• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.343-349
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• 1994

A number of neurological syndromes(e.g. tardive dyskinesia) are developed as a consequence of chronic treatment with neuroleptics or antipsychotic agents. Despite the long and succesful use of phenothiazine derivatives and related agents in the treatment of certain states of mental disease, the mechanisms of these drugs are still poorly understood. One current hypothesis from extensive reviews is that these compounds might significantly interfere with the cyclic nucleotide system in brain (Levin and Weiss, 1977; Nowicki et al., 1991; Haley et al., 1992). Nitric oxide (NO), one of an interesting messenger molecule and aberrant transmitter, is believed to play a important role in biological functions of cyclic nucleotides in nervous system. It has been reported that calcium-dependent NO synthesis in endothelial cytosol is mediated by calmodulin which is supposed to be tightly related to pharmacological actions of antipsychotic agents. In the present study, the effect of several antipsychotic agents on the activity of NO synthesis and formation of cyclic GMP were investigated. These agents inhibited both the formation of $[^3H]L-citrulline$ and that of $[^3H]cyclic$ GMP by concentration-dependent manner, and their inhibiting patterns are so similar to that of calmodulin antagonist.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.103-103
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• 2018

Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.543-551
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• 2016

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

• Journal of Life Science
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• v.25 no.11
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• pp.1255-1264
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• 2015

Cnidium officinale, a traditional herb, has diverse beneficial pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, and antiangiogenesis effects. However, the cellular and molecular mechanisms of apoptosis by C. officinale are poorly defined. The present study investigated the proapoptotic effects of water, ethanol, and methanol extract of C. officinale (WECO, EECO, and MECO, respectively) in human leukemia U937 cells. The antiproliferative activity of EECO was higher than that of WECO and MECO. The antiproliferative effect of EECO treatment in U937 cells was associated with the induction of apoptotic cell death, including increased populations of annexin-V positive cells, the formation of apoptotic bodies, DNA fragmentation, and increased numbers of cells with a loss of mitochondrial membrane potential (MMP, Δψm). EECO-induced apoptotic cell death was associated with upregulation of death receptor 4 (DR4) and down-regulation of cellular inhibitor of apoptosis protein-1 (cIAP-1), Bcl-2, and total Bid. The EECO treatment also induced the proteolytic activation of caspases (-3, -8, and -9), and degradation of caspase-3 substrate proteins, such as poly(ADP-ribose) polymerase (PARP), β-catenin, and phospholipase C-γ1 (PLCγ1). In addition, the EECO treatment effectively activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. However, compound C, a specific inhibitor of AMPK, significantly reduced EECO-induced apoptosis. These results indicate that AMPK is a key regulator of apoptosis in response to EECO in human leukemia U937 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6191-6196
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• 2012

Aims and Background: Traditional chemotherapy strategies for human leukemia commonly use drugs based on cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likely to occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectively eliminate malignant cells without affecting normal cells. Our previous studies indicated that ginsenoside $Rg_1$ ($Rg_1$), a major active pharmacological ingredient of ginseng, could delay normal hematopoietic stem cell senescence. However, whether $Rg_1$ can induce cancer cell senescence is still unclear. Methods: In the current study, human leukemia K562 cells were subjected to $Rg_1$ exposure. The optimal drug concentration and duration with K562 cells was obtained by MTT colorimetric test. Effects of $Rg_1$ on cell cycle were analyzed using flow cytometry and by SA-${\beta}$-Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessed by Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting. Ultrastructural morphology changes were observed by transmission electron microscopy. Results: K562 cells demonstrated a maximum proliferation inhibition rate with an $Rg_1$ concentration of $20{\mu}\;mol{\cdot}L^{-1}$ for 48h, the cells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, larger mitochondria and increased number of lysosomes. Senescence associated-${\beta}$-galactosidase (SA-${\beta}$-Gal) activity was increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as well as reduction of proliferating potential and arrestin $G_2$/M phase after $Rg_1$ interaction. The senescence associated proteins P21, P16 and RB were significantly up-regulated. Conclusion: Ginsenoside $Rg_1$ can induce a state of senescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways.

• International Journal of Industrial Entomology and Biomaterials
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• v.4 no.2
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• pp.93-100
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• 2002

Cocoon production, which is a representative of traditional sericulture shifted into silkworm powder production in the spring of 1995. This, infect, signifies the change from the dress-centered textile business to the bio-industry and the functional resource industry. One of the most outstanding shifting is utilization of silkworm larvae for anti-diabetic agent. In Asian countries including Korea, silkworm powder derived from the domestic silkworm (Bombyx mori L.) has long been favored for anti-diabetic agent, but its efficacy was not tested until last decade by modern scientific methods. In this article, we reviewed the major researches on the silkworm powder as a blood glucose-lowering substance. After the beginning test of the efficacy of silkworm powder by a cooperative research between Department of Sericulture and Entomlogy, NIAST, RDA and Kyung Hee University, substantial data have been accumulated so far, In a serial experiment to select best condition, the fifth instar larvae prepared by freeze dry method turned out to have the best blood glucose-lowering effect. In the pharmacological experiment to understand the mechanism of silkworm powder in small intestine, the silkworm powder turned out to inhibit the activity of ${\alpha}$-glucosidase, by competitively binding to $\alpha$-type disaccharides. The animal experiment showed that the extract of silkworm powder prevents a rapid increase of blood glucose level after meal and prevents hunger and law blood glucose level during empty stomach. In the experiment to isolate the major component of silkworm powder, which exerts blood glucose-lowering effect, 1-deoxynojirimy-cin (DNJ) was eventually mass-purified, and it turned out that DNJ isolated from silkworm powder was excellent in its blood glucose-lowering effect. In the experiment to understand the personal difference of the efficacy of the silkworm powder, clinical candidates were divided on the basis of the criterion of traditional Chinese medicine: Tae-Yang, Tae-Um, So-yang, and So-Um. The result showed that silkworm powder has a tendency to reduce blood glucose level at fasting and at 2 hours after meal, and this trend was somewhat obvious in the Tae-Um body type. In summary, we reviewed scientific papers on the efficacy of silkworm powder and its purified DNJ as a blood glucose-lowering agent. These suggest that silkworm powder truly possesses blood glucose-lowering effect as documented in the traditional Chinese medicine, although further researches will be required to develop them as "medical" resource instead of functional food.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.27-42
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• 2005

Objectives : Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. These plaques are associated with degenerating neuronal processes and consist primarily of fibrillary aggregates of beta-amyloid$ protein, generated from amyloid precursor protein (APP). Another amyloidogenic fragment, the carboxyl terminus (CT) of APP, which is composed of 99-105 amino acid residues containing the complete $A{\beta}$ sequence, also appears to be toxic to neurones. Recent evidence suggest that CT105, carboxy terminal 105 amino acids peptide fragment of APP, may be an important factor causing neurotoxicity in AD. Methods : Although a variety of oriental prescriptions including Pinelliae rhizoma have traditionally been utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. In the present study, we investigated effects of the dichloromethane extract of Pinelliae rhizoma (PINR) on neurotoxicity and the formation of reactive oxygen species (ROS) and nitric oxide (NO) in SK-N-SH cells overexpressed with CT105. In addition, we evaluated its radical scavenging activity and effects on acetylcholinesterase (AChE) activity. Furthermore, effects on cognitive deficits induced by scopolamine treatment in rats were evaluated. Results ; We found in this study that PINR significantly inhibited apoptotic neuronal death induced by CT105 overexpression in SK-N-SH cells. Based on morphological examinations by phase-contrast microscopy, PINR reversed apoptotic changes of CT105-expressed cells. It was also found that PINR significantly promoted neurite outgrowth and inhibited formation of ROS nd NO. PINR was shown to scavenge DPPH radicals and noncompetitively inhibit AChE activity. Furthermore, it reduced scopolamine-induced memory impairment in rata, assessed by passive avoidance test. Conclusions : Taken together, these results demonstrate that PINR exhibits neuroprotective, antioxidant, and memory enhancing effects, and therefore may bs beneficial for the treatment of AD.

• The Journal of Korean Medicine
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• v.28 no.2 s.70
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• pp.213-223
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• 2007

Objective : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. With an aging populace, AD is a looming problem in public health service. Alzheimer's disease is characterized by specific neuronal degeneration in certain areas of the brain. Mutations and abnormal expression of several genes are associated with ${\beta}-amyloid$ deposits and Alzheimer's disease; among them APP, PS1, and PS2, SOD, free radical, ROS. Methods:We studied herbal medicines that have a relationship to brain degeneration. From pre-modern times, although a variety of oriental prescriptions of Aster tataricus have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. Result : Based on morphological observations by phase-contrast microscope, TUNEL assay and MTT in the culture media, $H_20_2-induced$ cell death was significantly inhibited by Aticus. We examined by ROS formation, catalase activity and GSH activity. We studied the protective effect and inhibitory effects of neurotoxicity in $H_20_2-induced$ PC-12 cells by Aticus. Findings from our experiments show that Aticus inhibits apoptosis, which has neurotoxicities and cell damage in PC-12 cells. In addition, treatment with Aticus ($>25{\mu}g/ml$ for 6hrs) partially prevented $H_20_2-induced$ cytotoxicity in PC-12 cells, and induced a protective effect. Conclusion : As the result of this study, in the Aticus group, the apoptosis in the nervous system was inhibited, protected against the degeneration of PC-12 cells by $H_20_2$. Taken together, Aticus exhibited inhibition of $H_20_2-induced$ apoptotic cell death. Aticus was found to induce protective effect on GSH and catalase in PC-12 cells. Based on these findings, Aticus may be beneficial for the treatment of AD.

• Journal of Nutrition and Health
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• v.49 no.4
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• pp.233-240
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• 2016

Purpose: Diabetic complications are a major concern to manage progression of diabetes. Production of advanced glycation end products (AGEs) due to high blood glucose is one of the mechanisms leading to diabetic complications. Multiple pharmacologic AGE inhibitory agents are currently under development, but clinical applications are still limited due to safety issues. Thus, it is necessary to identify a safe anti-glycation agent. It is known that burdock roots have antioxidant, anti-inflammatory, and anti-cancer activities. The objective of the present study was to investigate the inhibitory role of burdock roots on the formation of high glucose-induced glycation of bovine serum albumin (BSA). Methods: In this study, glycation of BSA by glucose, galactose, or fructose at $37^{\circ}C$ for 3 weeks was assessed based on levels of ${\alpha}$-dicarbonyl compounds (early-stage glycation products), fructosamine (intermediate products of glycation), and fluorescent AGEs (late-stage glycation products). In order to compare the inhibitory actions of burdock root extract in AGE formation, aminoguanidine (AG), a pharmacological AGE inhibitor, was used as a positive control. Results: BSA glycation by glucose, fructose, and galatose was dose- and time-dependently produced. Burdock root extract at a concentration of 4 mg/mL almost completely inhibited glucose-induced BSA glycation. The results demonstrate that burdock root extract inhibited AGE formation with an $IC_{50}$ value of 1.534 mg/mL, and inhibitory activity was found to be more effective than the standard anti-glycation agent aminoguanidine. This study identified a novel function of burdock root as a potential anti-glycation agent. Conclusion: Our findings suggest that burdock root could be beneficial for preventing diabetic complications.

• Herbal Formula Science
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• v.24 no.2
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• pp.80-99
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• 2016

Objectives : Instrumental chemical analysis was utilized to investigate the effect of Add-Omit-Saenghyeoryunbu-eum(AO-SHU) on diabetic treatment. One of the most exciting, yet also controversial, arguments is the safety and biological mechanisms of the natural medicine on human body. Therefore, the aim of this study is to provide a better understanding on bioactive chemical components, hazards of heavy metal contamination and biological mechanism of the diabetic medicine composed of 12 different natural herbs. Methods : To study bioactive compound and metallic component in the diabetic medicine in detail, LC-MS/MS (Liquid Chromatography-Mass/Mass), GC (Gas Chromatography) and ICP (Inductively Coupled Plasma) were utilized to characterize the extract of the diabetic medicine and the result was compared with 18 marker substances selected from literature survey. In addition, in vitro assay experiments including GPR 119 activity and human DGAT-1 inhibition, and OGTT (Oral Glucose Tolerance Test) were performed to verify the effectiveness of this medicine on diabetic treatment. Results : Out of 18 marker substances, 9 bioactive compounds were identified from LC-MS/MS analysis which include Citruline, Catalpol, Berberine, Ginsenoside Rb1, Ginsenoside Rg1, Oleanolic acid, β-Sitosterol, Mangiferin, and Schizandrin. ICP study on 245 residual pesticides revealed that 239 species were not detected but 6 species, Dimethomorph, Trifloxystrobin, Pyraclostrobin, Isoprocarb, Carbaryl and Flubendiamide, while the amounts are trace levels, below permitted concentrations. The biological activity was observed in vitro assay and Oral Glucose Tolerance Test(OGTT), which are consistent with a preliminary clinical test result, a drop in blood sugar level after taking this herbal medicine. Conclusions : Instrumental chemical analysis using LC-MS/MS, GC, and ICP was conducted successfully to identify bioactive compounds in AO-SHU for the treatment of diabetes, finding 9 bioactive compounds. Furthermore, in vitro assay experiments and OGTT show that AO-SHU has its biological activities, which imply that it can be a candidate for the future diabetes remedy.