• Title/Summary/Keyword: medicinal reaction

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Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer

  • Kim, Hyunhee;Choi, Pilju;Kim, Taejung;Kim, Youngseok;Song, Bong Geun;Park, Young-Tae;Choi, Seon-Jun;Yoon, Cheol Hee;Lim, Won-Chul;Ko, Hyeonseok;Ham, Jungyeob
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.134-148
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    • 2021
  • Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

Immunostimulatory activity of hydrolyzed and fermented Platycodon grandiflorum extract occurs via the MAPK and NF-κB signaling pathway in RAW 264.7 cells

  • Jae In, Jung;Hyun Sook, Lee;So Mi, Kim;Soyeon, Kim;Jihoon, Lim;Moonjea, Woo;Eun Ji, Kim
    • Nutrition Research and Practice
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    • v.16 no.6
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    • pp.685-699
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    • 2022
  • BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG) has long been known as a medicinal herb effective in various diseases, including bronchitis and asthma, but is still more widely used for food. Fermentation methods are being applied to increase the pharmacological composition of PG extracts and commercialize them with high added value. This study examines the hydrolyzed and fermented PG extract (HFPGE) fermented with Lactobacillus casei in RAW 264.7 cells, and investigates the effect of amplifying the immune and the probable molecular mechanism. MATERIALS/METHODS: HFPGE's total phenolic, flavonoid, saponin, and platycodin D contents were analyzed by colorimetric analysis or high-performance liquid chromatography. Cell viability was measured by the MTT assay. Phagocytic activity was analyzed by a phagocytosis assay kit, nitric oxide (NO) production by a Griess reagent system, and cytokines by enzyme-linked immunosorbent assay kits. The mRNA expressions of inducible nitric oxide synthase (iNOS) and cytokines were analyzed by reverse transcription-polymerase chain reaction, whereas MAPK and nuclear factor (NF)-κB activation were analyzed by Western blots. RESULTS: Compared to PGE, HFPGE was determined to contain 13.76 times and 6.69 times higher contents of crude saponin and platycodin D, respectively. HFPGE promoted cell proliferation and phagocytosis in RAW 264.7 cells and regulated the NO production and iNOS expression. Treatment with HFPGE also resulted in increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand10, granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, and the mRNA expressions of these cytokines. HFPGE also resulted in significantly increasing the phosphorylation of NF-κB p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. CONCLUSIONS: Taken together, our results imply that fermentation and hydrolysis result in the extraction of more active ingredients of PG. Furthermore, we determined that HFPGE exerts immunostimulatory activity via the MAPK and NF-κB signaling pathways.

Synthesis and Biodistribution of Flumazenil Derivative [F-18](3-(2-Fluoro) flumazenil for Imaging Benzodiazepine Receptor (벤조디아제핀 수용체 영상용 양전자 방출 핵종 표지 플루마제닐 유도체 [F-18](3-(2-Fluoro)flumazenil의 합성과 생체 내 분포)

  • Hong, Sung-Hyun;Jeong, Jae-Min;Chang, Young-Soo;Lee, Dong-Soo;Chung, June-Key;Cho, Jung-Hyuck;Lee, Sook-Ja;Kang, Sam-Sik;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.6
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    • pp.527-536
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    • 1999
  • Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F-18]fluoro)flumazenil, a new fluorine-18 ($t_{1/2}$= 110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at $85^{\circ}C$ in the hot ceil for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. Results: The total chemical yield of tosylated flumazenil derivative was ${\sim}40%$. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were $2.5{\pm}0.37,\;2.2{\pm}0.26,\;2.1{\pm}0.11$ and blood activities were $3.7{\pm}0.43,\;3.3{\pm}0.07,\;3.3{\pm}0.09%ID/g$, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.

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Strategic Direction and Road Map of Expanding Prevention of Winter Disease in the Summer (동병하치 확산을 위한 전략적 방향과 이행방안)

  • Song, Ho-Sueb
    • Journal of Acupuncture Research
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    • v.27 no.3
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    • pp.147-157
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    • 2010
  • Objectives : The purpose of this study was to propose appropriate strategic directions and road maps for successful achievement of programs preventing winter disease in the summer. Methods : Details on programs preventing winter disease in the summer such as clear concept, theoretical basis, current status, intervention or available prescriptions and indication/contraindication/caution were prepared through the related journal review, upon which an observational study was devised and done for simulation to find out even a trivial problem and to guarantee the safety beforehand. The experimental group was divided into 5 groups by the size of pill and the way ginger is treated; 1cm pill with ginger group, 3cm pill group without ginger, 3cm pill group dipped into ginger, 3cm pill group applying ginger to acupoints and 3cm pill group with ginger Results 1. program preventing winter disease in the summer was defined as representative winter diseases such as common cold, influenza, chronic asthma, chronic bronchitis, allergic rhinitis, emphysema, chronic gastritis and rheumatoid arthritis, and preventive care in the summer, reinforcing deficient yang qi of five viscera by using exuberant yang qi from summer heat. 2. It was based upon historically established theories which is 'nourishing yang qi in the spring and summer', 'long summer, namely rainy spell in the summer overwhelms the winter, because of earth winning water according to the five phases theory' and 'To replenish yang qi is major principle to treat winter diseases, which can be most appropriately and timely applied to the patient with deficient yang qi of five viscera inherently, especially in the three dog days of the summer, because of exuberant exterior yang qi and deficient interior yang qi in the five viscera'. 3. In the adjacent China and Taiwan, acupoint applying method in the three dog days named 'San Fu Tie' have been stirring a boom throughout the nation, in which Xiaochuan Gao was used as a basic prescription and it mainly was applied at bilateral $BL_{13}$, $_{15}$ and $_{17}$ for about 4 hours. As far as domestic current status, the necessity of adopting the above method prior to Herbal formula was also recognised, because not a few koreans have apprehension for the safety of it including medicinal herbs and are reluctant to take it any more due to negative advertisement of narrow minded doctors' association. 4. Indication of acupoint applying method in the three dog days included most of winter diseases such as common cold, influenza, chronic asthma, chronic bronchitis, allergic rhinitis, emphysema, chronic gastritis. contraindication was pregnant woman and the weak such as infants and the old. More attention was paid to grasp firmly the normal reaction following the treatment for preventing side effect and teasing blister. recommendation was also given to abstain from food inducing phlegm and dampness such as meat, shrimp and crab as well as cold drinks and foods 5. In the simulation observational study based upon the above findings following review the related articles, no blister was shown on the acupoints icluding bilateral $BL_{13}$, $_{15}$ and $_{17}$ in every experimental group during 24hr observation following the acupoint applying treatment with pills made by modified and devised prescription. At 4 hr, the effectiveness of it reached a peak showing redness and mild tenderness and there is little difference between groups 3cm pills groups regardless of the way ginger was treated. abdominal distention and growling was found in all the volunteers during the treatment at CV 8. Strategic directions and road maps : Through successful fulfillment of the program preventing winter disease in the summer, Korean traditional medicine should be integrated into mainstream national health care services. Cultural access was thought to be as important as Scientific EBM approach. First of all, To evoke potential cultural homogeneity from campaigns and press advertisement was needed for promoting public awareness about preventing winter disease in the summer by enhancing immunity via acupoint applying treatment in the three dog days, and then indigenous name as Sambokcheop, protocol, Clinical Research Form for data collection of it should be developed and prepared. Once the first step was taken this summer, through a thorough data collection and scrutinized scientific evaluation, drawbacks should be compensted for and the efficacy and safety should be substantiated.

Antioxidant activity and anti-tumor immunity by Propolis in mice

  • Choi, In-Sook;Itokawa, Yuka;Maenaka, Toshihiro;Yamashita, Takenori;Mitsumoto, Morihide;Tano, Kaoru;Kondo, Hiroyo;Ishida, Torao;Nakamura, Takashi;Saito, Kiyoto;Terai, Kaoru;Monzen, Hajime;Oshima, Masami;Takeuchi, Tetsuo;Mituhana, Yuicti;Bamen, Kenichi;Ahn, Kyoo-Seok;Gu, Yeun-Hwa
    • Advances in Traditional Medicine
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    • v.5 no.2
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    • pp.100-109
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    • 2005
  • In South America, natural products with unknown drug effects are used as folk remedies and for preventive medicine. Among South American natural products, we directed our attention to Propolis, which have been known as medicinal plants, and examined the mechanisms by which these substances affect antioxidant activity, anti-tumor activity and immunoresponse. When the antioxidant activities of Propolis were examined by the DPPH and Rhoudan iron methods, since Propolis contains high levels of flavonoids, it is thought that flavonoids may be responsible for the antioxidant activity in this study. In the examination of immunoenhancement activity, we measured lymphocyte versus polymorphonuclear leukocyte ratios (L/P activity). The number of lymphocytes was significantly increased in groups treated with Proplolis. Specifically, slightly high levels of $IFN-{\gamma}$ were measured in mice bearing the S-180 carcinoma, after administration of Propolis. This strongly suggests that cellular immunity is especially activated by treatment with Propolis, because production of $IFN-{\alpha}$ is limited to the T cells and NK cells stimulated by mitogen and sensitized antigen. $TNF-{\alpha}$ shows a different extent and mechanism of action depending on the target cells. When $TNF-{\alpha}$ was measured in mice bearing the S-180 carcinoma, mice treated with Propolis showed slightly higher $TNF-{\alpha}$ levels as compared to the control group. This suggests that activated macrophages produce $TNF-{\alpha}$ in mice treated with Prapolis, since activated macrophages and lymphocytes are the source of most $TNF-{\alpha}$. When anti-tumor action was examined using two kinds of sarcoma (Ehrlich solid carcinoma and Sarcoma-180 carcinoma), tumor-suppressive ratios after treatment with Propolis was 29.1%. When Sarcoma-180 solid carcinoma was used, tumor-suppressive ratios were 62%. Thus, Propolis showed strong anti-tumor activity against two kinds of solid carcinoma. Taken altogether, this strongly suggests that Propolis enhances original functions of macrophages and NK cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth.

Potent Antimutagenic Activity of Caryophyllene Oxide for Aflatoxin $B_1\;(AFB_1)$ and 2-Amino-3-Methyl-imidazo[4,5-f]Quinoline (IQ) (Aflatoxin $B_1\;(AFB_1)$과 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)에 대한 caryophyllene oxide의 항돌연변이성)

  • Lee, Jung-M.;Lee, Eun-J.;Bahn, Kyeong-N.;Kim, Jeong-O.;Ha, Yeong-L.
    • Applied Biological Chemistry
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    • v.38 no.5
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    • pp.468-472
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    • 1995
  • Substantial amount of caryophyllene oxide (CPO) is present in the essential oils of traditionally-used folk medicinal plants and herbal spices. The CPO, produced via chemical and/or enzymatic reaction of caryophyllene (CP), has largely being used as a flavoring component and exhibited a variety of biological activities. Now, we report the antimutagenic activity of CPO determined by Ames's preincubation test. S-9 fraction was prepared from the liver of rats treated with Arochor 1254. Anatoxin $B_1\;(AFB_1)$ and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were used as mutagens. Reduction of mutagenicity of $AFB_1$ or IQ for S. typhimurium TA98 and TA100 by CPO was found to be a dose-dependant manner. CPO (500 ${\mu}g/plate$) reduced mutagenicity of AEB1 for S. typhimurium TA98 and TA100 to 89% and 71%, respectively. For IQ, similar results were observed against S. typhimurium TA98 and TA100, resulting in the inhibition percentage of 77% and 51%, respectively. CP also reduced mutagenicity of AEB1 and IQ for S. typhimurium TA98 and TA100, but the reduction rate was somewhat lowered relative to that of CPO. These results indicate that CPO could be developed as a potent antimutagenic flavoring agent.

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The Physiological Efficacy of Aloe Gel (Aloe Gel의 생리 효과에 대한 고찰 - Gel의 다당류와 미량 성분을 중심으로 -)

  • 서화중
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.6
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    • pp.1026-1038
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    • 1995
  • Although aloe lost a lot of its previous popularity in modern clinical uses as medicine numerous scientific researches still have claimed the beneficial properties(curing and general tonic effect) of aloe gel. Whereas considerable contradictory reports have helped to confuse the aloe gel issue and continually aroused controversy about aloe gel efficacy. However health food, cosmetic and medicinal products made from aloe gel are widely available in the world market especially in U.S.A. so the growing of Aloe plant and the processing of A. vera gel have become big industries in some countries. In some previous papers the salicylic acid, one of the common trace gel components, was thought to have an analgetic and antinflammatory effect. Large amount of Mg ion in the gel was suggested to act as anesthetic, Mg-lactate as antihistamic, and Aloctin A(a glycoprotein) as wound healer by promoting the cell growth. The carboxypeptidase and bradykinase activity in the gel were proposed to have the pain relieving and antiinflammatory effect. But any of thes etheories concerining the physiological action of the trace gel components has not been demonstrated by modern pharmacology, and failed to be supported by clinical research. It was suggested by some research workers that trace amount of anthraquinone compounds in the gel play an important role to act as false substrate inhibitors for PG and TX production(antiprostanoid effect), by which, they believed, inflammation, burn and frostbite, and infected wound could be healed. This hypothesis has not been substantiated. Butthe suggested antimicrobial action, antidiabetic, and antidotic effect of aloe gel are likely to be attributed to the trace anthraquinone compounds. In a lot of recent experimental reports it has been claimed that aloe gel polysaccharides(acetylglucomannan, acetylmannan, and glycoprotein) have the antimicrobial, antinflammatory, antitumour, and infected wound healing effect by immunoenhancement. It is hoped that these effects will be soon documented in clinical studies, then the controversy on aloe gel beneficial effect will cease. In the 30 days subchronic toxicity test the lowest observed adverse effect level of acemannan(acetylmannan) on dog was 5.0 mg/kg, IP. But the aloe gel is generally agreed to be harmless and non toxic even for the internal use such as health food. In the case of idiosynrasy one must keep the delayed type hypersensitivity reaction of aloe gel in mind. In conclusion it seem to be impossible to simply refuse a lot of evidences made by research workers who have claimed aloe gel's beneficial effects and to deny the fact that there had been long therapeutic histories of Aloe plants.

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A Study of Current Perception Threshold of Trigeminal Nerve after Tooth Implantation (치아임플란트 시술 후 삼차신경에서의 전류인지역치에 대한 연구)

  • Lim, Hyun-Dae;Lee, Jung-Hyun;Lee, You-Mee
    • Journal of Oral Medicine and Pain
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    • v.32 no.2
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    • pp.187-200
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    • 2007
  • This study attempted to contribute to the clinical application of implant operation by making a quantitative nerve examination using a neurometer for the evaluation of sensory disturbances that could be incurred after the implantation in the dental clinics, and it intended to establish an objective guideline in the evaluation of sensory nerve after the operation of implant. An inspection was performed with the frequencies of 2000Hz, 250 Hz and 5 Hz before and after the operations of tooth implant using $Neurometer^{(R)}$ CPT/C (Neurotron, Inc. Baltimore, Maryland, USA) for 44 patients who had performed an implant operation among the patients coming to Daejeon Sun Dental Hospital in 2006 and 30 people for control group. The measuring sites were maxillary nerve ending and mandibular nerve ending of trigeminal nerve according to the implant operating regions. The current perception threshold (CPT) by each nerve fiber was specifically responded under the electric stimulation of 2000 Hz in case of $A{\beta}$ fiber and of 250 Hz in case of $A{\delta}$ fiber and of 5Hz in case of C fiber. The CPT test could be performed to assess the damages of peripheral nerve in the trigeminal nerve area and it stimulated selective nerve fibers by generating the electricity of specific frequency in the peripheral nerve area. The nerve fibers with varied thickness were responsive selectively to the electric stimulation with different frequencies; accordingly, they applied the electric stimulation with different frequencies and the reaction threshold of $A{\beta},\;A{\delta}$ and C fibers selectively responsive to each electric current could be individually evaluated. In the assessment through the CPT, the increase and decrease of the CPT could be measured so that sensory disturbances such as hyperaesthesia or hypoaesthesia could be diagnosed. This study could obtain the following results after the assessment of the CPT before and after the implant operation. 1. In the assessment before and after the implant operation, the CPT in the frequencies of 2000 Hz, 250 Hz, 5 Hz for maxillary branch increased on the whole after the operation and the CPT for mandibular branch in the $A{\beta}$-fiber(2000 Hz) and C-fiber(5 Hz )after the operation increased statistically significantly. 2. For the groups of patients with medically compromised or its subsequent medicinal prescription, there were no significant differences before and after the implant operation and for the control groups, significantly high CPT was shown after the implant operation in the left $A{\beta}$-fiber(2000 Hz) and C-fiber(5 Hz). 3. In the comparison of the measured value of the CPT before the operation between the control group and the implant operation group, the latter group had a significantly high measured value of the CPT in the right $A{\beta}$-fiber(2000 Hz) and C-fiber(5 Hz) and there were significant differences in $A{\beta}$-fiber(2000 Hz) in the CPT assessment after the implant operation for the control group. 4. Male participants had higher CPT than female counterparts; however, there were no statistic significances. In the CPT evaluation before and after implant operation, there were no statistical differences in the male group while the right C-fiber(5 Hz) and left $A{\beta}$-fiber(2000Hz) were significantly high in the female group. 5. In the comparison between the group who complain sensory disturbance and the other group, the CPT increased on the whole in the former group, but there were no statistical significances. In the groups, whom there was an increase in VAS, the CPT after the implant operation in the right C-fiber(5 Hz) increased significantly; meanwhile, in case that the VAS mark was '0' before and after the operation, the CPT after the operation in the left $A{\beta}$-fiber(2000 Hz) increased significantly. This study suggested that the CPT measurements using $Neurometer^{(R)}$ CPT/C, provide useful information of objective and quantitative sensory disturbances for tooth implantation.