraffe, kudu and nyala. The species possess a number of beneficial volatile compounds [34][35][36][37]. Peltophorum africanum (weeping wattle) belongs to the Fabaceae family, and is inherent to Southern Africa, is well known for its antimicrobial activity [30], antioxidant properties and non-toxicity at low concentrations [38]. ...
This study aimed to determine the extraction yield, phytochemical content, antibacterial, antioxidant, and cytotoxic activities of leaves extracts from Eucalyptus globulus, Peltophorum africanum, and Vangueria infausta. Leaves were harvested, separated from the stems, and dried for chemical analysis. Crude and oil extraction, antioxidant activity, cytotoxicity, and minimum inhibitory concentration were determined, and tannins, flavonoids and alkaloids were quantified by standard protocols. The phenolic, flavonoids, and condensed tannin contents were higher (P < 0.05) in V. infausta extract than in E. globulus and P. africanum. The radical scavenging activities were higher (P < 0.05) in V. infausta, E. globulus than in P. africanum. The antibacterial activity was lower (P < 0.05) for P. africanum and E. globulus oil, and was strongly related to the presence of phenolics and flavonoids. The lack of toxicity of plant extracts suggests that extracts can be used as animal feed additives with no risk of toxicity. Vangueria infausta, Eucalyptus globulus had the highest antioxidant capability and can thus modulate nutrient metabolism in animals.
... Recently, the integration of chemometrics and metabolomics has found extensive applications in natural product research because of their combined effectiveness in the rapid spotting and precise annotation of bioactive metabolites before putative lengthy isolation processes (Wolfender et al. 2019;Cornejo-Báez et al. 2020). Over the past decade, a number of studies have reported the successful application of this combination of techniques to discover bioactive compounds from different plant species, including leishmanicidal metabolites from Colubrina greggii S.Watson (Álvarez-Zapata et al. 2015), tyrosinase inhibitors from Morus alba L. Moraceae (Chaita et al. 2017), and antihelminthic products from Lysiloma latisiliquum (L.) Benth., Fabaceae (Hernández-Bolio et al. 2018), as well as antiplasmodial indole alkaloids from different plant species (Bapela et al. 2019), isoquinoline alkaloids as acetylcholinesterase (AChE) inhibitors in species of Zanthoxylum L., Rutaceae (Plazas et al. 2019), antiplasmodial triterpenes in species of Keetia E.Phillips (Freire et al. 2019), and anti-inflammatory metabolites from the green alga Klebsormidium flaccidum var zivo (Qiu et al. 2020). ...
The emergence and reappearance of a growing number of diseases, together with the loss of biodiversity, have restructured bioprospecting methodologies when studying secondary metabolites, which continue to play a key role in the discovery of natural products with pharmacological activity. In this investigation, a combined approach using chemometric analyses of 1H-NMR and HPLC metabolic and chromatographic profiles, respectively, and 13C-NMR dereplication analysis has been used to identify inhibitors of virulence factors in bacteria as part of a new approach in the fight against antimicrobial resistance. Multivariate statistical analysis was used to correlate the 1H-NMR metabolic and HPLC chromatographic profiles of the root crude extract and semipurified fractions from Colubrina yucatanensis (M.C.Johnst.) G.L.Nesom, Rhamnaceae, with the results from their inhibition of the production of pyocyanin, proteases, and biofilm formation in a model of Pseudomonas aeruginosa. The methodology used allowed the identification of activity-associated signals and components in the 1H-NMR metabolic and HPLC chromatographic profiles of the bioactive extract and semipurified fractions, respectively. 13C-NMR dereplication analysis of the semipurified bioactive fractions using the MixONat software confirmed that one of the activity-associated signals detected in the 1H-NMR profile belonged to 3-O-acetyl-ceanotic acid. Purification and evaluation of the pure ceanotane confirmed its identification as one of the bioactive metabolites produced by C. yucatanensis. This is the first report of 3-O-acetyl-ceanotic acid as a natural inhibitor of bacterial virulence factors.
... Wild medlar has been utilized to treat roundworm, snake bites, malaria, fever, fungal infections (candidiasis), pneumonia, and chest-related problems in traditional medicine [56,88,92]. The successful use of wild medlar in traditional medicine can be traced back to its antioxidant, antibacterial, antifungal, antiplasmodial, and anti-inflammatory properties [88,[93][94][95][96][97][98][99][100]. The cytotoxicity activities of methanolic and aqueous root extracts of this plant against MAGI CC5+ cells showed cytotoxic halfmaximal concentrations (CC50) of 0.1 mg/mL [101]. ...
Africa is home to diverse medicinal plants that have been used for generations for the treatment of several different cancers and, presently, they are gaining interest from researchers as promising approaches to cancer treatment. This review aims to provide a comprehensive review of dietary and medicinal African fruits including their traditional uses, botanical description, ethnobotanical uses, bioactive phytochemical compositions, and anticancer properties investigated to date in vitro, in vivo, and in clinical studies. Data on recent updates concerning the traditional uses and anticancer properties of these fruits were collected from a myriad of available publications in electronic databases, such as Web of Science, PubMed, ScienceDirect, Scopus, SpringerLink, and Google Scholar. The results suggest that approximately 12 native or commercially grown African fruits belonging to different plant species, including Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia Africana, Annona muricata, Persea americana, and Punica granatum, have been reported for their potential as treatment options for the management of cancer. We further found that approximately eight different fruits from native plant species from Africa, namely, Sclerocarya birrea, Dovyalis caffra, Parinari curatellifolia, Mimusops caffra, Carpobrotus edulis, Vangueria infausta, Harpephyllum caffrum, and Carissa macrocarpa, have been widely used for the traditional treatment of different ailments but somehow failed to gain the interest of researchers for their use in anticancer research. In this review, we show the potential use of various fruits as anticancer agents, such as Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia Africana, Annona muricata, Persea americana, and Punica granatum; unfortunately, not enough reported research data have been published to gain thorough mechanistic insights and clinical applications. Additionally, we discuss the possibility of the utilization of potential phytochemicals from fruits like Persea americana and Punica granatum in anticancer research, as well as future directions.
... This traditional medicine therefore presents itself as a credible alternative in the fight against malaria. We would then understand the craze for screening plant extracts for compounds with antimalarial activity, as shown by several works carried out at the continental level [14,15] . In DRC antimalarial activity of several plant was previously evaluated [16][17][18] . ...
... The aqueous extract had a SI of 30.01 and 25.23 for Pf3D7 and PfDd2, respectively, and was higher than that of the ethanol extract which was 15.9 and 8.51 for Pf3D7 and PfDd2, respectively. A similar study was conducted by Bapela et al. [36] on B. mollis Hutch where they had a CC 50 of 51.4 μg/ml with a SI of 17. The difference observed here may be due to the cell strain used for the cytotoxicity test. ...
Introduction:
Resistance to common antimalarial drugs and persistence of the endemicity of malaria constitute a major public health problem in Cameroon. The aim of this study was to evaluate the in vitro antiplasmodial, antioxidant, and cytotoxic activities of aqueous and ethanol extracts of Bridelia micrantha used by Cameroonian traditional healers for the treatment of malaria.
Methods:
Aqueous and ethanolic stem bark extracts were prepared according to standard procedures. The SYBR Green method was used for antiplasmodial activity on strains of Plasmodium falciparum sensitive to chloroquine (3D7) and resistant (Dd2). In vitro antioxidant activities of B. micrantha were determined using the scavenging activity of 2,2'-diphenyl-1-picrylhydrazyl, nitric oxide, ferric reducing power, and hydrogen peroxide as well as their cytotoxicity on RAW 264.7 macrophage cells and red blood cells (RBC).
Results:
The aqueous and ethanol extracts of Bridelia micrantha showed antiplasmodial activity on the 3D7 strain with IC50 of 31.65 ± 0.79 μg/ml and 19.41 ± 2.93 μg/ml, respectively, as well as 37.64 ± 0.77 μg/ml and 36.22 ± 1.04 μg/ml for the Dd2 strain, respectively. The aqueous and ethanol extracts showed free radical scavenging properties. The IC50 aqueous and ethanol extract was approximately 0.0001737 μg/ml, 42.92 μg/ml, 1197 μg/ml, 63.78 μg/ml and 4.617 μg/ml, 429.9 μg/ml, 511 μg/ml, and 69.32 μg/ml for DPPH, NO, H2O2, and FRAP, respectively, which were compared to ascorbic acid (8.610e - 005 μg/ml, 2901 μg/ml, 3237 μg/ml, and 18.57 μg/ml). The aqueous and ethanol extracts of B. micrantha were found to be nontoxic with CC50 values of 950 ± 6.6 μg/ml and 308.3 ± 45.4 μg/ml, respectively. Haemolysis test showed that the two extracts were not toxic.
Conclusion:
These results suggest that B. micrantha can serve as an antimalarial agent. However, further studies are needed to validate the use of B. micrantha as an antimalarial.
... It has successfully been used for metabolic fingerprinting of various herbal materials [9]. The 1 H-NMR-based metabolic evaluation has also been used for quality control of herbal materials [10][11][12]. As a chemometric approach, the analyzed data are further evaluated through multivariate data analysis, including principal component analysis, to extract information out of the large amount of data obtained in metabolomics studies. ...
Adhatoda vasica (L.), Nees is a widespread plant in Asia. It is used in Ayurvedic and Unani medications for the management of various infections and health disorders, especially as a decoction to treat cough, chronic bronchitis, and asthma. Although it has a diverse metabolomic profile, this plant is particularly known for its alkaloids. The present study is the first to report a broad range of present compounds, e.g., α-linolenic acid, acetate, alanine, threonine, valine, glutamate, malate, fumaric acid, sucrose, β-glucose, kaempferol analogues, quercetin analogues, luteolin, flavone glucoside, vasicine and vasicinone, which were identified by NMR spectroscopy-based metabolomics. Multivariate data analysis was used to analyze 1H-NMR bucketed data from a number of Adhatoda vasica leave samples collected from eight different regions in Pakistan. The results showed large variability in metabolomic fingerprints. The major difference was on the basis of longitude/latitude and altitude of the areas, with both primary and secondary metabolites discriminating the samples from various regions.
... This traditional medicine therefore presents itself as a credible alternative in the fight against malaria. We would then understand the craze for screening plant extracts for compounds with antimalarial activity, as shown by several works carried out at the continental level [14,15] . In DRC antimalarial activity of several plant was previously evaluated [16][17][18] . ...
... It requires metabolites at microgram/micromole levels, while MS can detect metabolites at femtomole or even attomole levels. The most common method used for analysis in plant metabolomics is 1D (1H) NMR, e.g., metabolomics of abiotic and biotic stresses [52][53][54], novel compound identification [55], and evolutionary research [56]. This method, 1D NMR, allows highthroughput analysis of hundreds, or even thousands, of samples, since it takes only a few minutes per sample. ...
In the past two decades, the post-genomic era envisaged high-throughput technologies, resulting in more species with available genome sequences. In-depth multi-omics approaches have evolved to integrate cellular processes at various levels into a systems biology knowledge base. Metab-olomics plays a crucial role in molecular networking to bridge the gaps between genotypes and phenotypes. However, the greater complexity of metabolites with diverse chemical and physical properties has limited the advances in plant metabolomics. For several years, applications of liquid/gas chromatography (LC/GC)-mass spectrometry (MS) and nuclear magnetic resonance (NMR) have been constantly developed. Recently, ion mobility spectrometry (IMS)-MS has shown utility in resolving iso-meric and isobaric metabolites. Both MS and NMR combined metabolomics significantly increased the identification and quantification of metabolites in an untargeted and targeted manner. Thus, hyphen-ated metabolomics tools will narrow the gap between the number of metabolite features and the identified metabolites. Metabolites change in response to environmental conditions, including biotic and abiotic stress factors. The spatial distribution of metabolites across different organs, tissues, cells and cellular compartments is a trending research area in metabolomics. Herein, we review recent technological advancements in metabolomics and their applications in understanding plant stress biology and different levels of spatial organization. In addition, we discuss the opportunities and challenges in multiple stress interactions, multi-omics, and single-cell metabolomics.
... In vitro antiplasmodial action has been tested in ethnopharmacologically selected South African plant species and several plant species have been shown to possess antimalarial activity. Tabernaemontana elegans, Vangueria infausta, Albizia versicolor, Capparis tomentosa, Dichrostachys cinerea, Rauvolfia caffra, Xylopia parviflora, Bridelia mollis, and Cussonia spicata all showed varying levels of antimalarial activity (Bapela et al., 2019). A previous study by Abbas et al (2007) was conducted to examine the aerial part of Commiphora opobalsamum L. (Burseraceae) growing in Saudi Arabia. ...
Malaria is a lethal parasitic disease affecting over two hundred million people worldwide and kills almost half a million people per year. Until now, there is no curative treatment for this disease that has a substantial morbidity. The available chemotherapeutic agents are unable to completely control the infection with the continuous appearance of drug resistance. Consequently, the search for new therapeutic agents with high safety profiles and low side effects is of paramount importance. Several natural products have been investigated and proven to have antimalarial effects either in vivo or in vitro. A large number of plants have been studied globally for their antimalarial activities. However, studies that have been conducted in this field in Saudi Arabia are not enough. This article presents global and local research on the need for novel natural antimalarial agents with a particular emphasis on studies involving plants from Saudi Arabian flora.
... ex Hiern, was moved to the genus Vangueria, based on taxonomical characters (Lantz and Bremer 2005). Surveying the current literature on the chemical constituents of the genus Vangueria revealed the reports on V. edulis (Bishay et al. 2012, Mohamed et al. 2015, V. infausta (Lee et al. 1995;Bapela et al. 2019), V. spinosa Sarma 1995, 1997), and V. tomentosa (Barton et al. 1962;Brieskorn and Wunderer 1966;Chatterjee et al. 2011). The nature of the identified constituents in these reports comprise coumarins, phenolic acids, flavonoids, iridoid glycosides, monoterpene glycosides, ursane-and oleanane-type triterpenoids/glycosides. ...
Phytochemical investigation of the methanolic extract of Vangueria agrestisaerial parts led to the isolation and characterization of four monoterpene rhamnosides, two ursane saponins, and six flavonoid glycosides. Of these constituents, are three undescribed monoterpene glycosides, vangagrestosides A-C. The reported constituents comprise the monoterpene glycoside [(2E,6Z)-2,6-dimethyl-8-[O-α-L-rhamnopyranosyl-(1→3)-α-L-rhamnopyranosyl)-oxy]-octadien-1-yl α-L-rhamnopyranoside], the saponins [3-O-[α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl]pomolic acid, and 3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl]pomolic acid], and the flavonoids [narcissoside, rutin, hyperoside, guajavarin, biorobin, and nicotifloroside].
... infausta. This showed that chemometrics can be used to globally identify the classes of specialized metabolites responsible for the biological activity of plant species [114]. ...
Natural products (NPs) are specialized metabolites from natural sources, such as plants, animals, fungi, and bacteria, that have had an important role in the discovery and development of new drugs. For many years, bioassay-guided isolation has been the most used strategy for the isolation of bioactive NPs. Chemometrics is the science of relating the measurements made in a system or chemical process to the application of mathematical and statistical methods. Recently, chemometric techniques have been widely used in NP studies, including the detection of bioactive NPs from medicinal plants, chemotaxonomy, determination of geographical origin of medicinal plants and herbal products, and for quality control purposes. In this review, we propose a chemometric-enhanced strategy as a new approach for speeding up the isolation of bioactive NPs while reducing the quantities of biological material and organic solvents used.
Introduction : Parkinsonia praecox is used in traditional medicine to treat different diseases; however, the antibacterial and anticancer properties from its bark have not been reported. Thus, this study aimed to evaluate the antibacterial activity, cytotoxicity and chemical study of methanolic extract of Parkinsonia praecox bark (PpBM).
Methods : The PpBM antibacterial activity was determined against pathogen strains using the broth microdilution method, the cytotoxic effect was assessed on cancerous (HepG2, SKOV-3 and HeLa) and non-cancerous (J774A.1 and HaCaT) cells using the crystal violet assay, the in vitro hemotoxicity was evaluated using the hemolysis assay on human erythrocytes and the identification of major compounds derived from PpBM was performed by 1H and 13C NMR and 2D NMR experiments.
Results : PpBM (2000 μg/mL) demonstrated antibacterial activity against Listeria monocytogenes, a potential breakthrough in the fight against this pathogen. PpBM decreased cell viability of HepG2 liver cancer cells (IC50, 104.56 μg/mL) with a selectivity index of 1.38 regarding J774A.1 macrophages and 2.04 to HaCaT keratinocytes, suggesting a selective anticancer potential. On the other hand, PpBM did not cause hemolysis to high concentrations (1000 μg/mL) or alterations in the morphology of human erythrocytes at doses lower than 200 μg/mL. For the first time, lupenone, germanicone, 3-oxo-oleanane-18-en-28-ol, and combretol were identified in P. praecox. PpBM showed antibacterial, selective anticancer, and nonhemotoxic properties. These activities may be related to the major compounds, such as lupenone.
Conclusion : P. praecox bark is a new option for obtaining bioactive compounds, further in vitro and in vivo studies are required to confirm their efficacy and safety.
Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae. They possess many pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. Friedelin also has an anti-insect effect and the ability to alter the soil microbial ecology, making it vital to agriculture. Ultrasound, microwave, supercritical fluid, ionic liquid, and acid hydrolysis extract friedelin with reduced environmental impact. Recently, the high demand for friedelin has led to the development of CRISPR/Cas9 technology and gene overexpression plasmids to produce friedelin using genetically engineered yeast. Friedelin with low cytotoxicity to normal cells can be the best phytochemical for the drug of choice. The review summarizes the structural interpretation, biosynthesis, physicochemical properties, quantification, and various forms of pharmacological significance.
There is widespread use of species belonging to family Araliaceae in traditional medicine in southern Africa. The aim of this review was to assess medicinal uses, phytochemistry, pharmacology and toxicological properties of indigenous species belonging to family Araliaceae in southern Africa. Relevant articles, books, theses, dissertations, patents, and other English-only reports on the medicinal uses, phytochemistry, pharmacological and toxicological properties of species belonging to the family Araliaceae in southern Africa (Angola, Botswana, Eswatini, Lesotho, Malawi, Mozambique, Namibia, South Africa, Zambia and Zimbabwe) were reviewed. Databases such as PubMed, Web of Science, Elsevier, Google Scholar, Scopus, Springer, Science Direct, Taylor and Francis between January and July 2022. Eleven species, namely Cussonia. arborea, C. arenicola, C. natalensis, C. nicholsonii, C. paniculata, C. sphaerocephala, C. spicata, C. transvaalensis, C. thyrsiflora, C. zuluensis and Neocussonia umbellifera are used as traditional medicines against 48 human and animal diseases. This study showed that alkaloids, anthocyanins, anthracene glycosides, botulin, flavonoids, free gallic acid, iridoids, phenolics, saponins, steroids, tannins, triterpenoids and volatile oils have been identified from these species. Pharmacological research revealed that the crude extracts and compounds demonstrated isolated from these species are characterized by Aβ42 protein reduction, acetylcholinesterase, analgesic, antibacterial, antifungal, antiviral, anticancer, antihyperglycemic, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, antiprotozoal, anti-ulcer, immunomodulatory, larvicidal, molluscicidal, spermicidal, cytotoxicity and toxicity activities. Reports of medicinal uses, phytochemistry, pharmacology and toxicological properties of species belonging to the family Araliaceae in southern Africa could only be found for 11 species, suggesting that further investigation of largely unexplored family members is necessary.
Volkameria glabra (E. Mey.) Mabb. & Y.W. Yuan is a deciduous shrub or a small tree widely used as traditional medicine throughout its distributional range in tropical Africa. This study is aimed at providing a critical review of pharmacological properties, phytochemistry, and medicinal uses of V. glabra. Documented information on pharmacological properties, phytochemistry and medicinal uses of V. glabra was collected from several online sources such as Scopus, Google Scholar, PubMed and Science Direct, and pre-electronic sources such as book chapters, books, journal articles and scientific publications obtained from the university library. This study revealed that the bark, leaf and root infusion and/or decoction of V. glabra are mainly used as immune booster, protective charm, anthelmintic and ethnoveterinary medicine, and traditional medicine for convulsions, fractured bones, fever, wounds, gastro-intestinal problems, snake bite and respiratory diseases. Phytochemical compounds identified from the species include aliphatic glycosides, anthraquinones, cardiac glycosides, flavonoids, iridoid, phenols, saponins, steroids, tannins and triterpenoids. The V. glabra and compounds isolated from the species exhibited acaricidal, anthelmintic, antibacterial, antifungal, antimycobacterial, anti-collagenase, antidiabetic, anti-elastase, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, antipyretic, cholinesterase enzyme inhibition, immune-stimulant and cytotoxicity activities. Volkameria glabra should be subjected to detailed phytochemical, pharmacological and toxicological evaluations aimed at correlating its medicinal uses with its phytochemistry and pharmacological activities.
Endophytic fungi are an important class of microorganisms, able to interact with a host plant via a mutualistic mechanism without visible symptoms of the fungal colonization. The synergy between endophytic fungi and their host plant can promote morphological, physiological and biochemical changes through the expression of bioactive metabolites. This work aims to correlate metabolic changes in the Combretum lanceolatum plant metabolome with its endophytic fungi Diaporthe phaseolorum ( Dp ) and Trichoderma spirale ( Ts ), and to discover corresponding metabolite‐biomarkers, with the principal focus being on its primary metabolism. The 1 H NMR metabolomic analysis of qualitative and quantitative changes was performed through multivariate statistical analysis and the identification of primary metabolites was achieved on the Madison Metabolomics Consortium Database. The presence of Dp significantly impacted the plant’s metabolic pathways, improving the biosynthesis of primary metabolites such as threonine, malic acid and N ‐acetyl‐mannosamine, which are precursors of special metabolites involved in plant self‐defence. This work represents a valuable contribution to advanced studies on the metabolic profiles of the interaction of plants with endophytes.
Malaria, caused by the genus Plasmodium, remains a global public health concern. It is estimated by the World Health Organization that over 40% of the world's population lives in areas at risk for malarial transmission, and around half a million people succumb to this infectious disease annually, which is related to the rapid spread of drug‐resistant parasite strains. Indole derivatives, which possess broad‐spectrum pharmacological properties, play a crucial role in the discovery of new drugs. Many indole derivatives exhibited potential in vitro and in vivo activity against both drug‐sensitive and drug‐resistant malaria, suggesting that the indole moiety is a useful template for the development of novel antimalarial agents. This review outlines the advances in indole alkaloids and hybrids with antimalarial potential in the recent decade. Many indole derivatives exhibited potential in vitro and in vivo activity against both drug‐sensitive and drug‐resistant malaria, suggesting that the indole moiety is a useful template for the development of novel antimalarial agents. This review outlines the current scenario of indole alkaloids and hybrids with potential therapeutic applications in the fight against malaria.
Malaria is a mosquito-borne infectious disease caused by Plasmodium spp. It has severely impacted on individual and community productivity, social behavior, urbanization, as well as cultural, political, and economic developments in countries, where it is endemic. Given the high efficacy of major antimalarial drugs in targeting different stages of the parasite life cycle and the access to prophylactic measures, malaria was near to be eradicated. However, the emergence of resistance by parasites towards both curative and preventive drugs, and by mosquitoes to insecticides and traps has reopened the challenge. Natural products are still considered by the global medical researchers as a rich source of new chemical entities for the development of safe, cheap, and sustainable therapeutic agents. Natural products have been the mainstay of antimalarial therapy for thousands of years, and some are used in the traditional medicine by local populations, where malaria is endemic. This chapter updates the recent discoveries in phytochemical remedies that are able to treat malaria at different stages (prevention, recurrence, and therapy) as a result of limitations of synthetic drugs. These active compounds are organized according to their plants and fungi families. This in-depth survey attempts to analyze not only plant extracts, but also their main component’s bioactivity, the mechanism of action, and the potential synergism with other known drugs and side effects. Medicinal chemists can take advantage of such scaffolds to derive semisynthetic compounds with improved pharmacodynamic and pharmacokinetic properties. It is important that the efficacy and safety of traditional medicines must be validated, and their active constituents should be identified to establish reliable structure activity relationships.
Here, we report the novel fabrication of ZnO nanoparticles using the Costus igneus leaf extract. Gas chromatography-mass spectrometry (GC–MS) and proton nuclear magnetic resonance (¹H NMR) spectroscopy to determine the bioactive components present in the plant extract. The synthesis of Ci-ZnO NPs (C. igneus- coated zinc oxide nanoparticles) was accomplished using a cost-effective and simple technique. Ci-ZnO NPs were specified using UV–visible spectroscopy, FTIR, XRD, and TEM. Ci-ZnO NPs was authenticated by UV–Vis and exhibited a peak at 365 nm. The XRD spectra proved the crystalline character of the Ci-ZnO NPs synthesized as hexagonal wurtzite. The FTIR spectrum illustrated the presence of possible functional groups present in Ci-ZnO NPs. The TEM micrograph showed evidence of the presence of a hexagonal organization with a size of 26.55 nm typical of Ci-ZnO NPs. The α-amylase and α-glucosidase inhibition assays demonstrated antidiabetic activity of Ci-ZnO NPs (74 % and 82 %, respectively), and the DPPH [2,2-diphenyl-1-picrylhydrazyl hydrate] assay demonstrated the antioxidant activity of the nanoparticles (75%) at a concentration of 100 μg/ml. The Ci-ZnO NPs exhibited promising antibacterial and biofilm inhibition activity against the pathogenic bacteria Streptococcus mutans, Lysinibacillus fusiformis, Proteus vulgaris, and Vibrio parahaemolyticus. Additionally, the Ci-ZnO NPs showed biocompatibility with mammalian RBCs with minimum hemolytic activity (0.633 % ± 0.005 %) at a concentration of 200 μg/ml.
O objetivo desse trabalho foi analisar a variação do comprimento das fibras no sentido radial, na direção medula-câmbio da espécie Cecropia sciadophylla Mart, para então determinar o ponto de transição entre os lenhos juvenil e adulto na árvore. Para este fim, uma árvore de Cecropia sciadophylla de ocorrência natural em uma floresta de terra firme no município de Dom Eliseu, Pará, Brasil, foi selecionada. Da árvore abatida obteve-se um disco a 1,30 m do solo do qual foram retirados corpos de prova da medula em direção ao câmbio a cada 2,5 mm de distância para determinação do comprimento, diâmetro do lume e espessura da parede das fibras. As zonas de madeira juvenil e adulta foram determinadas pela medição do comprimento da fibra da medula ao câmbio. Os resultados mostraram que: (1) a árvore apresentava zona de transição entre a madeira juvenil e adulta em cerca de 9,5 cm distante da medula; (2) com exceção do diâmetro do lume, todos os demais parâmetros apresentaram maior média na madeira adulta, e houve diferença estatística significativa entre as médias. Os resultados indicam que
mesmo sendo uma espécie de ciclo de vida curto, C. sciadophylla forma madeira adulta a pouco distância da medula, indicando a possibilidade de utilização com maior valor agregado para a madeira.
K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives.
In the Greater Mekong subregion (GMS), artemisinin resistance is increasingly compounded by partner drug resistance, causing high failure rates of artemisinin combination therapies in some areas. For its containment, an accelerated elimination strategy will be needed. This includes high-quality implementation of conventional malaria control measures: early case management with quality artemisinin combination therapies (avoiding artesunate monotherapies) and single gametocytocidal low dose of primaquine, vector control and surveillance. Village health workers (VHWs) play a key role in the provision of community-based services which have to reach even the most remote populations. Additional, more aggressive, approaches will be important to accelerate malaria elimination, which could include mass drug administrations, potentially in combination with ivermectin and vaccination, mass screening and treatment with novel diagnostics, reactive case detection, and other measures.
Background:
Appropriate treatment of life-threatening Plasmodium falciparum malaria requires in-patient care. Although the proportion of severe cases accessing in-patient care in endemic settings strongly affects overall case fatality rates and thus disease burden, this proportion is generally unknown. At present, estimates of malaria mortality are driven by prevalence or overall clinical incidence data, ignoring differences in case fatality resulting from variations in access. Consequently, the overall impact of preventive interventions on disease burden have not been validly compared with those of improvements in access to case management or its quality.
Methods:
Using a simulation-based approach, severe malaria admission rates and the subsequent severe malaria disease and mortality rates for 41 malaria endemic countries of sub-Saharan Africa were estimated. Country differences in transmission and health care settings were captured by use of high spatial resolution data on demographics and falciparum malaria prevalence, as well as national level estimates of effective coverage of treatment for uncomplicated malaria. Reported and modelled estimates of cases, admissions and malaria deaths from the World Malaria Report, along with predicted burden from simulations, were combined to provide revised estimates of access to in-patient care and case fatality rates.
Results:
There is substantial variation between countries' in-patient admission rates and estimated levels of case fatality rates. It was found that for many African countries, most patients admitted for in-patient treatment would not meet strict criteria for severe disease and that for some countries only a small proportion of the total severe cases are admitted. Estimates are highly sensitive to the assumed community case fatality rates. Re-estimation of national level malaria mortality rates suggests that there is substantial burden attributable to inefficient in-patient access and treatment of severe disease.
Conclusions:
The model-based methods proposed here offer a standardized approach to estimate the numbers of severe malaria cases and deaths based on national level reporting, allowing for coverage of both curative and preventive interventions. This makes possible direct comparisons of the potential benefits of scaling-up either category of interventions. The profound uncertainties around these estimates highlight the need for better data.
The global market for herbal medicine is growing steadily. The usage of herbal medicine is particularly common in many parts of Africa; the World Health Organization estimates that approximately 80% of Africans rely on traditional African medicines (TAMs) for treating various diseases. TAMs hold promise in preventive treatment, early disease intervention and personalized medicine. However, clinical integration of TAMs is restricted due to limited information concerning their characterization. Presently, many studies on TAMs utilize a reductionist approach, making it extremely difficult to understand the holistic modifying effects that these therapeutic agents may have on biological systems. Fortunately, emerging technologies such as metabolomics platforms adopt a 'top-down' strategy that permits a holistic evaluation of the components, metabolic pathways and biomarkers modified by TAMs, which can aid in addressing common concerns over safety and toxicity, while also ensuring that quality control standards are met. Metabolomics approaches may also be beneficial for advancing our understanding of the efficacy and mechanism of action of TAMs, and may contribute to the advancement of research and drug discovery, early diagnosis, preventive treatment and TAMs-driven personalized medicine in Africa. This review also considers the main challenges that may hinder the adoption and integration of metabolomics approaches in research on TAMs in Africa and suggests possible solutions.
Background
2015 was the target year for malaria goals set by the World Health Assembly and other international institutions to reduce malaria incidence and mortality. A review of progress indicates that malaria programme financing and coverage have been transformed since the beginning of the millennium, and have contributed to substantial reductions in the burden of disease.
Findings
Investments in malaria programmes increased by more than 2.5 times between 2005 and 2014 from US 2.5 billion, allowing an expansion in malaria prevention, diagnostic testing and treatment programmes. In 2015 more than half of the population of sub-Saharan Africa slept under insecticide-treated mosquito nets, compared to just 2 % in 2000. Increased availability of rapid diagnostic tests and antimalarial medicines has allowed many more people to access timely and appropriate treatment. Malaria incidence rates have decreased by 37 % globally and mortality rates by 60 % since 2000. It is estimated that 70 % of the reductions in numbers of cases in sub-Saharan Africa can be attributed to malaria interventions.
Conclusions
Reductions in malaria incidence and mortality rates have been made in every WHO region and almost every country. However, decreases in malaria case incidence and mortality rates were slowest in countries that had the largest numbers of malaria cases and deaths in 2000; reductions in incidence need to be greatly accelerated in these countries to achieve future malaria targets. Progress is made challenging because malaria is concentrated in countries and areas with the least resourced health systems and the least ability to pay for system improvements. Malaria interventions are nevertheless highly cost-effective and have not only led to significant reductions in the incidence of the disease but are estimated to have saved about US$ 900 million in malaria case management costs to public providers in sub-Saharan Africa between 2000 and 2014. Investments in malaria programmes can not only reduce malaria morbidity and mortality, thereby contributing to the health targets of the Sustainable Development Goals, but they can also transform the well-being and livelihood of some of the poorest communities across the globe.
Electronic supplementary material
The online version of this article (doi:10.1186/s40249-016-0151-8) contains supplementary material, which is available to authorized users.
Terminalia avicennioides is used to treat tuberculosis in the folk medicine of the Nupes of North Central Nigeria. Activity guided fractionation of the extract resulted in the isolation of triterpenoid friedelin. The structure of the isolated compound was elucidated with the aid of spectral comparison of IR, UV, one and two dimensional NMR experiments values. To the best of our knowledge, this is the first time friedelin is reported from this plant. The in vitro antimycobacterial activity of the isolated compound (friedelin) was performed against Bacillus Calmette Guerin (BCG) with MIC value at 4.9 μg/mL.
The full potential of the herbal market is mainly not realised due to the lack of knowledge of the chemical composition of most herbal products.
The growth potential of the herbal medicine industry can only be achieved if the composition of herbal medicine is standardised to ensure proper
quality control and accountability. Plant-based nuclear magnetic resonance metabolomics is one such way of ensuring quick and reliable quality
control and metabolite profiling to ensure quality and reproducibility of herbal medicine. Nuclear magnetic resonance-based metabolomics is
robust and relatively easy to use, thus ensuring that herbal medicine can be verified and quality controlled much quicker and more accurate than is
currently the case. Although nuclear magnetic resonance is not as sensitive as other analytical techniques such as liquid chromatography and gas
chromatography–mass spectroscopy, it is far more reproducible, non-destructive, covers a much wider dynamic range and sample preparation is
simpler and quicker to use. Economical development of herbal medicine and the use of nuclear magnetic resonance-based metabolomics should go
hand in hand for a better future for herbal medicine. In this review an introduction is given to herbal extracts as therapeutic agents and to the quality
control aspects of herbal medicine by means of metabolomics. The experimental methodology for plant metabolomics which covers extraction, nuclear
magnetic resonance analysis and multivariate data analysis is also discussed. Some examples are given on the possible applications of nuclear magnetic
resonance-based metabolomics in the industry and finally the future of nuclear magnetic resonance-based metabolomics is discussed regarding
advances in research and development.
The ethnopharmacological approach toward the understanding and appraisal of traditional and herbal medicines is characterized by the inclusions of the social as well as the natural sciences. Anthropological field-observations describing the local use of nature-derived medicines are the basis for ethnopharmacological enquiries. The multidisciplinary scientific validation of indigenous drugs is of relevance to modern societies at large and helps to sustain local health care practices. Especially with respect to therapies related to aging related, chronic and infectious diseases traditional medicines offer promising alternatives to biomedicine. Bioassays applied in ethnopharmacology represent the molecular characteristics and complexities of the disease or symptoms for which an indigenous drug is used in “traditional” medicine to variable depth and extent. One-dimensional in vitro approaches rarely cope with the complexity of human diseases and ignore the concept of polypharmacological synergies. The recent focus on holistic approaches and systems biology in medicinal plant research represents the trend toward the description and the understanding of complex multi-parameter systems. Ethnopharmacopoeias are non-static cultural constructs shaped by belief and knowledge systems. Intensified globalization and economic liberalism currently accelerates the interchange between local and global pharmacopoeias via international trade, television, the World Wide Web and print media. The increased infiltration of newly generated biomedical knowledge and introduction of “foreign” medicines into local pharmacopoeias leads to syncretic developments and generates a feedback loop. While modern and post-modern cultures and knowledge systems adapt and transform the global impact, they become more relevant for ethnopharmacology. Moreover, what is traditional, alternative or complementary medicine depends on the adopted historic-cultural perspective.
Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.
Malaria remains a serious health problem world wide, especially in developing countries. Recent advances in the treatment of malaria have taken place and today combination therapies containing artemisinin (isolated in 1971 from Artemisia annua) and its derivatives have become the main weapon in the fight against this disease. Many herbal companies are now trying to make use of the success of artemisinin by selling Artemisia plant material in various formulations. We have therefore decided to test the product of one such company which claims that its capsules contain artemisinin. We have used a rapid NMR targeted metabolomics approach combined with principle component analysis (PCA) to verify that the capsules are indeed A. afra and not A. annua. In addition the concentration of artemisinin in the plant material was determined with a sensitive LC–MS method. This analysis indicated that even if the company has used A. annua in their capsules the dosage of artemisinin will be far to low to be effective. Our analysis shows that NMR with PCA can be a rapid and valuable tool in the quality control of herbal supplements.
A vast majority Chinese herbal medicines (CHM) are traditionally administered as individually prepared water decoctions (tang) which are rather complicated in practice and their dry extracts show technological problems that hamper straight production of more convenient application forms. Modernised extraction procedures may overcome these difficulties but there is lack of clinical evidence supporting their therapeutic equivalence to traditional decoctions and their quality can often not solely be attributed to the single marker compounds that are usually used for chemical extract optimisation. As demonstrated by the example of the rather simple traditional TCM formula Danggui Buxue Tang, both the chemical composition and the biological activity of extracts resulting from traditional water decoction are influenced by details of the extraction procedure and especially involve pharmacokinetic synergism based on co-extraction. Hence, a more detailed knowledge about the traditional extracts' chemical profiles and their impact on biological activity is desirable in order to allow the development of modernised extracts that factually contain the whole range of compounds relevant for the efficacy of the traditional application. We propose that these compounds can be identified by metabolomics based on comprehensive fingerprint analysis of different extracts with known biological activity. TCM offers a huge variety of traditional products of the same botanical origin but with distinct therapeutic properties, like differentially processed drugs and special daodi qualities. Through this variety, TCM gives an ideal field for the application of metabolomic techniques aiming at the identification of active constituents.
A recent discussion meeting convened by the Medicines for Malaria Venture examined how best to manage the discovery and preclinical pipeline to achieve novel combination therapies which would address the key clinical needs in malaria. It became clear that dose optimisation of components within combination therapy was a key issue in achieving antimalarial efficacy and for preserving that efficacy against parasite resistance emergence. This paper outlines some of the specific issues in malaria that cause dose-ranging and dose-optimisation studies to be particularly challenging and discusses the potential of factorial study design to address such challenges.
The relationship between common medicinal plants and major health problems in Africa, specifically Mozambique, is presented here. Emphasis is given to plant species largely used to solve or slow down diarrhoea, malaria, respiratory, and sexual complaints. These diseases, together with malnutrition/ anaemia, mental diseases, and rheumatism/arthritis are the main concern of healthcare countrywide. Diarrhoea is divided into common diarrhoea, bloody-diarrhoea, and cholera; plant species are normally used to slow down diarrhoea recurrence. Tannin is the main chemical compound with both anti-diarrhoeal and antiseptic properties. Traditional medicine seems to be rather helpful in alleviating malaria symptoms such as fever, vomiting, and diarrhoea. Special reference is made to Momordica balsamina, which is highly used to cure vomiting apparently associated with bilis and fever. Rauvolfia caffra contains reserpine, a compound used as anti-hypertension agent. This species is also used as an anti-malarial agent. Traditional medicine seems to have a role in slowing opportunistic infections related to the AIDS virus such as diarrhoea, pneumonia, and skin infections. Prostate hypertrophy is traditionally medicated using mostly Prunus africana and Hypoxis hemerocallidea, species known to contain phytosterol. Research for bioactive compounds in African plants is still in its infancy.
Nuclear magnetic resonance (NMR)-based metabolomics has many applications in plant science. Metabolomics can be used in functional genomics and to differentiate plants from different origin, or after different treatments. In this protocol, the following steps of plant metabolomics using NMR spectroscopy are described: sample preparation (freeze drying followed by extraction by ultrasonication with 1:1 CD(3)OD:KH(2)PO(4) buffer in D(2)O), NMR analysis (standard (1)H, J-resolved, (1)H-(1)H correlation spectroscopy (COSY) and heteronuclear multiple bond correlation (HMBC)) and chemometric methods. The main advantage of NMR metabolomic analysis is the possibility of identifying metabolites by comparing NMR data with references or by structure elucidation using two-dimensional NMR. This protocol is particularly suited for the analysis of secondary metabolites such as phenolic compounds (usually abundant in plants), and for primary metabolites (e.g., sugars and amino acids). This procedure is rapid; it takes not more than 30 min for sample preparation (multiple parallel) and a further 10 min for NMR spectrum acquisition.
A one-step non-radioactive assay to determine the proliferation of murine lymphocytes, lymphoid tumor cells and hybridoma cells is described. This assay requires the addition of Alamar Blue dye to cell cultures and the degree of change in its color, which is reflective of the extent of cellular proliferation, can be determined by an ELISA plate reader. Alamar Blue must be added during the initial phase of cell culture. The pattern of concanavalin A (ConA) or anti-CD3 antibody-induced proliferative response of murine lymphocytes as assessed by Alamar Blue was similar to that of a [3H]thymidine assay. Similarly, the spontaneous proliferation curve of anti-CD3 antibody secreting cell line (YCD3-1), monocytic macrophage cell lines (PU5-1.8, P388D1, J774.1) and myeloma cells (Sp2/0) as determined by Alamar Blue closely resembled that of the [3H]thymidine assay. The minimum detectable number of proliferating cells was comparable in Alamar Blue and [3H]thymidine assays. Since cell lysis/extraction and washing procedures are not involved in the Alamar Blue assay, this approach has several distinct advantages over currently available assays (eg. [3H]thymidine). First, it allows daily monitoring of proliferation without compromising the sterility of cultures. An indication of proliferation can be evaluated (spectrophotometrically or visually) as early as 24 h after ConA stimulation. Second, unlike previously reported assays, Alamar Blue permits further analysis of proliferating cells by other methods. Analysis of cells in culture with Alamar Blue for various surface antigens (CD44, CD45RB, CD4, heat stable antigen) by flow cytometry revealed that the fluorescent profile and relative percentage of cells in cultures with the Alamar Blue were comparable to those without this reagent. The salient advantages of Alamar Blue assay over the [3H]thymidine assay include: (i) non-radioactivity; (ii) simplicity; (iii) less costly; (iv) non-labor intensive; (v) rapidity of assessment of proliferation of large number of samples; (vi) non-toxicity; (vii) usefulness in determining the kinetics of cell growth of hybridomas; and (viii) non-interference of secretion of antibodies by a hybridoma cell line.
From the ethyl acetate extract of the stem bark of Endodesmia calophylloides (Guttiferae), a novel friedelane triterpenoid named endodesmiadiol (1), as well as the known compounds friedelin (2), canophyllol (3), canophyllal (4), cerin (5), morelloflavone (6), volkensiflavone (7), 8-deoxygartanin (8), 3 beta-acetoxyoleanolic acid (9) and 1,8-dihydroxy-3-isoprenyloxy-6-methylxanthone (10) have been isolated. The structures of these compounds were established by spectroscopic analysis, and the relative configuration of endodesmiadiol (1) was confirmed by X-ray diffraction. The antiplasmodial activity of the isolated compounds was evaluated against the W2 strain of Plasmodium falciparum which is resistant to chloroquine and other antimalarial drugs. All the compounds were found to be active with IC50 values ranging from 7.2 to 23.6 microM. The IC50 of endodesmiadiol was found to be 11.8 microM.
Chromatographic purification of methanolic extract of Vangueria infausta leaves grown in Egypt led to isolation of five flavonoids namely luteolin-7-O- rutinoside, apigenin- 7-O- rutinoside, luteolin-4` -O- glucoside, quercetin-3-O-glucoside and quercetin. Also, the extract revealed both free radical (DPPH), H2O2 scavenging activities and reducing power potential as compared to rutin. The extract showed promising activity that may limit free radical and oxidative damage.
This chapter describes the Plasmodium falciparum malaria parasite cultures and their use in immunology. Plasmodium falciparum is still the only malaria parasite species that can be maintained in long-term culture and is the best characterized of the plasmodia from the biochemical and molecular biological points of view. The availability of cultured parasites gave a strong impetus to research on immunity to the parasite and to efforts to develop a malaria vaccine. The life cycle of a parasite is complex. Infection starts with the entry of a sporozoite into the bloodstream, injected by a mosquito of the genus Anopheles. Of the life cycle stages, only the asexual blood stages are easy to culture in a standard laboratory. The only special requirements are an incubator devoted to parasite culture and a guaranteed supply of human serum and erythrocytes from a blood bank. However, it is possible, using specialized facilities and techniques, to obtain all stages of the life cycle in culture.
Ethanolic and ethyl acetate extracts of Cussonia spicata, C. paniculata and Schefflera umbellifera were screened for anti-bacterial, anti-malarial and anti-inflammatory activities. Root and bark extracts of C. spicata showed anti-bacterial activity against Staphylococcus aureus in the disc-diffusion assay. All species inhibited cyclooxygenase in the cyclooxygenase-1 assay. S. umbellifera ethanolic and ethyl acetate extracts inhibited Plasmodium falciparum, a malaria-causing agent, in an in vitro assay. The results obtained rationalised the use of the three selected species of Araliaceae for specific types of diseases in traditional medicine.
South Africa being home to more than 35% of the world's Helichrysum species (c.a. 244) of which many are used in traditional medicine, is seen potentially as a significant resource in the search of new anti-HIV chemical entities. It was established that five of the 30 Helichrysum species selected for this study had significant anti-HIV activity ranging between 12 - 21μg/mL (IC50) by using an in-house developed DeCIPhR method on a full virus model. Subsequent toxicity tests also revealed little or no toxicity for these active extracts. With the use of NMR-based metabolomics, the search for common chemical characteristics within the plant extract was conducted, which resulted in specific chemical shift areas identified that could be linked to the anti-HIV activity of the extracts. The NMR chemical shifts associated with the activity were identified to be 2.56 - 3.08ppm, 5.24 - 6.28ppm, 6.44 - 7.04ppm and 7.24 - 8.04ppm. This activity profile was then used to guide the fractionation process by narrowing down and focusing the fractionation and purification process to speed up the putative identification of five compounds with anti-HIV activity in the most active species, H. populifolium. The anti-HIV compounds identified for the first time from H. populifolium were three dicaffeoylquinic acid derivatives, i.e. 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid as well as two tricaffeoylquinic acid derivatives i.e. 1,3,5-tricaffeoylquinic acid and either 5-malonyl-1,3,4-tricaffeoylquinic or 3-malonyl-1,4,5-tricaffeoylquinic acid, with the latter being identified for the first time in the genus.
Copyright © 2015. Published by Elsevier B.V.
Introduction:
Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class - the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development.
Areas covered:
Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations.
Expert opinion:
Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.
A new iridoid glucoside, cornusoside
A (1), and four
new natural product iridoid aglycones, cornolactones A–D (2–5), together with 10 known compounds
were isolated from the leaves of Cornus florida.
The structures of compounds 1–5 were
established by interpretation of their spectroscopic data. Cornolactone
B (3) is the first natural cis-fused
tricyclic dilactone iridoid containing both a five- and a six-membered
lactone ring. A biosynthesis pathway is proposed for cornolactones
C (4) and D (5), the C-6 epimers of compounds 1–3.
Harpagophytum procumbens (Pedaliaceae) and its close taxonomical ally Harpagophytum zeyheri, indigenous to southern Africa, are being harvested for exportation to Europe where phytomedicines are developed to treat inflammation-related disorders. The phytochemical variation within and between natural populations of H. procumbens (n = 241) and H. zeyheri (n = 107) was explored using proton nuclear magnetic resonance (H-1-NMR) and ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) in combination with multivariate data analysis methods. The UHPLC-MS results revealed significant variation in the harpagoside content: H. procumbens (0.17-4.37%); H. zeyheri (0.00-3.07%). Only 41% of the H. procumbens samples and 17% of the H. zeyheri samples met the pharmacopoeial specification of >= 1.2%. Both principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) indicated separation based on species (UHPLC-MS data OPLS-DA model statistics: (RX)-X-2 = 0.258, (RY)-Y-2 (cum) = 0.957 and Q(2)(cum) = 0.934; H-1-NMR data OPLS-DA model statistics: (RX)-X-2 = 0.830, (RY)-Y-2 = 0.865 (cum) and Q(2)(cum) = 0.829). It was concluded that two species are not chemically equivalent and should not be used interchangeably.
Metabolomics studies aim at a better understanding of biochemical processes by studying relations between metabolites and between metabolites and other types of information (e.g., sensory and phenotypic features). The objectives of these studies are diverse, but the types of data generated and the methods for extracting information from the data and analysing the data are similar. Besides instrumental analysis tools, various data-analysis tools are needed to extract this relevant information. The entire data-processing workflow is complex and has many steps. For a comprehensive overview, we cover the entire workflow of metabolomics studies, starting from experimental design and sample-size determination to tools that can aid in biological interpretation. We include illustrative examples and discuss the problems that have to be dealt with in data analysis in metabolomics. We also discuss where the challenges are for developing new methods and tailor-made quantitative strategies.
The present state-of-the-art of NMR in plant metabolomics is reviewed. Attention is paid to the diff erent practical aspects of the application of NMR. The sample preparation, the measurement of the spectrum, quantitative aspects and data analysis are discussed. Each stage has its specifi c problems, which are pointed out and recommendations are made.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Three known (1-3) and a novel (4) monoterpene indole alkaloids have been isolated from the methanol extract of leaves of Tabernaemontana elegans and their structures were elucidated by a series of spectroscopic experiments, involving NMR, MS, UV, and IR techniques. The isolated monoterpene indole alkaloids along with previously described beta-carbolines (5-7) from the same specimen were studied for their apoptosis induction activity in human hepatoma HuH-7 cells. Methodology for apoptosis induction studies included cell viability assays, nuclear morphology assessments, and general caspase-3-like activity assays. The monoterpene indole alkaloids, tabernaemontanine (1) and vobasine (3) showed the most promising apoptosis induction profile in HuH-7 cells.
A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against
cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum. Microtitration plates were used
to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured
in these plates for 42 h. Inhibition of uptake of a radiolabeled nucleic acid precursor by the parasites served as the indicator
of antimalarial activity. Results of repeated measurements of activity with chloroquine, quinine, and the investigational
new drug mefloquine demonstrated that the method is sensitive and precise. Several additional antimalarial drugs and compounds
of interest were tested in vitro, and the results were consistent with available in vivo data. The use of P. falciparum isolates
with known susceptibility to antimalarial drugs also permitted evaluation of the cross-resistance potential of each compound
tested. The applications and expectations of this new test system within a drug development program are discussed.
The taxonomy, phytochemistry, ethnobotany, and pharmacology of the genus Tabernaemontana L. (Apocynaceae) is reviewed. The genus is currently being revised taxonomically; most of the segregate genera are being reunited with it and the number of species that will ultimately be recognized will probably be about 100. All the names encountered in the chemical and ethnobotanical literature have been evaluated as far as possible, and a list is presented of the recognized species and their synonyms. The biogenesis and classification of the indole alkaloids found in Tabernaemontana species is set out and some problems in the determination of their stereochemistry are discussed. To facilitate access to the information, three lists have been compiled: the alkaloids in alphabetical order; the alkaloids in order of increasing molecular weight; and the alkaloids grouped according to their biogenetic classification, together with the species and plant part(s) in which they are known to occur. Biogenetic and chemotaxonomic aspects are briefly considered. A table of the non-alkaloidal constituents is also included. The ethnobotany of individual Tabernaemontana species is outlined and an overall assessment made. Likewise, information on the pharmacology of crude extracts and individual alkaloids from Tabernaemontana species has been assembled and appraised.
Many researchers in different parts of the world are actively involved in recording the available information on traditional medicine. To contribute to this vast task, we chose Venda, one of the more remote tribes in Southern Africa. We found traditional healing to be very much alive and functioning in this area. Within 2 years of research, we could tabulate 151 medicinal plants with their galenics. Many of the plants listed were frequently used by different healers to treat the same ailment which might substantiate their reliability. On the other hand, certain plants were employed for various indications. Moreover, although the toxic effects of some plants are not included in our list, they are encountered by the Western medical doctors. Therefore, the benefits of compiling such lists on medicinal uses of different plants are twofold. To gain from the positive aspects of the traditional medicine and to eradicate, if possible, the harmful effects of some plants used by the traditional healers. However, during our study, it became clear that the plants used were with some exceptions mainly found in the vicinity of the habitat of the healer or the herbalist. It would therefore be useless to compile a more general pharmacopoeia for the African traditional healing as many of the useful plants in one area cannot be found in another. Hence, a more specific pharmacopoeia for each area would be necessary.
Thirteen isolates of Plasmodium falciparum obtained from cases of malaria imported into the Netherlands and established in culture were tested for their sensitivity to chloroquine. Reproducibility of the test results depended on the exposure of a standardized number of parasites in culture to the drug. The maximum activity of chloroquine was obtained when medium with the drug was added to parasite cultures twice at 24 hour intervals. The result of drug action over a period of 48 hours was estimated best when parasites were counted 72 hours after the commencement of the test. Sensitivity to chloroquine could not provide a basis for the characterisation of strains.
The resistance of Plasmodium spp. to currently used drugs has become a serious problem and efforts are being directed in obtaining new drugs with different structural features. One option favoured is the search for new plant derived antimalarial drugs. Bark and leaves of 20 extracts from 14 South African plant species were tested for in vitro antiplasmodial activity by means of the flow cytometric test. The most active extract of each species giving more than 70% inhibition at 50 microg/ml was selected for determination of IC(50) values. Two extracts had IC(50) values below 2 microg/ml, another seven had IC(50) values between 2 and 5 microg/ml while one had an IC(50) of 10.1 microg/ml. Chloroquine had an IC(50) of 0.043 microg/ml. Cytotoxicities of the five most active extracts at 50 microg/ml were determined with the monkey kidney cell toxicity test and the ID(50) values ranged between 35 and 100 microg/ml.
Ephedra sinica, known as Ma Huang, is one of the oldest medicinal herbs in Traditional Chinese Medicine (TCM). Preparations, namely teas, of E. sinica have been used for over 5000 years as a stimulant and as an antiasthmatic. In the West, extracts of E. sinica, E. intermedia or E. equisetina are most commonly used in dietary supplements as a stimulant and to promote weight loss. More than 50 species of Ephedra are native to both hemispheres, but the detection of ephedrine alkaloids has been limited to species in Eurasia. Currently, methods exist to quantitate the ephedrine alkaloids in extracts of plant material or dietary supplements, but the methods are not able to verify the extract is of an Ephedra species. Reverse phase high performance liquid chromatography with photodiode array detection was applied for the chemical fingerprinting of the Ephedra species. Two regions of comparison were determined in the chromatograms at 320 nm. The series of peaks between 52 and 64 min confirms an Ephedra species is being analyzed. The aforementioned peaks also could distinguish between Ephedra species from Eurasia, North America and South America. Peaks at ca. 57 and 59 min were isolated and determined to be two new compounds, 4-(2-eicosyloxycarbonyl-vinyl)-benzoic acid and 4-(2-docosyloxycarbonyl-vinyl)-benzoic acid respectively. Authentication of ground plant material as Ephedra can be achieved by this chemical fingerprinting method.
We describe the application of 1H NMR spectroscopy and chemometrics to the analysis of extracts of Artemisia annua. This approach allowed the discrimination of samples from different sources, and to classify them according to anti-plasmodial activity without prior knowledge of this activity. The use of partial least squares analysis allowed the prediction of actual values for anti-plasmodial activities for independent samples not used in producing the models. The models were constructed using approximately 70% of the samples, with 30% used as a validation set for which predictions were made. Models generally explained >90% of the variance, R(2) in the model, and had a predictive ability, Q(2) of >0.8. This approach was also able to correlate 1H NMR spectra with cytotoxicity (R2=0.9, Q2=0.8). This work demonstrates the potential of NMR spectroscopy and chemometrics for the development of predictive models of anti-plasmodial activity.
The metabolomic analysis of wild type and constitutive salicylic acid producing tobacco plants (CSA tobacco, Nicotiana tabacum 'Samsun' NN) plants overexpressing salicylate biosynthetic genes was carried out by 1H NMR spectrometry and multivariate analysis techniques. The principle component analysis (PCA) of the 1H NMR spectra showed a clear discrimination between those samples by PC1 and PC2. The discrimination of non-inoculated, TMV-virus inoculated, and systemic leaves or veins could also be obtained by PCA analysis. Major peaks in 1H NMR spectra contributing to the discrimination were assigned as those of chlorogenic acid, malic acid, and sugars. This method allows an efficient differentiation between wild type and transgenic plants without any pre-purification steps.
Metabolomics, including both targeted and global metabolite profiling strategies, is fast becoming the approach of choice across a broad range of sciences including systems biology, drug discovery, molecular and cell biology, and other medical and agricultural sciences. New analytical and bioinformatics technologies and techniques are continually being created or optimized, significantly increasing the crossdisciplinary capabilities of this new biology. The metabolomes of medicinal plants are particularly a valuable natural resource for the evidence-based development of new phytotherapeutics and nutraceuticals. Comparative metabolomics platforms are evolving into novel technologies for monitoring disease development, drug metabolism, and chemical toxicology. An efficient multidisciplinary marriage of these emerging metabolomics techniques with agricultural biotechnology will greatly benefit both basic and applied medical research.
Bioactive diterpenes and other constituents of Croton steenkampianus
- A M Adelekan
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- A A Hussein
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- P H Van Rooyen
- D C Liles
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Adelekan, A.M., Prozesky, A.E., Hussein, A.A., Ureña, L.D., Van Rooyen, P.H.,
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1 -Monoterpenes and related compounds from the medicinal plants of Africa
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related compounds from the medicinal plants of Africa, in: Kuete, V., (Eds.) Plant
Research in Africa: Pharmacology and Chemistry, Elsevier, pp.1-32.
A research agenda for malaria eradication: drugs
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Multi-and Megavariate Data Analysis, Part 1: Basic Principles and Applications
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Applications, Umetrics, Sweden
Geneva: World Health Organization
World Malaria Report 2017. Geneva: World Health Organization; 2017