Advances and Therapeutic Potential of Anthraquinone Compounds in Neurodegenerative Diseases: A Comprehensive Review

Rhubarb, traditionally used in China for neurological disorders, has recently attracted considerable scientific attention for its neuroprotective and cerebrovascular benefits. The main therapeutic components of rhubarb are anthraquinones, including emodin, aloe-emodin, chrysophanol, rhein, and physcion. Accumulating experimental evidence indicates that anthraquinones are of importance in neurodegenerative diseases (NDDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. However, as a promising candidate for drug development, the mechanisms by which anthraquinones treat NDDs have not been systematically reviewed. Therefore, this article outlines the anti-neurodegenerative effects of anthraquinones, focusing on their molecular mechanisms.

This article reviews recent research progress of anthraquinones in NDDs, focusing on their potential targets and pathways to provide new ideas for the intervention and treatment of NDDs.

A comprehensive search of PubMed, Web of Science, and Google Scholar was conducted for articles on the intervention of anthraquinones in NDDs in the past 20 years. The collected information was then summarized and analyzed.

Anthraquinones ameliorate NDDs through multiple mechanisms. They exhibit antioxidant and anti-inflammatory effects, protect mitochondria, and regulate microglial polarization. Furthermore, anthraquinones inhibit pyroptosis, apoptosis, tau phosphorylation, Aβ/α-synuclein aggregation, and acetylcholinesterase activity, while restoring metal homeostasis, activating estrogen receptors, modulating gut microbiota, increasing BDNF levels, and preserving blood-brain barrier permeability. More notably, these compounds play a neuroprotective role by mediating multiple signaling pathways and targets, including Nrf2, ERK1/2, PI3K/mTOR, ROS/TXNIP, SIRT1/PCG-1α, NLRP3, PI3K/Akt, MAPK, TLR4-NFκB, CaM/CaMKIV, and Ca²⁺/EGFR/PLCγ.

The pleiotropic actions of anthraquinones highlight their potential as therapeutic candidates for NDDs, yet clinical validation remains essential. Future studies should emphasize rigorously designed clinical trials and optimized brain-targeted delivery platforms. This review consolidates current evidence to support their translational development.