• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.692-699
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• 2023

The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.

• Journal of Environmental Science International
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• v.32 no.10
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• pp.723-729
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• 2023

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neuronal loss in the substantia nigra, resulting in reduced dopamine levels and consequent motor dysfunction. Genetic and environmental factors contribute to oxidative stress in PD. Cicadidae Periostracum (CP), a traditional Korean medicine, has shown neuroprotective effects against MPTP-induced neurotoxicity in PD. However, its effects on the 6-hydroxydopamine (6-OHDA) model have not been established. This study examined CP's effects on a 6-OHDA-induced PD model. CP protected against 6-OHDA damage in both in vitro and in vivo studies. Furthermore, CP reduced the production of reactive oxygen species, inhibited apoptosis, preserved dopamine levels, protected tyrosine hydroxylase in the substantia nigra, and improved motor function. These findings suggest that CP may delay PD progression by maintaining the redox balance.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.671-676
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• 1998

In the present study, we first examined whether the changes in the DNA binding activities of the transcription factors, cAMP response element binding protein (CREB) and activator protein-1 (AP-1) mediate the long-term effects of morphine in differentiated SH-SY5Y human neuroblastoma cells. The increases in CREB and AP-1 DNA binding activities were time-dependent up to 6 days of morphine treatment (1, 4, and 6 days). However, the significant reduction in the DNA binding activities of CREB and AP-1 was observed after 10 days of chronic morphine $(10\;{\mu}M)$ administration. Secondly, we examined whether the changes of CREB and AP-1 DNA binding activities could be modulated by dopamine and haloperidol. Dopamine cotreatment moderately increased the levels of the CREB and AP-1 DNA binding activities induced by 10 days of chronic morphine treatment, and haloperidol cotreatment also resulted in a moderate increase of the CREB and AP-1 DNA binding activities. However, dopamine or haloperidol only treatment showed a significant increase or decrease of the CREB and AP-1 DNA binding activities, respectively. In the case of acute morphine treatment, the CREB and AP-1 DNA binding activities were shown to decrease in a time-dependent manner (30, 60, 90, and 120 min). Taken these together, in differentiated SH-SY5Y cells, morphine tolerance seems to involve simultaneous changes of the CREB and AP-1 DNA binding activities. Our data also suggest the possible involvement of haloperidol in prevention or reversal of morphine tolerance at the transcriptional level.

• Herbal Formula Science
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• v.22 no.1
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• pp.105-112
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• 2014

Background and objective: Methamphetamine (Meth) is a widely abused psychostimulant that produces hyperlocomotion in rodents. Radix of Glycyrrhizae uralensis comprises a variety of bioactive components that have neuroprotective effects. In a previous study, we have demonstrated methanol extracts from radix of Glycyrrhizae uralensis (MEGR) suppress acute cocaine-induced extracellular dopamine release in the nucleus accumbens. In the present study, we investigated the effect of MEGR on acute Meth-induced hyperlocomotion. Methods: Male Sprague-Dawley rats were orally administered with MEGR (60 mg/kg and 180 mg/kg) 60 min prior to an intraperitoneal injection of Meth (1.0 mg/kg). Results: Behavioral analysis showed acute Meth greatly increased locomotor activities, while pretreatment with MEGR dose dependently inhibited the hyperlocomotion. In parallel, there were markedly increased levels of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid in the nucleus accumbens tissues in Meth-treated rats, which were also almost completely reversed by 180 mg/kg MEGR. Conclusions: These results showed that radix of Glycyrrhizae uralensis attenuates Meth-induced hyperlocomotion by inhibiting dopamine synthesis and utilization, suggesting that radix of Glycyrrhizae uralensis might be effective in blocking the rewarding effect of Meth.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.287-291
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• 1999

Dopamine agonists are commonly used in the medical treatment of prolactinomas. Bromocriptine has been the most widely used ergot derivative for two decades. Its oral administration, at a daily dose of $2.5{\sim}7.5mg$, restored normal gonadal function and normoprolactinemia in about 80% of patients. Nevertheless, a subset of patients could not achieve normal prolactin levels or resume normal gonadal function despite $15{\sim}30mg$/day bromocriptine for at least 6 months. Subsequently, these prolactinomas were consedered to be resistant to bromocriptine. The percentage of bromocriptine - resistant prolactinoma patients reported in the literature varies between 5 and 17% according to the series. Patients with bromocriptine resistance or bromocriptine intolerance have, however, been treated with other dopamine agonists, such as lysuride, pergolide, cabergoline, or quinagolide. Until cabergoline recently gained a product licence in the UK, there was no alternative dopamine agonist with a licence for this purpose. Quinagolide (CV $205{\sim}502$, Norprolac, Sandoz) is a nonergot dopamine agonist with improved selectivity for the D2 receptor, designed to retain the active pharmacophore of bromocriptine without the ergot moiety that might be responsible for side - effects. We have experienced a case of bromocriptine resistant hyperprolactinemia which was reponsive to pergolide. So we report this case with a brief review of literatures.

• Journal of Ginseng Research
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• v.15 no.3
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• pp.179-182
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• 1991

The relationship between the brain monoamines and morphine tolerance was examined in ginseng total saponins treated mice. Ginseng total saponins (100 mg/kg, i.p.) did not antagonize morphine (10 mg/kg, s.c.) analgesia in mice. Daily treatment with ginseng total saponins (100 mg/kg) did not affect the brain levels of noradrenaline, dopamine and serotonin for 5 days but inhibited the development of morphine tolerance. This inhibition of the development of morphine tolerance was not attributed to the reductions of brain noradrenaline, dopamine and serotonin in mice treated with ginseng total saponins (100 mg/kg) daily. This result suggest that a newly equilibrated state of neurologic function may involve an underlying mechanism in mice treated with ginseng total saponins.

• Korean Journal of Pharmacognosy
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• v.42 no.1
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• pp.32-37
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• 2011

The effects of herbal ethanol extract from Gynostemma pentaphyllum (GP extract) on chronic stress-induced anxiety in mice were investigated. The animals were treated with GP extracts (50 and 100 mg/kg/day, p.o.) for 21 days before exposure to electric footshock (EF; duration and interval 10 sec for 3 min, 2 mA) for chronic stress once a day. The ambulatory locomotor activity was reduced by chronic EF stress and it was recovered by 12.9-15.1% in GP extract-treated groups. The grip strength was also significantly decreased by chronic EF stress, however, the EF-stressed groups treated with GP extract increased grip strength from 13.9% to 56.8% compared to EF-stressed groups. In addition, the serum levels of corticosterone were significantly elevated by chronic EF stress to 197% of the control levels, which was reduced to 73.1% by treatment with GP extract (100 mg/kg). In contrast, the brain levels of dopamine and serotonin were reduced to 67.6% and 63.1% by chronic EF stress, which was recovered to 90% of the control levels by treatment with GP extract. These results indicate that GP extract shows the ameliorating effects on chronic EF stress-induced anxiety in mice and it can be developed as the promising anti-anxiety agent.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.95-101
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• 1997

The recent hypothesis about the pathophysiology of schizophrenia has been centered mainly on two theories, i.e. dopamine hypothesis and serotonin hypothesis. We investigate the correlations between plasma monoamine metabolite concentrations and clinical symptoms in schizophrenic patients. The first purpose of our study was to examine whether the plasma levels of HVA(homovanillic acid) and 5-HIAA(hydroxyindoleacetic acid) are significantly different in schizophrenics, compared to normal controls. And, with the intention of clarifying the interaction between dopaminergic system and serotoninergic system, the ratio of HVA/5-HIAA also was measured. The second purpose was whether the basal(pre-treatment) levels of these metabolites show the correlation with clinical symptoms. Finally, third purpose was whether basal HVA and 5-HIAA levels can be held as a predictor of treatment response. We used Scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms(SANS) as the clinical symptom rating scales. Our results were as followed, 1) only the level of basal plasma HVA was significantly differ in schizophrenics. 5-HIAA and HVA/5-HIAA were not. 2) basal HVA showed significant correlation with SAPS score, especially delusion subscale. 3) the higher was the basal HVA level, the more improvement in clinical symptoms was observed. The basal 5-HIAA level and the HVA/5-HIAA ratio did not show any significant findings. These results support the dopamine hypothesis of schizophrenia, but fail to examine on the possible involvement of serotonin in schizophrenia.

• Anxiety and mood
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• v.4 no.1
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• pp.19-27
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• 2008

Objective : This study was conducted to evaluate the changes in the levels of neurotransmitters and cortisol in patients with chronic posttraumatic stress disorder (PTSD) and to evaluate their correlation with symptoms after long-term pharmacological treatment. Methods : Twenty-eight Vietnam veterans with chronic PTSD and 34 non-PTSD patients were consecutively recruited. The Combat Exposure Scale (CES), Mississippi Scale for Combat-Related Posttraumatic Stress Disorder (M-PTSD), Clinician Administered PTSD Scale (CAPS), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Scale (HAS) were used to evaluate symptom severity. High performance liquid chromatography (HPLC) was used to measure the plasma levels of epinephrine, norepinephrine, and dopamine, and a radioimmunoassay (RIA) was performed to evaluate the plasma level of cortisol. Results : Plasma cortisol was significantly lower in PTSD patients than in control subjects, while there was no significant difference in plasma epinephrine, norepinephrine and dopamine between the two groups. The scores of M-PTSD, CAPS, HAMD and HAMA were signigicantly higher in PTSD patients than control group. Conclusion : After long-term treatment, the levels of neurotransmitters in PTSD patients returned to within the normal range, and the patients' symptoms showed some improvement. However, the core symptoms of PTSD continued to appear intermittently, and they are thought to be associated with hormonal systems, such as the HPA axis. It is also suggested that PTSD should be considered to be a complex disorder associated with multiple systems and that combinations of the effective medications for each system should be used to treat patients with PTSD.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.255-264
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• 2023

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF⁺NeuN⁺ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.