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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal of Pharmacopuncture
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Journal DOI :
KOREAN PHARMACOPUNCTURE INSTITUTE
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Volume & Issues
Volume 18, Issue 4 - Dec 2015
Volume 18, Issue 3 - Sep 2015
Volume 18, Issue 2 - Jun 2015
Volume 18, Issue 1 - Mar 2015
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Computational Optimization of Bioanalytical Parameters for the Evaluation of the Toxicity of the Phytomarker 1,4 Napthoquinone and its Metabolite 1,2,4-trihydroxynapththalene
Gopal, Velmani ; AL Rashid, Mohammad Harun ; Majumder, Sayani ; Maiti, Partha Pratim ; Mandal, Subhash C ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 7~18
DOI : 10.3831/KPI.2015.18.010
Objectives: Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4. Methods: The 3D structure of ligands such as hydrogen peroxide (
), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by
followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of
, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10. Results: Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids. Conclusion: Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.
The Anticancer Role of Capsaicin in Experimentally-induced Lung Carcinogenesis
Anandakumar, Pandi ; Kamaraj, Sattu ; Jagan, Sundaram ; Ramakrishnan, Gopalakrishnan ; Asokkumar, Selvamani ; Naveenkumar, Chandrashekar ; Raghunandhakumar, Subramanian ; Vanitha, Manickam Kalappan ; Devaki, Thiruvengadam ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 19~25
DOI : 10.3831/KPI.2015.18.011
Objectives: Capsaicin (CAP) is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a) pyrene (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks to induce lung cancer at the end of
week. CAP was administrated (10 mg/kg body weight dissolved in olive oil) intraperitoneally. Extracellular matrix components were assayed; Masson`s trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(a)pyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline), elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(a)pyrene along with CAP supplemented animals when compared to benzo(a) pyrene alone supplemented animals. The results of Masson`s trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti-cancer role working against experimentally induced lung carcinogenesis.
Association of a Methanol Extract of Rheum undulatum L. Mediated Cell Death in AGS Cells with an Intrinsic Apoptotic Pathway
Hong, Noo Ri ; Park, Hyun Soo ; Ahn, Tae Seok ; Jung, Myeong Ho ; Kim, Byung Joo ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 26~32
DOI : 10.3831/KPI.2015.18.012
Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at
, 15.94% at
, 26.56% at
and 38.08% at
). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.
The Effects of Sa-am Acupuncture Simpo-jeongkyeok Treatment on the Blood Pressure, Pulse Rate, and Body Temperature
Choi, Woo-Jin ; Cho, Yoon-Young ; Sun, Seung-Ho ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 33~41
DOI : 10.3831/KPI.2015.18.013
Objectives: The present study evaluated the effects of sa-am acupuncture (SAA) simpo-jeongkyeok (SPJK) treatment on the blood pressure (BP), pulse rate (PR), and body temperature (BT) of patients with hwa byung (HB). Methods: This patient assessor blind, randomized, placebo controlled trial included 50 volunteers, divided randomly into two groups. The treatment group underwent SPJK (PC9, LR1, PC3, KI10) while the control (sham) group received minimal needle insertion at non acupoints. The BP in both arms, PR, and BT at several acupoints were measured before and after treatment at the
visits and before treatment at the follow-up visit. We analyzed data by using the repeated measured analysis of variance (RM ANOVA), Mann-Whitney U, and wilcoxon signed rank tests; differences at P < 0.05 were considered significant. Results: No significant differences in the systolic blood pressure (SBP), diastolic blood pressure (DBP) and PR between the treatment and control group were observed at each visit. However, the decrease in the SBP for the treatment group before and after each visit was significantly higher than it was in the control group. The SBP in both arms in the treatment group was decreased between visits 1 and 2, 1 and 3, 1 and 4, and 1 and follow-up. The DBP in both arms and in the right arm between visits 1 and 3 in the treatment group showed decreases. A minimal BT increase for treatment at CV06 and CV12 and a minimal BT decrease for treatment at CV17 and (Ex) Yintang were found. Patients in the treatment group who visited more frequently experienced a greater decrease in the PR, but that effect was not maintained. Conclusion: The results suggest that SAA SPJK treatment has instant positive effects on the BP, PR, and BT in patients with HB, but the effects on the BP and PR are not maintained.
Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmacopuncture in Sprague-Dawley Rats
Sun, Seung-Ho ; Park, Sunju ; Jeong, Jong-Jin ; Lee, Kwang-Ho ; Yu, Jun-Sang ; Seo, Hyung-Sik ; Kwon, Ki-Rok ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 42~50
DOI : 10.3831/KPI.2015.18.014
Objectives: The aims of the study were to test the single- dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.
A Pilot Study on Single-dose Toxicity Testing of Hominis placenta Pharmacopuncture in Sprague-Dawley Rats
Lee, Yoo-Hwan ; Yoon, Hyun-Min ; Jang, Kyung-Jeon ; Kim, Cheol-Hong ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 51~59
DOI : 10.3831/KPI.2015.18.015
Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Hominis placenta pharmacopuncture when used as a single-dose in 6 week old, male and female Sprague-Dawley (SD) rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea), an institution authorized to perform non clinical studies, under the regulations of Good Laboratory Practice (GLP). SD rats were chosen for the pilot study. Doses of Hominis placenta pharmacopuncture extracts, 0.125, 0.25 and 0.5 mL, were administered to the experimental group, and 0.5 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the groups. Also, no significant changes in body weights were observed among the groups, and no significant differences in hematology/biochemistry, necropsy, and histopathology results were noted. Hematologically, some changes in the male rats in two experimental groups were observed, but those changes had no clinical or toxicological meaning because they were not dose dependent. Histopathological tests on the injected parts showed cell infiltration in the male rats in one of the experimental groups; however, that result was due to spontaneous generation and had no toxicological meaning. Therefore, this study showed that Hominis placenta pharmacopuncture had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single-dose tests of the test substance Hominis placenta pharmacopuncture in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, the above findings suggest that treatment with Hominis placenta pharmacopuncture is relatively safe. Further studies on this subject are needed.
Toxicity of Single-dose Intramuscular Injection of Samjeong Pharmacopuncture in Sprague-Dawley Rats
Kwon, Kang ; Kim, Chul-Yun ; Kim, Nam-Kwen ; Sun, Seung-Ho ; Seo, Hyung-Sik ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 60~66
DOI : 10.3831/KPI.2015.18.016
Objectives: This study was carried out in order to find both the single-dose intramuscular injection toxicity and the approximate lethal dose of samjeong pharmacopuncture (SP) in Sprague-Dawley (SD) rats. Methods: The SD rats in this study were divided into four groups, one control group (1.0 mL/animal, normal saline) and three experimental groups (0.25, 0.5, and 1.0 mL/animal, SP). All groups consisted of five male and five female rats. SP was injected as a single-dose intramuscularly at the thigh. After the injection, general symptoms and weight were observed for 14 days. After the observations had ended, hematologic and serum biochemical examinations, necropsy and a local tolerance test at the injection site were performed. The experiments were carried out at the Good Laboratory Practice firm, Biotoxtech Co. (Cheongwon, Chungbuk). Animal experiments were approved by the Ethics Committee (Approval Number: 130379). Results: No deaths occurred in any of the three experimental groups. The injection of SP had no effects on the general symptoms, body weights, results of the hematologic, and serum biochemical examinations, and necropsy findings. In local tolerance tests at the injection sites, mild inflammation was observed in the experimental group, but it did not appear to be a treatment related effect. Conclusion: Under the conditions of this test, the results from the injection of SP suggest that the approximate lethal dose of SP is above 1.0 mL/animal for both male and female SD rats. Therefore, the clinical use of SP is thought to be safe.
Single-dose Toxicity of ShinYangHur Herbal Acupuncture
Cha, Eunhye ; Lee, Jongcheol ; Lee, Seongjin ; Park, Manyong ; Kim, Sungchul ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 67~75
DOI : 10.3831/KPI.2015.18.017
Objectives: This study was carried out to analyze the single-dose toxicity of ShinYangHur (SYH) herbal acupuncture injected into the muscles of Sprague-Dawley (SD) rats. Methods: The SYH herbal acupuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, Korea-Good Manufacturing Practice, K-GMP). After the mixing process with sterile distilled water, the pH was controlled to between 7.0 and 7.5. Then, NaCl was added to make a 0.9% isotonic solution by using sterilized equipment. All experiments were conducted at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). SD rats were chosen for the pilot study. Doses of SYH herbal acupuncture, 0.25, 0.5, and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy was used to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above outcomes suggest that treatment with SYH herbal acupuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.
Single-dose Toxicity of Water-soluble Ginseng Pharmacopuncture Injected Intramuscularly in Rats
Yu, Junsang ; Sun, Seungho ; Lee, Kwangho ; Kwon, Kirok ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 76~85
DOI : 10.3831/KPI.2015.18.018
Objectives: Radix Ginseng has been traditionally used as an adaptogen that acts on the adrenal cortex and stimulates or relaxes the nervous system to restore emotional and physical balance and to improve well-being in cases of degenerative disease and/or old age. Radix Ginseng has been used for a long time, but the safety of ginseng pharmacopuncture needs testing. This study was done to analyze the single-dose toxicity of water- soluble ginseng pharmacopuncture (GP) intramuscular injections in rats. Methods: All experiments were performed at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). Each group contained 10 Sprague-Dawley rats, 5 males and 5 females. GP was prepared in a sterile room at the Korean Pharmacopuncture Institute under regulations of Good Manufacturing Practice (GMP). GP dosages were 0.1, 0.5 and 1.0 mL for the experimental groups; normal saline was administered to the control group. The animals general condition was examined daily for 14 days, and the rats were weighed on the starting day and at 3, 7 and 14 days after administration of the pharmacopuncture. Hematological and biochemistry tests and autopsies were done to test the toxicological effect of GP after 14 days. This study was performed with approval from the Institutional Animal Ethics Committee of Biotextech. Results: No deaths were found in this single-dose toxicity test of intramuscular injections of GP, and no significant changes in the general conditions, body weights, hematological and biochemistry tests, and autopsies were observed. The local injection site showed no changes. Based on these results, the lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results suggest that GP is relatively safe. Further studies, including a repeated toxicity test, are needed to provide more concrete evidence for the safety of GP.
Correction: Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung Cancer of Rats -Condurango Ameliorates BaP-induced Lung Cancer in Rats-
Sikdar, Sourav ; Mukherjee, Avinaba ; Khuda-Bukhsh, Anisur Rahman ;
Journal of Pharmacopuncture, volume 18, issue 2, 2015, Pages 86~87
DOI : 10.3831/KPI.2015.18.019
Objectives: Condurango is widely used in various systems of complementary and alternative medicine (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats in vivo to validate its use as a traditional medicine. Methods: After one month of scheduled BaP feeding (50 mg/kg body-weight), lung cancer developed after four months. BaP-intoxicated rats were then treated with Condurango (0.06 mL) twice daily starting at the end of the four months for an additional one, two and three months, respectively. Effects of Condurango were evaluated by analyzing lung histology, reactive oxygen species (ROS) and antioxidant biomarkers, DNA-fragmentation, RT-PCR (Reverese Transcriptase-Polymerase Chain Reaction), ELISA (Enzyme linked immunosorbent assay) and western blot of several apoptotic signalling markers and comparing the results against those obtained for controls. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer-cell death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusions: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.