Bioavailability and Pharmaco-therapeutic Potential of Luteolin in Overcoming Alzheimer’s Disease

Abstract

Luteolin is a naturally occurring, yellow crystalline flavonoid found in numerous dietary supplements we frequently have in our meals. Studies in the last 2 decades have revealed its therapeutic potential to reduce the Alzheimer’s disease (AD) symptoms in various in vitro and in vivo models. The anti-Alzheimer’s potential of luteolin is attributed to its ability to suppress Aβ as well as tau aggregation or promote their disaggregation, down-regulate the expression of COX-2, NOS, MMP-9, TNF-α, interleukins and chemokines, reduce oxidative stress by scavenging ROS, modulate the activities of transcription factors CREB, cJun, Nrf-1, NF-κB, p38, p53, AP-1 and β-catenine and inhibiting the activities of various protein kinases. In several systems, luteolin has been described as a potent antioxidant and anti-inflammatory agent. In addition, we have also discussed about the bio-availability of the luteolin in the plasma. After being metabolized luteolin persists in plasma as glucuronides and sulphate-conjugates. Human clinical trials indicated no dose limiting toxicity when administered at a dose of 100 mg/day. Improvements in the formulations and drug delivery systems may further enhance the bioavailability and potency of luteolin. The current review describes in detail the data supporting these studies.

Neuroinflammation in Alzheimer's disease and beneficial action of luteolin

“…122 Inhibition of brain inflammation could be accomplished with natural molecules, especially the polyphenolic flavonoids. [123][124][125][126][127] The flavone luteolin improved AD 128,129 and other disorders via different mechanisms (Table 1). 130 These include inhibiting activation of microglia, 131,132 inhibiting AchE 133 and preventing Ab42 plaque formation, 134 inhibiting fibrillary β-amyloidinduced inflammation, 135 reducing zinc-induced tau phosphorylation 136 as well as inhibiting reducing mucintype O-gycosylation of amyloid precursor protein, 137 thus resulting in increased memory in rodent models of AD.…”

Luteolin Attenuates IL-1β-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways

“…In previous studies, it was demonstrate that luteolin shows anti-inflammatory, anticancer, neuroprotective, and antiviral properties in vitro and in animal models [ 21 – 25 ]. Thus, luteolin has been investigated for potential use in the treatment of obesity [ 26 ] and obesity-related diseases and for antidiabetic [ 27 – 29 ] and neuroprotective therapies [ 30 , 31 ]. In ophthalmological research, luteolin protects against oxidative stress-related damage and decreases inflammation in ARPE-19 cells [ 32 , 33 ].…”

Neuroprotective effects of Apium graveolens against focal cerebral ischemia occur partly via antioxidant, anti‐inflammatory, and anti‐apoptotic pathways

“…Other antioxidants found in this plant include the flavonoids luteolin and apigenin 51–53 . Several studies have shown that luteolin and apigenin have beneficial neuroprotective effects both in vitro and in vivo 54–59 …”