Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5—trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1–42 (Aβ1–42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1–42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels.

Effects of a solid lipid curcumin particle formulation on chronic activation of microglia and astroglia in the GFAP-IL6 mouse model

“…Motor function impairment GFAP-IL6 mice in the rotarod test have been previously reported by our group 25 . IL-6 mediated motor function impairment has also been found in mouse models taking the rotarod test following experimental traumatic brain injury (TBI) 39 . Similar studies have provided evidence for IL-1 and TNF-α mediated motor function deficits in mice subjected to TBI 40 .…”

Phloroglucinol protects retinal pigment epithelium and photoreceptor against all‐trans‐retinal–induced toxicity and inhibits A2E formation

“…Phloroglucinol can exert protective effects against oxidative stress-induced cytotoxicity in vitro and in vivo. [24,36,37] As examples, phloroglucinol was recently reported to attenuate motor functional and cognitive deficits in animal models of Parkinson's and Alzheimer's diseases [30,38]. This neuroprotective effect was mainly caused by its antioxidative activity, both preventing the increase in intracellular ROS and the loss of expression of antioxidant enzymes.…”

Phloroglucinol, a nutraceutical for IR‐induced cardiac damage in diabetic rats

“…Phloroglucinol is a benzenetriol, a secondary plant metabolite available for treating GI disorders. It is an algal metabolite and is abundantly found in Ecklonia cava . In recent studies it was observed that phloroglucinol has diverse pharmacological activities including antispasmodic activity.…”