• Journal of Life Science
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• v.30 no.11
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• pp.999-1006
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• 2020

The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH₂) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

• Journal of Life Science
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• v.31 no.2
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• pp.237-247
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• 2021

Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.

• Food Science and Preservation
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• v.12 no.5
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• pp.482-488
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• 2005

Oxidant stress is well-known for a pivotal parameter related to neuro-inflammatory diseases including Alzheimer's disease, Parkinson's disease, and ALS (Lou Gehrig's disease). In order to effectively screen for anti-inflammatory agents, we first established the infrastructure of high throughput screening for anti-oxidant agents from medicinal insect library extracted with water, methanol, ethanol, and dimethyl sulfoxide. By the screening system, we found that Tenodera angustipennis Saussure, Pyrocoela rupa Olivier and Papilio maackii Mntris had strong anti-oxidant activity. Moreover, Tenodera angustipennis Saussure and Tenodera aridifolia (Stoll) exhibited protection effects of cellular damage by treatment of an oxidant hydrogen peroxide. Together, the results suggest that some selected hits could be a potential agent against neuro-inflammation, although the in vivo studies should be clearly tested.

• Journal of Life Science
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• v.21 no.8
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• pp.1163-1167
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• 2011

Excessive alcohol consumption causes various degenerative brain diseases including Alzheimer's disease and Parkinson's disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.

• Journal of the East Asian Society of Dietary Life
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• v.14 no.1
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• pp.64-69
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• 2004

The deficiency of the neurotransmitter acetylcholine(ACh) is responsible for the initiation of Alzheimer's disease. In addition, there is a simple evidence that oxidative stress significantly increases in persons with Parkinson's disease compared to age-matched healthy persons. Therefore, the objective of the study was to investigate the neurodegeneration inhibitory effect of soybean(Glycine Max) and Yak-Kong(Rhynchosia Nolubilis) by measuring the degree of inhibiting Acetylcholinesterase (AChE) catabolizing the ACh and the free radical scavenger effect in vitro. AChE was measured by the minor modified Ellman assay. Free radical scavenging activity was measured using l-diphenyl-2-picrylhydrazyl (DPPH). First, the MeOH extracts of Soybean and Yak-Kong showed the AChE inhibiting activity of 62.0$\pm$2.43％ and 65.0$\pm$3.29％ at the 5 mg/$m\ell$ concentration. The 50％ inhibitory concentration ($IC_{50}$/) of AChE was 1.96 and 1.31 mg/$m\ell$ in the MeOH extracts of soybean and Yak-Kong. Second, the MeOH extracts of soybean and Yak-Kong showed the free radical scavenger activity of 23.1$\pm$4.26％ and 80.7$\pm$4.61％ at the 5 mg/$m\ell$. IC50 of free radical scavenger activity in Soybean and Yak-Kong was 13.00 and 1.41 mg/$m\ell$ in MeOH extracts and was 5.95 and 2.74 mg/$m\ell$ in hot-water extracts, respectively. In this study, the extracts of Soybean and Yak-Kong showed powerful effects in the AChE inhibition and free radical scavenging. The extracts of Soybean and Yak-Kong were expected to prevent the many neurodegenerative diseases.

• Korean Journal of Pharmacognosy
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• v.45 no.1
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• pp.55-61
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• 2014

Microwaves are non-ionizing electromagnetic waves of frequency between 300MHz to 300GHz and positioned between the X-ray and infrared rays in the electromagnetic spectrum. In recent years, the use of microwave for extraction of ingredient from plant material has shown remarkable research interest and potential. Scutellaria radix has been used as a traditional medicine for a variety of diseases. It has been reported to exert beneficial health effects, such as anti-bacterial, antiviral, anti-inflammatory, and free-radical scavenging. Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. In this study, we aimed to compare the neuroprotective and antioxidant effect of Scutellaria radix extracted by different methods using hot-water extraction (SBE-DW) or microwave extraction (SBE-DW-MW). As a result, we first examined HPLC analysis of hot-water and microwave extracts of Scutellaria radix. The hot-water and microwave extracts of Scutellaria radix showed the discernible difference patterns of HPLC analysis. Microwave-water extracts of Scutellaria radix increased DPPH radical scavenging activity more than hot-water extraction. Microwave-water extracts of Scutellaria radix also showed neuroprotective effects and ROS inhibition against glutamate-induced oxidative stress in mouse hippocampal HT22 cells, but hot-water extraction not showed. In addition, the phosphorylation of MAPKs induced by glutamate insult was prevented by microwave-water extracts of Scutellaria radix. Thus, these results suggested that microwave extraction can be utilized for improving the extraction efficiency and biological activity of Scutellaria radix.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.70-78
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• 2009

Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

• Korean Journal of Agricultural Science
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• v.49 no.2
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• pp.175-184
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• 2022

The present study investigated the neuroprotective effects of Coreopsis lanceolate extract against hydrogen-peroxide (H₂O₂)-induced oxidative damage and cell death in pheochromocytoma 12 (PC12) cells. Reactive oxygen species (ROS), 2,2'-azinobis (3-ethylbebzothiazoloine-6-sulfonic acid) diammonium salt, and 1,1-diphenyl-2-picrrylhydrazyl radical scavenging activities, as well as the expression levels of proteins associated with oxidative damage and cell death were investigated. According to the results, C. lanceolate extract exhibited inhibitory activity against intracellular ROS generation and cell-damaging effects induced by hydroxyl radicals in a dose-dependent manner. Total phenolic and flavonoid contents were 22.3 mg·g^-1 gallic acid equivalent and 16.2 mg·g^-1 catechin equivalent, respectively. Additionally, a high-performance liquid chromatography (HPLC) assay based on the internal standard method used to detect phenolic compounds. The phenolic compounds identified in C. lanceolata extract contained (+)-catechin hydrate (5.0 ± 0.0 mg·g^-1), ferulic acid (1.6 ± 0.0 mg·g^-1), chlorogenic acid (1.5 ± 0.0 mg·g^-1), caffeic acid (1.2 ± 0.0 mg·g-1), naringin (0.9 ± 0.0 mg·g^-1), and p-coumaric acid (0.5 ± 0.0 mg·g^-1). C. lanceolata extract attenuated pro-apoptotic Bax expression levels and enhanced the expression levels of anti-apoptotic Bcl-2, caspase-3, and caspase-9 proteins. Therefore, C. lanceolata is a potential source of materials with neuroprotective properties against neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases.

• Journal of Acupuncture Research
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• v.28 no.6
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• pp.1-17
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• 2011

Objectives : This study aimed to review randomized controlled trials of acupuncture performed in South Korea that used sham acupuncture as a control group. Methods : The following databases were searched through the end of September 2011: Koreanstudies information service system (KISS), Korean medical database (KMbase), national discovery OR science leaders (NDSL), oriental medicine advance searching integrated system (OASIS), and research information service system (RISS). The following search terms were used: acupuncture AND (sham or placebo). The reference lists of searched articles and Korea institute of oriental medicine (KIOM) reports(2005~2009) were identified. The following data were extracted: year/first author, disease, number of participants, blinding, intervention, outcome, and result. Where appropriate, we performed meta-analysis. The methodological quality was assessed according to the Jadad scale and 'risk of bias' by Cochrane Handbook procedure. Results : Twenty-nine studies were included in this review. In eighteen studies, penetrating sham controls were used as the control intervention, whereas the remaining eleven studies adopted non-penetrating sham controls such as the Park Sham Device or blunt auricular acupuncture. Nine studies showed statistically significant difference in outcomes. Twelve studies concerning insomnia after stroke, chronic tension-type headache, idiopathic Parkinson's disease, Hwa-Byung, and smoking cessation were included in meta-analysis. A meta-analysis of insomnia after stroke only found significant difference(MD -4.31, 95% Cl -6.19 to -2.42, $p$<0.00001). In general, all of the studies showed low methodological quality(Jadad score: mean 2.1). Risk of bias by Cochrane Handbook procedure varied. Conclusions : The results of this study could not suggest conclusive evidence that acupuncture is more effective than sham acupuncture in several diseases. In the future, more studies with rigorous acupuncture trials using sham controls should be conducted.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1152-1156
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• 2009

Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson’s disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.