• Journal of Ginseng Research
• /
• v.47 no.2
• /
• pp.302-310
• /
• 2023

Background: The most common type of dementia, Alzheimer's disease (AD), is marked by the formation of extracellular amyloid beta (Aβ) plaques. The impairments of axons and synapses appear in the process of Aβ plaques formation, and this damage could cause neurodegeneration. We previously reported that non-saponin fraction with rich polysaccharide (NFP) from Korean Red Ginseng (KRG) showed neuroprotective effects in AD. However, precise molecular mechanism of the therapeutic effects of NFP from KRG in AD still remains elusive. Methods: To investigate the therapeutic mechanisms of NFP from KRG on AD, we conducted proteomic analysis for frontal cortex from vehicle-treated wild-type, vehicle-treated 5XFAD mice, and NFP-treated 5XFAD mice by using nano-LC-ESI-MS/MS. Metabolic network analysis was additionally performed as the effects of NFP appeared to be associated with metabolism according to the proteome analysis. Results: Starting from 5,470 proteins, 2,636 proteins were selected for hierarchical clustering analysis, and finally 111 proteins were further selected for protein-protein interaction network analysis. A series of these analyses revealed that proteins associated with synapse and mitochondria might be linked to the therapeutic mechanism of NFP. Subsequent metabolic network analysis via genome-scale metabolic models that represent the three mouse groups showed that there were significant changes in metabolic fluxes of mitochondrial carnitine shuttle pathway and mitochondrial beta-oxidation of polyunsaturated fatty acids. Conclusion: Our results suggested that the therapeutic effects of NFP on AD were associated with synaptic- and mitochondrial-related pathways, and they provided targets for further rigorous studies on precise understanding of the molecular mechanism of NFP.

• The Korea Journal of Herbology
• /
• v.24 no.4
• /
• pp.205-213
• /
• 2009

Objectives : Cancer incidence is increasing in all countries and chemotherapy-induced peripheral neuropathy (CIPN) in patients undergoing chemotherapeutic agents have been a clinically serious problems. So far therapeutic options for CIPN patients are limited and no confirmed methods have yet been established for dealing with peripheral neuropathy. Therefore this review is to provide an evidence-based summary of oriental medicine and CAM (complementary and alternative medicine) neuroprotective and treatment therapies which have gone through clinical trials. Methods : An overview of the domestic and international papers of adult clinical trials relating management of only CIPN symptoms through 1990 to present were searched by electronic databases. Search key words were chemotherapy-induced neurotoxicity, chemotherapy-induced peripheral neuropathy, chemotherapy toxicity & herb, chemotherapy toxicity & acupuncture, chemotherapy toxicity & CAM. Only English and Korean written papers were reviewed. Total 25 papers were reviewed in this study, 18 papers were retrieved by electronic search. Results : Clinical studies of managing CIPN were rare, two acupuncture clinical studies and four herb medicinal studies were found. Rest of 19 papers were about other CAM clinical studies. Total 25 papers were analyzed, and all interventions were focused on their pain control efficacy. Other 24 trials of potential therapies except one proved to be effective for CIPN, however some described to be inadequate positive or sufficient negative. Conclusions : As most of the studies were pilot studies, interventions for the prevention and treatment of CIPN have to go through prospective confirmatory studies, such as larger scale randomized, double-blinded, placebo controlled clinical trials must be done for the safe and effective use of proposed therapies. Also standard measurement scales have to be developed for the better clinical study of CIPN.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.458-468
• /
• 2023

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca²⁺) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca²⁺ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.22 no.1
• /
• pp.15-30
• /
• 2009

Purpose: In this rapidly aging society, the research and development of traditional oriental medicine treatment is one of the critical factors to protect the increasing neuro-degenerative disorders. In this study, we wanted to verify the effect of Yukul-tang (YUT) on neuro-degenerative disease model by assessing the antioxidant and anti-inflammation effects. Methods: To assess the antioxidant effects of YUT, we carried out DPPH radical and ABTS radical scavenging assays and determined the total polyphenolic contents in YUT. To evaluate the neuro-protective effects of YUT, we performed the MTT and ROS assays and TH immunohistochemistry, NO and TNF-${\alpha}$ assays in SH-SY5Y or mesencephalic dopaminergic neurons damaged by 6-OHDA. Results: The treatment of YUT showed eliminating effects on DPPH radical and ABTS radical. it showed deterring effects on ROS, NO and TNF-${\alpha}$ and protecting effects on TH-positive cell in SH-SY5Y cells or mesencephalic dopaminergic neurons. Especially in the case of the treatment of YUT with 0.2ug/mL + 6-OHDA 10uM, the protective effect on dopaminergic neurons was most outstanding. Conclusion: In this study, we have demonstrated that YUT has an antioxidant effect and a neuro-protective effect on neuro-degenerative disease model caused by neurotoxin such as 6-OHDA. The results of our present study suggest that YUT can be useful agent to prevent and to treat neuro-degenerative diseases.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.366-375
• /
• 2023

Background: Ginseng contains three active components: ginsenosides, gintonin, and polysaccharides. After the separation of 1 of the 3 ingredient fractions, other fractions are usually discarded as waste. In this study, we developed a simple and effective method, called the ginpolin protocol, to separate gintonin-enriched fraction (GEF), ginseng polysaccharide fraction (GPF), and crude ginseng saponin fraction (cGSF). Methods: Dried ginseng (1 kg) was extracted using 70% ethanol (EtOH). The extract was water fractionated to obtain a water-insoluble precipitate (GEF). The upper layer after GEF separation was precipitated with 80% EtOH for GPF preparation, and the remaining upper layer was vacuum dried to obtain cGSF. Results: The yields of GEF, GPF, and cGSF were 14.8, 54.2, and 185.3 g, respectively, from 333 g EtOH extract. We quantified the active ingredients of 3 fractions: L-arginine, galacturonic acid, ginsenosides, glucuronic acid, lysophosphatidic acid (LPA), phosphatidic acid (PA), and polyphenols. The order of the LPA, PA, and polyphenol content was GEF > cGSF > GPF. The order of L-arginine and galacturonic acid was GPF >> GEF = cGSF. Interestingly, GEF contained a high amount of ginsenoside Rb1, whereas cGSF contained more ginsenoside Rg1. GEF and cGSF, but not GPF, induced intracellular [Ca²⁺]_i transient with antiplatelet activity. The order of antioxidant activity was GPF > GEF = cGSF. Immunological activities (related to nitric oxide production, phagocytosis, and IL-6 and TNF-α release) were, in order, GPF > GEF = cGSF. The neuroprotective ability (against reactive oxygen species) order was GEF > cGSP > GPF. Conclusion: We developed a novel ginpolin protocol to isolate 3 fractions in batches and determined that each fraction has distinct biological effects.

• Molecules and Cells
• /
• v.45 no.3
• /
• pp.134-147
• /
• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• Journal of agriculture & life science
• /
• v.50 no.3
• /
• pp.129-139
• /
• 2016

Curcumin plays a protective role in brain injury through its anti-oxidant and anti-inflammatory activities. Moreover, peroxiredoxin-5 exerts a protective effect against oxidative stress. The aim of this study was to investigate whether curcumin modulated the peroxiredoxin-5 expression in focal cerebral ischemic animal model. Middle cerebral artery occlusion(MCAO) was performed to induce cerebral ischemic injury in rats. Adult male rats were injected intraperitoneally with vehicle or curcumin(50mg/kg B.W.) 1 h after MCAO and cerebral cortex tissues were collected 24 h after MCAO. Photographs of hematoxylin and eosin staining showed that MCAO induced necrotic changes with scalloped shrunken form and apoptotic changes with nuclear chromatin condensations. However, curcumin treatment attenuated MCAO-induced histopathological changes. Moreover, this study clearly showed that peroxiredoxin-5 expression was decreased in MCAO operated animal with vehicle using a proteomics approach. However, this decrease in peroxiredoxin-5 expression was attenuated by curcumin treatment. Reverse-transcription PCR and Western blot analyses confirmed that curcumin treatment alleviated the MCAO injury-induced decrease in peroxiredoxin-5 expression(p<0.05). These results demonstrated that curcumin regulates peroxiredoxin-5 expression in MCAO animal model. In conclusion, our findings suggest that curcumin exerts a neuroprotective effect in cerebral ischemia by attenuating the MCAO-induced decrease in peroxiredoxin-5 expression.

• Journal of Korean Neurosurgical Society
• /
• v.67 no.4
• /
• pp.418-430
• /
• 2024

Objective : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 µM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 µM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 µM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

• IMMUNE NETWORK
• /
• v.20 no.4
• /
• pp.32.1-32.15
• /
• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.272-281
• /
• 2023

It has been known that Paeoniae Radix (PR) contains monoterpene glycosides showing a variety of biological activities such as anti-spasmodic, anti-inflammatory, anti-viral, neuroprotective, and sedative effects. This study aimed to find the cytotoxic compounds isolated from the dichloromethane (CH₂Cl₂)- and ethyl acetate-soluble fractions of PR. As results, thirteen compounds (1-13) were isolated and the chemical structures were identified. In addition, the human alveolar adenocarcinoma cell line (A549) was treated with isolated compounds to determine the cytotoxic effect via evaluation of cell viability. The reduction of A549 cell viability was shown as following order; gallic acid (8) > (2S)-naringenin (9) > methyl gallate (10)>6'-O-benzoylpaeoniflorin (7) > palmitic acid (3). Especially, 7 did not show the cytotoxicity in the human lung fibroblast cell line (MRC-5). The effect of 7 on the cell viabilities in A549 and MRC-5 is firstly reported in this study. Further study is required to find out the cytotoxic mechanism and the selectivity for the cancer cells of 7 in detail.