The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.

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The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway arose early during evolution of eukaryotic cells, when it appears to have been involved in the response to glucose starvation and perhaps also in monitoring the output of the newly acquired mitochondria. Due to the advent of hormonal regulation of glucose homeostasis, glucose starvation is a less frequent event for mammalian cells than for single-celled eukaryotes. Nevertheless, the AMPK system has been preserved in mammals where, by monitoring cellular AMP:adenosine triphosphate (ATP) and adenosine diphosphate (ADP):ATP ratios and balancing the rates of catabolism and ATP consumption, it maintains energy homeostasis at a cell-autonomous level. In addition, hormones involved in maintaining energy balance at the whole-body level interact with AMPK in the hypothalamus. AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as "nutraceuticals."

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Ethnopharmacological relevance The plant species reported here are traditionally used in Northern Peru for a wide range of illnesses. Most remedies are prepared as ethanol or aqueous extracts and then ingested. The aim of this study was to evaluate the potential toxicity of these extracts. Materials and methods The toxicity of ethanolic and water extracts of 341 plant species was determined using a brine-shrimp assay. Results Overall 24% of the species in water extract and 76% of the species in alcoholic extract showed elevated toxicity levels to brine-shrimp. Although in most cases multiple extracts of the same species showed very similar toxicity values, in some cases the toxicity of different extracts of the same species varied from non-toxic to highly toxic. Conclusions Traditional preparation methods take different toxicity levels in aqueous and ethanol extracts into account when choosing the appropriate solvent for the preparation of a remedy.

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Infections of the reproductive tract, complications after childbirth, and reproductive problems continue to be a major health challenge worldwide. An impressive number of plant species is traditionally used to remedy such afflictions, and some have been investigated for their efficacy with positive results. A total of 105 plant species belonging to 91 genera and 62 families were documented and identified as herbal remedies for reproductive problems in Northern Peru. Most species used were Asteraceae (9.52%), followed by Lamiaceae and Fabaceae (8.57% and 6.67%). The most important families are clearly represented very similarly to their overall importance in the local pharmacopoeia. The majority of herbal preparations for reproductive afflictions were prepared from the leaves of plants (22.72%), the whole plant (21.97%), and stems (21.21%), while other plant parts were used less frequently. More than 60% of the cases fresh plant material was used to prepare remedies. Over 70% of the remedies were applied orally, while the remaining ones were applied topically. Many remedies were prepared as mixtures of multiple ingredients. Little scientific evidence exists to prove the efficacy of the species employed as reproductive disorder remedies in Northern Peru. Only 34% of the plants found or their congeners have been studied at all for their medicinal properties. The information gained on frequently used traditional remedies might give some leads for future targets for further analysis in order to develop new drugs.

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Aim The plant species reported here are traditionally used in Northern Peru to treat bacterial infections, often addressed by the local healers as "inflammation". The aim of this study was to evaluate the minimum inhibitory concentration (MIC) of their antibacterial properties against gram-positive and gram-negative bacteria. Materials and methods The antimicrobial activity of ethanolic and water extracts of 141 plant species was determined using a deep-well broth microdilution method on commercially available bacterial strains. Results The ethanolic extracts of 51 species inhibited Escherichia coli, and 114 ethanolic extracts inhibited Staphylococcus aureus. In contrast, only 30 aqueous extracts showed activity against Escherichia coli and 38 extracts against Staphylococcus aureus. The MIC concentrations were mostly very high and ranged from 0.008 to 256 mg/ml, with only 36 species showing inhibitory concentrations of Conclusions The presence of antibacterial activity could be confirmed in most species used in traditional medicine in Peru which were assayed in this study. However, the MIC for the species employed showed a very large range, and were mostly very high. Nevertheless, traditional knowledge might provide some leads to elucidate potential candidates for future development of new antibiotic agents.

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