• Journal of Ginseng Research
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• v.42 no.3
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• pp.379-388
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• 2018

Background: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. Methods: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/ kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. Results: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. Conclusion: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.390-399
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• 2023

Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.118-125
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• 2011

Free radical scavenging and antioxidants have attracted attention as a way to prevent the progression of Parkinson's disease (PD). This study was carried out to investigate the effects of n-hexane fraction from Laurus nobilis L. (Lauraceae) leaves (HFL) on dopamine (DA)-induced intracellular reactive oxygen species (ROS) production and apoptosis in human neuroblastoma SH-SY5Y cells. Compared with apomorphine (APO, $IC_{50}=18.1\;{\mu}M$) as a positive control, the HFL $IC_{50}$ value for DA-induced apoptosis was $3.0\;{\mu}g/ml$, and two major compounds from HFL, costunolide and dehydrocostus lactone, were $7.3\;{\mu}M$ and $3.6\;{\mu}M$, respectively. HFL and these major compounds significantly inhibited ROS generation in DA-induced SH-SY5Y cells. A rodent 6-hydroxydopamine (6-OHDA) model of PD was employed to investigate the potential neuroprotective effects of HFL in vivo. 6-OHDA was injected into the substantia nigra of young adult rats and an immunohistochemical analysis was conducted to quantitate the tyrosine hydroxylase (TH)-positive neurons. HFL significantly inhibited 6-OHDA-induced TH-positive cell loss in the substantia nigra and also reduced DA induced $\alpha$-synuclein (SYN) formation in SH-SY5Y cells. These results indicate that HFL may have neuroprotective effects against DA-induced in vitro and in vivo models of PD.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.178-185
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• 2020

In this study, the effect of complex hot water extracts of Cirsium jaonicum, Artemisia annua and Curcuma longa (CAC) on the improvement of non-alcoholic fatty liver disease (NAFLD) was investigated. CAC inhibited fatty acid synthesis and lipid accumulation in HepG2 cells cultured with free fatty acid (FFA). In the NAFLD animal model, CAC extract suppressed the increase in body weight, liver, and epididymis fat weight, and suppressed the increase in hepatocyte fat and blood triglyceride. In addition, by blocking the Nrf2/HO-1 signaling pathway, cells were protected from oxidative stress in hepatocytes. Moreover, CAC inhibited the expression of COX-2, iNOS, TNF-α and IL-17 in hepatocytes. These results suggest the possibility that CAC extract can be applied in the field of health functional foods and pharmaceuticals for improvement and prevention of NAFLD.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.347-350
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• 2003

Dialysis and renal transplantation, the current therapies for end-stage renal disease (ESRD), have many limitations including severe complications, organ shortage, and graft failure. To overcome the limitations, the present study investigated the reconstruction of renal tissue in vivo by transplanting isolated fetal renal cells using fibrin gel to the kidney of renal failure rat model. After 4 weeks from the transplantation, blood urea nitrogen(BUN) and creatinine were examined from blood samples and histological examination of the implanted tissues revealed formation of renal-like structures and restoration of renal function.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.49-56
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• 2013

Chrysanthemum boreale(CB) is an oriental medicinal herb which has been used traditionally for the treatment of various brain disease including headache, dizziness and sedation. In order to examine the mechanism of anti-parkinsonism effect, water extract of CB(100 mg and 200 mg/kg of b.w.) were administered orally during 28 days in MPTP-induced parkisonism mice model. Water extract of CB increased the motor activities. CB did not affect total MAO and MAO-B activity in the brain of MPTP-induced mice. CB significantly increased the concentration of lipid peroxidation in the mid brain. Also, CB significantly increased antioxidant enzyme including were SOD, catalase and glutathione peroxidase in the mid brain activity. CB significantly increased the concentration of dopamine and homovanillic acid in the brain. These results suggest that the anti-parkinsonism effect of CB is possibly due to the antioxidative effects at mid brain in MPTP-induced animal model.

• Food Science and Biotechnology
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• v.16 no.1
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• pp.43-48
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• 2007

Collagen-induced arthritis (CIA) is a model for some types of human autoimmune rheumatoid arthritis (RA). In this study, we examined whether ethanol extract of potato (Solanum tuberosum) is efficacious against CIA in mice. Potato extracts (100 and 200 mg/kg) were orally administered to DBA/1J mice once daily for 49 day after initial immunization with type II collagen. Clinical assessment of disease and measurement of paw edema were conducted throughout the study. The production of CIA-related rheumatoid factor, anti-type II collagen antibody, and cytokines were examined in DBA/1J mice. Serum levels of AST, ALT, creatinine, and lipids were measured, and antioxidant enzyme activity in the spleen was also determined. The arthritis score and paw edema were markedly suppressed in the groups treated with potato extract. Levels of rheumatoid factor, anti-type II collagen antibody, interleukin (IL)-1, IL-6, LDL-cholesterol, and malondialdehyde in sera were also reduced by potato extract treatment. The activities of glutathione peroxidase and glutathione reductase were increased in the spleens of CIA mice treated with potato extract. These findings suggest that potato extract has suppressive effects on type II collagen-induced arthritis, an animal model for human RA.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.212-219
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• 2022

Recently, the efficacy of probiotics in treatment of neurodegenerative disorders has been reported in animal and clinical studies. Here, we assessed the effects of Bacillus coagulans JA845 in counteracting the symptoms of D-galactose (D-gal)/AlCl₃-induced Alzheimer's disease (AD) in a mice model through behavioral test, histological assessment and biochemical analysis. Ten weeks of pre-treatment with B. coagulans JA845 prevented cognitive decline, attenuated hippocampal lesion and protected neuronal integrity, which demonstrated the neuroprotective features of B. coagulans JA845 in vivo. We also found that supplementation of B. coagulans JA845 alleviated amyloid-beta deposits and hyperphosphorylated tau in hippocampus of D-gal/AlCl₃-induced AD model mice. Furthermore, B. coagulans JA845 administration attenuated oxidative stress and decreased serum concentration of inflammatory cytokines by regulating the Nrf2/HO-1 and MyD88/TRAF6/NF-κB pathway. Our results demonstrated for the first time that B. coagulans has the potential to help prevent cognitive decline and might be a novel therapeutic approach for the treatment of neurodegenerative diseases.