Kim, Min-Jung;Yun, Hee;Kim, Dong-Hyun;Kang, Insug;Choe, Wonchae;Kim, Sung-Soo;Ha, Joohun
Journal of Ginseng Research
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제38권1호
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pp.16-21
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2014
Ginseng saponins exert various important pharmacological effects with regard to the control of many diseases, including cancer. In this study, the anticancer effect of ginsenosides on human cancer cells was investigated and compared. Among the tested compounds, ginsenoside-Rh2 displays the highest inhibitory effect on cell viability in HepG2 cells. Ginsenoside-Rh2, a ginseng saponin isolated from the root of Panax ginseng, has been suggested to have potential as an anticancer agent, but the underlying mechanisms remain elusive. In the present study, we have shown that cancer cells have differential sensitivity to ginsenoside-Rh2-induced apoptosis, raising questions regarding the specific mechanisms responsible for the discrepant sensitivity to ginsenoside-Rh2. In this study, we demonstrate that AMP-activated protein kinase (AMPK) is a survival factor under ginsenoside-Rh2 treatment in cancer cells. Cancer cells with acute responsiveness of AMPK display a relative resistance to ginsenoside-Rh2, but cotreatment with AMPK inhibitor resulted in a marked increase of ginsenoside-Rh2-induced apoptosis. We also observed that p38 MAPK (mitogen-activated protein kinase) acts as another survival factor under ginsenoside-Rh2 treatment, but there was no signaling crosstalk between AMPK and p38 MAPK, suggesting that combination with inhibitor of AMPK or p38 MAPK can augment the anticancer potential of ginsenoside Rh2.
The frequency of the hypertension is increasing as the life level is improved and an average span of the life is extended since we approached modern stage. The hypertension is also dangerous disease which raises fatal complication for example with the bleeding aproplexy and the ischemic attack. The medicinal treatment about the hypertension is required patients to take continually. The acupuncture have been introduced because a medicine-chemical treatment hasn't good influence on the human body. It recently has been processed that studies acupuncture effect for blood pressure and have been found out that blood pressure go down. The object of this study observe the effect of LR3 acupuncture on hypertension in Renal Hypertension RAT induced by 2K1C. The 2K1C model was based on renin-angiotensin system. We put the silver clip in renal artery to induce renal hypertension. We try to observe that LR3 acupuncture influence on the blood pressure and c-fos expression in CVLM, NTS, RVLM. In results, the blood pressure was decreased during acupuncture than before acupuncture, after acupuncture. The heart rate was also decreased during acupuncture than before acupuncture, after acupuncture. The LR3 acupuncture significantly effects on blood pressure and heart rate (P<0.05). The increased expression of c-fos was shown in CVLM, NTS, but not in RVLM. In conclusion, LR3 was relived the action of control upon the hypertension and related with medulla, particularly CVLM, NTS. It needs to be closely examined pharmacological mechanism and studied combination with other acupoints.
Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.
Kim, Hee-Jin;Joo, So-Hyun;Choi, In-Ha;Kim, Pitna;Kim, Min-Kyoung;Park, Seung-Hwa;Cheong, Jae-Hoon;Shin, Chan-Young
Journal of Ginseng Research
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제34권1호
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pp.8-16
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2010
Attention deficit hyperactivity disorder (ADHD) affects 4-12% of chool-age children worldwide and is characterized by three core symptoms: hyperactivity, inattention, and impulsivity. Although standard pharmacological treatments, such as methylphenidate and atomoxetine, are available, concerns about drug-induced psychological and cardiovascular problems, as well as growth retardation and sleep disturbances, highlight the continuing need for new therapeutic interventions. Using a neonatal hypoxia-induced hyperactivity model in rats, the potential positive role that oral administration of red ginseng extract may have in relation to the hyperactive phenotype was investigated. Hypoxia was induced in 2-day-old male Sprague-Dawley (SD) rat pups by placing them in a nitrogen chamber for 15 min. The neonatal hypoxia-induced rats showed a significant increase in hyperactivity phenotype, such as increased movement duration, movement distance, and rearing frequency, which was determined by monitoring their spontaneous locomotor activity using the Ethovision video tracking system. One week of oral treatment with red ginseng extract decreased the hyperactivity phenotype of the neonatal hypoxia-induced rats and increased the locomotor activity of the control rats. In the neonatal hypoxia-induced rats, expression of the norepinephrine transporter in the forebrain was increased, and red ginseng treatment partially prevented its up-regulation, while increasing its level in the control rats. Taken together, these results suggest that red ginseng extract decreased the neonatal hypoxia-induced hyperactivity phenotype, although it increased locomotor activity in normal animals.
Korean red ginseng (KRG) has been shown to enhance endothelium-dependent vasorelaxation in experimental animals; however, little is known about its pharmacological effects on vascular stiffness in patients with coronary artery disease (CAD). This randomized, double-blind, placebo-controlled crossover trial was carried out to determine whether KRG has beneficial effects on arterial stiffness, cardiovascular risk factors such as plasma lipid profiles and blood pressure (BP), and Rho-associated kinase (ROCK) activity. Twenty patients (mean age, 62.5 years) with stable angina pectoris were given KRG (2.7 g/day) and a placebo alternatively for 10 weeks. Blood biochemical analysis and pulse wave velocity (PWV) recording were performed on day 0 and after the completion of each treatment. ROCK activity was assessed based on the level of phospho-$Thr^{853}$ in the myosin-binding subunit of myosin light chain phosphatase, determined by Western blot analysis of peripheral blood mononuclear cells. KRG significantly decreased the systolic BP, brachial ankle PWV, and heart femoral PWV in the patients (all p<0.05), but did not significantly alter the serum lipid profiles, including triglycerides and total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. The ROCK activity tended to decrease (p=0.068) following KRG treatment. The placebo did not significantly alter any of the variables. In conclusion, KRG decreased systolic BP and arterial stiffness, probably via the inhibition of ROCK activity, in patients with CAD, but had a neutral effect on serum lipid profiles. Our data suggest that KRG has a therapeutic effect on CAD.
Expression of xenobiotic-metabolizing enzymes can be altered by xenobiotics, which represents changes in the production of reactive metabolic intermediates as well as toxicities in tissues. Metabolic intermediates derived from xenobiotics are considered to produce the reactive oxygen species including drug free radicals and hydroxyl free radicals, which would be ultimately responsible for drug-induced toxicities. The effects of 1,2-benzothiazine anti-inflammatory agents on the expression of xenobiotic-metabolizing enzymes including major cytochrome P450s, microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) were studied in the liver with the aim of providing the part of information on potential production of reactive metabolites and hepatotoxicity by the agents. The synthetic compounds 24, 36 and 39 exhibited anti-inflammatory effects in rats as assessed by the Randall-Selitto method. The anti-inflammatory effect was detected as early as at 30 min after gavaging the agents with the ED5O being noted at 80 mg/kg, which was comparable to that of ibuprofen. Treatment of rats with each compound (100 mg/kg, 3d) resulted in no significant induction in the immunochemically-detectable cytochromes P45O 1A1/2, P450 2B1/2, P45O 2 Cl1 and P45O 2El. Changes in the mEN expression were also minimal, as evidenced by both Western blot and Northern blot analyses. Hepatic GST expression was slightly increased by the agents: GST Ya protein and mRNA expression was ~1.5-fold increased after treatment with compounds 24 and 39, whereas GST Yb1/2 and Yc1/2 mRNA levels were elevated 2- to 3-fold. In summary the effects of the synthetic 1,2-benzothiazines on the expression of major P45O, mEH and G57 were not significant, providing evidence that metabolic activation of the agents, potential drug interaction and hepatotoxicity would be minimal.
Inguinal hernia repair can result in paresthesia and/or pain in the inguinal region. Pharmacological and surgical management often yield inconsistent results associated with considerable risks and side effects. Radiofrequency thermocoagulation (RF) is a neuro-destructive treatment for severe pain, but associated with hypoesthesia, neuritis-like reactions, and occasional neuroma formation. Pulsed radiofrequency (PRF), unlike RF, delivers high intensity currents in pulses, is non-neurodestructive, and therefore less painful, without the potential complications. Here we report on PRF in chronic postoperative inguinal pain. A 23-year-old male who received right inguinal hernia repair and complained of right sided groin pain for approximately 10 years underwent PRF at the L1 and L2 dorsal root ganglia (DRG). He then reported a decrease in pain from 80-90/100 mm to 15-30/100 mm on a visual analogue scale (VAS), which lasted for twelve months.
Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of triacylglycerol, cholesterol, protein, albumin and A/G ratio levels in serum, of histopathological appearances of liver, and that of hepatic microsomal cytochrome P-450 contents. Increased serum triacylglycerol levels by ANIT were significantly decreased with AMWE. However, AMWE posttreatment aggravated ANIT-induced cholesterol increase. Serum total protein and albumin contents, and A/G ratio were decreased in all ANIT-treated groups, and there were increased compared with control by AMWE posttreatment. Hepatic microsomal cytochrome P-450 contents were decreased in either AMWE and ANIT treatment, which greatly increased with AMWE pretreatment. On the other hand, in histological findings, our results shown that ANIT induced increase of lipid droplets and widening of sinusoidal capillary and these phenomena were disappeared with AMWE treatment. In conclusion, AMWE have choleresis effect. Also, AMWE improved lipid metabolism, protection and regeneration of hepatocytes in ANIT-induced cholestasis.
DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.
Kim, Hee-Jin;Oh, Jeng-In;Park, Hee-Dong;Kang, Ju-Seop;Ko, Hyun-Chul;Lee, Chang-Ho
Biomolecules & Therapeutics
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제7권3호
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pp.271-277
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1999
Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.
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