Ameliorative Effect of Ginsenoside Rg1 on Lipopolysaccharide-Induced Cognitive Impairment: Role of Cholinergic System

Evidence-Based Complementary and Alternative Medicine

Yeom

Shim

et al. 2020

Recently, neuroinflammation is thought to be one of the important causes of many neuropsychiatric diseases. Quercetin (QUER) is a natural flavonoid, and it is well known that QUER has antioxidative, anti-inflammatory, and neuroprotective effects. In our study, lipopolysaccharide (LPS) was injected into the lateral ventricle of rats to induce anxiety-like behaviors and neuroinflammation, and it was confirmed that chronic administration of QUER could improve anxiety-like symptoms. We also investigated the effects of QUER on inflammatory markers and its major mechanisms associated with inflammation in the hippocampus. Daily administration of QUER (10, 50, and 100 mg/kg) daily for 21 days significantly improved anxiety-like behaviors in the elevated plus-maze test and open field test. QUER administration significantly reduced inflammatory markers such as interleukin-6, interleukin-1β, cyclooxygenase-2, and nuclear factor-kappaB levels in the brain. In addition, QUER significantly increased the brain-derived neurotrophic factor (BDNF) mRNA level and decreased the nitric oxide synthase (iNOS) mRNA level. Therefore, our results have shown that QUER can improve anxiety-like behaviors caused by chronic neuroinflammation. This anxiolytic effect of QUER has been shown to be due to its anti-inflammatory effects and appropriate regulation of BDNF and iNOS expression. Thus, QUER provides the potential as a therapeutic agent to inhibit anxiety-like symptoms in neuropsychiatric diseases, such as anxiety.

Section: Discussionmentioning

confidence: 99%

Protective Effects of Quercetin on Anxiety‐Like Symptoms and Neuroinflammation Induced by Lipopolysaccharide in Rats

Evidence-Based Complementary and Alternative Medicine

Yeom

Shim

et al. 2020

“…In addition, it significantly reduced caspase-3 activity, upregulated the expression of PI3K/protein kinase B/glycogen synthase-3β, and downregulated the mRNA expression levels of p21WAF1/CIP1 and p53 in aged rats exposed to isoflurane anesthesia [ 90 ]. It has a protective effect against LPS-induced cognitive deficit and its prevention of LPS-induced changes in the cholinergic system is crucial to this ameliorating effect [ 91 ]. In a dexamethasone-induced cognitive impairment mice model, Rg1 (2 and 4 mg/kg) treatment increased spontaneous motor activity and exploratory behavior in an open field test and increased the number of entries into the new object zone in a novel object recognition test.…”

Section: Pharmacological Potential Of Active Ginseng Constituents In mentioning

confidence: 99%

Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study

et al. 2018

Cognitive impairment is a state that affects thinking, communication, understanding, and memory, and is very common in various neurological disorders. Among many factors, age-related cognitive decline is an important area in mental health research. Research to find therapeutic medications or supplements to treat cognitive deficits and maintain cognitive health has been ongoing. Ginseng and its active components may have played a role in treating chronic disorders. Numerous preclinical studies have confirmed that ginseng and its active components such as ginsenosides, gintonin, and compound K are pharmacologically efficacious in different models of and are linked to cognitive impairment. Among their several roles, they act as an anti-neuroinflammatory and help fight against oxidative stress and modulate the cholinergic signal. These roles may be involved in enhancing cognition and attenuating impairment. There have been some clinical studies on the activity of ginseng in cognitive impairment, but many ginseng species and active compounds remain to be investigated. In addition, new formulations of active ginseng components such as nanoparticles and liposomes could be used for preclinical and clinical models of cognitive impairment. Here, we discuss the therapeutic potential of active ginseng components in cognitive impairment and their chemistry and pharmacokinetics and consider prospects for their delivery and clinical study with respect to cognitive impairment.

“…Systemic injection of LPS is associated with neuroinflammation in the hippocampus critical for learning and memory processes [ 9 ], leading to cognitive dysfunction [ 10 ]. Therefore, LPS has been often used to research the biochemical mechanisms of cognitive dysfunction due to inflammation and to develop targeted remedial for neurological symptoms in animal model [ 11 ]. LPS stimulates proinflammatory cytokine cascades by toll-like receptor 4 (TLR4) causing production of many proinflammatory cytokines including IL-6, IL-1 β , and TNF- α , and activation of the nuclear factor-kappaB (NF- κ B) system [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Gypenosides Attenuate Lipopolysaccharide‐Induced Neuroinflammation and Memory Impairment in Rats

Shim

Evidence-Based Complementary and Alternative Medicine

2018

Neuroinflammation is deliberated a major factor in various neurodegenerative diseases. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including anti-inflammatory, antioxidative, and protective properties. In the present study, whether GPS could improve cognitive dysfunction and chronic inflammation caused by injecting lipopolysaccharide (LPS) in the hippocampus was investigated. Effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Induction of LPS into the lateral ventricle caused inflammatory reactions and memory impairment on the rats. Every day treatment of GPS (25, 50, and 100 mg/kg) for 21 consecutive days attenuated spatial recognition, discrimination, and memory deficits. GPS treatment significantly decreased proinflammatory mediators such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-kappaB (NF-κB) levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of inducible nitric oxide synthase (iNOS) and toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA level. Collectively, these results showed that GPS may improve cognitive function and provide a potential therapy for memory impairment caused by neuroinflammation. Based on these, GPS may be effective in inhibiting the progress of neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and appropriate modulation of NF-κB/iNOS/TLR4/BDNF.