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• South Africa affords a rich and diverse source of Amaryllidaceae plant species. • Boophone, Nerine, Brunsvigia, Strumaria and Crossyne well-represented in the region. • This survey covers biological studies of these five genera for 2013–2020. • Around 20 areas identified in which their extracts have been probed for such effects. • Traditional usage of several of the representative species is also highlighted. The presence of plants in human health and well-being has been trenchant since time immemorial. Some of the most crucial medicines in use today are derived from plant-based materials. Traditional plant usage has played a pivotal role in guiding many of the discoveries that were accomplished in the clinical realm. The plant family Amaryllidaceae is recognized for its interesting biological properties, notably in the areas of cancer and motorneuron disease therapeutics. Its members are well-represented in South Africa, with a proliferation hub centered over its Western Cape Province. Boophone, Nerine, Brunsvigia, Strumaria and Crossyne are genera of the Amaryllidaceae that are prominent amongst the local floral biodiversity. Previous reviews on the biological action of these genera were up to date until 2012. The present account is an update of the field covering material published between 2013 and 2020. It examines the plant parts studied, the solvents utilized in the extraction procedures as well as the biological assays against which the extracts have been screened. These were seen to involve antimicrobial, anti-inflammatory, antioxidant, anticancer, anticholinesterase, cardiovascular, hypertensive and anxiolytic effects. Studies were also identified which addressed the herbicidal and insecticidal effects of some of the plants. Some efforts focused on the molecular basis to the biological activities, notably in regards to anti-inflammatory and anticancer action as well as to motorneuron-related effects. Significant effort is made throughout the text to emphasize the traditional medicinal usage and how such indigenous knowledge has guided the biological evaluation of the plants. [ABSTRACT FROM AUTHOR]

• Five genera of the South African Amaryllidaceae surveyed for the period 2013–2020. • These are inclusive of Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia. • Around 90 isoquinoline alkaloids and 25 non-alkaloidal entities described. • Chemosystematics of selected alkaloids considered. • Biological properties of isolated compounds also described. There is considerable interest in the plant family Amaryllidaceae for its biologically-active isoquinoline alkaloid principles. Some of these (such as galanthamine and narciclasine) have demonstrated their applicability in the clinical arena, particularly as cancer and motorneuron disease therapeutics. While synthetic organic chemistry affords ideal opportunities for drug development with such targets, the phytochemical approach is considered a somewhat more amenable option. In this regard, southern Africa has garnered widespread attention due to the abundance of Amaryllidaceae plants in its territory. Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia are genera of the family that are likewise well-represented in southern Africa. Up to 2012, thirty members from these genera were examined for their chemical and biological properties, culminating with the identification of nearly one-hundred alkaloid entities several of which exhibited notable biological activities. The present effort covers studies since 2013 that have been undertaken on the title genera in regards to their chemical and biological characteristics. Close to ninety alkaloids and twenty-five non-alkaloid entities were described during this time-frame from fifteen representative species. Biological studies included cholinesterase inhibiton, cytotoxicity, antidiabetes and antihypertensive effects, herbicidal, insecticidal and plant growth regulatory effects, as well as anti-inflammatory, antioxidant and antiplasmodial effects. The structural variety of the compounds isolated in cases allowed for structure-activity probes to be made in some of the assays. There were also studies carried out to establish the molecular basis to these activities, notably in the area of molecular cancer chemotherapeutics. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Boophone disticha is the most common member of the South African Amaryllidaceae used extensively in traditional medicine of the various indigenous population groups, including the Sotho, Xhosa and Zulu as well as the San. This survey was carried out to identify and highlight areas relevant to the traditional usage of Boophone disticha. Pharmacological aspects were examined with the purpose of reconciling these with the traditional usage of the plant. In relation to phytochemical make-up, particular attention was paid on how its alkaloid constitution might corroborate the various biological effects manifested by the plant. Materials and methods: Information gathering involved the use of four different database platforms, including Google Scholar, ScienceDirect, SciFinder® and Scopus. Arrangement and detailing of this information is as reflected in the various sections of the paper. Results: Sixteen categories were identified under which Boophone disticha finds use in traditional medicine. These were shown to include general usage purposes, such as ‘cultural and dietary’, ‘well-being’, ‘personal injury’, ‘divinatory purposes’, ‘psychoactive properties’ and ‘veterinary uses’. Furthermore, traditional usage was seen to involve six body systems, including functions pertaining to the circulatory, gastrointestinal, muscular, neurological, respiratory and urinary systems. The four remaining categories relate to use for inflammatory conditions, cancer, malaria and tuberculosis. Overall, three areas were discernible in which Boophone disticha finds most usage, which are (i) ailments pertaining to the CNS, (ii) wounds and infections, and (iii) inflammatory conditions. In addition, several aspects pertaining to the toxic properties of the plant are discussed, including genotoxicity, mutagenicity and neurotoxicity. Conclusion: The widespread ethnic usage of Boophone disticha has justified its standing as a flagship for the Amaryllidaceae and its relevance to South African traditional medicine. Furthermore, its promising pharmacological and phytochemical profiles have stimulated significant interest in the clinical realm, especially in the areas of cancer and motor neuron disease chemotherapy. These collective properties should prove useful in steering the progress of the plant towards a wider audience. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Plants of the family Amaryllidaceae are used widely in traditional medicine in South Africa. Several of these, including representatives of the genus Cyrtanthus find use in the treatment of mental illness and age-related dementia. Aim of the study: Based on the distribution of central nervous system-activating alkaloidal constituents within the genus Cyrtanthus, Cyrtanthus contractus was here explored for such compounds which could interact with acetylcholinesterase (AChE), of significance in the progression of neurodegeneration associated with Alzheimer''s disease. Materials and methods: The known phenanthridone alkaloid narciprimine was isolated via column chromatography of the ethanolic extract of bulbs of Cyrtanthus contractus. The structure of the compound was determined by high field 2D NMR and mass spectroscopic techniques. The classical method of Ellman et al. was used in the determination of AChE inhibitory activity. Results: The isolation of narciprimine from Cyrtanthus contractus is a landmark find since it has previously only been identified in Zephyranthes, Narcissus and Lycoris, genera endemic to the Americas, Europe and Asia, respectively. Narciprimine exhibited micromolar inhibitory activity (IC50 78.9) against the enzyme acetylcholinesterase. Conclusion: This work represents the first isolation of narciprimine from an African Amaryllidaceae species, which may be of chemotaxonomic significance. The AChE inhibitory activity of narciprimine, taken together with activities of other structurally similar inhibitors within the series affords further insight to the structural details of the lycorine alkaloid acetylcholinesterase inhibitory pharmacophore. [Copyright &y& Elsevier]

Review: 115 refs. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: The family Amaryllidaceae has been documented in traditional systems of medicine around the globe. Its member tribe Haemantheae occurs chiefly in South Africa, where around twenty of its species are identifiable with a wide variety of functions in such practices., Aim of the Study: This account details work published from 2013 to 2020 on the tribe Haemantheae involving Clivia, Cryptostephanus, Haemanthus, Scadoxus and Gethyllis. Focus is maintained on the traditional medicinal aspects, pharmacological activities and identification of the active principles. Significant effort is also made to outline the molecular basis to some of these effects., Materials and Methods: The major search engine platforms including, SciFinder, Scopus, ScienceDirect, PubMed and Google Scholar were utilized at the literature consolidation stage. Keywords engaged in the process included 'Amaryllidaceae' and 'Haemantheae' as well as individual genera and specie names., Results: Twenty-four species of the five genera were encountered over the designated time frame. New traditional medicinal information has emerged on nine of these species, where usage ranged from the treatment of wounds and infections, circulatory and gastrointestinal issues to AIDS and TB. Significant amounts of new data also appeared in relation to the antimicrobial, anti-inflammatory, antioxidant, anticholinesterase, antidepressive and cytotoxic effects of these plants. Potent activities were observed in some instances, as they were in regards to the anti-inflammatory effects of some Gethyllis species in their cyclooxygenase-inhibitory effects. The entities behind these activities, with few exceptions, were shown to be isoquinoline alkaloids which are known to dominate the chemistry of the Amaryllidaceae. Interesting observations were also made for the mechanisms behind some of the effects, notably in the inflammatory and motorneuron disease arenas., Conclusions: The tribe Haemantheae has proved to be a rich and diverse platform for studies of the Amaryllidaceae in the key areas of traditional medicine, pharmacology and phytochemistry. Indigenous knowledge has played a significant role in guiding the biological evaluations, while identification of the active principles has been bolstered by the exceedingly rich alkaloid diversity of the Amaryllidaceae. As such, Haemantheae should continue to feature prominently in drug discovery efforts targeted at the family., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The plant family Amaryllidaceae is known for its horticultural and ornamental appeal as well as its medicinal value. In relation to these characteristics, trade in Amaryllid flower varieties (especially daffodils) is a multi-million dollar revenue generator for the floriculture industry. Of greater significance are the medicinal attributes of the family, which has already spawned the Alzheimer's prescription drug galanthamine, a potent and selective inhibitor of the enzyme acetylcholinesterase, of significance in the progression of neurodegeneration associated with motor neuron diseases, with annual global sales of around $150 million. Furthermore, it is anticipated that an anticancer drug target related to the Amaryllidaceae alkaloid pancratistatin, presently under advanced clinical evaluation, will enter commercial circulation within the next decade. Members of the Amaryllidaceae are distributed through both tropical and subtropical regions of the globe, but are of prominence within three distinct geographical locations, including Andean South America, the Mediterranean basin, and southern Africa. The southern African zone is known to harbor at least a third of the worldwide complement of around 1000 species, many of which are widely utilized in the traditional medicinal practices of the indigenous people of the region. Given its therapeutic and economic value, its natural abundance in the southern African region, coupled to its widespread usage in ethnic medicine, the family Amaryllidaceae provides a diverse and accessible platform for phytochemical based drug discovery. A consolidation of its traditional usage as well as its chemical and pharmacological profiles will thus guide efforts aimed at maximizing this potential. In undertaking this survey of the Amaryllidaceae of southern African, we aimed to achieve these goals.

Objective: To compare the incidence of tuberculosis over two years in infants vaccinated at birth with intradermal BCG or with percutaneous BCG., Design: Randomised trial., Setting: South Africa., Participants: 11,680 newborn infants., Interventions: Infants were randomised by week of birth to receive Tokyo 172 BCG vaccine through the percutaneous route (n=5775) or intradermal route (n=5905) within 24 hours of birth and followed up for two years., Main Outcome Measures: The primary outcome measure was documented Mycobacterium tuberculosis infection or radiological and clinical evidence of tuberculosis disease. Secondary outcome measures were rates of adverse events, all cause and tuberculosis specific admissions to hospital, and mortality., Results: The difference in the cumulative incidence of definite, probable, and possible tuberculosis between the intradermal group and the percutaneous group, as defined using study definitions based on microbiological, radiological, and clinical findings was -0.36% (95.5% confidence interval -1.27% to 0.54%). No significant differences were found between the routes in the cumulative incidence of tuberculosis using a range of equivalence of "within 25%." Additionally, no significant differences were found between the routes in the cumulative incidence of adverse events (risk ratio 0.98, 95% confidence interval 0.91 to 1.06), including deaths (1.19, 0.89 to 1.58)., Conclusion: Equivalence was found between intradermal BCG vaccine and percutaneous BCG in the incidence of tuberculosis in South African infants vaccinated at birth and followed up for two years. The World Health Organization should consider revising its policy of preferential intradermal vaccination to allow national immunisation programmes to choose percutaneous vaccination if that is more practical. Trial registration ClinicalTrials.gov NCT00242047.