• Korean Journal of Oriental Medicine
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• v.17 no.2
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• pp.47-56
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• 2011

Objective : This study reviews the articles about 'Side effect' published in the Japanese Journal of Oriental Medicine to better understand about side effects of herbal medication and to encourage clinicians, the authorities and the public to establish side effects reporting system. Method : We searched articles published in the Japanese Journal of Oriental Medicine by using keyword '副作用(Side effect)' in the CiNii. Results : Among the 118 articles collected, 14 are clinical articles about side effect of prescriptions, 13 are reports about side effect of prescriptions presented from Japanese Ministry of Health, Labour and Welfare, 36 are clinical articles about relief of side effects derived from taking western medicine by taking a herbal prescription, 8 are studies about the effect of a herbal prescription combined with western medicine or comparative studies between a herbal prescription and western medicine, and so on. Conclusions : Lots of articles deal with side effects of Aconiti Lateralis Radix Preparata, Bupleuri Radix and so on. When side effects occurred, removing a certain herbal drug or quitting a herbal prescription is helpful to relieve or disappear the side effects. And Side effects reporting system should be established to guide safe medication use and treatment for patients. In order to establish side effects reporting system, the standardization of herbal drugs is needed.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.159-174
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• 2007

Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one's biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides $(Rb_1$ Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

• Journal of Chest Surgery
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• v.19 no.1
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• pp.1-11
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• 1986

Using an experimental model of pulmonary hypertension, the effects of anticonstrictive drugs on the development of pulmonary vascular remodeling and right ventricular hypertrophy were studied. Male Sprague-Dawley rats weighing 200~250 gm were used. For the experimental model of pulmonary hypertension, a group of animal was given by a subcutaneous injection of monocrotaline on a dose of 20mg, 40mg, or 60mg per kg of body weight. After 4 weeks of injection, all animals were sacrificed. Another group of animal was given by a subcutaneous injection of monocrotaline in a dose of 40 mg per kg of body weight. The animals were sacrificed, in which they were kept alive for 1, 2, 3 and 4 weeks, respectively. For the effects of anticonstrictive drugs on the development of pulmonary vascular remodeling and right ventricular hypertrophy, the animals treated with monocrotaline were given daily by an intraperitoneal injection of phenoxybenzamine in a dose of 1.3mg/kg of body weight, and were given propranolol via their drinking water at a concentration of 400mg/liter. The animals were sacrificed after 4 weeks of administration. The hearts and lungs were examined histopathologically and morphometrically. The results obtained were summarized as follows: 1. The rats treated with monocrotaline showed an interstitial pneumonitis, medial thickening of the pulmonary small arteries and hypertrophy of the right ventricular wall. 2. The medial thickening of the pulmonary arteries in rats treated with monocrotaline was due to muscular hypertrophy and hyperplasia, and the right ventricular hypertrophy was due to hypertrophy of cardiac muscles. Both medial thickening of the pulmonary arteries and hypertrophy of right ventricular wall were more marked with time and with dose. 3. The daily intraperitoneal injection of phenoxybenzamine suppressed significantly the percentage medial thickness of pulmonary small arteries and the index of right ventricular hypertrophy in rats given a single subcutaneous injection of monocrotaline, but propranolol has shown no protective effect on the development of medial thickening of pulmonary arteries and right ventricular hypertrophy in treated with monocrotaline. The results described above suggested that monocrotaline is an alkaloid selectively inducing pulmonary hypertension and that a-adrenergic receptor is responsible for the pathogenesis of monocrotaline induced pulmonary hypertension in rat.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.99-108
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• 1991

The effect of racemic Ketamine HCl was observed on excitable membranes of sciatic nerve fibres and toe muscles from frog. Ketamine significantly depressed the amplitude of the action potential, maximum rate of rise and that of fall of action potentials of sciatic nerve by dose-dependent and time-course manner, and also it produced the inhibition of $K^+-contracture$ in toe muscle. We used two different ways of sucrose gap method to to obtain the better results from sciatic nerve. We observed and compared the effect of ketamine on sciatic nerve with naloxone, 4-AP (4-aminopyridine) and TEA (Tetraethylammonium). Naloxone significantly but not totally blocked the effect of ketamine both on nerve and on skeletal muscle. 4-AP or TEA by itself had a significant depressant effect on the action potentials on nerve by central perfusion (extracellular perfusion), but both of these drugs did not much affect the action of Ketamine on nerve. The reversibility of effect of Ketamine (10 mM) was observed both on nerve and on skeletal muscles when exposed to drug for short duration. The effects of racemic ketamine described may provide to support that one of the mechanisms of the action of Ketamine on nerve and on muscles of frog might be related to non-specifically effect on receptors within the ion channels $(K^+-channel,\;Na^+-channel\;or\;slow\;Ca^{++}\;channel)$ at higher dose which produces anesthetic effect and also it interacts specifically with one of the opioid receptors or subtype of these receptors which is sensitive to Naloxone at lower dose which produces analgesia.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.902-916
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• 2017

Objectives: The aim of this study was to review the clinical research on antihypertensive effects of Korean herbal medicines that function by inducing diuresis. Methods: Literature searches were performed using PubMed, Cochrane, CNKI, Wanfang, Cinii, Oasis, KISS, NDSL, RISS, DBPia, with the keywords "利水", "利尿", "高血壓", "hypertension", and "lishui." The search range included only randomized controlled trials that verified the effects of Korean herbal medicine interventions on hypertension. The selected studies were assessed by risk of bias (RoB). Results: 26 reports were selected from a total of 532 identified. For these reports, meta-analysis was performed using Revman 5.3. From this analysis, it was observed that the combined treatment of Korean medicine and antihypertensive drugs had a significantly higher total effective rate (TER) and improvement in systolic blood pressure (SBP) and diastolic blood pressure (DBP) than did the use of a single antihypertensive drug. The risk ratio of TER for lowering blood pressure was 1.25. The mean differences of SBP, DBP were -19.63 mm Hg (95% confidential interval (CI), -22.45 mm Hg, -16.80 mm Hg, p<0.00001), and -5.39 mm Hg (95% CI, -7.36 mm Hg, -3.42 mm Hg, p<0.00001) respectively. The use of Korean medicine only did not improve blood pressure, as compared to the use of an antihypertensive drug. Most of items of RoB were unclear, and the methodological quality was low. Conclusions: The combination of antihypertensive drugs and Korean medical treatment can effectively improve SBP, DBP, and TER. This finding could be widely utilized in clinical practice in Korean medicine.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1317-1323
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• 2005

In an attempt to examine the ability of benzisothiazole-based drugs to interact with $\beta$-adrenoceptors, a series of 1,2-benzisothiazole derivatives, which were substituted with various propanolamine or oxypropanolamine side chains in the 2 or 3 position, were synthesised and tested. The pharmacological activity of these compounds at the ,$\beta$-adrenoceptors was examined using isolated rat atria and small intestinal segments, which preferentially express the $\beta_{1}$- and $\beta_{3}$-adrenoceptor-mediated responses, respectively. None of these products showed any $\beta$-adrenoceptor agonistic activity. In contrast, the 2- and 3-substituted isopropyl, tert-butyl, benzyl, and piperonyl derivatives 2a-d and 3a-d elicited surmountable inhibition of the isoprena­line-induced chronotropic effects in the atria, suggesting competitive antagonism at the $\beta_{1}$­recognition site. The $pA_{2}$ values revealed tert-butyl 3b and the isopropyl substituted piperonyl derivatives 3a to be the most effective. Remarkably, many of the 2-substituted propanolamines were less active than the corresponding 3-substituted oxypropanolamines. With the exception of compound 3b, none of these drugs antagonised the muscle relaxant activity of isoprenaline in the intestine, suggesting no effect on the $\beta_{3}$-adrenoceptors. These results confirm the ability of the benzisothiazole ring to interact with the $\beta$-adrenoceptors, and demonstrate that 2-substitution with propanolamine or 3-substitution with oxypropanolamine groups yields compounds with preferential antagonistic activity at the cardiac $\beta_{1}$adrenoceptors. The degree of antagonism depends strongly on both the nature of the substituent and its position on the benzisothiazole ring.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.8-29
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• 2013

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.370-378
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• 2018

Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.2
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• pp.105-108
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• 2011

Aconitine is an anti-inflammatory agent with therapeutic uses in oriental medicine as an analgesic and for treatment of stroke. Because of its sodium channel effect, aconitine can promote undesirable, wide complex tachyarrhythmia. If tachycardia develops during use of aconitine, class Ia and class III anti arrhythmic drugs can be utilized for treatment. However there are no single anti-arrhythmia agents which are uniformly effective. We report a case, characterized by wide complex tachyarrhythmia and severe hypotension, which was successfully treated by simultaneous injections of amiodarone and lidocaine. A 59-year-old woman exhibiting clinical signs of drowsiness as a result of ingesting 6 g of aconitine, was admitted to the emergency department. Initially, wide complex tachyarrhythmia (ventricular tachycardia and pulse rate of 180 beats/min) and severe hypotension (blood pressure of 53/26 mmHg) was observed. After simultaneous injection of amiodarone and lidocaine, the patient's rhythm pattern changed to an accelerated junctional rhythm with ventricular premature complex. Two hours later, the patient's heart pattern became a sinus rhythm. As demonstrated by this case, simultaneous injections of amiodarone and lidocaine can be useful in treating ventricular arrhythmia induced by aconitine.

• Molecules and Cells
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• v.46 no.7
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.