Validation of a Monte Carlo simulated cardiac phantom for planar and SPECT studies.

PURPOSE: This work aimed to validate Monte Carlo (MC) simulated cardiac phantoms for the evaluation of planar- and SPECT-gated-blood-pool (GBP-P and GBP-S) studies. METHODS: A comparison of gamma camera system performance criteria measurements (energy resolution, spatial resolution, sensitivity) with MC simulations was conducted. Furthermore, the accuracy of measured and simulated volumes of two stereolithography-printed cardiac phantoms (based on 4D-XCAT phantoms) was assessed. Finally, the simulated GBP-P and GBP-S XCAT studies were validated by comparing calculated left ventricular ejection fraction (LVEF) and ventricle volume values with known parameters. RESULTS: The simulated performance criteria compared well with measured values (energy resolution difference: 0.1 ± 0.10%; spatial resolution (full width at half maximum) difference ≤ 0.5 ± 0.8 mm and system sensitivity difference ≤ 6.2 ± 0.62cps/MBq). The measured and simulated cardiac phantoms were in good agreement; the left anterior oblique views compared well. This is supported by line profiles through these phantoms and on average, simulated counts were 5.8% lower than measured counts. The LVEF values calculated from the GBP-P and GBP-S simulated data differ from known values (2.8 ± 0.64% and 0.8 ± 0.52%). The differences between the known XCAT LV volumes and simulated GBP-S calculated volumes were -1.2 ± 1.91 ml and -1.5 ± 0.96 ml for the end-diastolic and end-systolic volumes. CONCLUSION: The MC-simulated cardiac phantom has been validated successfully. Stereolithography-printing allows researchers to create clinically realistic organ phantoms and is a valuable tool for validating MC simulations and clinical software. By conducting GBP simulation studies with various XCAT models, the user will be able to generate GBP-P and GBP-S databases for future software evaluation.

Chemical Principles of Boophone, Nerine, Crossyne, Clivia, Cryptostephanus, Haemanthus and Scadoxus of the South African Amaryllidaceae and Their Biological Properties.

The Amaryllidaceae features prominently amongst bulbous flowering plant families. Accommodating about a third of its species, South Africa affords a sound basis for Amaryllidaceae plant research. Boophone, Nerine, Crossyne, Clivia, Cryptostephanus, Haemanthus and Scadoxus have been well-represented in such endeavors. The account herein summarizes the studies undertaken between 2013 - 2020 on these genera in regards to their chemical and biological characteristics. A total of 136 compounds comprising 63 alkaloids and 73 non-alkaloid entities were described during this period from eighteen members of the title genera. The alkaloids were reflective of the structural diversity found in eight isoquinoline alkaloid groups of the Amaryllidaceae. Of these, the crinane (29 compounds), lycorane and homolycorine (11 compounds each) groups were the most-represented. The non-alkaloid substances were embracive of the same number of unrelated groups including, acids, phenolics, flavonoids and triterpenoids. A wide variety of assays were engaged to ascertain the biological activities of the isolated compounds, notably in regards to cancer and motorneuron-related diseases. There were also attempts made to determine the antimicrobial, anti-inflammatory and antioxidant effects of some of the substances. New information has also emerged on the herbicidal, insecticidal and plant growth regulatory effects of selected alkaloid principles. Coupled to the biological screening measures were in instances probes made to establish the molecular basis to some of the activities, particularly in relation to cancer and Parkinson's disease.

Accuracy of two dosimetry software programs for 177Lu radiopharmaceutical therapy using voxel-based patient-specific phantoms.

Purpose: Virtual dosimetry using voxel-based patient-specific phantoms and Monte Carlo (MC) simulations offer the advantage of having a gold standard against which absorbed doses may be benchmarked to establish the dosimetry accuracy. Furthermore, these reference values assist in investigating the accuracy of the absorbed dose methodologies from different software programs. Therefore, this study aimed to compare the accuracy of the absorbed doses computed using LundADose and OLINDA/EXM 1.0. Methods: The accuracy was based on 177Lu-DOTATATE distributions of three voxel-based phantoms. SPECT projection images were simulated for 1, 24, 96, and 168 h post-administration and reconstructed with LundADose using 3D OS-EM reconstruction. Mono-exponential curves were fitted to the bio-kinetic data for the kidneys, liver, spleen, and tumours resulting in SPECT time-integrated activity (SPECT-TIA). The SPECT-TIA were used to compute mean absorbed doses using LundADose (LND-DSPECT) and OLINDA (OLINDA-DSPECT) for the organs. Pre-defined true activity images, were used to obtain TRUE-TIA and, together with full MC simulations, computed the true doses (MC-DTrue). The dosimetry accuracy was assessed by comparing LND-DSPECT and OLINDA-DSPECT to MC-DTrue. Results: Overall, the results presented an overestimation of the mean absorbed dose by LND-DSPECT compared to the MC-DTrue with a dosimetry accuracy ≤6.6%. This was attributed to spill-out activity from the reconstructed LND-DSPECT, resulting in a higher dose contribution than the MC-DTrue. There was a general underestimation (<8.1%) of OLINDA-DSPECT compared to MC-DTrue attributed to the geometrical difference in shape between the voxel-based phantoms and the OLINDA models. Furthermore, OLINDA-DSPECT considers self-doses while MC-DTrue reflects self-doses plus cross-doses. Conclusion: The better than 10% accuracy suggests that the mean dose values obtained with LND-DSPECT and OLINDA-DSPECT approximate the true values. The mean absorbed doses of the two software programs, and the gold standard were comparable. This work shall be of use for optimising 177Lu dosimetry for clinical applications.

Carbon dioxide expanded liquid: an effective solvent for the extraction of quercetin from South African medicinal plants.

BACKGROUND: Quercetin is one of the most important bioflavonoids having positive effects on the biological processes and human health. Typically, it is extracted from plant matrices using conventional methods such as maceration, sonication, infusion, and Soxhlet extraction with high solvent consumption. Our study aimed to optimize the environmentally friendly carbon dioxide-based method for the extraction of quercetin from quince fruit with an emphasis on extraction yield, repeatability, and short extraction time. RESULTS: A two-step design of experiments was used for the optimization of the key parameters affecting physicochemical properties, including CO2/co-solvent ratio, co-solvent type, temperature, and pressure. Finally, gas expanded liquid combining CO2/ethanol/H2O in a ratio of 10/81/9 (v/v/v) provided the best extraction yield. Extraction temperature 66 °C and pressure 22.3 MPa were the most suitable conditions after careful optimization, although both parameters did not significantly affect the process. It was confirmed by experiments in various pressure and temperature conditions and statistical comparison of obtained data. The optimized extraction procedure at a flow rate of 3 mL/min took 30 min. The repeatability of the extraction method exhibited an RSD of 20.8%. CONCLUSIONS: The optimized procedure enabled very fast extraction in 30 min using environmentally friendly solvents and it was successfully applied to 16 different plant samples, including 14 bulbs and 2 fruits from South Africa. The quercetin content in extracts was quantified using ultra-high performance liquid chromatography (UHPLC) with tandem mass spectrometry. UHPLC hyphenated with high-resolution mass spectrometry was used to confirm chemical identity of quercetin in the analyzed samples. We quantified quercetin in 11 samples of all 16 tested plants. The quercetin was found in Agapanthus praecox from the Amaryllidaceae family and its presence in this specie was reported for the first time.

Chemical Composition and Cytotoxic Activity of the Essential Oil and Oleoresins of In Vitro Micropropagated Ansellia africana Lindl: A Vulnerable Medicinal Orchid of Africa.

Orchids are rich treasure troves of various important phytomolecules. Among the various medicinal orchids, Ansellia africana stands out prominently in the preparing of various herbal medicines due to its high therapeutic importance. The nodal explants of A. africana were sampled from asymbiotically germinated seedlings on basal Murashige and Skoog (MS) medium and were micropropagated in MS medium supplemented with 3% sucrose and 10 µM meta topolin (mT) + 5 µM naphthalene acetic acid (NAA) +15 µM indole butyric acid (IBA) + 30 µM phloroglucinol (PG). In the present study, the essential oil was extracted by hydrodistillation and the oleoresins by the solvent extraction method from the micropropagated A. africana. The essential oil and the oleoresins were analysed by Gas Chromatography (GC) and GC/MS (Mass spectrometry). A total of 84 compounds were identified. The most predominant components among them were linoleic acid (18.42%), l-ascorbyl 2,6-dipalmitate (11.50%), linolenic acid (10.98%) and p-cresol (9.99%) in the essential oil; and eicosane (26.34%), n-butyl acetate (21.13%), heptadecane (16.48%) and 2-pentanone, 4-hydroxy-4-methyl (11.13%) were detected in the acetone extract; heptadecane (9.40%), heneicosane (9.45%), eicosane (6.40%), n-butyl acetate (14.34%) and styrene (22.20%) were identified and quantified in the ethyl acetate extract. The cytotoxic activity of essential oil and oleoresins of micropropagated A. africana was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide) assay on Vero cells compared to the standard drug doxorubicin chloride. The present research contains primary information about the therapeutic utility of the essential oil and oleoresins of A. africana with a promising future research potential of qualitative and quantitative improvement through synchronised use of biotechnological techniques.

Cytotoxic Agents in the Minor Alkaloid Groups of the Amaryllidaceae.

Over 600 alkaloids have to date been identified in the plant family Amaryllidaceae. These have been arranged into as many as 15 different groups based on their characteristic structural features. The vast majority of studies on the biological properties of Amaryllidaceae alkaloids have probed their anticancer potential. While most efforts have focused on the major alkaloid groups, the volume and diversity afforded by the minor alkaloid groups have promoted their usefulness as targets for cancer cell line screening purposes. This survey is an in-depth review of such activities described for around 90 representatives from 10 minor alkaloid groups of the Amaryllidaceae. These have been evaluated against over 60 cell lines categorized into 18 different types of cancer. The montanine and cripowellin groups were identified as the most potent, with some in the latter demonstrating low nanomolar level antiproliferative activities. Despite their challenging molecular architectures, the minor alkaloid groups have allowed for facile adjustments to be made to their structures, thereby altering the size, geometry, and electronics of the targets available for structure-activity relationship studies. Nevertheless, it was seen with a regular frequency that the parent alkaloids were better cytotoxic agents than the corresponding semisynthetic derivatives. There has also been significant interest in how the minor alkaloid groups manifest their effects in cancer cells. Among the various targets and pathways in which they were seen to mediate, their ability to induce apoptosis in cancer cells is most appealing.

Phytomedicinal relevance of South African Cucurbitaceae species and their safety assessment: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: South Africa has a very rich flora. Many of these species such as those in the Cucurbitaceae family are exploited as medicines for the treatment of various infections. AIM OF THE REVIEW: The aim of the review was to synthesize the existing but scattered literature of some plant species in the Cucurbitaceae family used as sources of medicines in South Africa. MATERIALS AND METHODS: A literature survey was carried out on the ethnopharmacology, phytochemistry, pharmacological relevance and safety assessment of the South African Cucurbitaceae used as medicines. RESULTS: A total of 11 plants namely; Coccinia rehmannii Cogn., Cucumis africanus L.f., Cucumis anguria L. var. longaculeatus J.H.Kirkbr., Cucumis myriocarpus Naudin subsp. myriocarpus, Cucumis zeyheri Sond., Cucumis metuliferus E. Mey ex Naudin, Kedrostis nana (Lam) Cogn., Lagenaria siceraria (Molina) Standl., Momordica balsamina L., Momordica charantia L., and Momordica foetida Schumach. and Thonn were identified. Various traditional medicinal uses for these plants, from common ailments to life-threatening infections were reported. Biological activities including antidiabetic, antioxidant, antimicrobial, anticancer, anti-inflammatory and hepatoprotective were reported. However, some of the plants have not been investigated for some of the biological activities related to their traditional uses. In addition, most of the studies were carried out using non-standardized extracts. Thus, only a few studies on their bioactive constituents exist. Common compounds identified within the species are hydroxycinnamic and hydroxybenzoic acids such as sinapic, gallic, vanillic and salicylic acids; flavonoids such as naringenin, quercetin, kaempferol and rutin; fatty acids such as linoleic, palmitoleic, myristic and stearic acids; the saponin glycosides, momordicin alkaloids and cucurbitacins. However, most of these compounds have not been tested for biological activities. Cucurbitacins were implicated as a major class of toxic compounds present in the plants resulting in poisoning and death. CONCLUSIONS: Adequate knowledge of the traditional use of these plants in medicine and the parts used are very important due to the presence of toxic substances and their wide usage. Proper screening of the safety of these plants and products derived from them calls for urgent attention.

A critical review on exploiting the pharmaceutical potential of plant endophytic fungi.

The escalating demand for secondary metabolites in international markets poses a severe threat to many plant species. An unscrupulous collection is also the immediate challenge to the survival of many unthreatened as well as vulnerable plants. Fungal endophytes have emerged in recent years as a promising substitute for sources of plant secondary metabolites. Many appealing secondary metabolites with potent antibacterial, antifungal, insecticidal, antioxidant, cytotoxic and anticancer properties have been discovered from endophytic fungi. Concerning their distinctive genetic and metabolic diversity and promising activities, they hold a plausible application in medicine and industry. However, there is little success in utilizing the pharmaceutical potential of fungal endophytes. Cutting-edge research is desirable to establish and bolster in vitro biosynthetic proficiency of fungal endophytes. Modern biotechnological techniques [such as multilocus sequence typing (MLST), metabolomics, metagenomics and next-generation sequencing (NGS) technologies] and bioinformatics approaches can fill a gap in fungal endophyte research. The present review focuses on how advanced chemical, biotechnological and computational molecular biology methods can be used for robust exploitation of bioactive compounds from these microorganisms.

Isolation and in silico prediction of potential drug-like compounds from Anethum sowa L. root extracts targeted towards cancer therapy.

Anethum sowa L. has been used as a spice herb in the Asian and European culinary systems to add flavour and taste. The studied plant has diverse folkloric medicinal value. Present study was designed to isolate phytochemicals from the hexane, chloroform and ethyl acetate extracts of the roots by various chromatographic techniques. Based on spectral analysis (IR, LC-MS, NMR) the isolated compounds were identified as physcione (1), ß-sitosterol (2), stigmasterol (3), 2-oxo-3-propyl-2H-chromene-7-carboxylic acid (4), bergapten (5), 3-ethyl-7-hydroxy-2H-chromen-2-one (6) and graveolone (7). The mentioned compounds have been isolated for the first time from the roots part of the plant. Based on extensive literature review, physcione and bergapten were inferred to exhibit crucial bioactivities including inhibitory efficacy against various forms of cancer. Accordingly, in the present research approach molecular docking investigations of the isolated phytochemicals have been robustly executed with different oncogenes that have been reported to be actively involved in various forms of carcinoma. In silico investigations encompassing molecular docking analysis and drug-likeness profiling was executed to estimate the potential therapeutic tendencies of the phytochemicals targeted towards effective cancer therapy. Current investigation offers meaningful know-how pertaining to potential anticancer activities of the phytochemicals extracted from the roots of Anethum sowa L. and might open up new revenues towards effective drug development against cancer.

Cell cycle modulatory effects of Amaryllidaceae alkaloids.

The birth, growth, proliferation and death of cells involve a rigorous and continuous process in place to ensure the survival of living organisms. The cell cycle prevails at the core of this process to facilitate the division of a parent cell as well as the duplication of its genetic matter. Although checkpoints exist to steer the course of a cell from one phase to the other, malfunctions at any point of the four active phases of the cell cycle can have detrimental effects. Cancer is thought to be a consequence of such a malfunction in the cell cycle which endows a cell with enhanced replicative potential, immunity to anti-growth signals and the ability to evade apoptosis. This characteristic has been exploited in cancer chemotherapy since a significant number of anticancer drugs manifest their action via cell cycle modulatory effects. The plant family Amaryllidaceae is distinguished for its alkaloid principles which exhibit potent (at the sub-nanomolar level in some cases) and cell line specific antiproliferative activities, with apoptosis induction a key feature of these properties. As a consequence there has been sustained interest in these chemical entities as a source of new anticancer drugs. This has been matched by the large body of work that has emerged over the past two decades addressing their cytotoxic potential, establishing a structure-activity relationship basis as well as probing their mode of action. This review focuses on studies which highlight how Amaryllidaceae alkaloids modulate the cell cycle of cancer cells.

Oil biosynthesis and transcriptome profiles in developing endosperm and oil characteristic analyses in Paeonia ostii var. lishizhenii.

Paeonia ostii var. lishizhenii, a well-known medicinal and horticultural plant, is indigenous to China. Recent studies have shown that its seed has a high oil content, and it was approved as a novel resource of edible oil with a high level of α-linolenic acid by the Chinese Government. This study measured the seed oil contents and fatty acid components of P. ostii var. lishizhenii and six other peonies, P. suffruticosa, P. ludlowii, P. decomposita, P. rockii, and P. lactiflora Pall. 'Heze' and 'Gansu'. The results show that P. ostii var. lishizhenii exhibits the average oil characteristics of tested peonies, with an oil content of 21.3%, α-linolenic acid 43.8%, and unsaturated fatty acids around 92.1%. Hygiene indicators for the seven peony seed oils met the Chinese national food standards. P. ostii var. lishizhenii seeds were used to analyze transcriptome gene regulation networks on endosperm development and oil biosynthesis. In total, 124,117 transcripts were obtained from six endosperm developing stages (S0-S5). The significant changes in differential expression genes (DEGs) clarify three peony endosperm developmental phases: the endosperm cell mitotic phase (S0-S1), the TAG biosynthesis phase (S1-S4), and the mature phase (S5). The DEGs in plant hormone signal transduction, DNA replication, cell division, differentiation, transcription factors, and seed dormancy pathways regulate the endosperm development process. Another 199 functional DEGs participate in glycolysis, pentose phosphate pathway, citrate cycle, FA biosynthesis, TAG assembly, and other pathways. A key transcription factor (WRI1) and some important target genes (ACCase, FATA, LPCAT, FADs, and DGAT etc.) were found in the comprehensive genetic networks of oil biosynthesis.

Antifungal constituents of the plant family Amaryllidaceae.

Globalization, the modern lifestyle, immuno-suppressive agents, invasive surgical procedures, the loss of efficacies of existing drugs, and multidrug resistance are some of the factors used to explain the rise in fungal infections in recent years. Significant advances have been made in attempts to replace existing antifungal schedules, especially with synthetic targets. The identification of other platforms for drug discovery is now entrenched in research programs across the globe. Plants offer significant benefits owing to their numerical superiority, exceedingly broad chemical basis and appealing sustainability characteristics. Furthermore, plants have a long and rich historical association with traditional approaches towards fungal diseases. These have in numerous instances served as markers in the bioassay-guided identification of the active constituents. Although the plant family Amaryllidaceae is conventionally associated with cancer and motor-neuron disease chemotherapies, around 30 of its species have been examined for antifungal activities with microgram per millilitre inhibitory activities detected in several instances. This review focuses on the nearly 40 constituents from the family, mainly isoquinoline alkaloids, which have been screened against around 50 fungal pathogens. Encouragingly, microgram per millilitre growth inhibitory activities were applicable for several of the compounds with a minimum inhibitory concentration of 4 µg/ml seen to be the lowest.

Ethnobotany, phytochemistry and pharmacology of Arctotis arctotoides (L.f.) O. Hoffm.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the genus Arctotis. Arctotis is an African genus of approximately 70 species that occur widely in the African continent with diverse medicinal values. This plant is used for the treatment of indigestion and catarrh of the stomach, epilepsy, topical wounds and skin disorders among the ethnic groups in South Africa and reported to have a wide spectrum of pharmacological properties. AIM OF THE REVIEW: The aim of the present review is to appraise the botany, traditional uses, phytochemistry, pharmacological potential, analytical methods and safety issues of A. arctotoides. Additionally, this review will help to fill the existing gaps in knowledge and highlight further research prospects in the field of phytochemistry and pharmacology. MATERIALS AND METHODS: Information on A. arctotoides was collected from various resources, including books on African medicinal herbs and Zulu medicinal plants, theses, reports and the internet databases such as SciFinder, Google Scholar, Pubmed, Scopus, Web of Science, and Mendeley by using a combination of various meaningful keywords. This review surveys the available literature of the species from 1962 to April 2017. RESULTS: In vitro and in vivo studies of the medicinal properties of A. arctotoides were reviewed. The main isolated and identified compounds were reported as sesquiterpenes, farnesol derivatives, germacranolide, guaianolides and some steroids, of which, nine were reported as antimicrobial. Monoterpenoids and sesquiterpenoids were the predominant essential oil compound classes of the leaves, flowers, stems and roots. The present review revealed potential pharmacological properties such as anti-oxidant, antibacterial, antifungal and anticancer activities of plant extracts as well as isolated compounds. Moreover, the review reports the safety profile (toxicity) of the crude extracts that had been screened on brine shrimps, rats and human cell lines. CONCLUSIONS: The present review has focused on the phytochemistry, botany, ethnopharmacology, biological activities and toxicological information of A. arctotoides. On the basis of reported data, A. arctotoides has emerged as a good source of natural medicine for the treatment of microbial infections, skin diseases, anti-inflammatory and anticancer agents and also provides new insights for further isolation of new bioactive compounds, especially the discovery of antimicrobial, anti-inflammatory and anticancer novel therapeutic lead drug molecules. Additionally, intensive investigations regarding pharmacological properties, safety assessment and efficacy with their mechanism of action could be future research interests before starting clinical trials for medicinal practices.

Distribution and Diversity of Usage of the Amaryllidaceae in the Traditional Remediation of Infectious Diseases.

Globalization and multidrug resistance are amongst the factors implicated in the resurgence of infectious diseases in recent years. This has fostered a compelling need in drug discovery to replace (or supplement) existing schedules. The floral biodiversity has been identified as a viable resource platform due to its inimitable chemical characteristics as well as the presence of numerous of its members in traditional medicinal approaches towards these diseases. Whilst the plant family Amaryllidaceae is conventionally associated with cancer and motor-neuron disease therapies, this survey shows that it has a significant presence in the remediation of infections and infection-related ailments. This verifiable indigenous knowledge could amplify efforts towards the identification of the active chemical constituents.

The effect of tumour geometry on the quantification accuracy of planar 123I phantom images.

INTRODUCTION: Accurate activity quantification is applied in radiation dosimetry. Planar images are important for quantification of whole-body images, enabling assessment of biodistribution from radionuclide administrations. We evaluated the effect of tumour geometry on quantification accuracy of 123I planar phantom studies, including various tumour sizes, tumour-liver distances and two tumour-background ratios. METHODS AND MATERIALS: An in-house manufactured abdominal phantom was equipped with a liver, different size cylindrical tumours, and a rod for tumour-liver distance variation. The geometric mean method with scatter and attenuation corrections was used for image processing. Scatter and attenuation corrections were made using the triple energy window scatter correction technique and a printed transmission sheet source, respectively. Region definitions for tumour activity distribution compensated for the partial volume effect (PVE). Activity measured in the dose calibrator served as reference for determining quantification accuracy. RESULTS: The smallest tumour had the largest percentage deviation with an average activity underestimation of 34.6±1.2%. Activity values for the largest tumour were overestimated by 3.1±3.0%. PVE compensation improved quantification accuracy for all tumour sizes yielding accuracies of <12.4%. Scatter contribution to the tumours from the liver had minimal effect on quantification accuracy at tumour-liver distances >3cm. With PVE compensation, increased tumour-background ratio resulted in a percentage increase of up to 26.3%. CONCLUSION: When applying relevant corrections for scatter, attenuation and PVE without background activity, quantification accuracy of <13% was obtained. We demonstrated the successful implementation of a practical technique to obtain quantitative information from 123I planar images.

In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids.

The plant family Amaryllidaceae is recognizable for its esthetic floral characteristics, its widespread usage in traditional medicine as well as its unique alkaloid principles. Few alkaloid-producing families rival the Amaryllidaceae in terms of the diversity of its structures as well as their wide applicability on the biological landscape. In particular, cytotoxic effects have come to be a dominant theme in the biological properties of Amaryllidacea alkaloids. To this extent, a significant number of structures have been subjected to in vitro studies in numerous cell lines from which several targets have been identified as promising chemotherapeutics. By contrast, in vivo models of study involving these alkaloids have been carried out to a lesser extent and should prove crucial in the continued development of a clinical target such as pancratistatin. This survey examines the cytotoxic effects of Amaryllidaceae alkaloids in vivo and contrasts these against the corresponding in vitro effects.

Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids.

The Amaryllidaceae occupies a privileged status amongst medicinal plants in having delivered the Alzheimer's drug galanthamine to the clinical market. Following its resounding success, there have been several positive indicators for the emergence of an anticancer drug from the family due to the potent antiproliferative activities manifested by several of its alkaloid constituents. Of these, the phenanthridones such as pancratistatin hold most promise as potential chemotherapeutics having succumbed to various phases of clinical trials. Other cytotoxic targets of the Amaryllidaceae are to be found within the lycorane and crinane groups, as exemplified by crinine and lycorine. Although the molecular targets of these alkaloids still remain elusive, much effort has gone into understanding their mode of action in cancer cells. Recent findings have shown that the apoptotic pathway may be a key factor in cancer cell death instigated by Amaryllidaceae alkaloids. As such, this review seeks to: (a) examine the apoptotic effects of Amaryllidaceae alkaloids in cancer cells; (b) explore the molecular basis to these effects; and (c) provide a pharmacophoric rationale in support of these activities.

Ethnobotany, therapeutic value, phytochemistry and conservation status of Bowiea volubilis: A widely used bulbous plant in southern Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Bowiea volubilis Harv. ex Hook.f. (Family: Asparagaceae) is a bulbous medicinal plant widely used against numerous ailments including headache, muscular pains, infertility, cystitis and venereal diseases in southern Africa. AIM OF THE REVIEW: To provide a critical and updated review of Bowiea volubilis with regards to its abundance, medicinal importance, conservation status and potential means to sustain its availability for future generations. METHODS: A comprehensive literature search using online databases such as Web of Science, Google Scholar, Scopus and Springerlink as well as ethnobotanical literature was done in order to obtain, collate, synthesize and critically analyze available information on Bowiea volubilis. RESULTS: On the basis of its wide distribution in many Provinces in South Africa, Bowiea volubilis has a long history of applications among the different ethnic groups. These applications include its uses as purgatives and for the treatment or relief of microbial infections, skin disorders, pains and inflammation. Scientific validation of its diverse uses in traditional medicine has been demonstrated via antimicrobial, anti-inflammatory and toxicity assays. Available results indicate a general poor antimicrobial activity especially with the bulb extracts while the anti-inflammatory activity appears promising. Phytochemical screenings revealed that Bowiea volubilis contains cardiac glycosides and related compounds while reports of other classes of compounds are unavailable. In line with its usage in traditional medicine, the majority of available studies on the species have focused on the use of different solvent extracts from the bulbs. The destructive harvesting of bulbs has led to a continuous decimation of wild populations. Consequently, there are increasing conservational concerns on the sustainability of this species for continuous supply to meet escalating demands. CONCLUSIONS: Bowiea volubilis remains a widely used medicinal plant and available but limited scientific evidence indicates its anti-inflammatory potential. The abundance of cardiac glycosides in its phytochemical composition provides an indication on the therapeutic potential. More research efforts including the application of different biotechnological techniques are still required in order to guarantee its sustainable use over time.

Cadmium translocation by contractile roots differs from that in regular, non-contractile roots.

BACKGROUND AND AIMS: Contractile roots are known and studied mainly in connection with the process of shrinkage of their basal parts, which acts to pull the shoot of the plant deeper into the ground. Previous studies have shown that the specific structure of these roots results in more intensive water uptake at the base, which is in contrast to regular root types. The purpose of this study was to find out whether the basal parts of contractile roots are also more active in translocation of cadmium to the shoot. METHODS: Plants of the South African ornamental species Tritonia gladiolaris were cultivated in vitro for 2 months, at which point they possessed well-developed contractile roots. They were then transferred to Petri dishes with horizontally separated compartments of agar containing 50 µmol Cd(NO3)2 in the region of the root base or the root apex. Seedlings of 4-d-old maize (Zea mays) plants, which do not possess contractile roots, were also transferred to similar Petri dishes. The concentrations of Cd in the leaves of the plants were compared after 10 d of cultivation. Anatomical analyses of Tritonia roots were performed using appropriately stained freehand cross-sections. KEY RESULTS: The process of contraction required specific anatomical adaptation of the root base in Tritonia, with less lignified and less suberized tissues in comparison with the subapical part of the root. These unusual developmental characteristics were accompanied by more intensive translocation of Cd ions from the basal part of contractile roots to the leaves than from the apical-subapical root parts. The opposite effects were seen in the non-contractile roots of maize, with higher uptake and transport by the apical parts of the root and lower uptake and transport by the basal part. CONCLUSIONS: The specific characteristics of contractile roots may have a significant impact on the uptake of ions, including toxic metals from the soil surface layers. This may be important for plant nutrition, for example in the uptake of nutrients from upper soil layers, which are richer in humus in otherwise nutrient-poor soils, and also has implications for the uptake of surface-soil pollutants.

Mechanistic insights to the cytotoxicity of Amaryllidaceae alkaloids.

With over 500 individual compounds, the Amaryllidaceae alkaloids represent a large and structurally diverse group of phytochemicals. Coupled to this structural diversity is the significant array of biological properties manifested by many of its members, of which their relevance in motor neuron disease and cancer chemotherapy has attracted considerable attention. To this extent, galanthamine has evolved into a successful commercial drug for Alzheimer's disease since its approval by the FDA in 2001. Concurrently, there have been several positive indicators for the emergence of an anticancer drug from the Amaryllidaceae due to the potency of several of its representatives as cell line specific antiproliferative agents. In this regard, the phenanthridones such as pancratistatin and narciclasine have offered most promise since their advancement into clinical trials, following which there has been renewed interest in the cytotoxic properties of these alkaloids. Given this background, this review seeks to highlight the various mechanisms which have been invoked to corroborate the cytotoxic effects of Amaryllidaceae alkaloids.