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Covering: up to 2019The large and medicinally important tropical plant genus Plectranthus (Lamiaceae) was recently split into three separate genera on the basis of molecular and morphological evidence; Plectranthus sensu stricto, Coleus and Equilabium. We found striking differences between the diterpenoids which strongly support this taxonomic split. Coleus is characterised by abietanes oxygenated at C-14 such as royleanones, spirocoleons and acylhydroquinones, which could be useful chemotaxonomic markers to distinguish this genus from Plectranthus s.s. In contrast, the abietanes in Plectranthus s.s. lack C-14 oxygenation, but are often acylated with unusual acids. Equilabium species do not seem to produce diterpenoids. The structures of the nearly 240 abietanes so far reported from Coleus and Plectranthus and their distribution are presented. The aim of this Highlight is to provide an overview of the differences in diterpenoid diversity between these newly defined genera, which are relevant to predict which previously understudied species could hold untapped potential for their medicinal and other economic uses, and to underpin future research on how these plants have evolved to synthesise distinct abietane types.

Societal Impact Statement Plants and fungi have provided, or inspired, key pharmaceuticals for global health challenges, including cancer, heart disease, dementia, and malaria, and are valued as traditional medicines worldwide. Global demand for medicinal plants and fungi has threatened certain species, contributing to biodiversity loss and depletion of natural resources that are important for the health of humanity. We consider the evolving role of plants and fungi in global healthcare as new challenges to human health and to biodiversity arise. We present current and emerging scientific approaches, to uncover and preserve nature‐based health solutions for the future, through harmonization with biodiversity conservation strategies. Summary Non‐communicable diseases, including cardiovascular disease, cancer, and diabetes, are the main causes of deaths globally, and communicable diseases such as malaria and tuberculosis affect billions of people. Plants and fungi have provided key pharmaceuticals in our armory against these global health challenges, while in some regions of the world, they continue to have a central role in healthcare systems as traditional medicines. Consequently, global demand for plants and fungi in healthcare has threatened certain medicinal species, and is a driving factor in biodiversity loss. Yet the future of therapeutics from nature is evolving. Scientific advances are enabling the untapped potential of the world's plants and fungi to be explored for their medicinal value, and to reveal other roles they may have for improving health and well‐being; this demonstrates the value of natural capital as an incentive for biodiversity conservation. Emerging technologies also offer new hope for safeguarding essential medicines for the future, by revealing more sustainable solutions for sourcing key natural products. This review discusses recent developments and future approaches for the discovery of natural products as medicines, for health and well‐being, and strategies to harmonize the therapeutic use of biodiversity with its proactive conservation through nature‐based solutions.

Societal Impact Statement Biodiversity is essential to food security and nutrition locally and globally. By reviewing the global state of edible plants and highlighting key neglected and underutilized species (NUS), we attempt to unlock plant food resources and explore the role of fungi, which along with the wealth of traditional knowledge about their uses and practices, could help support sustainable agriculture while ensuring better protection of the environment and the continued delivery of its ecosystem services. This work will inform a wide range of user communities, including scientists, conservation and development organizations, policymakers, and the public of the importance of biodiversity beyond mainstream crops. Summary As the world's population is increasing, humanity is facing both shortages (hunger) and excesses (obesity) of calorie and nutrient intakes. Biodiversity is fundamental to addressing this double challenge, which involves a far better understanding of the global state of food resources. Current estimates suggest that there are at least 7,039 edible plant species, in a broad taxonomic sense, which includes 7,014 vascular plants. This is in striking contrast to the small handful of food crops that provide the majority of humanity's calorie and nutrient intake. Most of these 7,039 edible species have additional uses, the most common being medicines (70%), materials (59%), and environmental uses (40%). Species of major food crops display centers of diversity, as previously proposed, while the rest of edible plants follow latitudinal distribution patterns similarly to the total plant diversity, with higher species richness at lower latitudes. The International Union for Conservation of Nature Red List includes global conservation assessments for at least 30% of edible plants, with ca. 86% of them conserved ex situ. However, at least 11% of those species recorded are threatened. We highlight multipurpose NUS of plants from different regions of the world, which could be key for a more resilient, sustainable, biodiverse, and community participation‐driven new “green revolution.” Furthermore, we explore how fungi could diversify and increase the nutritional value of our diets. NUS, along with the wealth of traditional knowledge about their uses and practices, offer a largely untapped resource to support food security and sustainable agriculture. However, for these natural resources to be unlocked, enhanced collaboration among stakeholders is vital.

Cognitive decline can occur with normal ageing and in age-related brain disorders, such as mild cognitive impairment and dementia, including Alzheimer's disease, with limited pharmacological therapies available. Other approaches to reduce cognitive decline are urgently needed, and so, the role of dietary interventions or nutraceuticals has received much attention in this respect. In this review, we examine the evidence for dietary plants and their chemical constituents as nutraceuticals, relevant to both cognitive decline in normal ageing and in dementia. Pharmacological (in vitro and in vivo), clinical and epidemiological evidence is assessed for both frequently consumed plants and their dietary forms, including tea, coffee, cocoa (chocolate), red wine, grapes, citrus and other fruits; in addition to plants used less frequently in certain diets and those that cross the blurred boundaries between foods, nutraceuticals and medicinal plants. For the latter, turmeric, saffron, sage, rosemary and lemon balm are examples of those discussed. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.

With more than two billion people suffering from malnutrition and diets homogenising globally, it is vital to identify and conserve nutrient-rich species that may contribute to improving food security and diversifying diets. Of the approximately 390,000 vascular plant species known to science, thousands have been reported to be edible, yet their nutritional content remains poorly characterised. Here we use phylogenetic information to identify plants with the greatest potential to support strategies alleviating B-vitamin deficiencies. We predict the B-vitamin profiles of >6,400 edible plants lacking nutritional data and identify 1,044 species as promising key sources of B vitamins. Several of these source species should become conservation priorities, as 145 (14%) are threatened in the wild and 272 (26%) are absent from seedbanks. Moreover, many of these conservation-priority source species overlap with hotspots of malnutrition, highlighting the need for safeguarding strategies to ensure that edible plant diversity remains a reservoir of nutrition for future generations, particularly in countries needing it most. Although by no means a silver bullet to tackling malnutrition, conserving a diverse portfolio of edible plants, unravelling their nutritional potentials and promoting their sustainable use are essential strategies to enhance global nutritional resilience.

Trigonella foenum-graecum L. (fenugreek), a member of the legume family (Fabaceae), is a promising source of bioactive phytochemicals, which explains its traditional use for a variety of metabolic disorders including cancer. The current study aimed to evaluate extracts of fenugreek seeds and sprouts, and some of their constituents, to compare their cytotoxic and antiproliferative activities in MCF-7 breast cancer cells. The extracts were chemically characterised using high-resolution accurate mass liquid chromatography-mass spectrometry to reveal the detection of compounds assigned as flavone C-glycosides including those derived from apigenin and luteolin, in addition to isoflavones. Five different flavones or their glycosides (apigenin, vicenin-2, vitexin, luteolin and orientin) and two isoflavones (daidzein and formononetin) were quantified in the fenugreek extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using MCF-7 cells treated with fenugreek methanolic extracts showed dose- and time-dependent effects on cell viability. The MCF-7 cancer cells treated with the fenugreek methanolic extracts also displayed increased relative mitochondrial DNA damage as well as suppressed metastasis and proliferation. This study demonstrates the potential anti-cancer effects of fenugreek seeds and sprouts and reveals fenugreek sprouts as an untapped resource for bioactive compounds.

Covering: up to 2019The large and medicinally important tropical plant genus

Anacyclus pyrethrum (L.) Lag has a long tradition of medical use in Algeria. We report for the first time the antioxidant, functional and neuroprotective properties of this plant from Algeria. Differences in biochemical and physiological properties for the aqueous and methanol extracts of A. pyrethrum are reported and related to the main chemical constituents. The A. pyrethrum extracts contained amino acids, caffeoylquinic acids, N-feruloyltyramine and alkaloids, including including N-alkylamides, common in this plant species. Aqueous extracts (0.1 mg/ml) are neuroprotective against H2O2-induced oxidative stress, while methanol extracts (high phenolic content), despite significant antioxidant and free-radical scavenging activity, caused dysregulation of calcium signalling in neurons and was not apparently neuroprotective. Such knowledge can provide incentive for the sustainable cultivation of Algerian A. pyrethrum, with the aim of supporting conservation strategies and preserving biodiversity.

Enset (Ensete ventricosum) is a major starch staple and food security crop for 20 million people. Despite substantial diversity in morphology, genetics, agronomy and utilization across its range, nutritional characteristics have only been reported in relatively few landraces. Here, we survey nutritional composition in 22 landraces from three enset growing regions. We present mineral characterization of enset corm tissue, free amino acid characterization of raw and processed (fermented) tissues and genomic analysis of the microbial community associated with fermentation. We show that compared to regionally important tubers and cereals, enset is high in calcium, iron, potassium and zinc and low in sodium. We report changes in free amino acid composition due to processing, and establish that the bacteria generaAcetobacter,LactobacillusandBifidobacterium, predominate during fermentation. Nutritional and microbial variation presents opportunities to select for improved composition, quality or safety with potentially significant impacts in food security and public health.

A phytochemical and biological investigation of the endemic Mascarene Aloes (Aloe spp.), including A. tormentorii (Marais) L.E.Newton & G.D.Rowley, A. purpurea Lam, A. macra Haw., A. lomatophylloides Balf.f and A. vera (synonym A. barbadensis Mill.), which are used in the traditional folk medicine of the Mascarene Islands, was initiated. Methanolic extracts of the Aloes under study were analysed using high resolution LC-UV-MS/MS and compounds belonging to the class of anthraquinones, anthrones, chromones and flavone C-glycosides were detected. The Mascarene Aloes could be distinguished from A. vera by the absence of 2″-O-feruloylaloesin and 7-O-methylaloeresin. GC–MS analysis of monosaccharides revealed the presence of arabinose, fucose, xylose, mannose and galactose in all the Mascarene Aloes and in A. vera. The crude extracts of all Aloes analysed displayed antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Only extracts of A. macra were active against P. aeruginosa and Klebsiella pneumoniae, while none of the Aloe extracts inhibited Propionibacterium acnes. A. macra displayed anti-tyrosinase activity, exhibiting 50% inhibition at 0.95 mg/mL, and extracts of A. purpurea (Mauritius) and A. vera displayed activity in a wound healing-scratch assay. In vitro cytotoxicity screening of crude methanolic extracts of the Aloes, using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) showed that only A. purpurea (Réunion) elicited a modest toxic effect against HL60 cells, with a percentage toxicity of 8.2% (A. purpurea-Réunion) and none of the Aloe extracts elicited a toxic effect against MRC 5 fibroblast cells at a concentration of 0.1 mg/mL. Mascarene Aloe species possess noteworthy pharmacological attributes associated with their rich phytochemical profiles.

To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function.Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6).Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed.This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.

Ethnopharmacological relevance Malaria remains a serious and challenging disease. Traditional antimalarial medicines are largely based on plants, while ethnopharmacological research has inspired the development of antimalarial pharmaceuticals such as artemisinin. Antimalarial drug resistance is an increasing problem in Plasmodium species, and new therapeutic strategies to combat malaria are needed. Although the number of malaria cases has been decreasing in Latin America, malaria remains a significant threat in many regions. Local people in Latin America have been using many plant species to treat malaria, some of which have been scientifically studied, but many others that have not. Aim of the study: Our principal objective is to harness ethnobotanical data on species used traditionally to treat malaria, combined with phylogenetic approaches, to understand how ethnobotany could help identify plant genera as potential sources of new medicines. Materials and Methods Plants used to treat malaria in Latin America were compiled from published and grey literature, unpublished data, and herbarium specimens. Initial assessment of potentially important species/genera/families involved compiling the number of species used within the genus, the number of use reports per genus and species, and the geographic distribution of their use. The analysis of taxonomic distribution of species reported as antimalarial in Latin America (excluding the Southern Cone) was conducted, to determine which genera and families with reputed antimalarial properties are over-represented, and phylogenetic analyses were performed to identify if there was evidence for antimalarial species being dispersed/clustered throughout the tree or at its tips. This approach enables ‘hot-nodes’ in certain families to be identified, to predict new genera with potential antimalarial properties. Results Over 1,000 plant species have been used to treat malaria in Latin America, of which over 600 species were cited only once. The genera with the highest number of antimalarial species were Aspidosperma, Solanum, Piper, Croton and Aristolochia. In terms of geographic distribution, the most widely used genera were Aspidosperma, Momordica, Cinchona, Senna and Stachytarpheta. Significant phylogenetic signal was detected in the distribution of native species used for malaria, analysed in a genus-level phylogenetic framework. The eudicot and magnoliidae lineages were over-represented, while monocots were not. Conclusion Analysis of ethnobotanical use reports in a phylogenetic framework reveals the existence of hot nodes for malaria across the Latin American flora. We demonstrate how species and genera currently lacking such reports could be pinpointed as of potential interest based on their evolutionary history. Extending this approach to other regions of the world and other diseases could accelerate the discovery of novel medicines and enhance healthcare in areas where new therapeutic strategies are needed.

Perilla frutescens is cultivated in East Asian countries including Thailand, and the nutlets (single-seeded fruits) are used as traditional and medicinal food. Perilla nutlets extracted by ethyl acetate (EA), 80% ethanol (Eth), and hot water (HW) sequentially were chemically characterized using high-resolution accurate liquid chromatography-mass spectrometry with the main compounds detected assigned as rosmarinic acid and derivatives of the flavones apigenin and luteolin, with the more diverse chemical composition observed with the Eth extract. All extracts showed dose-dependent free-radical scavenging activity, with the Eth extract the most potent (IC50 = 3.43 mg/ml for ABTS• scavenging and 0.27 mg/ml for DPPH• scavenging). The Eth extract also inhibited AAPH-induced hemolysis (IC50 = 0.07 mg/ml) more potently than did the HW (IC50 = 0.38 mg/ml) and EA extracts (IC50 = 1.63 mg/ml). An MTT test revealed all the extracts were noncytotoxic at concentrations up to 200 μg/ml. Only the Eth and EA extracts showed protective effects against the generation of reactive oxygen species and lipid peroxidation in FeCl3 -induced HuH7 cells in a dose-dependent manner. Our findings suggest the Eth extract of Thai perilla nutlets, containing rosmarinic acid and flavones and their derivatives, may have potential to provide protection against oxidative stress in hepatic disorders.

The data described in this article is related to the review article “Medicinal plants used in the traditional management of diabetes and its sequelae in Central America: a review” (Giovannini et al., 2016) [1]. We searched publications on the useful plants of Central America in databases and journals by using selected relevant keywords. We then extracted reported uses of medicinal plants within the disease categories: diabetes mellitus, kidney disease, urinary problems, skin diseases and infections, cardiovascular disease, sexual dysfunction, vision loss, and nerve damage. The following countries were included in our definition of Central America: Belize, Guatemala, Honduras, El Salvador, Nicaragua, Costa Rica and Panama. Data were compiled in a bespoke Access database. Plant names from the published sources were validated against The Plant List (TPL, (The Plant List, 2013) [2]) and accepted names and synonyms were extracted. In total, the database includes 607 plant names obtained from the published sources which correspond to 537 plant taxa, 9271 synonyms and 1055 use reports. Keywords: Diabetes, Central America, Medicinal plants, Hypoglycemic, Traditional medicine, Herbal remedies, Ecosystem services, Natural capital

Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK−1)B9Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK−1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD.

More than 31,000 useful plant species have been documented to fulfil needs and services for humans or the animals and environment we depend on. Despite this diversity, humans currently satisfy most requirements with surprisingly few plant species; for example, just three crops – rice, wheat and maize – comprise more than 50% of plant derived calories. Here, we synthesize the projected impact of global climatic change on useful plants across the spectrum of plant domestication. We illustrate the demographic, spatial, ecophysiological, chemical, functional, evolutionary and cultural traits that are likely to characterise useful plants and their resilience in the next century. Using this framework, we consider a range of possible pathways for future human use of plants. These are centred on two trade-offs: i) diversification versus specialization in the range of species we utilize, and ii) substitution of the species towards those better suited to future climate versus facilitating adaptation in our existing suite of dominant useful plants. In the coming century, major challenges to agriculture and biodiversity will be dominated by increased climatic variation, shifting species ranges, disruption to biotic interactions, nutrient limitation and emerging pests and pathogens. These challenges must be mitigated, whilst enhancing sustainable production to meet the needs of a growing population and a more resource intensive standard of living. With the continued erosion of biodiversity, our future ability to choose among these pathways and trade-offs is likely to be diminished.

Background: Extracts of several members of the monoterpene-rich Lamiaceae sub-family Nepetoideae, including those from the Salvia (sage), Melissa (Lemon balm) and Rosmarinus (rosemary) genera, evince cognitive and mood effects in humans that are potentially related to their effects on cholinergic and GABAergic neurotransmission. To date, despite promising in vitro properties, the cognitive and mood effects of the closely related Mentha spicata (spearmint) and Mentha piperita (peppermint) remain unexplored. This study therefore assessed the human cognitive/mood effects of the M. spicata/piperita essential oil with the most promising, brain-relevant in vitro properties according to pre-trial in vitro screening.\ud \ud Design: Organic spearmint and peppermint (Mentha spicata/piperita) essential oils were pre-screened for neurotransmitter receptor binding and acetylcholinesterase (AChE) inhibition. In a double-blind, placebo-controlled, balanced cross-over study, 24 participants (mean age 25.2 years) consumed single doses of encapsulated placebo and 50 µL and 100 µL of the most promising essential oil (peppermint with nicotinic/GABAA receptor binding and AChE inhibitory properties, that increased calcium influx in a CAD cell neuronal model). Psychological functioning was assessed with mood scales and a range of standardised, cognitively demanding tasks pre-dose and at 1, 3 and 6 h post-dose.\ud \ud Results: The highest (100 µL) dose of essential oil improved performance on the cognitively demanding Rapid Visual Information Processing task (RVIP) at 1 h and 3 h post-dose and both doses attenuated fatigue and improved performance of the Serial 3 s subtraction task at 3 h post-dose.\ud \ud Conclusion: Peppermint (Mentha piperita) essential oil with high levels of menthol/menthone and characteristic in vitro cholinergic inhibitory, calcium regulatory and GABAA/nicotinic receptor binding properties, beneficially modulated performance on demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive task performance in healthy adults. Future investigations should consider investigating higher doses.

Inflammatory processes have been associated with a wide range of chronic diseases including cardiovascular disease, cancer, dementia, and diabetes. Emerging evidence from mechanistic, clinical, and epidemiological studies associates some dietary factors, including a diverse array of phytochemicals, with effects relevant to modulating inflammatory processes that may contribute to their suggested health benefits. In this context, there is much interest in the use of dietary phytochemicals as nutraceuticals that are considered to maintain health or prevent disease, although the scientific evidence to support their use is often variable. Inflammation may also occur in other circumstances such as following injury or in other pathologies. Plants have been used for centuries for their reputed medicinal effects and scientific evidence is also emerging to explain their medicinal uses, including studies that suggest some plant species and their constituents have anti-inflammatory effects relevant for a particular therapeutic use. In these circumstances, plants may be used as phytopharmaceuticals to treat or alleviate inflammatory diseases. This chapter describes some plant constituents that have been associated with anti-inflammatory effects relevant for use as nutraceuticals, phytopharmaceuticals, or as both.

Alzheimer's disease (AD) is reaching epidemic proportions yet treatment strategies are limited and are restricted to providing symptomatic relief for the cognitive and behavioral and psychological symptoms of dementia (BPSD). Chinese herbal medicine (CHM) has been a valuable source of medicines for centuries and research has burgeoned in recent years to understand the scientific basis for their use. Some plants have been used in CHM for AD symptoms (e.g., Polygala tenuifolia), while others are CHMs for different conditions, but they show mechanistic effects relevant to AD (e.g., Salvia miltiorrhiza). Some CHMs (e.g., Ginkgo biloba extract, and huperzine A from Huperzia serrata) show pharmacological activities relevant to AD, and promising effects on cognitive functions in clinical trials. Other CHMs show effects relevant to BPSD (e.g., Crocus sativus). This chapter discusses available scientific evidence for CHM plants and formulae that have been used both traditionally for AD, and those that have been used traditionally but not specifically for AD symptoms, and encompasses chemical, pharmacological and clinical studies. The ethnopharmacological approach to understanding the use of CHMs for AD is also discussed.

Alzheimer's disease (AD) is reaching epidemic proportions yet treatment strategies are limited and are restricted to providing symptomatic relief for the cognitive and behavioral and psychological symptoms of dementia (BPSD). Chinese herbal medicine (CHM) has been a valuable source of medicines for centuries and research has burgeoned in recent years to understand the scientific basis for their use. Some plants have been used in CHM for AD symptoms (e.g., Polygala tenuifolia), while others are CHMs for different conditions, but they show mechanistic effects relevant to AD (e.g., Salvia miltiorrhiza). Some CHMs (e.g., Ginkgo biloba extract, and huperzine A from Huperzia serrata) show pharmacological activities relevant to AD, and promising effects on cognitive functions in clinical trials. Other CHMs show effects relevant to BPSD (e.g., Crocus sativus). This chapter discusses available scientific evidence for CHM plants and formulae that have been used both traditionally for AD, and those that have been used traditionally but not specifically for AD symptoms, and encompasses chemical, pharmacological and clinical studies. The ethnopharmacological approach to understanding the use of CHMs for AD is also discussed.

Ethnopharmacological relevance Every year between 1.2 and 5.5 million people worldwide are victims of snakebites, with about 400,000 left permanently injured. In Central America an estimated 5500 snakebite cases are reported by health centres, but this is likely to be an underestimate due to unreported cases in rural regions. The aim of this study is to review the medicinal plants used traditionally to treat snakebites in seven Central American countries: Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and Panama. Materials and methods A literature search was performed on published primary data on medicinal plants of Central America and those specifically pertaining to use against snakebites. Plant use reports for traditional snakebite remedies identified in primary sources were extracted and entered in a database, with data analysed in terms of the most frequent numbers of use reports. The scientific evidence that might support the local uses of the most frequently reported species was also examined. Results A total of 260 independent plant use reports were recorded in the 34 sources included in this review, encompassing 208 species used to treat snakebite in Central America. Only nine species were reported in at least three studies: Cissampelos pareira L., Piper amalago L., Aristolochia trilobata L., Sansevieria hyacinthoides (L.) Druce, Strychnos panamensis Seem., Dorstenia contrajerva L., Scoparia dulcis L., Hamelia patens Jacq., and Simaba cedron Planch. Genera with the highest number of species used to treat snakebite were Piper , Aristolochia , Hamelia , Ipomoea , Passiflora and Peperomia . The extent of the scientific evidence available to understand any pharmacological basis for their use against snakebites varied between different plant species. Conclusion At least 208 plant species are traditionally used to treat snakebite in Central America but there is a lack of clinical research to evaluate their efficacy and safety. Available pharmacological data suggest different plant species may target different symptoms of snakebites, such as pain or anxiety, although more studies are needed to further evaluate the scientific basis for their use.

The cultivation of apples ( Malus x domestica ) can be traced back for thousands of years to Asia and to Malus sieversii , which grows in temperate forests of central Asia. As the apple spread through Asia, into Europe, Russia and then into the Americas, Australia, and New Zealand, the number of locally grown cultivars increased. The difference in the diversity and levels of phenolic compounds in heritage and commercial cultivars is reviewed. Overall, older cultivars have higher levels of phenolic compounds than many of the modern commercial cultivars. Most phenolic compounds occur in higher concentrations in the peel than in the flesh. The biological activity of many of the phenolics found in apples is reviewed. Apples clearly contain compounds that have potential health benefits; however, more research is needed to evaluate what levels of these compounds are needed to have a beneficial impact on our health.

Ethnobotany encompasses the cultural uses of plants by humans, including their uses as medicines (ethnopharmacology). The reputed medicinal properties of plants have been documented for centuries in different cultures, and there are many plant species that have been traditionally used for memory disorders, which are now being explored to determine any scientific basis for their reputed uses. Plants have been a valuable source of drugs, and phytochemicals have also provided templates to develop synthetic drugs (e.g. rivastigmine, based on the chemical structure of physostigmine from Physostigma venenosum). Although drug development from botanical origin is one aim, the use of plants as herbal medicines is still popular. Scientific evidence for efficacy and safety has been explored for many species, although more research is needed, particularly to identify active phytochemicals to produce standardised herbal products. For Alzheimer's disease (AD) there are relatively few drugs available to treat symptoms, and there is a lack of successful therapies that modulate disease progression. Since two of the currently licensed drugs for AD are based on natural products (galantamine and rivastigmine), it is not surprising that many plants are now being investigated as a potential source of new therapies for AD. This review discusses those plants that have ethnobotanical uses suggestive of alleviation of AD pathology and associated symptoms, for cognitive and for behavioural and psychological symptoms of dementia (BPSD). An emphasis is placed on those plants that have shown some promising effects in clinical studies with dementia patients (e.g. Crocus sativus, Ginkgo biloba, Salvia species), but other plants and their phytochemicals showing relevant mechanistic effects for AD (e.g. Bacopa monnieri, Centella asiatica, Ptychopetalum olacoides) are also discussed.

Dementia pathologies such as Alzheimer's disease (AD) are reaching epidemic proportions, yet they are not successfully managed by effective symptomatic treatments. Only five drugs have been developed to alleviate cognitive symptoms, and more effective and safe treatments are needed for both the cognitive symptoms and behavioural and psychological symptoms of dementia (BPSD). As two of these licensed drugs (cholinesterase inhibitors [ChEIs]) are naturally derived (galantamine and rivastigmine), the potential for plants to yield new therapeutic agents has stimulated extensive research to discover new ChEIs together with plant extracts, phytochemicals and their derivatives with other mechanistic effects relevant to dementia treatment. This review presents the potential and actual therapeutic strategies for dementia in relation to the known mechanisms of dementia pathology. Phytochemicals that have shown mechanistic effects relevant to the pathological targets in dementia are discussed, with an emphasis on those showing positive clinical trial evidence. Those phytochemicals discussed include the alkaloid physostigmine, a ChEI from the calabar bean (Physostigma venenosum), which has been used as a template for the development of synthetic derivatives that inhibit acetylcholinesterase, including the drug rivastigmine. Also discussed are other ChEI alkaloids including huperzine A, from Huperzia serrata, and galantamine, originally from the snowdrop (Galanthus woronowii); both alkaloids improve cognitive functions in AD patients. Other phytochemicals discussed include cannabinoids (e.g. cannabidiol) from Cannabis sativa, which are emerging as potential therapeutic agents for BPSD, and resveratrol (occurs in various plants) and curcumin (from turmeric [Curcuma longa]), which have been investigated for their pharmacological activities relevant to dementia and their potential effects on delaying dementia progression. The review also discusses plant extracts, and their known constituents, that have shown relevant mechanistic effects for dementia and promising clinical data, but require more evidence for their clinical efficacy and safety. Such plants include Ginkgo biloba, which has been extensively studied in numerous clinical trials, with most outcomes showing positive effects on cognitive functions in dementia patients; however, more reliable and consistent clinical data are needed to confirm efficacy. Other plants and their extracts that have produced promising clinical data in dementia patients, with respect to cognition, include saffron (Crocus sativus), ginseng (Panax species), sage (Salvia species) and lemon balm (Melissa officinalis), although more extensive and reliable clinical data are required. Other plants that are used in traditional practices of medicine have been suggested to improve cognitive functions (e.g. Polygala tenuifolia) or have been associated with alleviation of BPSD (e.g. the traditional prescription yokukansan); such remedies are often prescribed as complex mixtures of different plants, which complicates interpretation of pharmacological and clinical data and introduces additional challenges for quality control. Evidence for the role of natural products in disease prevention, the primary but considerably challenging aim with respect to dementia, is limited, but the available epidemiological and clinical evidence is discussed, with most studies focused on ChEIs, nicotine (from Nicotiana species), curcumin, wine polyphenols such as resveratrol and G. biloba. Challenges for the development of phytochemicals as drugs and for quality control of standardized plant extracts are also considered.

Background/Aims: Behavioural and psychological symptoms (BPSD) are frequent in people with Alzheimer’s disease and cause considerable stress to patients and their carers. Antipsychotics have been widely used as a first-line treatment, resulting in an estimated 1,800 excess strokes and 1,600 excess deaths in the UK alone. Safe and effective alternatives are urgently needed. Based upon preliminary evidence from clinical trials, aromatherapy with melissa oil may be such an alternative, but initial studies have been modest in size, and adequate blinding has been problematic. Our objective was to assess the efficacy of melissa aromatherapy in the treatment of agitation in people with Alzheimer’s disease in an adequately powered and robustly blinded randomized controlled trial comparing it with donepezil, an anticholinesterase drug used with some benefit to treat BPSD. Methods and Findings: The study was a double-blind parallel-group placebo-controlled randomized trial across 3 specialist old age psychiatry centres in England. Participants had probable or possible Alzheimer’s disease, were resident in a care home, had clinically significant agitation (defined as a score of 39 or above on the Cohen Mansfield Agitation Inventory) and were free of antipsychotics and/or anticholinesterase for at least 2 weeks. Participants were allocated to 1 of 3 groups: placebo medication and active aromatherapy; active medication and placebo aromatherapy or placebo of both. Main Outcome: The primary outcome measure was reduction in agitation as assessed by the Pittsburgh Agitation Scale (PAS) at 4 weeks. This is an observational scale, and raters were required to wear nose clips to ensure that full blinding was maintained. The PAS, Neuropsychiatric Inventory (NPI; another measure of BPSD) and other outcome measures were completed at baseline, 4-week and 12-week follow-ups. 114 participants were randomized, of whom 94 completed the week 4 assessment and 81 completed the week 12 assessment. Aromatherapy and donepezil were well tolerated. There were no significant differences between aromatherapy, donepezil and placebo at week 4 and week 12, but importantly there were substantial improvements in all 3 groups with an 18% improvement in the PAS and a 37% improvement in the NPI over 12 weeks. Conclusion: When assessed using a rigorous design which ensures blinding of treatment arms, there is no evidence that melissa aromatherapy is superior to placebo or donepezil, in the treatment of agitation in people with Alzheimer’s disease. However, the sizeable improvement in the placebo group emphasizes the potential non-specific benefits of touch and interaction in the treatment of agitation in people with Alzheimer’s disease.

An escalating "epidemic" of diseases like Alzheimer's has not yet been met by effective symptomatic treatments or preventative strategies. Among a few current prescription drugs are cholinesterase inhibitors including galantamine, originating from the snowdrop. Research into ethnobotanicals for memory or cognition has burgeoned in recent years. Based on a multi-faceted review of medicinal plants or phytochemicals, including traditional uses, relevant bioactivities, psychological and clinical evidence on efficacy and safety, this overview focuses on those for which there is promising clinical trial evidence in people with dementia, together with at least one other of these lines of supporting evidence. With respect to cognitive function, such plants reviewed include sage, Ginkgo biloba, and complex mixtures of other traditional remedies. Behavioral and psychological symptoms of dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can be alleviated by some plant species (e.g., lemon balm and lavender alleviate agitation in people with dementia; St John's wort treats depression in the normal population). The ultimate goal of disease prevention is considered from the perspective of limited epidemiological and clinical trial evidence to date. The potential value of numerous plant extracts or chemicals (e.g., curcumin) with neuroprotective but as yet no clinical data are reviewed. Given intense clinical need and carer concerns, which lead to exploration of such alternatives as herbal medicines, the following research priorities are indicated: investigating botanical agents which enhance cognition in populations with mild memory impairment or at earliest disease stages, and those for BPSD in people with dementia at more advanced stages; establishing an ongoing authoritative database on herbal medicine for dementia; and further epidemiological and follow up studies of promising phytopharmaceuticals or related nutraceuticals for disease prevention.

A new genus Kindia (Pavetteae, Rubiaceae) is described with a single species, Kindia gangan, based on collections made in 2016 during botanical exploration of Mt Gangan, Kindia, Republic of Guinea in West Africa. The Mt Gangan area is known for its many endemic species including the only native non-neotropical Bromeliaceae Pitcairnia feliciana. Kindia is the fourth endemic vascular plant genus to be described from Guinea. Based on chloroplast sequence data, the genus is part of Clade II of tribe Pavetteae. In this clade, it is sister to Leptactina sensu lato (including Coleactina and Dictyandra). K. gangan is distinguished from Leptactina s.l. by the combination of the following characters: its epilithic habit; several-flowered axillary inflorescences; distinct calyx tube as long as the lobes; a infundibular-campanulate corolla tube with narrow proximal section widening abruptly to the broad distal section; presence of a dense hair band near base of the corolla tube; anthers and style deeply included, reaching about mid-height of the corolla tube; anthers lacking connective appendages and with sub-basal insertion; pollen type 1; pollen presenter (style head) winged and glabrous (smooth and usually hairy in Leptactina); orange colleters producing a vivid red exudate, which encircle the hypanthium, and occur inside the calyx and stipules. Kindia is a subshrub that appears restricted to bare, vertical rock faces of sandstone. Fruit dispersal and pollination by bats is postulated. Here, it is assessed as Endangered EN D1 using the 2012 IUCN standard. High resolution LC-MS/MS analysis revealed over 40 triterpenoid compounds in the colleter exudate, including those assigned to the cycloartane class. Triterpenoids are of interest for their diverse chemical structures, varied biological activities, and potential therapeutic value.

The volatile compounds from the pericarps of Illicium anisatum L., Illicium brevistylum A.C.Sm., Illicium griffithii Hook.f. & Thomson, Illicium henryi Diels, Illicium lanceolatum A.C.Sm., Illicium majus Hook.f. & Thomson, Illicium micranthum Dunn, and Illicium verum Hook.f. were examined by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). The volatiles desorbed from the pericarps of I. verum (Chinese star anise), the species traded for culinary purposes, were generally characterized by a high proportion of (E)-anethole (57.6-77.1%) and the presence of foeniculin; the latter was otherwise only detected in the pericarps of I. lanceolatum. In the pericarps of all other species analyzed, the percentage composition of (E)-anethole was comparatively lower (

Both Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils have putative anti-agitation properties in humans, indicating common components with a depressant action in the central nervous system. A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically validated essential oil derived from La, which has shown clinical benefit in treating agitation. La inhibited [35S] TBPS binding to the rat forebrain gamma aminobutyric acid (GABA)(A) receptor channel (apparent IC50 = 0.040 +/- 0.001 mg mL(-1)), but had no effect on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or nicotinic acetylcholine receptors. A 50:50 mixture of Mo and La essential oils inhibited [3H] flunitrazepam binding, whereas the individual oils had no significant effect. Electrophysiological analyses with rat cortical primary cultures demonstrated that La reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01-1 mg mL(-1)), whereas no inhibition of NMDA- or AMPA-induced currents was noted. La elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classic GABA(A) antagonist picrotoxin which evoked profound epileptiform burst firing in these cells). These properties are similar to those recently reported for Mo. The anti-agitation effects in patients and the depressant effects of La we report in neural membranes in-vitro are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here. These data suggest that components common to the two oils are worthy of focus to identify the actives underlying the neuronal depressant and anti-agitation activities reported.