• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.253-262
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• 1998

Objectives : Risperidone, an atypical antipsychitics which blocks both dopaminergic and serotonergic receptors, have a good response to the negative symptoms as well as positive symptoms, and improve cognitive dysfunction of schizophrenic patients. Furthermore, it has few extrapyramidal side effects and tardive dyskinesia. Although it had been reported that the atypical antipsychotics have less effect on prolactin(PRL) than the classical antipsychotics, we could experience PRL-associated symptoms such as amenorrhea, galactorrhea and hyperprolactinemia in practice. Therefore, we tried to identify the sex differences of risperidone-induced hyperprolactinemia, to evaluate factors affecting PRL levels, and to know the association between cognitive disorders and PRL. Methods : The baseline levels of PRL and TSH prior to risperidone administration were measured by enzyme immunoassay method for 50 patients(25 ma-les and 25 females) admitted with schizophrenia, schizoaffective disorder or schizophreniform disorder according to the DSM-IV classification, and the measurements of PRL were repeated on the 2nd and the 4th wks of risperidone administration. Concomitantly, the severity of psychotic symptoms using CGI, BPRS and PANSS, and the cognitive dysfunction using PANSS-CF were assessed prior to, on the 2nd and the 4th wks of risperidone administration. The PRL and TSH levels of 54 healthy controls(29 males and 25 females) who had no medical, neurological and psychiatric illnesses were also evaluated. Furthermore, the correlation with the psychiatric diagnosis, education, age, sex, duration of illnesses, risperidone dosage, duration of risperdone administration, TSH concentration, cognitive function, severity of psychotic symptoms were also identified. Results : 1) The baseline PRL levels of female schizophrenics($74.3{\pm}49.6ng/ml$) were significantly(p<0.005) higher than those of males($36.3{\pm}24.6ng/ml$), which were significantly(p<0.0001 respectively) higher than those of controls(females $16.9{\pm}6.1ng/ml$, males $13.3{\pm}4.9ng/ml$). The PRL levels measured on the 2nd wks(females $133.7{\pm}47.8ng/ml$, males $56.9{\pm}23.6ng/ml$) and on the 4th wks(females $146.1{\pm}45.9ng/ml$, males $70.0{\pm}31.5ng/ml$) after risperidone administration were significantly(p<0.0001 respectively) higher in females. The mean dosages of risperidone on the 2nd wks were $3.8{\pm}1.7mg$(2-6mg) for the females and $4.0{\pm}1.6mg$(2-6mg) for the males, and on the 4th wks were $4.5{\pm}2.1mg$(2-8mg) for the females and $5.4{\pm}2.2mg$(2-8mg) for the males. 2) The rise of PRL levels were positively correlated with increased risperidone dosage in males(${\gamma}$=0.307 on the 2nd wks and ${\gamma}$=0.280 on the 4th wks), while they were not correlated with dosages in females. For the females, the PRL levels were negatively correlated(${\gamma}$=-0.320) with decrease of TSH concentration. The baseline PRL levels were not correlated with age, education, duration of illnesses, psychopathology, cognitive disorders in both males and females, while it was negatively correlated with TSH levels only in females(${\gamma}$=-0.320). 3) The cognitive dysfunction was not correlated with PRL levels in males, while PANSS-CF scores were negatively correlated with PRL levels(${\gamma}$=-0.220 on the 2nd wks and ${\gamma}$=-0.366 on the 4th wks) in females. The psychopathology was positively correlated with cognitive dysfunction in both males and females. Therefore, the risperidone-induced cognitive improvement seemed to be correlated with improvement of psychopathology in both males and females, and with increase in PRL levels only in females. Conclusions : The fact that the serum PRL levels of schizophrenics were higher than those of controls, especially in females suggested that it could be related with risperidone dosage in males and with primary pathological process in females. The risperidone-associated cognitive improvement seemed to be related with general improvement of psychopathology as well as the rise of PRL levels especially in females. The facts that the effect of risperidoneinduced hyperprolactinemia and the cognitive function were more in females suggested that somewhat different mechanisms could be exerted on them.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.70-81
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• 2000

DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

• Journal of Ginseng Research
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• v.41 no.4
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• pp.578-588
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• 2017

Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated. Methods: Male Sprague-Dawley rats (4 wk old, 60-70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups. Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular pellet diet and was administered orally for 24 wk. For inducing heat stress, rats in the NC group were maintained at $25^{\circ}C$, whereas rats in the HC, HG100, and HG200 groups were exposed to $32{\pm}1^{\circ}C$ for 2 h daily for 6 mo. At week 25, the testes and serum from each animal were analyzed for various parameters. Results: Significant (p < 0.01) changes in the sperm kinematic values and blood chemistry panels were observed in the HC group. Furthermore, spermatogenesis-related molecules, sex hormone receptors, and selected antioxidant enzyme expression levels were also altered in the HC group compared to those in the NC group. GINST (HS100 and HS200) administration significantly (p < 0.05) restored these changes when compared with the HC group. For most of the parameters tested, the HG200 group exhibited potent effects compared with those exhibited by the HG100 group. Conclusion: GINST may be categorized as an important medicinal herb and a potential therapeutic for the treatment of male subfertility or infertility caused by hyperthermia.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.390-400
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• 2021

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.

• Journal of Life Science
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• v.14 no.2
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• pp.275-279
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• 2004

Gene polymorphisms of cytokines and their receptors are attractive candidates as genetic factors in the pathogenesis of immune-mediated diseases and have been reported to be associated with disease susceptibility to autoimmune, inflammatory and infectious diseases. IL-29 is one of important candidate genes for complex trait of genetic diseases but there is no published survey of single nucleotide polymorphisms (SNPs) in this gene. In this study, for the first time, we have examined the full genomic sequence of IL-29 including the promoter regions to identify SNPs. We examined the frequencies of genotypes and alleles at the SNP site of IL-29 in allergic rhinitis patients and non-allergic rhinitis controls using the direct sequencing method to determine whether this IL-29 SNP is associated with allergic rhinitis in Korean population. We identified one novel SNP (1184C＞A) in the intron 2 and one novel variation site (-1842_-1841dupGA) in the promoter region of human IL-29 gene. The P values of SNP or variation site were not significant between the healthy controls and allergic rhinitis patients. Our results suggest that the 1184C＞A polymorphism and -1842_-1841dupGA variation site in human IL-29 gene were not associated to allergic rhinitis.

• Journal of Ginseng Research
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• v.29 no.1
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• pp.37-43
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• 2005

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

• The Korean Journal of Pharmacology
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• v.17 no.1 s.28
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• pp.17-25
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• 1981

No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.209-213
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• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Salicis Radicis Cortex, A decoction has been mainly used for improvement of ozena and a diuretic effect in oriental medicine, but there was no study on the molecular mechanism of Salicis Radicis Cortex as an immunomodulator. Here we investigated the role of the aqueous extract of Salicis Radicis Cortex in the expression of inflammatory mediators, surface molecule, and related receptors in vitro and in vivo. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Salicis Radicis Cortex increased the production of secretary TNF-alpha and Nitric oxide, and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. Moreover, i.p. injection of water extract of Salicis Radicis Cortex significantly increased the secretion level of IFN-gamma and TNF-alpha, IL-2, IL-4 and IL-5 in serum of mice in vivo. Taken together, these results suggest that Salicis Radicis Cortex may regulate the immune response by secreting Th1 and Th2 types of cytokines in vivo and the possibility of its as natural immunostimulator.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.223-229
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• 2002

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP VII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, $23.75{\pm}1.96$ years in age and $68.77{\pm}10.41\;kg$ in body weight, were divided into two groups with a randomized $2{\times}2$ cross-over study. After one tablet containing 500 mg as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at 떠1 dissolution media. The pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed $AVC_t\;and\;C_{max}$, untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.94){\sim}log(1.09)\;and \;log(1.01){\sim}log(1.15)$\;for\;AVC_t\;and\;C_{max},\;respectively)$, indicating that Glycomin tablet is bioequivalent to Glucophage tablet.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6651-6661
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• 2015

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.