Dual Neuroprotective and Nephroprotective Effects of Mucuna pruriens, Moringa oleifera, and Silybum marianum (Milk Thistle) via Modulation of PI3K/AKT/mTOR and Nrf2/NF-κB Pathways in a Murine Comorbid PD–AKI Model

Parkinson’s disease (PD) and acute kidney injury (AKI) are two conditions with increasing prevalence and severe systemic complications and consequences. This research examines the combined neuroprotective and nephroprotective properties of three medicinal plants, Mucuna pruriens (Muc), Moringa oleifera (Mor), and Silybum marianum (SM), in a murine model of PD, AKI, and their comorbid state (PD–AKI), highlighting the role of the PI3K/AKT/mTOR and Nrf2/NF-κB signaling pathways. The mice were grouped as PD, AKI, or PD-AKI, and with or without the herbal pre-treatment, along with their respective controls. Motor impairments were assessed using the rotarod and pole climb assays. Biochemical indicators of renal function, oxidative stress markers, and inflammatory cytokines were quantified in kidney and brain tissues. Assessment of Nrf2, NF-κB, PI3K, AKT, and mTOR expression levels was performed using qRT-PCR. The AKI groups had significant renal impairment (4-fold increase in creatinine and 7.5-fold increase in BUN), oxidative stress (~5.5-fold increase), and increased cytokine levels (~1.5-fold increase), with downregulation of the PI3K/AKT/mTOR (~2-fold decrease) and Nrf2 signaling pathways (~1.8-fold decrease), alongside upregulation of NF-κB (~2.5-fold increase). The PD and PD-AKI groups exhibited significant neuroinflammation (~1.5-fold increase) and redox imbalance (~6-fold increase) in brain tissue, accompanied by motor impairments (1.6 to 4.6-fold decrease). Pre-treatment with Muc, Mor, and SM significantly ameliorated renal impairments (3.5-fold decrease in creatinine and ~5-fold decrease in BUN) and neurological deficits. These findings establish Muc, Mor, and SM extracts as potent, multi-target interventions capable of disrupting the feed–forward cycle of neuro-renal damage.