Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

Abstract

Neuroinflammation is pathological evidence of Alzheimer’s disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42)-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight), orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42) into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR) test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats.

Black Garlic and Its Therapeutic Benefits

“…These findings are identical with the results from Indonesian report, in which black garlic improves motor coordination function and the number of Purkinje cells in the cerebellar cortex of the rat brain [45]. The protection effect of black garlic on nerve system from neuroinflammation, a pathological evidence of Alzheimer's disease, and cognitive impairment has been well documented [46]. Β amyloid (Aβ) deposition leads to inflammation of the neuron, which triggers a host defense response to neuronal damage and eventually neuronal degeneration.…”

“…Β amyloid (Aβ) deposition leads to inflammation of the neuron, which triggers a host defense response to neuronal damage and eventually neuronal degeneration. Nillert and collaborators had established a neuronal degenerative model by treatment with 1 μl of aggregated Aβ in the lateral ventricles; eventually they observed that ethanol extract-aged black garlic, a variant form of black garlic produced by aging the fresh garlic in room temperature, could ameliorate short-term recognition memory and inhibit activation of microglia as well as production of IL1β, a proinflammatory cytokine [46]. Additionally, ethyl acetate fraction of aged garlic extract protects PC12 neuron-like cells and ICR mice from neurotoxicity and amnesia induced by Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) [47].…”

Bioactive components from garlic on brain resiliency against neuroinflammation and neurodegeneration (Review)

“…The increased expression of synaptic proteins may underlie the improved cognitive functions (29). This effect was also accompanied by the attenuation of the loss of cholinergic neurons and neuroinflammation via the suppression of microglial activation and the secretion of interleukin (IL)-1β (30,31). Neuroinflammation plays an important role in the pathogenesis of a number of neurodegenerative disorders (32,33).…”

“…AGE can reduce the activation of microglia and astrocytes [by immune-detection of the respective ionized calcium-binding adapter molecule 1 (Iba1) and Glial fibrillary acidic protein (GFAP) expression levels], and can thus mitigate neuroinflammatory responses (13,39). Additionally, AGE can reduce the expression levels of neuroinflammatory mediators, including IL-1β, nuclear factor (NF)-κB, TLR4, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in microglial and endothelial cells and/or Aβ-induced neuroinflammation in rats (21,30,40). AGE has also been found to alleviate oxidative stress by scavenging ROS, inhibiting LDL oxidation, enhancing antioxidant signaling [such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione (GSH)] and mitigating lipid peroxidation [malondialdehyde (MDA)] (41-45).…”

Brief Challenges on Medicinal Plants: An Eye‐Opening Look at Ageing‐Related Disorders

“…Thus, a daily dose of 600–900 mg garlic powder proved to be effective to significantly decrease triglyceride and serum cholesterol levels . Another study showed that garlic extract exerted neuroprotective effects on cognitive dysfunction and neuroinflammation through decreasing the activation of microglia and IL‐1β to basal levels . Numerous biological effects of garlic, including antimicrobial, antioxidant, antidiabetic, anticarcinogenic, antimutagenic, anti‐atherosclerotic and immunomodulatory activities have been recently documented, and many of them are related with ageing‐dependent disorders .…”