• 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.

• Korean Journal of Acupuncture
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• 제23권3호
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• pp.55-71
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• 2006

Objectives : The present study was investigated the effect and pathway of heterotopic electroacupuncture (EA) on pain induced by formalin in rats. Methods : Acupoints in the right forepaws, $HT_7$ and $PC_7$, were stimulated with 3 mA, 2 ms, and 10 Hz before subcutaneously formalin injection (5%, $50{\mu}l$) to the left hind paw. Moreover, it was investigated whether the dorsolateral funiculus (DLF), as known to the descending inhibition, mediates analgesia of the heterotopic EA, and an administration of naltrexone blocks the effect of EA. Results : In the immunohistochemistry of cFos-like protein (cFL), there were inhibitory effects of EA on the increased expression of cFL in the lumbar spinal dorsal horn neurons following formalin injection. Especially, EA inhibited the expression of cFL on the superficial laminae than that on the deep laminae at 1 hr after, but that on the deep laminae than that on the superficial laminae at 2 hr after. Also, EA suppressed the increased expression of nitric oxide (NO) and neuronal nitric oxide synthase (nNOS) in the lumbosacral spinal cord after formalin injection, but not Sham-EA. Suppressed expressions of cFL, NO and nNOS in the spinal cord were eliminated after transection of the ipsilateral DLF at $T_{10}{\sim}T_{11}$ levels. However, pretreatment of naltrexone could not prevent the suppressive expressions of cFL, NO and nNOS at the spinal cord. Conclusions : These results suggest that the analgesia of heterotopic EA may be modulated through the DLF constituting the descending inhibition.

• 대한본초학회지
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• 제38권5호
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• pp.9-19
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• 2023

Objectives : Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density and increased risk of fractures. Bisphosphonates and selective estrogen receptors, which are bone resorption inhibitors that are currently widely used as osteoporosis treatments, show serious side effects when administered for a long time. Research on bone resorption inhibitors that complement the problems of existing treatments is needed. The purpose of this study was to investigate the effect of inhibiting osteoclast differentiation and activity on the tuberous root of Ampelopsis japonica (Thunb.) Makino (AM). Methods : After extracting AM using distilled water and ethanol, the inhibitory effects of the two solvents on osteoclast differentiation were compared using the RANKL-induced in vitro experimental model and the TRAP assay kit. The impact of AM on bone resorption was investigated through the pit formation assay, and its effect on F-actin formation was assessed through fluorescent staining. Additionally, protein and mRNA expression levels of osteoclast differentiation markers (NFATc1, c-Fos, TRAP and ATP6v0d2) and resorption markers (MMP-9, CTK, and CA2) were analyzed via western blot and RT-PCR. Results : AM treatment significantly decreased the number of TRAP-positive cells and pit formation area. Furthermore, AM suppressed both the protein and mRNA expression of NFATc1 and c-Fos, key transcription factors involved in osteoclast differentiation and it downregulated the expression of osteoclast-associated genes such as TRAP, CTK, MMP-9, CA2, and ATP6v0d2. Conclusions : These results suggest that AM can inhibit bone resorption and osteoclast differentiation, indicating its potential for use in the treatment and prevention of osteoporosis.

• Korean Journal of Acupuncture
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• 제36권1호
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• pp.52-62
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• 2019

Objectives : The objective of this study was to investigate the effects of Zingiberis Rhizoma Pharmacopuncture(ZP) at GB30 and ST36 in neuropathic pain induced SD rats by the block of Transient Receptor Potential Vanilloid 1(TRPV1). Methods : Neuropathic pain in rats was induced by tibial and common peroneal nerve transection of right leg. The rat subjects were divided into 6 groups : normal(Nor, n=5), control(Con, n=5), neuropathic pain plus 2 mg/kg ZP injection at GB30 and ST36(ZP-A, n=5), 10 mg/kg ZP(ZP-B, n=5), 20 mg/kg ZP(ZP-C, n=5) and 0.45 mg/kg Tramadol(Tra, n=5). Three days after the surgery, injections were administered once a day for 17 days. Withdrawal response of neuropathic rats' legs were measured by stimulating the paw of Right leg with von frey filament, acetone and radient heat on day 3, 7, 11, 15, 19 after surgery. After all treatments were completed, c-Fos in the midbrain central gray and TRPV1 & TRPA1 of DRG(L5) were analyzed. Results : Groups ZP-B and ZP-C showed a meaningful decrease in the withdrawal response of mechanical allodynia, thermal hyperalgesia and cold allodynia compared to the control group(p<0.05, p<0.01, p<0.001). Groups ZP-B and ZP-C showed a meaningful decrease in the expression of c-fos and TRPV1 protein level compared to the control group(p<0.05, p<0.01, p<0.001). Conclusions : These results suggest that Zingiberis Rhizoma Pharmacopuncture at GB30 and ST36 could decrease mechanical & cold allodynia and thermal hyperalgesia by block the TRPV1 on the model of neuropathic pain.

• 한국미생물·생명공학회지
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• 제48권3호
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• pp.310-315
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• 2020

본 연구는 와송에 유기용매를 활용하여 순차적으로 추출하여 항염증 활성에 대한 가능성을 평가하기 하기 위해 수행되었다. 대식세포에 와송 hexane 추출물을 전처리하고 LPS로 염증을 자극하여 염증과 관련한 세포내 신호전달 경로에 미치는 영향을 확인하고자 하였다. 대식세포에 와송 hexane 추출물은 LPS 자극에 의해 세포 독성이 나타나지 않았고, ROS의 생성을 억제하는 것으로 확인되었다. 또한, IL-1β, IL-2, IL-6, IP-10과 같은 전염증성 사이토카인의 분비를 mRNA 수준에서 확인한 결과 탁월하게 억제하였다. 이러한 전염증성 사이토카인의 생성 억제는 상위 전사인자인 AP-1과 IRF3의 조절을 통해 이루어지므로 이들을 단백질 수준에서 발현량을 확인하였다. 그 결과 c-Jun, c-Fos, IRF-3의 인산화 억제로 핵 내 전사활성이 제한되었을 것으로 생각된다. 이들 결과를 종합해볼 때, 와송 hexane 추출물은 염증 반응을 저해하는 효과가 있는 것으로 나타나 다양한 염증성 질환의 예방 및 개선에 유용하게 활용할 수 있을 것으로 생각된다.

• 동의생리병리학회지
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• 제26권3호
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• pp.330-337
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• 2012

This study was performed to assess the Effect of SCF(Schisandrae Chinensis Fructus) on Keratinocyte Damage by UV irradiation. The effect of SCF were determined in UV irradiated HaCaT. We measured LDH release and NO release from HaCaT to elucidate the effect of SCF. And iNOS, TNF-${\alpha}$, COX-2, Bax, Bcl-2, Bcl-xL, c-jun, c-fos gene expression were determined in HaCat using real time PCR method. The results are as follows. SCF inhibited LDH-release, NO production in UV irradiated HaCaT. SCF increased the gene expression Bax, Bcl-2 and Bcl-xL protein in UV irradiated HaCaT. SCF suppressed the gene expression TNF-${\alpha}$ in UV irradiated HaCaT. SCF suppressed the gene expression iNOS, c-fos, and c-jun in UV irradiated HaCaT. SCF not affected the suppression of the gene expression COX-2 in UV irradiated HaCaT. The study showed SCF inhibited the cell damage in UV irradiated HaCaT.

• 대한한방부인과학회지
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• 제23권2호
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• 생명과학회지
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• 제21권7호
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• pp.985-991
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• 2011

본 연구는 고지방식이로 인한 비만으로 불균형된 지질구성과 산화적 손상이 신경세포형성과 초기발현단백질에 미치는 생물학적 영향을 알아보고, 규칙적인 운동의 효과를 알아보기 위하여 실시하였다. 실험동물은 4주령 SD rat 수컷 30마리를 1주간의 적응기간을 둔 뒤, 15주간 고지방식이를 통해 비만으로 유도하였으며, high fat diet sedentary (HDS, n=15)와 high fat diet and training (HDT, n=15)으로 분류하여 연구하였다. 운동강도는 1~4주는 저강도, 5~8주는 중강도로 주5회 실시하였다. 8주 트레이닝 후 혈청지질, 8-OHdG, MDA, neurotrophic factor, 그리고 IEG를 분석하였다. 그 결과 TC와 TG에서 HDS와 HDT 사이 유의한 차이가 나타났다(p<0.05). 8-OHdG에서 HDT는 트레드밀 트레이닝 후에 HDS보다 낮게 나타났다(p<0.05). 해마에서 c-jun, BDNF 그리고 간에서 MDA의 단백질 발현은 HDT가 트레드밀 트레이닝 후 HDS보다 높게 나타났다(p<0.05). 결론적으로 8주간 트레드밀 훈련은 고지방식이 비만 유도 쥐의 혈청지질 성분의 불균형을 개선시키고, 조직과 혈청의 산화적 손상과 DNA 손상을 완화시켜 주어, 비만으로 인한 합병증 예방에 도움을 줄 수 있을 것으로 사료된다. 또한 NT의 발현을 증가시킴으로써 손상된 뇌기능과 신경세포의 생성 기전 활동에 긍정적 영향을 나타냄으로써 공간적 학습기능의 향상을 가져온 것으로 판단된다.

• BMB Reports
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• 제32권4호
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• pp.379-384
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• 1999

Taxol, a natural product with significant anti-tumor activity, stabilizes microtubules and arrests cells in the G2/M phase of the cell cycle. It has been reported that taxol has additional effects on the cell such as an increase in tyrosine phosphorylation of proteins and activation of mitogen-activated protein (MAP) kinase. This phosphorylated kinase translocates into the nucleus and phosphorylates its substrate c-jun, c-fos, ATF2, and ATF3. The MAP kinase family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. First examination was cytotoxicity and apoptosis-induced concentration with paclitaxel in HeLa cell. A half-maximal inhibition of cell proliferation ($IC_{50}$) occurred at 13 nM paclitaxel. When DNA fragmentation was analyzed by agarose gel electrophoresis, a nucleosomal ladder became evident 24 h after a taxol (50 nM) addition to the cells. In addition, an apoptotic body was detected by electron microscopy. Taxol-treated cells were arrested at the S phase at 10 nM. Treatment of 50 nM taxol activated the extracellular signal-regulated protein kinase (ERK1), and a fraction of the activated MAP kinases entered the nucleus. It was also discovered that nucleus substrates c-jun was phosphorylated and activated in the cell. The activated ERK1 could subsequently translocate into the nucleus and phosphorylate its substrate c-jun as well. This study suggests that taxol-induced apoptosis might be related with signal transduction via MAP kinases.

• Journal of Ginseng Research
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• 제27권3호
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• pp.93-97
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• 2003

Alternative or complementary medicine plays an important role in health care system. Ginseng, being one of the most popular oriental herbs, is believed to contain various steroid hormone activity. Ginseng has been demonstrated pharmacological effect in the cardiovascular, endocrine, central nervous, and immune system. Our objective was to study that total saponin might mediate some of their actions by binding to the steroid hormone receptor, as they share many of the actions of steroid hormone in various physiological system. Using total saponin from Panax Ginseng, we have studied the possibility of total saponin being a potential estrogen receptor, androgen receptor, and retinoic acid receptor ligand. Total saponin activated the transcription of both the estrogen and androgen responsive luciferase reporter plasmids at a concentration of 100$\mu\textrm{g}$/ml in COS cells transiently transfected with the corresponding receptor and hormone responsive receptor plasmids. And total saponin caused a concentration-dependent stimulation of estrogen receptor. Total saponin increased the expression of estrogen responsive c-fos proto-oncogene at the protein level in MCF7 cells at 24 h treatment as examined by Western analysis. The c-fos induction was used as a specific marker of estrogen responsiveness. This activation was inhibited by the specific estrogen receptor antagonist, ICI 182,780. However, total saponin failed to activate the retinoic acid receptor in COS cells transiently transfected with the corresponding receptor and retinoic acid responsive reporter plasmids. These results show that total saponin is capable of activating estrogen and androgen receptors.