COMPARATIVE PHARMACOCHEMICAL ANALYSIS OF NATURAL L-DOPA FROM MUCUNA PRURIENS AND SYNTHETIC L-DOPA: BIOAVAILABILITY, STABILITY, AND NEUROTHERAPEUTIC IMPLICATIONS

Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to severe motor and non-motor symptoms. L-3,4-dihydroxyphenylalanine (L-DOPA) remains the cornerstone of PD therapy due to its efficacy in replenishing depleted dopamine levels. However, long-term administration of synthetic L-DOPA is hindered by several limitations, including oxidative instability, auto-oxidation to quinones, and the development of motor complications such as dyskinesias and wearing-off phenomena. These drawbacks necessitate the search for safer and more effective alternatives. Natural L-DOPA derived from Mucuna pruriens, a tropical legume traditionally used in Ayurvedic medicine, has emerged as a promising candidate due to its high L-DOPA content (up to 9% w/w of dry seed) and additional phytoconstituents with potential neuroprotective effects. This study presents a comparative pharmacochemical analysis of natural L-DOPA from Mucuna pruriens and synthetic L-DOPA, with emphasis on bioavailability, stability, and neurotherapeutic implications. Using high-performance liquid chromatography (HPLC), UV–Vis spectroscopy, and LC-MS/MS, natural and synthetic L-DOPA were quantified and characterized. Results confirmed that natural M. Pruriens extracts not only contained L-DOPA but also flavonoids, alkaloids, tannins, saponins, and trace bioinorganic elements (Zn, Cu, Mn, Fe), which may act synergistically to enhance dopaminergic metabolism and reduce oxidative stress. Stability assays revealed that natural L-DOPA exhibited significantly reduced auto-oxidation compared with synthetic formulations, owing to the antioxidant and metal-chelating environment provided by co-occurring phytochemicals. Pharmacokinetic evaluation demonstrated superior oral absorption, prolonged plasma half-life, and slower degradation of natural L-DOPA, which translated into more sustained dopaminergic activity in vivo. Comparative in vivo studies in 6-hydroxydopamine (6-OHDA) and rotenone-induced PD rat models showed that M. Pruriens extract restored motor function more effectively than equivalent doses of synthetic L-DOPA. Furthermore, animals treated with natural L-DOPA exhibited reduced oxidative biomarkers (malondialdehyde [MDA], nitric oxide [NO]) and increased antioxidant defenses (superoxide dismutase [SOD], catalase [CAT], glutathione [GSH]). In addition, molecular docking and enzymatic kinetic studies revealed differences in interactions with key metabolic enzymes, such as aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT). Natural L-DOPA displayed lower susceptibility to COMT-mediated O-methylation, while co-existing phytochemicals showed modulatory binding to inflammatory and oxidative stress-related targets, suggesting an integrated neuroprotective profile. Collectively, this work demonstrates that natural L-DOPA from Mucuna pruriens not only matches the efficacy of synthetic L-DOPA in replenishing dopamine but also surpasses it by offering improved bioavailability, enhanced stability, and synergistic neuroprotective mechanisms. These findings highlight the potential of M. Pruriens-derived L-DOPA as a foundation for developing next-generation PD therapies with reduced side effects, better stability, and broader neurotherapeutic benefits.