Therapeutic landscape of Parkinson's disease: Recent advances in saponin-mediated interventions

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, leading to debilitating motor and non-motor symptoms. Current therapeutic strategies, including levodopa, dopamine agonists, monoamine oxidase-B inhibitors, and surgical interventions primarily offer symptomatic relief without halting disease progression. Long-term use of these treatments is often associated with complications such as motor fluctuations, dyskinesia, and systemic side effects, underscoring the urgent need for safer and disease-modifying approaches. In recent years, increasing attention has been directed toward natural products as potential therapeutic agents for PD due to their multi-targeted mechanisms and favorable safety profiles. Among these, plant-derived saponins have emerged as promising candidates owing to their diverse pharmacological properties. Saponins exhibit potent antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, enabling them to modulate key pathological pathways involved in PD, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and α-synuclein aggregation. Experimental studies have demonstrated the neuroprotective effects of various saponins such as astragaloside IV, ginsenosides, bacosides, dioscin, and notoginsenosides in animal models of PD. These compounds have been shown to preserve dopaminergic neuronal integrity, enhance mitochondrial function, regulate apoptotic signalling, and promote autophagy. Despite these promising findings, challenges such as poor bioavailability in natural products and limited access to brain remain significant barriers to clinical translation. This review provides a comprehensive overview of current PD therapies and their limitations, while highlighting the therapeutic potential of plant-derived saponins as multi-target agents. It also discusses recent advances in drug delivery strategies that may enhance their clinical applicability. Overall, saponins represent a promising avenue for the development of novel neuroprotective and disease-modifying therapies for PD.