Oxidative stress, driven by reactive oxygen, nitrogen, and sulphur species (ROS, RNS, RSS), poses a significant threat to cellular integrity and human health. Generated during mitochondrial respiration, inflammation, UV exposure and pollution, these species damage cells and contribute to pathologies like cardiovascular issues, neurodegeneration, cancer, and metabolic syndromes. Lifestyle factors exert a substantial influence on oxidative stress levels, with mitochondria emerging as pivotal players in ROS generation and cellular equilibrium. Phytochemicals, abundant in plants, such as carotenoids, ascorbic acid, tocopherols and polyphenols, offer diverse antioxidant mechanisms. They scavenge free radicals, chelate metal ions, and modulate cellular signalling pathways to mitigate oxidative damage. Furthermore, plants thriving in high-altitude regions are adapted to extreme conditions, and synthesize secondary metabolites, like flavonoids and phenolic compounds in bulk quantities, which act to form a robust antioxidant defence against oxidative stress, including UV radiation and temperature fluctuations. These plants are promising sources for drug development, offering innovative strategies by which to manage oxidative stress-related ailments and enhance human health. Understanding and harnessing the antioxidant potential of phytochemicals from high-altitude plants represent crucial steps in combating oxidative stress-induced disorders and promoting overall wellbeing. This study offers a comprehensive summary of the production and physio-pathological aspects of lifestyle-induced oxidative stress disorders and explores the potential of phytochemicals as promising antioxidants. Additionally, it presents an appraisal of high-altitude medicinal plants as significant sources of antioxidants, highlighting their potential for drug development and the creation of innovative antioxidant therapeutic approaches.

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High elevation temperate mountains have long been considered species poor owing to high extinction or low speciation rates during the Pleistocene. We performed a phylogenetic and population genomic investigation of an emblematic high-elevation plant clade (Androsace sect. Aretia, 31 currently recognized species), based on plant surveys conducted during alpinism expeditions. We inferred that this clade originated in the Miocene and continued diversifying through Pleistocene glaciations, and discovered three novel species of Androsace dwelling on different bedrock types on the rooftops of the Alps. This highlights that temperate high mountains have been cradles of plant diversity even during the Pleistocene, with in-situ speciation driven by the combined action of geography and geology. Our findings have an unexpected historical relevance: H.-B. de Saussure likely observed one of these species during his 1788 expedition to the Mont Blanc and we describe it here, over two hundred years after its first sighting.

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The major intention of the present study was to investigate whether an approach combining the use of niche-based palaeodistribution modeling and phylo-geography would support or modify hypotheses about the Quaternary distributional history derived from phylogeographic methods alone. Our study system comprised two closely related species of Alpine Primula. We used species distribution models based on the extant distribution of the species and last glacial maximum (LGM) climate models to predict the distribution of the two species during the LGM. Phylogeographic data were generated using amplified fragment length polymorphisms (AFLPs). In Primula hirsuta, models of past distribution and phylogeographic data are partly congruent and support the hypothesis of widespread nunatak survival in the Central Alps. Species distribution models (SDMs) allowed us to differentiate between alpine regions that harbor potential nunatak areas and regions that have been colonized from other areas. SDMs revealed that diversity is a good indicator for nunataks, while rarity is a good indicator for peripheral relict populations that were not source for the recolonization of the inner Alps. In P. daonensis, palaeo-distribution models and phylogeographic data are incongruent. Besides the uncertainty inherent to this type of modeling approach (e.g., relatively coarse 1-km grain size), disagreement of models and data may partly be caused by shifts of ecological niche in both species. Nevertheless, we demonstrate that the combination of palaeo-distribution modeling with phylogeographical approaches provides a more differentiated picture of the distributional history of species and partly supports (P. hirsuta) and partly modifies (P. daonensis and P. hirsuta) hypotheses of Quaternary distributional history. Some of the refugial area indicated by palaeodistribution models could not have been identified with phylogeographic data.

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The taxonomy of alpine Primula species has long been in dispute because of high morphologic variability and several hybridisations. In Primula species, the trichome height and the colour of hair-tips are usually indicated as diacritic characters, but in our experience this is not adequate. The present study, focused on Primula auricula, Primula daonensis and Primula hirsuta, therefore proposes the use of other morphologic trichome parameters (size and dimensional ratio of stalk, neck and gland head). Phytochemical investigations about the flavonoid composition (epicuticular and vacuolar) of leaves, as taxonomic markers, have also been performed. We report the isolation and identification of two new flavonol glycosides, isorhamnetin 3-O-(2,6-di-O-beta-D-glucopyranosyl-beta-D-glucopyranoside) (1) and kaempferol 3-O-(2-O-alpha-L-rhamnopyranosyl-6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside) (2) and of eight known flavonoids. Size and dimensional ratio of the three trichome elements (stalk, neck and glandular head) are typical for each species analysed. The flavonoid profile well characterise the entities under study. Three different profiles have been obtained with both vacuolar and epicuticular flavonoids. The morphologic and phytochemical markers proposed in this work seem to be parameters which significatively discriminate the species under study.

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