Bioactive compounds from traditional Chinese medicine for mitochondrial dysfunction-oriented nanodelivery in neurodegenerative diseases.

BACKGROUND

Bioactive compounds from traditional Chinese medicine (TCM) have shown therapeutic potential in neurodegenerative diseases (NDDs), particularly through the regulation of mitochondrial function. Recent studies indicate that encapsulating these TCM bioactive compounds in nanodelivery systems significantly enhances their bioavailability, improves their ability to target the central nervous system, and offers more precise drug delivery.

PURPOSE: This review aims to synthesize current evidence on how TCM bioactive compounds modulate mitochondria-related pathological nodes in NDDs and discuss how nanodelivery systems can be rationally engineered for blood-brain barrier (BBB) traversal, neuronal uptake, and mitochondrial or mitochondrial dysfunction-responsive delivery.

METHODS

This is a structured narrative review. Relevant literature on TCM bioactive compounds, mitochondrial dysfunction, and nanodelivery systems for NDDs was retrieved from PubMed, Web of Science, and Scopus through April 2026. After applying predefined inclusion criteria, studies published between 2014 and 2025 were selected for analysis. The emphasis was placed on mechanistic studies, representative nanoformulations, and recent translational evidence.

RESULTS

Current evidence indicates that bioactive compounds from traditional Chinese medicine, particularly polyphenols, alkaloids, flavonoids, saponins, and terpenoids, converge on several shared mitochondrial pathological nodes in neurodegenerative diseases, including oxidative stress, impaired bioenergetics, disrupted mitochondrial dynamics, defective mitophagy, and mitochondria-mediated apoptosis. Nanodelivery systems consistently improve the physicochemical properties, pharmacokinetic stability, blood-brain barrier transport, and intracellular exposure of these compounds, thereby enhancing their therapeutic potential. Mechanistically, rational integration of disease-responsive nanocarriers with mitochondria-regulating compounds enables spatiotemporal modulation of mitochondrial function rather than merely increasing drug accumulation. However, current evidence remains predominantly preclinical, with most formulations achieving brain targeting rather than verified mitochondrial subcellular targeting. Standardized evaluation of multistage BBB-neuron-mitochondria delivery efficiency, long-term safety, and translational performance is still lacking.

CONCLUSION

Mitochondrial dysfunction-oriented nanodelivery of TCM bioactive compounds represents a promising strategy for NDD intervention. Future progress depends on more rigorous quality control from the herbal materials to the final nanoformulations, improved pharmacokinetic and safety evaluations, better disease-relevant animal models, and regulatory science frameworks tailored for botanical nanomedicines.