Post-stroke depression (POSD) is a common difficulty and most predominant emotional syndrome after stroke often consequences in poor outcomes. In the present investigation, we have designed and studied the neurologically active celastrol/minocycline encapsulated with macrophages-derived exosomes functionalized PLGA nanoformulations (CMC-EXPL) to achieve enhanced anti-inflammatory behaviour and anti-depressant like activity in a Rat model of POSD. The animal model of POSD was established through stimulating process with chronic unpredictable mild stress (CUM) stimulations after procedure of middle cerebral artery occlusion (MCAO). Neuronal functions and Anti-inflammation behaviours were observed by histopathological (H&E) examination and Elisa analyses, respectively. The anti-depressive activity of the nanoformulations treated Rat models were evaluated by open-field and sucrose preference test methods. Microglial polarization was evaluated via flow-cytometry and qRT-PCR observations. The observed results exhibited that prepared nanoformulations reduced the POSD-stimulated depressive-like activities in rat models as well alleviated the neuronal damages and inflammatory responses in the cerebral hippocampus. Importantly, prepared CMC-EXPL nanoformulation effectively prevented the M1 pro-inflammatory polarization and indorsed M2 anti-inflammatory polarization, which indicates iNOS and CD86 levels significantly decreased and upsurged Arg-1 and CD206 levels. CMC-EXPL nanoformulation suggestively augmented anti-depressive activities and functional capability and also alleviated brain inflammation in POSD rats, demonstrating its therapeutic potential for POSD therapy.

Parkinson’s disease (PD), as a refractory neurological disorder with complex etiology, currently lacks effective therapeutic agents. Natural products (NPs), derived from plants, animals, or microbes, have shown promising effects in PD models through their antioxidative and anti-inflammatory properties, as well as the enhancement of mitochondrial homeostasis and autophagy. The misfolding and deposition of α-Synuclein (α-Syn), due to abnormal overproduction and impaired clearance, being central to the death of dopamine (DA) neurons. Thus, inhibiting α-Syn misfolding and aggregation has become a critical focus in PD discovery. This review highlights NPs that can reduce α-Syn aggregation by preventing its overproduction and misfolding, emphasizing their potential as novel drugs or adjunctive therapies for PD treatment, thereby providing further insights for clinical translation.