Abstract
Brain aging and neurodegenerative diseases share the hallmarks of slow and progressive loss of neuronal cells. Flavonoids, a subgroup of polyphenols, are broadly present in food and beverage and numerous studies have suggested that it could be useful for preventing or treating neurodegenerative diseases in humans. Dihydromyricetin (DHM) is one of the main flavonoids of some Asian medicinal plants that are used to treat diverse illness. The effects of DHM have been studied in different in vitro systems of oxidative damage and neuroinflammation, as well as in animal models of several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Here we analyzed the most important effects of DHM, including its antioxidant, anti-inflammatory, and neuroprotective effects, as well as its ability to restore GABA neurotransmission and improve motor and cognitive behavior. We propose new areas of research that might contribute to a better understanding of the mechanism of action of this flavonoid, which could help develop a new therapy for aging and age-related brain diseases.
Highlights
Aging is a major risk factor for developing brain illnesses such as Alzheimer’s disease (AD) (Lindsay et al, 2002; Katz et al, 2012), Parkinson’s disease (PD) (Collier et al, 2011), and other age-related dementias (López-Valdés and Martínez-Coria, 2016), as well as cerebrovascular disorders (Choi et al, 1998)
In the few past decades, scientific knowledge about the effects of DHM has increased considerably. This molecule has a wide range of positive effects, including anti-oxidative, antiinflammatory and neuroprotective properties, and has been shown to cause motor and memory improvements, all of which can help treat dysfunctions associated with brain aging and some neurodegenerative diseases such as AD and PD
Feng et al (2018) used another Alzheimer’s mouse model, termed APP/PS1 double-transgenic, in which the mouse/ human amyloid precursor protein and the mutant human presenilin-1 are overexpressed. They showed that DHM treatment improves memory and decreases the number of activated microglia and the NLRP3 inflammasome, the activation of which plays an important role in chronic brain neuroinflammation (Heneka et al, 2018). Another recent study (Sun et al, 2019) done in an AD rat model induced by intracerebroventricular injection of Aβ1–42, found that DHM (100 and 200 mg/kg for 21 days) improves learning and memory, decreased hippocampal neuronal apoptosis, IL-1β, IL-6, and TNF-α in serum and hippocampus and changes in different proteins such as decreased pro-apoptotic Bax and NF-κB and increased anti-apoptotic Bcl-2, pAMPK, AMPK, and sirtuin 1 (SIRT1), suggesting that beneficial effects of DHM are mediated by up-regulation of AMPK/SIRT1 pathway
Summary
Aging is a major risk factor for developing brain illnesses such as Alzheimer’s disease (AD) (Lindsay et al, 2002; Katz et al, 2012), Parkinson’s disease (PD) (Collier et al, 2011), and other age-related dementias (López-Valdés and Martínez-Coria, 2016), as well as cerebrovascular disorders (Choi et al, 1998) These diseases share pathophysiological mechanisms with aging such as oxidative stress and chronic inflammation. Dihydromyricetin (DHM), known as ampeloptin, rac-ampelopsin, and ampelopsin, is a flavonoid isolated mainly from Japanese raisin trees (Hovenia dulcis Thum) and Chinese Rattan tea [Ampelopsis grossedentata (Hand.-Mazz.) W.T.Wang]. These plants have been used for a long time in Asian traditional medicine to treat different health problems (Hyun et al, 2010; Kou and Chen, 2012). DHM is one of the main flavonoids found in the Japanese raisin tree and Chinese Rattan tea, together with myricetin and quercetin (Zhang et al, 2007; Hyun et al, 2010)
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