Galangin Rescues Alzheimer’s Amyloid-β Induced Mitophagy and Brain Organoid Growth Impairment

Abstract

Dysfunctional mitochondria and mitophagy are hallmarks of Alzheimer’s disease (AD). It is widely accepted that restoration of mitophagy helps to maintain cellular homeostasis and ameliorates the pathogenesis of AD. It is imperative to create appropriate preclinical models to study the role of mitophagy in AD and to assess potential mitophagy-targeting therapies. Here, by using a novel 3D human brain organoid culturing system, we found that amyloid-β (Aβ1-42,10 μM) decreased the growth level of organoids, indicating that the neurogenesis of organoids may be impaired. Moreover, Aβ treatment inhibited neural progenitor cell (NPC) growth and induced mitochondrial dysfunction. Further analysis revealed that mitophagy levels were reduced in the brain organoids and NPCs. Notably, galangin (10 μM) treatment restored mitophagy and organoid growth, which was inhibited by Aβ. The effect of galangin was blocked by the mitophagy inhibitor, suggesting that galangin possibly acted as a mitophagy enhancer to ameliorate Aβ-induced pathology. Together, these results supported the important role of mitophagy in AD pathogenesis and suggested that galangin may be used as a novel mitophagy enhancer to treat AD.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation

“…Through extensive research and clinical application, natural botanical remedies have demonstrated distinct efficacy and reduced toxicity in the treatment of various ailments, gaining gradual acceptance among individuals [ 10 , 11 ]. As one of the most active ingredients in A. officinarum , galangin has shown important effects in the prevention and treatment of many diseases, including but not limited to anti-cancer, regulation of apoptosis and inflammation, cardiovascular diseases, and neurodegenerative diseases [ 12 – 20 ]. Given the limited research on the therapeutic effects and potential mechanisms of galangin in anti-inflammatory pain, this study aimed to evaluate its anti-inflammatory and analgesic effects and explore its mechanism pathways.…”

Promising Prospects for Human Cerebral Organoids to Advance Alzheimer's Disease Research

“…Another alternative is based on inducing the pathology by stimulating them with Aβ [133,134] or with serum from AD patients, which makes it possible to observe, in addition to Aβ and Tau aggregates, neuronal loss and other alterations [135].…”

“…Continuing with this type of stimulation to obtain AD in organoids, a decrease in mitophagy has also been observed, as well as one of its associated genes, PINK1. It was observed that this reduction could be alleviated with the addition of a flavonoid called galangin [134].…”