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Ma, Shi-Xun,Kim, Hyoung-Chun,Lee, Seok-Yong,Jang, Choon-Gon Elsevier 2018 Neurochemistry International Vol.121 No.-
<P><B>Abstract</B></P> <P>Opioid addiction is a growing problem for public health, and opioids have correspondingly become more heavily regulated over time. We have previously shown that TRPV1 plays a critical role in morphine addiction using a self-administration paradigm in rats, and the current study evaluates the effects of the TRPV1 signaling pathway on morphine self-administration (SA). We found that treatment with a selective TRPV1 antagonist, SB366791, significantly decreased the morphine SA-induced activation of Ca2<SUP>+</SUP>/calmodulin-dependent protein kinase II (CaMKII), Akt and the cAMP response element binding protein (CREB) in the nucleus accumbens (NAc). In addition, phospho-PKA and phospho-PKC expression levels were significantly increased in the NAc of the morphine-SA groups, regardless of SB366791 treatment. Finally, local microinjection of SB366791 into the NAc significantly suppressed the maintenance of morphine SA. Taken together, our findings highlight that TRPV1 plays an important role in morphine addiction, likely via activation of the CaMKII-CREB pathway in the NAc.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TRPV1 antagonist, SB366791, decreased the activation of CaMKII, Akt, and CREB induced by morphine SA. </LI> <LI> p-PKA and p-PKC expression levels were significantly increased in the NAc of the morphine-SA groups, regardless of SB366791 treatment. </LI> <LI> Local microinjection of SB366791 into the NAc suppressed the maintenance of morphine SA. </LI> </UL> </P>
( Seung Hwan Kwon ),( Shi Xun Ma ),( Hyun Joong Joo ),( Seok Yong Lee ),( Choon Gon Jang ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.6
Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE signifi cantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and signifi cantly reversed learning and memory defi cits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE signifi cantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these fi ndings, we suggest that EUE may be useful for the treatment of cognitive defi cits, and that the benefi cial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.
Xi Bu,Jian-Xun Ma,You-Chen Xia,Bi Li,Yue Lang,Shi-Lu Yin 대한외과학회 2024 Annals of Surgical Treatment and Research(ASRT) Vol.106 No.1
Purpose: Polyacrylamide hydrogel (PAHG), which had been used widely for breast augmentation, has been banned for more than 15 years. Patients who had been injected PAHG for breast augmentation need evacuation surgery to remove as much as possible. To provide a series of diagnosis and treatment process MRI and intraoperative color Doppler ultrasound are combined for maximal removal of PAHG. Methods: The patients who received evacuation surgery in Peking University Third Hospital from 2010 to 2022 after PAHG injection for breast augmentation were included in this research. MR scanning was performed preoperatively and postoperatively in some of these patients and color Doppler ultrasound was applied to help evacuate PAHG intraoperatively. The mean clearance rate of PAHG was calculated according to the MRI outcomes. Results: Two hundred and 4 patients had received evacuation surgery after PAHG injection for breast augmentation with an average age of 42.8 years and an average body mass index of 21.2 kg/m2. The average PAHG retention time was 13.5 years. Among them, 52 patients underwent pre- and postoperative MRI scanning. The mean three-dimensional (3D) volume of PAHG was 684.8 mL (range, 350.0–1,123.9 mL), and the average residual 3D volume of PAHG was 53.7 mL (range, 12.4–98.3 mL). The mean clearance rate was 92.1%. Conclusion: MRI and intraoperative color Doppler ultrasound can provide effective and precise location information of PAHG for evacuation surgery, which is a reliable method to ensure the maximal removal of PAHG.
Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22
( Kwang-hyun Hur ),( Shi-xun Ma ),( Bo-ram Lee ),( Yong-hyun Ko ),( Jee-yeon Seo ),( Hye Won Ryu ),( Hye Jin Kim ),( Seolmin Yoon ),( Yong-sup Lee ),( Seok-yong Lee ),( Choon-gon Jang ) 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.4
Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects. The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.
( Seung-hwan Kwon ),( Shi-xun Ma ),( Yong-hyun Ko ),( Jee-yeon Seo ),( Bo-ram Lee ),( Taek Hwan Lee ),( Sun Yeou Kim ),( Seok-yong Lee ),( Choon-gon Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5
This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE₂ and LPS-mediated upregulation of iNOS and COX-2 expression in a dosedependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB- α, phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.
( Seung Hwan Kwon ),( Shi Xun Ma ),( Ji Young Hwang ),( Yong Hyun Ko ),( Ji Yeon Seo ),( Bo Ram Lee ),( Seok Yong Lee ),( Choon Gon Jang ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3
In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase kinase-3β (GSK-3β), and their downstream transcription factor, nuclear factor-kappa B (NF-κB). EUE also blocked the nuclear translocation of NF-κB and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and PGE2 production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and GSK-3β, consequently suppressing NF-κB activation and inducing Nrf2-dependent HO-1 activation.
Kwon, Seung-Hwan,Ma, Shi-Xun,Ko, Yong-Hyun,Seo, Jee-Yeon,Lee, Bo-Ram,Lee, Taek Hwan,Kim, Sun Yeou,Lee, Seok-Yong,Jang, Choon-Gon The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5
This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.
Kwon, Seung-Hwan,Ma, Shi-Xun,Hwang, Ji-Young,Ko, Yong-Hyun,Seo, Ji-Yeon,Lee, Bo-Ram,Lee, Seok-Yong,Jang, Choon-Gon The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.3
In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.
Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice
( Yang Hee Jung ),( Sa Ik Hong ),( Shi Xun Ma ),( Ji Young Hwang ),( Jun Sup Kim ),( Ju Hyun Lee ),( Jee Yeon Seo ),( Seok Yong Lee ),( Choon Gon Jang ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.5
Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice.