Nanotechnology is one of the methods that influenced human life in different ways and is a substantial approach that assists to overcome the multiple limitations of various diseases, particularly neurodegenerative disorders (NDs). Diverse nanostructures such as polymer nanoparticles, lipid nanoparticles, nanoliposomes, nano-micelles, and carbon nanotubes (CNTs); as well as different vehicle systems including poly lactic-co-glycolic acid, lactoferrin, and polybutylcyanoacrylate could significantly increase the effectiveness, reduce the side effects, enhance the stability, and improve the pharmacokinetics of many drugs. NDs belong to a group of annoying and debilitating diseases that involve millions of people worldwide. Previous studies revealed that several nanoformulations from a number of natural products such as curcumin (Cur), quercetin (QC), resveratrol (RSV), piperine (PIP), Ginkgo biloba, and Nigella sativa significantly improved the condition of patients diagnosed with NDs. Drug delivery to the central nervous system (CNS) has several limitations, in which the blood brain barrier (BBB) is the main drawback for treatment of NDs. This review discusses the effects of herbal-based nanoformulations, their advantages and disadvantages, to manage NDs. In summary, we conclude that herbal-based nano systems have promising proficiency in treatment of NDs, either alone or in combination with other drugs.

Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross‐linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant‐derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post‐SCI complications.

Alzheimer’s disease (AD) is a progressive neuronal/cognitional dysfunction, leading to disability and death. Despite advances in revealing the pathophysiological mechanisms behind AD, no effective treatment has yet been provided. It urges the need for finding novel multi-target agents in combating the complex dysregulated mechanisms in AD. Amongst the dysregulated pathophysiological pathways in AD, oxidative stress seems to play a critical role in the pathogenesis progression of AD, with a dominant role of nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1)/antioxidant responsive elements (ARE) pathway. In the present study, a comprehensive review was conducted using the existing electronic databases, including PubMed, Medline, Web of Science, and Scopus, as well as related articles in the field. Nrf2/Keap1/ARE has shown to be the upstream orchestrate of oxidative pathways, which also ameliorates various inflammatory and apoptotic pathways. So, developing multi-target agents with higher efficacy and lower side effects could pave the road in the prevention/management of AD. The plant kingdom is now a great source of natural secondary metabolites in targeting Nrf2/Keap1/ARE. Among natural entities, phenolic compounds, alkaloids, terpene/terpenoids, carotenoids, sulfur-compounds, as well as some other miscellaneous plant-derived compounds have shown promising future accordingly. Prevailing evidence has shown that activating Nrf2/ARE and downstream antioxidant enzymes, as well as inhibiting Keap1 could play hopeful roles in overcoming AD. The current review highlights the neuroprotective effects of plant secondary metabolites through targeting Nrf2/Keap1/ARE and downstream interconnected mediators in combating AD.