• BMB Reports
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• 제41권11호
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• pp.765-770
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• 2008

Undesirable hyperpigmentation that can arise from increased melanocyte activity may be alleviated by targeting active melanocytes for apoptosis. The role of Stathmin 1 as an important regulator of microtubule dynamics is well documented. The current study examined the potential of Stathmin 1-targeting strategies in eliminating active melanocytes. A vector to overexpress Stathmin 1 and vectors to express three distinct small hairpin RNAs to knockdown Stathmin 1 expression in normal melanocytes were produced and in cell cultures acted accordingly. Both overexpression and knockdown of Stathmin 1 led to a marked increase in melanocyte apoptosis, as indicated by the accumulation of apoptotic cells and increased levels of cleaved caspase-3. Both up- and down-regulation of Stathmin 1 expression inhibited the activity of differentiated melanocytes, as indicated by decreases in both melanin production and tyrosinase activity. Taken together, these results indicate that hyperactive melanocytes can be inhibited by altering Stathmin 1 expression.

• Journal of Ginseng Research
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• 제48권1호
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• pp.59-67
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• 2024

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid β (Aβ) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract. Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aβ_25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting. Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brainderived neurotrophic factor (BDNF) expression levels in Aβ_25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D. Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aβ accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

• 생명과학회지
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• 제19권2호
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• pp.163-168
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• 2009

천초근은 전통적으로 동양의학에서 항암제로 사용되어왔는데 인간 급성 백혈병 세포주인 Jurkat T 세포를 사용하여 천초근의 세포독성기작을 알아보았다. 천초근 뿌리(3 kg)를 메탄올로 추출, 증류한 후 물에 녹여 다시 dichloromethane으로 추출분획 하였다. 세포독성 활성을 보이는 dichloromethane 추출물을 연속적으로 HPLC를 통해 분리하였고 그 활성물질(65 mg)을 CCH1이라 명명하였다. CCH1을 0.5 ${\mu}g$/ml에서 2.0 ${\mu}g$/ml의 농도로 처리하고 세포사멸 과정을 보았다. 즉, mitochondria cytochrome c 방출, casapase-8, -9 및 caspase-3의 활성화, PARP 분해, DNA 단편화 현상들이 일어나는 것을 관찰하였다. 하지만, mitochondria cytochrome c 방출 억제자인 Bcl-xL이 과발현되는 Jurkat T 세포에서는 세포사멸현상이 일어나지 않았다. 이러한 결과는 CCH1이 mitochondria 의존적인 신호전달 과정을 통해서 세포사멸을 유도 한다고 할 수 있다. 그리고 CCH1에 의한 세포독성은 혈액에서 분리한 단핵구 세포보다 Jurkat T 세포에서 보다 강한 활성을 보였다.

• 생명과학회지
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• 제27권8호
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• pp.951-957
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• 2017

후박은 전통적으로 동양의학에서 사용되어왔는데 인간 급성 백혈병 세포주인 Jurkat T 세포를 사용하여 후박의 세포독성 관련 기작을 알아보았다. 후박 뿌리(3 kg)를 메탄올로 추출, 증류한 후 내용물을 물에 녹여 동결 건조 후 사용 하였다. 그 활성물질을 MTWE이라 명명하였다. MTWE을 0, 25, 50, $100{\mu}g/ml$의 농도로 처리하고 세포사멸 과정을 보았다. 즉, mitochondria cytochrome c 방출, caspase-3의 활성화 및 ICAD 분해를 관찰하였다. 더욱이, mitochondria cytochrome c 방출 억제자인 Bcl-xL이 발현이 감소되는 것을 Jurkat T 세포에서는 확인하였다. 이러한 결과는 MTWE가 mitochondria 신호전달 과정을 통해서 세포사멸을 유도 한다고 할 수 있다. 또한, MTWE를 0, 25, 50, $100{\mu}g/ml$ 처리에 대한 암세포 성장억제인자인 DUSP6가 증가되는 것을 확인하였고 핵의 apoptotic morphology 변화를 DAPI를 통해 관찰할 수 있었다. 비록 DUSP6와 다른 관련인자들간의 관련성을 찾아야 하지만, 이상의 결과는 MTWE가 T세포에 의한 급성 백혈병을 조절하는데 이용 될 수 있다는 것의 의미한다.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.561-571
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• 2002

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

• 한국약용작물학회지
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• 제26권2호
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• pp.141-147
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• 2018

Background: Astilbe chinensis (Maxim.) Franch. Et Savat. is a plant belonging to Saxifragaceae family and contains various active ingredients including astilbin and bergenin. It has been used as a traditional Korean medicine to improve fever, pain, and cough. Recently, a number of Korean medical resources have been studied for cancer and inflammation treatment, but A. chinensis (Maxim.) Franch. Et Savat. has not yet been investigated. Consequently, this study investigated the inhibitory effect of ethanol extracts from A. chinensis (Maxim.) Franch. Et Savat. (ARE) on oxidative stress and colorectal cancer using RAW264.7 and the human colorectal cancer cell line HCT-116. Methods and Results: In total, $500{\mu}g/m{\ell}$ ARE reduced cell viability by $38.96{\pm}1.32%$, and increased caspase-3 activity by $133.08{\pm}3.41%$ in HCT-116 cells. Moreover, TUNEL signaling and the early apoptosis ratio ($34.56{\pm}1.67%$) increased by $500{\mu}g/m{\ell}$ ARE treatment. $H_2O_2$-induced oxidative stress and cell death were diminished by $500{\mu}g/m{\ell}$ ARE treatment through decreasing ROS (reactive oxygen species). Conclusions: The inhibitory effects of ARE against human colorectal cancer cells is mediated by apoptosis and caspase-3 activation, and $H_2O_2$-induced ROS generation and cell death are decreased by ARE treatment in RAW264.7 cells. However, further study is required to explore how ARE treatment is involved in the signaling pathway to decrease ROS.

• 생명과학회지
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• 제23권10호
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• pp.1223-1229
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• 2013

우르솔산(Ursolic acid)은 다양한 약재, 과일 그리고 야채 등으로 부터 분리되는 식물성 생리활성물질로서, 천연 항산화제로 널리 알려져 있지만, 배아줄기세포에서 우르솔산의 기능에 대한 연구는 아직까지 잘 이해되지 않고 있다. 본 연구에서는 저산소 상태에서 우르솔산이 배아줄기세포의 성장에 미치는 효과에 대해 조사하였다. 48시간 동안의 저산소 환경은 배아줄기세포의 미분화상태 및 전능성을 유지에 있어서 영향을 미치지 않았지만, 세포 내 활성산소종의 지속적인 생산과 이로 인한 lactate dehydrogenase 활성을 촉진 시켰다. 저산소에 의해 유도된 배아줄기세포의 산화적 스트레스는 $30{\mu}M$의 우르솔산의 처리로 인해 유의적으로 감소되었으며, 이러한 우르솔산의 활성산소 소거능력은 항산화제인 N-acetyl-cysteine (NAC)의 효과와 유사하였다. 저산소 환경은 또한 유의적으로 배아줄기세포의 생존과 증식을 감소 시킬 뿐만 아니라, 세포의 자살 및 노화를 유도함이 관찰되었지만, 강한 항산화 능력을 지닌 우르솔산은 세포를 저산소로부터 보호하여 정상수준으로 세포의 생존과 증식을 유지시키고, 세포 자살 관련 단백질(cleaved caspase-3, Bcl-2, 그리고 cIAP) 및 세포 노화 관련 단백질(beta-galactosidase)을 조절하는 탁월한 약리학적 효과를 가지고 있었다. 따라서 본 연구결과를 통해, 우르솔산은 강력한 천연 항산화제이며, 저산소에 의해 유도된 유해 기작을 제어함으로서, 배아줄기세포의 전능성을 유지시킬 수 있는 기능성 물질이라는 것을 알 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.125-130
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• 2016

Nepeta cataria L. has been used in traditional medicine of some countries. Here the cytotoxic and apoptogenic activity of methanol extracts, n-hexane, dichloromethane, ethyl acetate, n-butanol, and acqueous extracts and the essential oil obtained from the aerial parts of the plant were evaluated with PC3, DU-145 and MCF-7 cell lines. Cell viability, histograms of PI stained fragmented DNA in apoptotic cells and Western blot analysis of proteins involved in the cascade of apoptosis were compared in all samples. Thirty components were identified as volatile, representing 99.7% of essential oil composition after GC-MS analysis of the oil obtained from aerial parts of the N. cataria by hydro-distillation. The major oil components of the essential oil were nepetalactone stereoisomers. Comparing IC50 values showed estrogen receptor positive PC3 cells were more sensitive to the cytotoxic effects of N. cataria in comparison with low hormone-receptor presenting DU-145 cells. Among multiple extracts and essential oils of the plant, only the ethyl acetate extract could significantly decrease cell viability in PC3 cells, in a concentration dependent manner. Ethyl acetate extract of N. cataria treated cells showed a sub-G1 peak in PC3 cells in a concentration dependent manner that indicates the involvement of an apoptotic process in ethyl acetate extract-induced cell death. Western blotting analysis showed that in PC3 cells treated with ethyl acetate (48 h) caspase 3 and PARP were cleaved to active forms. Overall, the results suggest that further analytical elucidation of N. cataria in respect to finding new cytotoxic chemicals with anti-tumor activity is warranted.

• Journal of Ginseng Research
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• 제34권3호
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• pp.246-253
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• 2010

Ginsenoside $Rg_3$ ($Rg_3$), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents in vitro and antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. In the present study, we examined the neuroprotective effects of $Rg_3$ on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that $Rg_3$ treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cortical neurons, with an $IC_{50}$ value of $28.7{\pm}7.5\;{\mu}m$. Furthermore, the $Rg_3$ treatment not only significantly reduced DNA damage, but also dose-dependently attenuated 24-OH-chol-induced caspase-3 activity. To study the mechanisms underlying the in vitro neuroprotective effects of $Rg_3$ against 25-OH-chol-induced cytotoxicity, we also examined the effect of $Rg_3$ on intracellular $Ca^{2+}$ elevations in cultured neurons and found that $Rg_3$ treatment dose-dependently inhibited increases in intracellular $Ca^{2+}$, with an $IC_{50}$ value of $40.37{\pm}12.88\;{\mu}m$. Additionally, $Rg_3$ treatment dose-dependently inhibited apoptosis with an $IC_{50}$ of $47.3{\pm}14.2\;{\mu}m$. Finally, after confirming the protective effect of $Rg_3$ using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that $Rg_3$ is an active component in ginseng-mediated neuroprotection. These results collectively indicate that $Rg_3$-induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated $Ca^{2+}$ channel. This is the first report to employ cortical neurons to study the neuroprotective effects of $Rg_3$ against 24-OH-chol. In conclusion, $Rg_3$ was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes $Rg_3$ a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.

• 동의생리병리학회지
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• 제22권6호
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• pp.1566-1571
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• 2008

Bone is a dynamic tissue that is constantly resorbed by osteoclasts and then replaced by osteoblasts. Osteoclasts, multinucleated cells of monocyte/macrophage lineage, are responsible for bone disorders, including osteoporosis and rheumatoid arthritis. In this study, we examined the effect of the curcumin on osteoclast survival and bone resorption. We found that curcumin significantly inhibited RANKL-mediated osteoclast survival. DAPI stainingrevealed that curcumin induced the apoptotic features of osteoclasts. Although curcumin did not suppress the phosphorylation of Akt and ERK in osteoclasts treated with RANKL, curcumin induced the cleavage of pro-caspase-9 and -3 its active forms. Also, curcumin inhibited the formation of actin rings of osteoclasts. RANKL-mediated bone resorption was inhibited by the addition of curcumin. Together with the results of this study, these findings suggest that the curcumin inhibited the survival of osteoclasts by activating caspase-9 and -3 and suppressed the bone resorptive activity. Thus, curcumin may be developed as antiresorptive drugs for the treatment of bone-related disorders.