Luteolin for neurodegenerative diseases: a review

Abstract

Neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and multiple sclerosis affect millions of people around the world. In addition to age, which is a key factor contributing to the development of all neurodegenerative diseases, genetic and environmental components are also important risk factors. Current methods of treating neurodegenerative diseases are mostly symptomatic and do not eliminate the cause of the disease. Many studies focus on searching for natural substances with neuroprotective properties that could be used as an adjuvant therapy in the inhibition of the neurodegeneration process. These compounds include flavonoids, such as luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity. Increasing evidence suggests that luteolin may confer protection against neurodegeneration. In this review, we summarize the scientific reports from preclinical in vitro and in vivo studies regarding the beneficial effects of luteolin in neurodegenerative diseases. Luteolin was studied most extensively in various models of Alzheimer's disease but there are also several reports showing its neuroprotective effects in models of Parkinson's disease. Though very limited, studies on possible protective effects of luteolin against Huntington's disease and multiple sclerosis are also discussed here. Overall, although preclinical studies show the potential benefits of luteolin in neurodegenerative disorders, clinical evidence on its therapeutic efficacy is still deficient.

Keywords: Apoptosis; Beta amyloid; Cognitive dysfunction; Learning and memory impairment; Neuronal loss; Parkinsonism; Polyphenols.

Fig. 1

Potential therapeutic benefits of luteolin

Fig. 2

Schematic overview of the possible mechanisms underlying the neuroprotective effects of luteolin Abbreviations: BBB: blood-brain barrier; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma protein 2; cAMP: cyclic adenosine monophosphate; ER: endoplasmic reticulum; ERK: extracellular signal-regulated kinase; ERK-dependent CREB: extracellular signal-regulated kinase-dependent cAMP response element-binding protein; FITC; fluorescein isothiocyanate; IRF-1: interferon regulatory factor 1; MAPK: mitogen-activated protein kinase; NaF: sodium fluoride; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; PKA; protein kinase A; ROS: reactive oxygen species; SOD: superoxide dismutase; STAT: signal transducer and activator of transcription; TEER: transepithelial electrical resistance

Fig. 3

A summary of the effect of luteolin on the prevention of apoptosis in the 6-OHDA-indcued model of PD in vitro Abbreviations: ATF4: activating transcription factor 4; BIM: Bcl-2-like protein 11; CHOP: C/EBP homologous protein; ER: endoplasmic reticulum; GRP78: glucose-regulated protein 78; HO-1: heme oxygenase-1; p53: tumor protein p53; TRB3: tribbles homolog 3