The Anti-Neuroinflammatory Role of Anthocyanins and Their Metabolites for the Prevention and Treatment of Brain Disorders

Abstract

Anthocyanins are naturally occurring polyphenols commonly found in fruits and vegetables. Numerous studies have described that anthocyanin-rich foods may play a crucial role in the prevention and treatment of different pathological conditions, which have encouraged their consumption around the world. Anthocyanins exhibit a significant neuroprotective role, mainly due to their well-recognized antioxidant and anti-inflammatory properties. Neuroinflammation is an intricate process relevant in both homeostatic and pathological circumstances. Since the progression of several neurological disorders relies on neuroinflammatory process, targeting brain inflammation has been considered a promising strategy in those conditions. Recent data have shown the anti-neuroinflammatory abilities of many anthocyanins and of their metabolites in the onset and development of several neurological disorders. In this review, it will be discussed the importance and the applicability of these polyphenolic compounds as neuroprotective agents and it will be also scrutinized the molecular mechanisms underlying the modulation of neuroinflammation by these natural compounds in the context of several brain diseases.

Keywords: anthocyanins; antioxidants; brain disorders; natural compounds; neuroinflammation; neuroprotection; polyphenols.

Figure 1

Chemical structure of common anthocyanins. The glycosidic form of anthocyanins is constituted by an aglycon, known as anthocyanidin, bounded to one or more sugar conjugates which may replace both R and OH groups.

Figure 2

Pharmacokinetic properties of anthocyanins. After oral ingestion, anthocyanins can be degraded in oral cavity or reach the stomach, where they are stable due to gastric acidity. Here, they can be absorbed or can be delivered to the small intestine, undergoing metabolism or moving into the bloodstream. The remaining parent anthocyanins and intermediate metabolites transit through the small intestine into the colon where they are absorbed or extensively metabolized. Then, anthocyanins can be eliminated by fecal excretion or transported to the liver, the main absorption site. When parent anthocyanins or metabolites enter the blood circulation, they are distributed to target tissues, exerting their biological functions or being eliminated by exhalation, renal or bile excretion. Notably, anthocyanins can prevail during several days in the organism due to the enterohepatic recirculation.

Figure 3

Schematic overview of regulation of microbiota–gut–brain axis by anthocyanins and their metabolites. (a) Peripheral inflammatory cells infiltrate into the brain, eliciting microglia activation which involves several inflammatory signaling pathways that can be modulated by anthocyanins and their metabolites; (b) Anthocyanins can be absorbed in the intestine, where they firstly promote the proliferation of beneficial bacteria and contribute to the elimination of pathogenic bacteria. The dysregulation of gut microbiota (dysbiosis) or the increase in the intestinal pathogenic community can lead to the disruption of gut wall mucosa (leaky gut), inciting a systemic inflammation and intensifying the neuroinflammatory response. Akt: Protein kinase B; AP-1: Activator protein 1; BBB: Blood–brain barrier; ERK: Extracellular signal-regulated kinase; IĸB: NF-ĸB inhibitor; IKK: IĸB kinase; JNK: c-Jun N-terminal kinase; LPS: Lipopolysaccharide; MEK: Ras/Raf/mitogen-activated protein kinase kinase; MKKs: Mitogen-activated protein kinase kinase; NF-ĸB: Nuclear factor kappa B; OTF: Other transcription factors; p38: Mitogen-activated protein kinase p38; PI3K: Phosphoinositide 3-kinase; TLR4: Toll-like receptor 4.