• [Archive]
  • Journal of Pharmacopuncture
  • pISSN : 2093-6966
  • eISSN : 2234-6856
  • DB Construction : 59 Issues, 667 Articles
1 Title
Keywords cardiac muscle, epigenetics, histones, protein kinases
Author(s) Yulia A Volkova, Isaac Opoku-Asare, Luc M Oke, Sudhakar Pemminati, Richard M Millis
  Abstract Pharmacopuncture treatments are proposed for cardiovascular disease and heart failure [1]. Heart failure results from complex environment-gene interactions. β-adrenergic receptors and protein kinase A (PKA) interact with histones and related segments of deoxyribonucleic acid (DNA) at promoter regions of genes for messenger ribo nucleic acid (mRNA) transcription. This increases cardiac muscle mass and contractility in normal hearts. In heart failure, activation of β-adrenergic receptors and PKA promote pathological hypertrophy and decreased contractility. Experimental models show that prenatal exposure to hypoxia, cocaine, or nicotine increases susceptibility to heart failure when animals reach adulthood. Hypermethylation of DNA is an epigenetic mechanism associated with downregulation of the protein kinase C (PKC) gene in such models of heart failure. Downregulation of PKC is also produced by the stress-related hormone norepinephrine with upregulation of the hypoxia-inducible differentiation regulator Nix in norepinephrine-induced cardiac fibrosis [2]. Norepinephrine is also the main mediator of sympathetic neural activity. Sympathetic neural overactivity, a significant cofactor in human heart failure, is, therefore, implicated as a cofactor in this epigenetic mechanism for heart failure. Other epigenetic mechanism for cardiac hypertrophy and heart failure involve endothelin- 1 induced downregulation of the cardiac myocyte differentiation factor RE1-silencing transcription signaler (REST) and GATA zinc-finger domain-containing protein-1 (GATAD1) induced inhibition of histone deacetylase (HDAC-2) in cardiac myocytes harvested from autosomal-recessive dilated cardiac myopathy patients with heart failure [3]. In contrast, both the HDAC-2 in cardiac myocytes and the HDAC-1 in cardiac fibroblasts are upregulated in experimental animal models of congestive heart failure [4]. A prominent role for inflammation in heart failure is suggested by tumor necrosis factor (TNF-α), a proinflammatory cytokine, inducing hypermethylation of the sarcoplasmic reticulum calcium ATPase (SERCA-2A) gene in cardiac myocytes, associated with diastolic dysfunction and heart failure. An important role for epigenetic mechanisms in heart failure is also suggested by HDAC-dependent stimulation of the stress-apoptosis intracellular signaling pathway, which induces hypertrophy of both cardiac and vascular smooth muscle [5].
2 Title
Keywords acupuncture, protocol, radial artery’s pressure pulse wave
Author(s) Jae-Young Shin, Boncho Ku, Tae-Hun Kim, Jang Han Bae, Min-Ho Jun, Jun-Hwan Lee, Jaeuk U. Kim
  Abstract Introduction: This study aims to investigate the effects of acupuncture stimulation on the radial artery’s pressure pulse wave, along with various hemodynamic parameters, and to explore the possible underlying mechanism of pulse diagnosis in healthy participants in their twenties. Methods and analysis: This study is a prospective, single- arm, exploratory clinical study. A total of 25 healthy participants, without regard to gender, in their twenties will be recruited by physicians. Written informed consent will be obtained from all participants. The participants will receive acupuncture once at ST36 on both sides. The radial arterial pulse waves will be measured on the left arm of the subjects by using an applicable pulse tonometric device (KIOM-PAS). On the right arm (appearing twice), electrocardiogram (ECG), photoplethysmogram (PPG), respiration and cardiac output (CO) signals, will be measured using a physiological data acquisition system (Biopac module), while the velocity of blood flow, and the diameter and the depth of the blood vessel will be measured using an ultrasonogram machine on the right arm (appearing twice). All measurements will be conducted before, during, and after acupuncture. The primary outcome will be the spectral energy at high frequencies above 10 Hz (SE10-30 Hz) calculated from the KIOM-PAS device signal. Secondary outcomes will be various variables obtained from the KIOM-PAS device, ECG, PPG, impedance cardiography modules, and an ultrasonogram machine.
3 Title
Keywords acupuncture, autoregressive, autonomic modulation, exercise, fast Fourier transform, heart rate variability
Author(s) Vernon Bond Jr, Bryan H Curry, Krishna Kumar, Sudhakar Pemminati, Vasavi R Gorantla, Kishan Kadur, Richard M Millis
  Abstract Objectives: Acupuncture treatments are safe and effective for a wide variety of diseases involving autonomic dysregulation. Heart rate variability (HRV) is a noninvasive method for assessing sympathovagal balance. The low frequency/high frequency (LF/HF) spectral power ratio is an index of sympathovagal influence on heart rate and of cardiovascular health. This study tests the hypothesis that from rest to 30% to 50% of peak oxygen consumption, the nonlinear Conte-Zbilut-Federici (CZF) method of computing the LF/HF ratio is a more reliable index of changes in the HRV than linear methods are. Methods: The subjects of this study were 10 healthy young adults. Electrocardiogram RR intervals were measured during 6-minute periods of rest and aerobic exercise on a cycle ergometer at 30% and 50% of peak oxygen consumption (VO2peak). Results: The frequency domain CZF computations of the LF/HF ratio and the time domain computations of the standard deviation of normal-to-normal intervals (SDNN) decreased sequentially from rest to 30% VO2peak (P < 0.001) to 50% VO2peak (P < 0.05). The SDNN and the CZF computations of the LF/HF ratio were positively correlated (Pearson’s r = 0.75, P < 0.001). fast Fourier transform (FFT), autoregressive (AR) and Lomb periodogram computations of the LF/HF ratio increased only from rest to 50% VO2peak. Conclusion: Computations of the LF/HF ratio by using the nonlinear CZF method appear to be more sensitive to changes in physical activity than computations of the LF/HF ratio by using linear methods. Future studies should determine whether the CZF computation of the LF/HF ratio improves evaluations of pharmacopuncture and other treatment modalities.
4 Title
Keywords cancer, compound K, genotoxic, ginseng, ginsenoside, toxicity
Author(s) Mi-Kyung Jeong, Chong-Kwan Cho, Hwa-Seung Yoo
  Abstract Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.
5 Title
Keywords antibacterial activity, Apis mellifera, bee venom, discdiffusion
Author(s) Hossein Zolfagharian, Mohammad Mohajeri, Mahdi Babaie
  Abstract Objectives: Mellitine, a major component of bee venom (BV, Apis mellifera), is more active against gram positive than gram negative bacteria. Moreover, BV has been reported to have multiple effects, including antibacterial, antivirus, and anti-inflammation effects, in various types of cells. In addition, wasp venom has been reported to have antibacterial properties. The aim of this study was to evaluate the antibacterial activity of BV against selected gram positive and gram negative bacterial strains of medical importance. Methods: This investigation was set up to evaluate the antibacterial activity of BV against six grams positive and gram negative bacteria, including Staphylococcus aureus (S. aureus), Salmonella typhimurium, Escherichia coli (E. coli) O157:H7, Pseudomonas aeruginosa, Burkholderia mallei and Burkholderia pseudomallei. Three concentrations of crude BV and standard antibiotic (gentamicin) disks as positive controls were tested by using the disc diffusion method. Results: BV was found to have a significant antibacterial effect against E. coli, S. aureus, and Salmonella typhyimurium in all three concentrations tested. However, BV had no noticeable effect on other tested bacteria for any of the three doses tested. Conclusion: The results of the current study indicate that BV inhibits the growth and survival of bacterial strains and that BV can be used as a complementary antimicrobial agent against pathogenic bacteria. BV lacked the effective proteins necessary for it to exhibit antibacterial activity for some specific strains while being very effective against other specific strains. Thus, one may conclude, that Apis mellifera venom may have a specific mechanism that allows it to have an antibacterial effect on certain susceptible bacteria, but that mechanism is not well understood.
6 Title
Keywords intravenous injection, pharmacopuncture, Saeng Maek San, toxicity test
Author(s) Hwa-Young Lee, Sungchul Kim, Seung-Hun Cho
  Abstract Objectives: This study used repeated intravenous injections of Saeng Maek San (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the stability of SMS. Methods: Six-week-old male and female SD rats reared by Orient bio Inc were chosen for this pilot study. They were randomly split into four groups: Group 1 (G1), the control group (0.3 mL of normal saline solution/day/ animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal received an intravenous injection of SMS once a day for four weeks. Clinical signs, body weight changes, and food consumption were monitored during the observation period, and urinalysis and hematology were conducted after four weeks of SMS or saline administration. Results: No deaths occurred in any of the four groups during the observation period. Compared to the control group, male and female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria, but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in the clinical signs test. No significant changes due to SMS were observed in the experimental groups regarding body weight changes, food consumption urinalysis, or hematology. Conclusion: During this study, no mortalities were observed in any of the experimental groups and no hemoglobinuria was observed in the low dosage group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4 (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect level (NOAEL) is 0.1 mL/animal/day in male and female SD rats.
7 Title
Keywords agarwood, histamine release, mast cells, scratching behavior
Author(s) Eiji Inoue, Yasuharu Shimizu, Ryo Masui, Tomoe Tsubonoya, Tomomi Hayakawa, Keiichi Sudoh
  Abstract Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3’,5’-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.
8 Title
Keywords bioactive dressing, chronic ulcer, nosocomial infections, phenolic-rich compound herbal medicine, Pseudomonas aeruginosa
Author(s) Mehrab Dashtdar, Mohammad Reza Dashtdar, Babak Dashtdar, Gazala Afreen Khan, Karima Kardi
  Abstract Objectives: The purpose of this study was to obtain a natural antibiotic from Phenol-rich compounds; for the dressing and the treatment of chronic wounds. Methods: The Phenol-rich compound sweet gel was prepared by blending four natural herbal extracts, Acacia catechu (L.F.), Momia (Shilajit), Castanea sativa, and Ephedra sinica stapf, with combination of a sweet gel medium, including honey, maple saps, Phoenix dactylifera L. (date), pomegranate extract and Azadirachta indica gum as a stabilizer. The combinations were screened by using a well-diffusion assay with cloxacillin as a control. Pseudomonas spp. was tested with our novel antimicrobial compound. The zones of inhibition in agar culture were measured for each individual component and for the compound, and the results were compared with those of the control group which had been treated with cloxacillin. Data were expressed as means ± standard deviations. Quantitative analyses were performed using the paired t-test. Results: The antibiotic effect of the Phenol-rich compound sweet gel was statistically shown to be more significant than that of cloxacillin against Pseudomonas aeruginosa (P < 0.05). Conclusion: Our novel approach to fighting the antibiotic resistance of Pseudomonas proved to be successful. The Phenol-rich compound sweet gel was found to be suitable for use as an alternative medicine and bioactive dressing material, for the treatment of patients with various types of wounds, including burns, venous leg ulcers, ulcers of various etiologies, leg ulcers on the feet of diabetic, unhealed graft sampling sites, abscesses, boils, surgical wounds, necrotic process, post-operative and neonatal wound infection, and should be considered as an alternative to the usual methods of cure.
9 Title
Keywords acute toxicity, Pistacia integerrima, sub-acute toxicity, tropical biomedicine
Author(s) Gotmi Sharwan, Parag Jain, Ravindra Pandey, Shiv Shankar Shukla
  Abstract Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/ kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD – 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single- dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.
10 Title
Keywords gefitinib, geonchilgyebok-jeong, hwanggibujeong-dan, Korean herbal medicine, lung cancer, woohwanggeosa-dan
Author(s) Kangwook Lee, Juyoung Ryu, Chang-Gue Son, Jung-Hyo Cho, Hwa-Seung Yoo, Jonghoon Lee, Yoon-sik Kim, Namhun Lee
  Abstract Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa- dan, hwanggibujeong-dan and geonchilgyebok- jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC.