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• Four genera of the South African Amaryllidaceae surveyed for the period 2013–2020. • These include representatives of Crinum, Ammocharis, Amaryllis and Cyrtanthus. • Shown to have a notable presence in South African traditional medicine. • Such indigenous knowledge systems guide pharmacological evaluation of target species. • Significant findings made in the cancer and motorneuron disease arenas. The plant family Amaryllidaceae has attracted widespread attention in view of the interesting biological properties of its alkaloid principles. Many of these discoveries are based on the traditional usage of its members in regions where they are prominent. Over a third of its complement is found in southern Africa, hence the heightened interest in the Amaryllidaceae from this territory. Up to 2012, over 80 species were examined, mainly for their alkaloid constitution. Given the medicinal potential of the family as well as its widespread usage in South African traditional medicine, efforts over the past decade have intensified in understanding its biological properties. This account focuses on the biological activities that have been reported since 2013 for extracts of four genera of the South African Amaryllidaceae, viz Crinum, Ammocharis, Amaryllis and Cyrtanthus. Fourteen related species were assayed during this period, with Crinum (5 species) and Cyrtanthus (6 species) affording the bulk of the targets. Although most studies utilized the bulbous extracts, there were some instances involving the use of root, leaf and flower materials. The extractants used ranged from water to hexane, with a few examples addressing the outcomes of environmentally-benign extraction procedures. Close to twenty different areas were identified wherein the biological properties of the extracts were examined including, cytotoxicity, AChE and BuChE inhibition, cardio and hypertensive effects, antioxidant and anti-inflammatory effects, as well as antibacterial, antifungal and antiparasitic effects. Some studies also probed the mechanistic basis to these activities, notably in regards to their cytotoxic and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

• 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]

Members of the plant family Amaryllidaceae are widely recorded in traditional systems of medicine. Their usage for inflammatory conditions is most prominent, with substantive evidence emerging from several locations around the world. This survey was undertaken to identify such plant taxa, highlight the countries from which they originate and afford details of the ailments against which they are utilized. The undertaking also sought to establish the in vitro and in vivo activities of Amaryllidaceae plant extracts in inflammation-based assays. Furthermore, it set out to unravel the molecular mechanisms used to explain these effects. Over six-hundred articles were identified in searches carried out on SciFinder, Scopus, ScienceDirect, PubMed and Google Scholar. These were condensed to around 170 that formulated the basis of the text. The keyword engaged was 'Amaryllidaceae' in conjunction with 'inflammation' or 'anti-inflammatory', as well as the names of individual genera combined with the latter two. Fifty-one species from thirty-five countries were identified for their uses against inflammation. Twenty-four of such conditions were discernible, of which their applicability in wound healing and pain management was most conspicuous. The utilization of all plant parts was apparent, preparations of which were used primarily via topical application. Extracts of seventy-three species (from twenty-three genera) were examined in nearly thirty inflammation-based assays where their activities in vitro and in vivo were shown to be significant. They were effective in vivo against pain and swelling as well as wound healing, without detriment towards test subjects. The in vitro studies were carried out mainly in mononuclear cells such as macrophages, leukocytes, lymphocytes and neutrophils against which their cytotoxic effects were seen to be minimal. The modes of operation were shown to involve modulation of both pro-inflammatory (such as NF-κB, TNF-α, IL-6, IFN-γ, COX and NO) and anti-inflammatory (such as IL-10) factors. The Amaryllidaceae is showcased as a platform highly conducive towards studies in the inflammation arena. Potent activities in instances were observed via in vitro and in vivo models of study, bolstered by the significant amounts of information emerging from traditional forms of medicine. It is conceivable that the family may yield future anti-inflammatory chemotherapeutics, particularly those related to its alkaloid principles. [Display omitted] • Fifty-one Amaryllidaceae species recorded worldwide for uses against inflammation. • Utilized most for wound healing, pain management and general inflammation purposes. • Extracts of seventy-three species have been examined in inflammation-related assays. • Good activities described from in vitro and in vivo models of study. • Effects manifested via modulation of both pro- and anti-inflammatory factors. [ABSTRACT FROM AUTHOR]

Malaria is prevalent in tropical and subtropical regions of the globe. With over 200 million cases reported annually, particularly in sub-Saharan Africa, it is an unnecessary burden to already overworked and ailing healthcare structures. Traditional medicine (TM) remains vibrant in most of these regions wherein plants often serve as the first line of defense against malaria. Given this fact as well as the successes elsewhere of therapies such as Artemisia annua emanating from evidence-based TM, interest in plants as a source of new antimalarial drugs has been rejuvenated. The bulbous plant family Amaryllidaceae is recognized for its structurally-diverse alkaloid constituents which exhibit interesting biological properties. This review focuses on the in vitro activities demonstrated by its crinane alkaloids against various strains of the malaria-causing parasite Plasmodium falciparum. The survey embraces the twelve genera of the Amaryllidaceae whose nineteen representative species have been examined for antiplasmodial crinane alkaloid principles. A total of seventy-two compounds were screened against nine strains of P. falciparum , with the α -crinanes reflecting better overall activities than their corresponding β -crinane subgroup congeners. In terms of potency, an ED 50 of 0.14 μg/mL (for augustine in the D-6 strain) and IC 50 of 0.35 μg/mL (for haemanthidine in the K1 strain) were the lowest activity indices observed. Structure-activity relationship studies afforded useful insight on the antiplasmodial pharmacophore and the features supporting its efficacy. Overall, crinane alkaloids have provided a useful platform for the study of antiplasmodial effects, not only in terms of potency but also in terms of structural diversity. The Amaryllidaceae as a source of antiplasmodial crinane alkaloid constituents. Jerald J. Nair, Johannes van Staden. Unlabelled Image • The Amaryllidaceae provides an abundant source of antiplasmodial constituents. • Nineteen species examined for antiplasmodial alkaloids. • Seventy-two crinane alkaloids screened against various Plasmodium falciparum strains. • Activities detected across both chloroquine sensitive and resistant strains. • Haemanthamine and haemanthidine identified with best overall activities. • Haemanthidine (IC 50 0.35 μg/mL) better than mefloquine (IC 50 3.94 μg/mL) in K1 strain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There is a pressing need in antibiotic drug discovery for new drugs to counterbalance the effects of multidrug resistance. Plants represent a viable platform for such endeavors owing to their traditional relevance in infectious disease therapies as well as their vast chemical resources. As many as fifty different species of the Amaryllidaceae are discernible with such functions in traditional medicine, thirty-nine of which have been subjected to pharmacological evaluations. Submicromolar antibacterial activities for several of these plants have been the driving force behind studies targeting their active constituents. This review accounts for close to a hundred of such entities, mainly isoquinoline alkaloids, which have been the focus in assays of thirty different bacterial pathogens. Promising activities were detected in several instances, although disappointingly the submicromolar level could not be breached. Also considered are structure–activity relationships which have emerged within the various groups of Amaryllidaceae alkaloids. [ABSTRACT FROM AUTHOR]

Background: Viral-borne diseases are amongst the oldest diseases known to mankind. They are responsible for some of the most ravaging effects wrought on human health and well-being. The use of plants against these ailments is entrenched in both traditional and secular medicine around the globe. Their natural abundance and chemical diversity have also boosted their appeal in drug discovery.Aim: The plant family Amaryllidaceae is distinguished for its alkaloid principles, some of which are of considerable interest in the clinical arena. This account is the outcome of a literature review undertaken to establish the applicability of these substances as antiviral agents.Methods: The survey utilized the search engines Google Scholar, PubMed, SciFinder, Scopus and Web of Science engaging the word 'antiviral' in conjunction with 'Amaryllidaceae' and 'Amaryllidaceae alkaloid'. The search returned over five hundred hits, of which around eighty were of relevance to the theme of the text.Results: Over eighty isoquinoline alkaloids have been screened against nearly fifty pathogens from fourteen viral families, the majority of which were RNA viruses. Potent activities were reported in some instances, such as that of trans-dihydronarciclasine against Yellow fever virus (IC50 0.003 μg/ml), with minimal effects being manifested on host cells. There were also promising results obtained from in vivo studies, in most cases without lethal effects on test subjects. Structure-activity relationship studies afforded useful insight to the antiviral pharmacophore, with the phenanthridone alkaloid nucleus shown to be the most enabling. Although the mechanistic basis to these activities pertained mostly to inhibition of DNA, RNA and protein synthesis, evidence was also forthcoming about the inhibitory action of some of the alkaloids against viral neuraminidase, protease and reverse transcriptase. In silico methods of analysis have offered further perspectives of how some of the alkaloids interact at the active sites of their targets.Conclusion: The Amaryllidaceae offers a viable platform for plant-based antiviral drug discovery. Its cause is strengthened not only by its wide proliferation and exploitation of its members in alternative forms of medicine, but also by its rich chemical diversity which has already spawned useful antiviral drug leads. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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. [Display omitted] • The tribe Haemantheae of the South African Amaryllidaceae surveyed from 2013 to 2020. • Genera represented are Clivia , Cryptostephanus , Haemanthus , Scadoxus and Gethyllis. • Traditional usage, pharmacology and bioactive constitution aspects are covered. • Anticancer, antimicrobial and anti-inflammatory are some of the effects described. • Insight also afforded to the molecular basis to some of the activities. [ABSTRACT FROM AUTHOR]

Background: Fungal pathogenesis continues to be a burden to healthcare structures in both developed and developing nations. The gradual and irreversible loss of efficacies of existing antifungal medicines as well as the emergence of drug-resistant strains have contributed largely to this scenario. There is therefore a pressing need for new drugs from diverse structural backgrounds with improved potencies and novel modes of action to fortify or replace contemporary antifungal schedules.Aim: Alkaloids of the plant family Amaryllidaceae exhibit good growth inhibitory activities against several fungal pathogens. This review focuses on the mechanistic aspects of these antifungal activities. It achieves this by highlighting the molecular targets as well as structural features of Amaryllidaceae constituents which serve to enhance such action.Methods: During the information gathering stage extensive use was made of the three database platforms; Google Scholar, SciFinder and Scopus. In most instances articles were accessed directly from journals licensed to the University of KwaZulu-Natal. In the absence of such proprietary agreements the respective corresponding authors were approached directly for copies of papers.Results: Although several classes of molecules from the Amaryllidaceae have been probed for their antifungal effects, it is the key constituents lycorine and narciclasine which have together afforded the most profound mechanistic insights. These may be summarized as follows: (i) effects on the fungal cell wall and cell membrane; (ii) effects on morphology such as budding and hyphal growth; (iii) effects on fungal organelles such as ribosomes; (iv) effects on macromolecules such as DNA, RNA and proteins and; (v) identification of the active sites for these constituents.Conclusion: The key feature in the antifungal effects of Amaryllidaceae alkaloids is the inhibition of protein synthesis. This involved the inhibition of peptide bond formation by binding to yeast ribosomes via the 60S subunit. Related effects involved the inhibition of both DNA and RNA synthesis. These adverse effects were reflected morphologically on both the fungal cell wall and cell membrane. Such observations should prove useful in the chemotherapeutic arena should efforts shift towards the development of a clinical candidate. [ABSTRACT FROM AUTHOR]

Protozoan-borne diseases are prominent amongst diseases caused by parasites. Given their alarming morbidity and mortality statistics, there is ever growing interest in new therapies against these diseases. Whilst synthetic drugs such as benznidazole and melarsoprol have had a profound influence on the clinical setup, there has been significant interest in the phytochemical platform to also deliver such drug candidates. The plant family Amaryllidaceae is recognizable for its isoquinoline alkaloids, which exhibit attractive molecular architectures and interesting biological properties. This survey focuses on the antiprotozoal activities of 73 of such substances described in 18 different species of the Amaryllidaceae. Of these, 2- O -acetyllycorine was identified as the most potent (IC 50 0.15 μg/mL against Trypansoma brucei brucei). Also considered are structure-activity relationships which have served to modulate activities, as well as the plausible mechanisms that underpin these effects and afford insight to the Amaryllidaceae alkaloid antiprotozoal pharmacophore. [ABSTRACT FROM AUTHOR]