Therapeutic Effect of Berberine on Huntington’s Disease Transgenic Mouse Model

Abstract

Huntington disease (HD) represents a family of neurodegenerative diseases that are caused by misfolded proteins. The misfolded proteins accumulate in the affected brain regions in an age-dependent manner to cause late-onset neurodegeneration. Transgenic mouse models expressing the HD protein, huntingtin, have been widely used to identify therapeutics that may retard disease progression. Here we report that Berberine (BBR), an organic small molecule isolated from plants, has protective effects on transgenic HD (N171-82Q) mice. We found that BBR can reduce the accumulation of mutant huntingtin in cultured cells. More importantly, when given orally, BBR could effectively alleviate motor dysfunction and prolong the survival of transgenic N171-82Q HD mice. We found that BBR could promote the degradation of mutant huntingtin by enhancing autophagic function. Since BBR is an orally-taken drug that has been safely used to treat a number of diseases, our findings suggest that BBR can be tested on different HD animal models and HD patients to further evaluate its therapeutic effects.

Berberis Vulgaris and Berberine: An Update Review

“…Berberine can also reduce the accumulation of mutant huntingtin in cultured cells. It seems that berberine can be tested on HD patients to further evaluate its effects in treatment of HD patients (Jiang et al ., ).…”

Proteostasis in Huntington's disease: disease mechanisms and therapeutic opportunities

“…This has been shown to help clear mHTT in drosophila HD models [113] . Berberine has also shown efficacy in HD models, and is postulated to induce autophagy via AMPK activation [114,115] . Many other molecules including clonidine [116] , modulate cAMP or IP 3 to induce autophagy and ameliorate phenotypes in HD animal models.…”

Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα–SREBP Pathway in 3T3-L1 Cells

“…BBR, an isoquinoline derivative alkaloid extracted from Berberis and Coptis herbs such as Hydrastis canadensis (goldenseal), Cortex phellodendri (Huangbai), and Rhizoma coptidis (Huanglian), is a commonly used traditional Chinese medicine for treatment of microbial diarrhea [21,22]. In addition, BBR has potential pharmacological effects, including effects on metabolic abnormalities, and antiarrhythmic, antihypertensive, anticancer, antidiabetic, and antihyperlipidenmic effects [23,24,25,26].…”