Intranasal Delivery of Natural Compounds: A Promising approach for Parkinson’s Disease therapy

The second most prevalent neurological condition in the world is Parkinson's disease (PD). Dopamine-deficit symptoms, including bradykinesia, postural instability, muscular rigidity, and resting tremors, are its hallmarks. This disease is caused by a variety of endogenous and exogenous causes, including as oxidative stress, genetics, mitochondrial malfunction, aging, inflammation, and various neurotoxins. Oxidative stress (OS) has been identified as the main cause of PD. More specifically, dopamine is converted into reactive oxygen species (ROS) such as hydrogen peroxide as a result of oxidative stress. Therefore, addressing dopamine deficiency is the main objective of most PD therapies. Extensive research on the development of novel neuroprotective pharmaceutical candidates suggests that natural items, such as plant extracts and their bioactive compounds, may hold great potential as lead neuroprotective choices in the treatment of PD. One way to improve the delivery of antioxidants to the brain is to use the nose-to-brain route, which involves delivering the antioxidant in specific nasal formulations and letting it enter the central nervous system (CNS) mainly through the olfactory nerve channel. We have focused on recent advancements in the research of herbal medicines and the bioactive components they contain that are used in cellular and animal neurotoxic models of PD in order to help future clinical trials. Although numerous studies have investigated the neuroprotective potential of natural compounds in Parkinson’s disease, limited attention has been given to effective delivery strategies for targeting these agents to the brain. Most existing research overlooks the challenge of brain accessibility, focusing either on conventional drugs or natural products in isolation. Nose-to-brain drug delivery offers a direct route to the brain via the olfactory pathway, bypassing the blood–brain barrier. This review highlights its potential to enhance the efficacy of natural neuroprotective compounds for Parkinson’s disease therapy.