A protocol for the impact of Tongmai Jiangtang capsules on the risk of cardiovascular and cerebrovascular events in metabolic syndrome.

Neurodegenerative diseases (NDDs) are a group of chronic disorders characterized primarily by the progressive dysfunction and loss of specific neuronal populations. The major NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease and amyotrophic lateral sclerosis (ALS) [,,,,]. While these diseases differ in the abnormal proteins involved, affected brain regions, and clinical manifestations, they share pathological processes such as protein misfolding and aggregation, oxidative stress, neuroinflammation, mitochondrial dysfunction, synaptic damage, and neuronal death [,,,,,]. As populations are aging faster than ever before, NDDs have become a leading cause of cognitive and motor impairment, as well as a significant long-term care burden [,,,]. Treating them presents the dual challenge of complex pathological networks and insufficient effective exposure within the brain. Abnormal protein aggregation, oxidative damage, chronic inflammation, disrupted energy metabolism, and neurovascular unit dysfunction interact, making single-target interventions generally insufficient to address the multiple pathological processes involved in disease progression [,,]. Meanwhile, the highly selective blood–brain barrier (BBB) restricts the entry of most therapeutic molecules into the central nervous system (CNS), making it difficult to achieve adequate and sustained drug exposure in affected regions [,]. Consequently, material-based systems capable of combining brain delivery with multimodal therapeutic intervention have attracted considerable attention [,]. Carbon dots (CDs) are fluorescent nanomaterials characterized by carbon-based nanostructures and tunable surface chemistry []. In this review, ‘CDs’ is used as an umbrella term encompassing carbon quantum dots (CQDs), graphene quantum dots, carbonized polymer dots, and related materials. When the structure or nomenclature of a material is explicitly defined in the original study, the specific designation is retained. The size, surface chemistry, and charge characteristics of CDs can influence their interactions with biological interfaces and the BBB, thereby conferring potential for delivery, tracking, and imaging applications [,]. However, small particle size does not necessarily indicate effective BBB penetration, and fluorescence signals detected in brain tissue do not demonstrate that the material has entered the brain parenchyma or achieved therapeutically relevant exposure in disease-associated regions [,]. Natural product-derived CDs can be prepared from medicinal plants, naturally occurring bioactive molecules, and other natural raw materials. Nevertheless, natural origin does not guarantee a well-defined composition, a favorable safety profile, or clinical translatability of the final material. Carbonization, post-processing, and purification can alter the material’s composition and complicate the attribution of biological effects. Therefore, the structure and function of the resulting CDs cannot be inferred solely from the properties of their precursors [,,,,]. Current studies have predominantly focused on AD-related cellular and animal models, suggesting that certain natural product-derived CDs may exert antioxidant and anti-inflammatory effects, modulate abnormal protein aggregation, and provide neuroprotection [,,]. Nevertheless, evidence regarding BBB transport, brain parenchymal exposure, pharmacokinetics, and long-term safety remains insufficient. BBB permeability, brain fluorescence signals, brain parenchymal exposure, and therapeutic benefit represent distinct levels of evidence and should not be considered interchangeable [,,,,]. Accordingly, this critical narrative review focuses on BBB-related delivery, neuroprotection, imaging applications, and the challenges of clinical translation associated with natural product-derived CDs in NDDs. Particular emphasis is placed on studies of natural product-derived CDs that provide material characterization and direct experimental evidence relating to NDDs, the BBB, or brain delivery. Other naturally derived materials, non-NDD models, model-protein studies, and composite nanosystems are included only as supplementary mechanistic or methodological references. The available evidence is critically evaluated with respect to material sources and characteristics, interactions with the BBB, brain exposure, functional outcomes, and translational feasibility. Particular attention is given to distinguishing brain-associated distribution, imaging capability, brain parenchymal exposure, and therapeutic effects while also considering key translational factors such as pharmacokinetics, long-term safety, material consistency, and manufacturability.