• Title/Summary/Keyword: Therapeutic mechanism

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Recent Progress in Inorganic Nanoparticles with Enzyme-Mimetic Activities and Their Applications to Diagnosis and Therapy (효소 모사 활성 무기 나노입자의 진단 및 치료 응용연구 동향)

  • Lee, Junsoo;Kim, Taeyeon;Kim, Bong-Geun;Na, Hyon Bin
    • Applied Chemistry for Engineering
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    • v.31 no.4
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    • pp.352-359
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    • 2020
  • Inorganic nanoparticles have been actively applied to the bio-medical field by utilizing their physical properties derived from the nanometer size regime, such as optical and magnetic properties. In recent years, diagnostic detection methods have been developed by employing chemical activity, particularly enzyme-mimetic activities, as well as physical properties of inorganic nanoparticles. After the initial study of verifying the enzyme-mimetic activities, the scope of research has been expanded to the direct use of therapeutic effects with active control of activity through understanding of the catalytic mechanism. This review summarizes recent research works on the active control of the enzyme-mimetic activities and newly demonstrated applications on the diagnosis and treatment of diseases, focusing on inorganic nanoparticles, so-called "nanozyme". It is expected that the enzyme-mimetic activity of inorganic nanoparticles will be combined with their inherent physical properties, leading to the development of new diagnostic and therapeutic methods.

Therapeutic Potential of Jeongjihwan for the Prevention and Treatment of Amnesia (정지환(定志丸)의 기억 및 인지기능 향상에 대한 효능 연구)

  • Jung, Tae-Young;Jeong, Won-Choon;Park, Jong-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.1
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    • pp.37-47
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    • 2011
  • This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.

Inhibitory Effects of Phylligenin on the Proliferation of Cultured Rat Neural Progenitor Cells

  • Lee, Sung-Hoon;Go, Hyo-Sang;Choi, Chang-Soon;Cheong, Jae-Hoon;Han, Sun-Young;Bae, Ki-Hwan;Ko, Kwang-Ho;Park, Seung-Hwa
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.48-55
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    • 2010
  • Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.

The therapeutic effects of WSY-0702 on benign prostatic hyperplasia in RWPE-1

  • Oh, Hyun-A;Kwon, Eun Bi;Hwang, Yun Gyeong;Park, Soon Eung;Mok, Ji Ye;Hwang, Sung Yeoun
    • CELLMED
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    • v.7 no.2
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    • pp.8.1-8.7
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    • 2017
  • Benign prostatic hyperplasia (BPH) is one of the major diseases of the urinary system in older men. WSY-0702 is the extracted from the traditional medicinal plant; Seoritae, and it has effects of anti-obesity, chronic cervical pain, and anti-oxidant. The present study aimed to investigate the therapeutic potential of WSY-0702 in the prevention and treatment of BPH. Several parameters including inflammatory mediators, hormones, and oxidative stress (OS) have been considered to play a role in the development of BPH. Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. An in vitro study showed that proliferation inhibited the human prostate epithelial cell line RWPE-1 in a dose-dependent manner. In cell line, the cell cycle at the G2/M and G0/G1 phase and downregulated the expression of CyclineB1 (CCNB1) and CyclineD1 (CCND1). In addition, we measured the $H_2O_2$-induced OS damage using RWPE-1 cells. We examined the relative expression of protein involved in the regulation of prostate apoptosis: transforming growth factor (TGF)-${\beta}$, a negative growth factor able to induced prostate apoptosis under physiological conditions. These results suggest that WSY-0702 that can inhibit the growth of prostate epithelial cell by a mechanism that may involve arresting the cell cycle and downregulating CCNB1 and CCND1 expression. In addition, WSY-0702 exposure resulted in significant protective effects in $H_2O_2$-stressed PWPE-1 cells by reduction in TGF-${\beta}$ levels.

The Preliminary Study for Therapeutic Mechanism of Gami-Bojungikgitang and Gami-Jwagwieum for Pulmonary Fibrosis (가미보중익기탕과 가미좌귀음의 폐 섬유화 치료 기전에 대한 예비 연구)

  • Lee, Hai-Ja;Shin, Gwon-Sung;Ahn, Jae-Sun
    • The Journal of Pediatrics of Korean Medicine
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    • v.24 no.1
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    • pp.126-133
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    • 2010
  • Objectives In this study, we evaluated the therapeutic effects of Gami-Bojungikgitang and Gami-Jwagwieum for bleomycin-induced lung fibrosis in mice. Methods Extracted lyophilization, Gami-Bojungikgitang (96g) and Gami-Jwagwieum (118g) boiled, filtered, depressed, concentrated, and are obtained. They were divided into five groups: normal, group IA; Animal group treated with bleomycin observed on the 21th day, group IB; Animal group treated with bleomycin observed on the 42th day, group IIA; Animal group treated with bleomycin and Gami-Bojungikgitang. Gami-Jwagwieum observed on the 21th day, group IIB; Animal group treated with bleomycin and Gami-Bojungikgitang/Gami-Jwagwieum observed on the 42th day. Mice are used on the 42th day and as a result, bronchoalveolar lavages fluid is obtained. Counting total number of cells, different ratio of macrophage, lymphocyte, and neutrophil are established. Results In animal group treated with bleomycin and Gami-Bojungikgitang, total cell count decreased by 50% in 3 weeks compared to animal group with non-administrated Gami-Bojungikgitang. However, total cell count in 6 weeks increased compared to 3 weeks although total cell count still decreased compared to animal group with non-administrated Gami-Bojungikgitang. In the view of differential cell counts in bronchoalveolar lavages fluid in treatment group on 3 and 6 weeks, neutrophile was a few and lymphocyte decreased. In animal group treated with bleomycin and Gami-Jwagwieum, total cell count decreased by 50% in 3 and 6 weeks compared to animal group with non-administrated Gami-Jwagwieum. In the view of differential cell counts in bronchoalveolar lavages fluid in treatment group on 3 and 6 weeks, lymphocyte also decreased. Conclusions Gami-Bojungikgitang and especially Gami-Jwagwieum for bleomycin-induced lung fibrosis in mice were effective in total cell count and differential cell count.

Effects of Melatonin on Improvement of Neurological Function in Focal Cerebral Ischemic Rats

  • Lee, Seung-Hoon;Shin, Jin-Hee;Lee, Min-Kyung;Lee, Sang-Kil;Lee, Sang-Rae;Chang, Kyu-Tae;Hong, Yong-Geun
    • Reproductive and Developmental Biology
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    • v.35 no.2
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    • pp.167-174
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    • 2011
  • Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

Recent Findings on the Mechanism of Cisplatin-Induced Renal Cytotoxicity and Therapeutic Potential of Natural Compounds

  • Lee, Dahae;Choi, Sungyoul;Yamabe, Noriko;Kim, Ki Hyun;Kang, Ki Sung
    • Natural Product Sciences
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    • v.26 no.1
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    • pp.28-49
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    • 2020
  • The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.

The Role of Receptor Activator of NF-κ Ligand in Smooth Muscle Cell Proliferation (Smooth muscle cell 증식에 있어 NF-κ ligand의 receptor activator의 역할)

  • Kim, Hyun-Ju
    • Journal of Life Science
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    • v.16 no.6
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    • pp.1066-1070
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    • 2006
  • Smooth muscle cell (SMC) proliferation is important in the pathogenesis of vascular proliferative disorders. Understanding of the molecular mechanism underlying SMC growth after arterial injury would have therapeutic implications. Here we report that receptor activator of $NF-{\kappa}B$ ligand (RANKL), a member of tumor necrosis factor (TNF) family, promotes the proliferation of SMC, leading to decreased expression of p21 and enhancement of SMC growth. ERK and p38 phosphorylation was enhanced after RANKL treatment in SMC. Inhibition of ERK/p38 MAPK activity by PD98059/SB203580 completely abolished RANKL-induced proliferation of SMC, indicating ERK and p38 MAPK are essential for RANKL-induced SMC proliferation. Taken together, our findings demonstrate that RANK-RANKL-ERK/p38 pathway is important for proliferation of SMC and that these molecules may be the new therapeutic targets for the prevention of vascular diseases.

Effects of HT7 Acupuncture on c-Eos Expression in Limbic System of the Brain in Maternally-Separated Rats (신문혈(神門穴) 침자극(鍼刺戟)이 모성분리(母性分離) 흰쥐의 대뇌(大腦) 변연계(邊緣系)의 c-Fos 발현(發顯)에 미치는 영향(影響))

  • Lim, Sabina;Hwang, Se-Hee;Ryu, Yeun-Hee;Lee, Hye-Jung;Park, Hi-Joon
    • Korean Journal of Acupuncture
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    • v.21 no.3
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    • pp.77-88
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    • 2004
  • Acupuncture has been shown to have therapeutic effects on many mental disorders such as depression, anxiety, and substance abuse in human and animal studies. Maternal separation (MS) is a risk factor in the development of mood-related disorders such as depression. This study investigated the effects of acupuncture during MS by evaluating locomotion as behavioral markers of depression and by observing changes in c-Fos expression in the limbic system (hippocampus, amygdala and cingulate cortex) to elucidate the mechanism of the therapeutic effect. The employed acupoint, Shinmun (HT7), has been clinically used to treat mental disorders. MS for 7 days beginning on postnatal day 14 induced a significant decrease in locomotion, while acupuncture treatment at acupoint HT7 resulted in a significant increase in locomotion. c-Fos immunoreactive cells in area dentate gyrus (DG) of the hippocampus were increased in the MS group, but significantly decreased in the acupuncture group. These findings suggest that acupuncture has an effect on the depression-like disorder caused by MS, possibly by modulating c-Fos expression in DC of the hippocampus.

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Preventive effect of fermented black ginseng against cisplatin-induced nephrotoxicity in rats

  • Jung, Kiwon;An, Jun Min;Eom, Dae-Woon;Kang, Ki Sung;Kim, Su-Nam
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.188-194
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    • 2017
  • Background: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. Methods: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) with 0.9% saline on the $4^{th}$ d. Results: The DPPH radical-scavenging activity of FBG ($IC_{50}=384{\mu}g/mL$) was stronger than that of raw ginseng. The improved DPPH radical-scavenging activity was mediated by the generation phenolic compounds. The decreased cell viability by cisplatin was recovered significantly after treatment with FBG in a dose-dependent manner. Then, the protective effect of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The decreased creatinine clearance levels, which are a reliable marker for renal dysfunction in cisplatin-treated rats, were reduced to the normal level after the administration of FBG. Moreover, FBG showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of $NF-{\kappa}B/p65$, COX-2, and caspase-3 activation. Conclusion: These results collectively show that the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating oxidative stress, inflammation, and apoptosis.