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Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease. Recently approved molecular/gene treatments do not solve the downstream inflammation-linked pathophysiological issues such that supportive therapies are required to improve therapeutic efficacy and patients' quality of life. Over the years, a plethora of bioactive natural compounds have been used for human healthcare. Among them, plumbagin, a plant-derived analog of vitamin K3, has shown interesting potential to counteract chronic inflammation with potential therapeutic significance. In this work we evaluated the effects of plumbagin on DMD by delivering it as an oral supplement within food to dystrophic mutant of the fruit fly Drosophila melanogaster and mdx mice. In both DMD models, plumbagin show no relevant adverse effect. In terms of efficacy plumbagin improved the climbing ability of the dystrophic flies and their muscle morphology also reducing oxidative stress in muscles. In mdx mice, plumbagin enhanced the running performance on the treadmill and the muscle strength along with muscle morphology. The molecular mechanism underpinning these actions was found to be the activation of nuclear factor erythroid 2-related factor 2 pathway, the re-establishment of redox homeostasis and the reduction of inflammation thus generating a more favorable environment for skeletal muscles regeneration after damage. Our data provide evidence that food supplementation with plumbagin modulates the main, evolutionary conserved, mechanistic pathophysiological hallmarks of dystrophy, thus improving muscle function in vivo; the use of plumbagin as a therapeutic in humans should thus be explored further., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) brains are histologically marked by the presence of intracellular and extracellular amyloid deposits, which characterize the onset of the disease pathogenesis. Increasing evidence suggests that certain nutrients exert a direct or indirect effect on amyloid β (Aβ)-peptide production and accumulation and, consequently, on AD pathogenesis. We exploited the fruit fly Drosophila melanogaster model of AD to evaluate in vivo the beneficial properties of Lisosan G, a fermented powder obtained from organic whole grains, on the intracellular Aβ-42 peptide accumulation and related pathological phenotypes of AD. Our data showed that the Lisosan G-enriched diet attenuates the production of neurotoxic Aβ peptides in fly brains and reduces neuronal apoptosis. Notably, Lisosan G exerted anti-oxidant effects, lowering brain levels of reactive oxygen species and enhancing mitochondrial activity. These aspects paralleled the increase in autophagy turnover and the inhibition of nucleolar stress. Our results give support to the use of the Drosophila model not only to investigate the molecular genetic bases of neurodegenerative disease but also to rapidly and reliably test the efficiency of potential therapeutic agents and diet regimens.

The natural compound plumbagin has a wide range of pharmacological and potential therapeutic activities, although its role in neuroretina degeneration is unknown. Here we evaluated the effects of plumbagin on retina homeostasis of the fruit fly Drosophila melanogaster fed with high glucose diet, a model of hyperglycemia-induced eye impairment to study the pathophysiology of diabetic retinopathy at the early stages. To this aim, the visual system of flies orally administered with plumbagin has been analyzed at structural, functional, and molecular/cellular level as for instance neuronal apoptosis/autophagy dysregulation and oxidative stress-related signals. Our results demonstrated that plumbagin ameliorates the visual performance of hyperglycemic flies. Drosophila eye-structure, clearly altered by hyperglycemia, i.e. defects of the pattern of ommatidia, irregular rhabdomeres, vacuoles, damaged mitochondria, and abnormal phototransduction units were rescued, at least in part, by plumbagin. In addition, it reactivated autophagy, decreased the presence of cell death/apoptotic features, and exerted antioxidant effects in the retina. In terms of mechanisms favoring death/survival ratio, Nrf2 signaling activation may be one of the strategies by which plumbagin reduced redox unbalance mainly increasing the levels of glutathione-S-transferase. Likewise, plumbagin may act additively and/or synergistically inhibiting the mitochondrial-endoplasmic reticulum stress and unfolded protein response pathways, which prevented neuronal impairment and eye damage induced by reactive oxygen species. These results provide an avenue for further studies, which may be helpful to develop novel therapeutic candidates and drug targets against eye neurotoxicity by high glucose, a key aspect in retinal complications of diabetes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)