Ashwagandha Extract Ameliorates Cognitive Impairment Associated with Systemic Inflammation

Written by Angeline A. De Leon, Staff Writer. An ashwagandha leaf water extract shows promise as a natural therapeutic remedy for preventing neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.

Epidemiological studies have linked systemic inflammation with chronic diseases such as atherosclerosis, type 2 diabetes, and ulcerative colitis ^1,2. Neuroinflammation specifically affects synaptic plasticity and neuronal function by activating microglia, thereby inducing neurotoxic effects ³ and leading ultimately to neurodegenerative disease and cognitive deficits ^4,5. A potential strategy for mitigating neurodegenerative disease, therefore, involves targeting systemic inflammation. Ashwagandha, a popular adaptogenic herb with natural anti-inflammatory and neuroprotective properties, has more recently been studied in experimental models of neurological disorders and neurodegenerative disease ^6,7. Evidence supports the efficacy of Ashwagandha leaf water extract (ASH-WEX) in preventing lipopolysaccharide (LPS, an endotoxin produced by many pathogenic bacteria)-induced activation of microglial cells and reducing secretion of pro-inflammatory cytokines in an in vitro model ⁸. ASH-WEX has also been shown to diminish oxidative stress products and prevent reactive gliosis ⁹. In a 2019 study ¹⁰ by Gupta and Kaur, the neuroprotective potential of ASH-WEX was further investigated by testing its protective effects against neurodegeneration and cognitive impairment caused by LPS-induced inflammation.

A group of 32 male Wistar albino rats were randomized to one of four groups: a control group; a group receiving water daily for 8 weeks and a single injection of LPS at the end of treatment (LPS); a group receiving ASH-WEX (4 ml/kg) daily for 8 weeks and a single injection of LPS at the end of treatment (LPS + ASH-WEX); or a group receiving only ASH-WEX daily for 8 weeks. A series of behavioral studies (rotarod test, narrow beam walk test, novel object recognition test) were administered to assess neuromuscular coordination, working memory, and learning ability. Animals were then sacrificed and regions of the brain were dissected and analyzed using Western blotting and mRNA expression analysis to determine relative expression of proteins associated with synaptic plasticity and cell survival.

Tests revealed improved neuromuscular coordination in association with ASH-WEX treatment: compared to LPS-treated rats, rats in the LPS + ASH-WEX and ASH-WEX groups experienced significantly less falls (p ≤ 0.01) and spent more time on the rotating rod (p ≤ 0.001). LPS + ASH-WEX and ASH-WEX rats were also able to cross the narrow beam quickly (p ≤ 0.01) and with the least number of paw slippages. Compared to LPS rats, both ASH-WEX-treated groups displayed a greater number of episodes and more time in exploring novel vs. old objects, indicating an intact, normal working memory (p ≤ 0.05 for all). Finally, Western blot analysis showed that ASH-WEX was able to normalize the expression of synaptic plasticity markers: LPS-induced upregulated expression of PSA-NCAM and NCAM (neural cell adhesion molecules involved in synaptogenesis, showing enhanced expression during stress) was attenuated in the hippocampus and pyriform cortex (PC) of rats in the ASH-WEX-treated groups (p ≤ 0.05 for all). Expression of neuronal growth-related protein GAP43 was also significantly upregulated in both brain regions in rats treated with ASH-WEX (p ≤ 0.05 for all), as compared to LPS rats.

Findings from the study indicate that treatment with ASH-WEX can mitigate LPS-induced diminishment in locomotor and cognitive function and regulate the expression of protein markers involved in synaptic plasticity and neuronal survival in the hippocampal and PC regions of rats. Behavioral tests showed ASH-WEX treatment was associated with better overall neuromuscular coordination and improved learning and memory, compared to LPS rats. These observations were also paralleled by relatively normalized expression of proteins involved in synaptogenesis and neuronal growth in the ASH-WEX groups, suggesting regulation of neuroprotective mechanisms involved in response to stress and neuroinflammation. Current data suggest that Ashwagandha, in the form of aqueous leaf extract, may effectively prevent LPS-induced impairments in cognition, locomotor function, and synaptic plasticity based on in vitro and in vivo models. Further translational research is warranted to examine the potential of ASH-WEX in the treatment of neurodegenerative disease and cognitive impairment in humans.

Source: Gupta M, Kaur G. Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairment associated with systemic inflammation. BMC Complementary and Alternative Medicine. 2019; 19: 217. DOI: 10.1186/s12906-019-2635-0.

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/publicdomain/zero/1.0)

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Posted November 6, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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