gingerol and Cognitive-Dysfunction

This study examined the protective effect of 6-Gingerol (6G) against lipopolysaccharide (LPS)-induced cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation. Male rats were allocated into six groups in this manner; Group I placed on normal saline only. Group II was treated for 7 days with LPS alone intraperitoneally at 250 µg/kg body weight (bw). Group III received 6G alone at 50 mg/kg bw orally for 14 days. Groups IV and V received 6G at 20 and 50 mg/kg bw for 7 days, respectively, and LPS for another 7 days to induce neurotoxicity. Group VI received 5 mg/kg bw of donepezil for 7 days and LPS for 7 days. Pretreatment with 20 and 50 mg/kg bw of 6G protected against LPS-mediated learning and memory function, and also locomotor and motor deficits. Besides, 20 and 50 mg/kg bw 6G mitigated LPS-induced alteration in markers of oxidative stress. Furthermore, induction of amyloidogenesis associated with disruption of histoarchitecture and high expression of interleukin 1β, inducible nitric oxide synthase, amyloid precursor protein (APP), β-secretase 1, and brain-derived neurotrophic factor by LPS was mitigated by the two doses of 6G in the rat hippocampus and cerebral cortex region of the brain. 6G pretreatment at the two doses mitigated LPS-mediated histopathological changes in the hippocampus and cerebral cortex of rats. Overall, our results demonstrate that the protective effect of 6G is mediated through the reversal of neurobehavioral deficit, oxidative stress, inflammation, and amyloidogenesis, thus making 6G a possible chemoprophylactic agent against brain injury as a result of LPS exposure. PRACTICAL APPLICATIONS: In the search for a holistic prevention of inflammation-associated neurodegeneration, nutraceuticals are becoming prominent. Hence, this study presents 6G, an active constituent of ginger, as a chemoprotective, antioxidant, and anti-inflammatory agent, which is able to ameliorate cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation in LPS-induced rat model of neuroinflammation.

Topics: Animals; Catechols; Cognition; Cognitive Dysfunction; Fatty Alcohols; Inflammation; Lipopolysaccharides; Male; Neuronal Plasticity; Rats; Zingiber officinale

6-Gingerol, the major component of gingerols extracted from Zingiber officinale, has been shown to exhibit anti-inflammatory and antioxidant bioactivities. Since neuroinflammation plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), and astrocytes have been considered important in the process of neurodegeneration, it was of interest to know whether 6-gingerol reduced astrocytes activation or even attenuated cognitive impairment. Here we examined the neuroprotective effects of 6-gingerol in lipopolysaccharide (LPS)-induced disorder models both in vitro and in vivo. C6 astroglioma cells treated with LPS were found to release excessive pro-inflammatory cytokines, including TNF-α and IL-6, and also increase intercellular ROS, NO, and iNOS (i.e. NOS2). All these were blocked by 6-gingerol in a concentration-dependent manner. The spatial learning and memory of rats challenged with LPS (10 μg, i.c.v.) in the absence or presence of 6-gingerol were evaluated using the Morris water-maze (MWM) test. 6-Gingerol attenuated LPS-induced imapirement of MWM learning and memory in a dose-dependent manner. Besides, 6-gingerol inhibited LPS-induced increases in levels of GFAP and TNF-α in the rat brain. The results suggest that 6-gingerol suppresses astrocyte overactivation, through which it contributes to improvement of cognitive ability.

Topics: Animals; Astrocytes; Catechols; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Alcohols; Glial Fibrillary Acidic Protein; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Maze Learning; Memory; Memory Disorders; Neurodegenerative Diseases; Neuroprotective Agents; Rats; Rats, Sprague-Dawley