Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides a comprehensive analysis of the effects of PSMs on mitochondrial health, with particular emphasis on their therapeutic potential. Emerging evidence shows that these metabolites improve mitochondrial function by reducing oxidative stress, promoting mitochondrial biogenesis, and regulating key processes such as apoptosis and mitophagy. Mitochondrial dysfunction, a hallmark of many pathologies, including neurodegenerative disorders, cardiovascular diseases, and metabolic syndrome, has been shown to benefit from the protective effects of PSMs. Recent studies show that PSMs can improve mitochondrial dynamics, stabilise mitochondrial membranes, and enhance bioenergetics, offering significant promise for the prevention and treatment of mitochondrial-related diseases. The molecular mechanisms underlying these effects, including modulation of key signalling pathways and direct interactions with mitochondrial proteins, are discussed. The integration of PSMs into therapeutic strategies is highlighted as a promising avenue for improving treatment efficacy while minimising the side effects commonly associated with synthetic drugs. This review also highlights the need for future research to elucidate the specific roles of individual PSMs and their synergistic interactions within complex plant matrices, which may further optimise their therapeutic utility. Overall, this work provides valuable insights into the complex role of PSMs in mitochondrial health and their potential as natural therapeutic agents targeting mitochondrial dysfunction.

Microfluidic systems are increasingly used in neuroprotection research, but their clearest value may be to show why candidate compounds fail before costly downstream models. This critical framework review examines CNS-relevant microfluidic studies through a within-program triage logic linking chemistry-aware prescreening, blood-brain barrier/neurovascular unit (BBB/NVU) filtering, and timed validation in neuronal ischemia/reperfusion models, and treats non-CNS organ-on-a-chip and analytical microfluidic studies as engineering analogies only. The available evidence most strongly supports BBB/NVU chips as exposure- and safety-aware filters and compartmentalized neuronal oxygen-glucose deprivation platforms as timing-sensitive validation tools; droplet microfluidics contributes mainly upstream through dense dose mapping, aggregation assays and counterscreens for assay interference. A compound-centered reading also suggests that apparent activity often fails for distinct reasons, including timing mismatch, poor solubility, surface adsorption, optical artifact, inadequate multicellular context, or loss of efficacy under transport-aware testing. Taken together, the literature supports a cautious, within-program triage logic in which microfluidics is used not as a universal disease model, but as an operational framework for exposing transport, barrier, timing and assay liabilities early in neuroprotective discovery.