The approach to studying diet–health relationships has progressively shifted from individual dietary components to overall dietary patterns that affect the interaction and balance of low-molecular-weight metabolites (metabolome) and host-enteric microbial ecology (microbiome). Even though the Mediterranean diet (MedDiet) has been recognized as a powerful strategy to improve health, the accurate assessment of exposure to the MedDiet has been a major challenge in epidemiological and clinical studies. Interestingly, while the effects of individual dietary components on the metabolome have been described, studies investigating metabolomic profiles in response to overall dietary patterns (including the MedDiet), although limited, have been gaining attention. Similarly, the beneficial effects of the MedDiet on cardiometabolic outcomes may be mediated through gut microbial changes. Accumulating evidence linking food ingestion and enteric microbiome alterations merits the evaluation of the microbiome-mediated effects of the MedDiet on metabolic pathways implicated in disease. In this narrative review, we aimed to summarize the current evidence from observational and clinical trials involving the MedDiet by (1) assessing changes in the metabolome and microbiome for the measurement of diet pattern adherence and (2) assessing health outcomes related to the MedDiet through alterations to human metabolomics and/or the microbiome.

Mucuna pruriens (Mucuna) has been prescribed in Ayurveda for various brain ailments including ‘kampavata’ (tremors) or Parkinson’s disease (PD). While Mucuna is a well-known natural source of levodopa (L-dopa), published studies suggest that other bioactive compounds may also be responsible for its anti-PD effects. To investigate this hypothesis, an L-dopa reduced (<0.1%) M. pruriens seeds extract (MPE) was prepared and evaluated for its anti-PD effects in cellular (murine BV-2 microglia and human SH-SY5Y neuroblastoma cells), Caenorhabditis elegans, and Drosophila melanogaster models. In BV-2 cells, MPE (12.5–50 μg/mL) reduced hydrogen peroxide-induced cytotoxicity (15.7−18.6%), decreased reactive oxygen species production (29.1−61.6%), and lowered lipopolysaccharide (LPS)-induced nitric oxide species release by 8.9–60%. MPE (12.5−50 μg/mL) mitigated SH-SY5Y cell apoptosis by 6.9−40.0% in a non-contact co-culture assay with cell-free supernatants from LPS-treated BV-2 cells. MPE (12.5−50 μg/mL) reduced 6-hydroxydopamine (6-OHDA)-induced cell death of SH-SY5Y cells by 11.85–38.5%. Furthermore, MPE (12.5−50 μg/mL) increased median (25%) and maximum survival (47.8%) of C. elegans exposed to the dopaminergic neurotoxin, methyl-4-phenylpyridinium. MPE (40 μg/mL) ameliorated dopaminergic neurotoxin (6-OHDA and rotenone) induced precipitation of innate negative geotaxis behavior of D. melanogaster by 35.3 and 32.8%, respectively. Therefore, MPE contains bioactive compounds, beyond L-dopa, which may impart neuroprotective effects against PD.

A number of plants used in folk medicine in Thailand and Eastern Asia are attracting interest due to the high bioactivities of their extracts. The aim of this study was to screen the edible leaf extracts of 20 plants found in Thailand and investigate the potential neuroprotective effects of the most bioactive sample. The total phenol and flavonoid content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity were determined for all 20 leaf extracts. Based on these assays, Glochidion littorale leaf extract (GLE), which showed a high value in all tested parameters, was used in further experiments to evaluate its effects on neurodegeneration in Caenorhabditis elegans. GLE treatment ameliorated H₂O₂-induced oxidative stress by attenuating the accumulation of reactive oxygen species and protected the worms against 1-methyl-4-phenylpyridinium-induced neurodegeneration. The neuroprotective effects observed may be associated with the activation of the transcription factor DAF-16. The characterization of this extract by LC-MS identified several phenolic compounds, including myricetin, coumestrin, chlorogenic acid, and hesperidin, which may play a key role in neuroprotection. This study reports the novel neuroprotective activity of GLE, which may be used to develop treatments for neurodegenerative diseases such as Parkinson’s syndrome.