Jiaqi Ding, Shenjie Zhang, Qi Li, Boyu Xia, Jingjing Wu, Xu Lu, Chao Huang, Xiaomei Yuan, Qingsheng You
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue. Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells. These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
香叶木素是一种多酚类物质,提取自Nephelium lappaceum L.的果皮,已被证明在心血管系统中具有抗炎和抗氧化特性。本研究探讨了龙葵素能否保护异丙肾上腺素(ISO)诱导的心肌肥大模型。ISO 组小鼠腹腔注射 ISO(5 毫克/千克),每天一次,连续 9 天;给药组小鼠在接受格拉宁或螺内酯治疗 5 天后再注射 ISO。通过解剖学系数、组织病理学、血液生化指标、逆转录-PCR和免疫印迹分析了潜在的治疗效果和相关机制。格拉宁能减少 ISO 诱导的心脏病理重塑和心肌纤维化,这体现在解剖学系数的改变、胶原 I/III á1mRNA和蛋白表达的减少以及肥厚型心脏组织横截面积的减少。此外,格拉宁还能降低 ISO 诱导的白细胞介素(IL)-6、IL-1β 和肿瘤坏死因子-α 的 mRNA 和蛋白表达水平,而 ISO 诱导的 IL-10 在肥厚的心脏组织中则表现出相反的行为。进一步的分析表明,格拉宁能部分逆转 ISO 诱导的丙二醛和一氧化氮的增加,以及 ISO 诱导的谷胱甘肽、超氧化物歧化酶和谷胱甘肽的减少。此外,它还抑制了 ISO 诱导的肥厚性心脏组织的细胞凋亡,具体表现为 Bcell 淋巴瘤-2(Bcl-2)相关 X/caspase-3/caspase-9 表达的减少、Bcl-2 表达的增加以及 TdT 介导的 dUTP 缺口标记阳性细胞的减少。这些研究结果表明,龙葵素能通过抑制炎症、氧化应激和细胞凋亡来减轻 ISO 诱导的心肌肥大。
{"title":"Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.","authors":"Jiaqi Ding, Shenjie Zhang, Qi Li, Boyu Xia, Jingjing Wu, Xu Lu, Chao Huang, Xiaomei Yuan, Qingsheng You","doi":"10.4196/kjpp.24.200","DOIUrl":"https://doi.org/10.4196/kjpp.24.200","url":null,"abstract":"<p><p>Geraniin, a polyphenol derived from the fruit peel of <i>Nephelium lappaceum</i> L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue. Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells. These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung
Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT)3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (Emax) and an increase in EC50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.
{"title":"Haloperidol, a typical antipsychotic, inhibits 5-HT<sub>3</sub> receptormediated currents in NCB-20 cells: a whole-cell patch-clamp study.","authors":"Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung","doi":"10.4196/kjpp.24.320","DOIUrl":"https://doi.org/10.4196/kjpp.24.320","url":null,"abstract":"<p><p>Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT)<sub>3</sub> receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT<sub>3</sub> receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E<sub>max</sub>) and an increase in EC<sub>50</sub> observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT<sub>3</sub> receptors. Haloperidol inhibited the activation of 5-HT<sub>3</sub> receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT<sub>3</sub> receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT<sub>3</sub> receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT<sub>3</sub> receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT<sub>3</sub> receptors and pharmacological actions of antipsychotics.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lactic acid bacteria are known to have various effects on the immune system. The type and extent of the effect differ, depending on the type of lactic acid bacteria. This study aimed to investigate the effects of Lactobacillus johnsonii bacterin on mouse-derived immune cells. Treating splenocytes with L. johnsonii bacterin slightly increased the metabolic activity. Additionally, the expression of the activation marker CD25 and production of the Th1-type inflammatory cytokine interferon (IFN)- gamma increased. We confirmed that the increase in IFN-gamma production due to L. johnsonii stimulation was mainly due to T and B cells among splenocytes. Treating dendritic cells (DCs) with L. johnsonii bacterin at concentrations of 106 and 107 cfu/ ml significantly increased tumor necrosis factor-alpha, a pro-inflammatory cytokine, and interleukin-12, a cell-mediated immunity cytokine. Additionally, the expression of surface markers increased. Allogeneic mixed lymphocyte reactions showed that L. johnsonii reduced the antigen-presenting ability of DCs. In cocultures of DCs and splenocytes, L. johnsonii decreased cellular metabolic activity and increased cell death. L. johnsonii upregulated the expression of programmed death ligand 1 on DCs. The findings of this study indicate that L. johnsonii bacterin has immunomodulatory and immunostimulatory effects. While L. johnsonii increased the expression of cytokines and surface markers of immune cells, it modulated DC-mediated immune response. Further studies are needed to determine the effects of L. johnsonii bacterin on DCs and related immune cells.
{"title":"<i>Lactobacillus johnsonii</i> JERA01 upregulates the production of Th1 cytokines and modulates dendritic cells-mediated immune response.","authors":"Si-Yeon Kim, Hong-Gu Joo","doi":"10.4196/kjpp.24.205","DOIUrl":"https://doi.org/10.4196/kjpp.24.205","url":null,"abstract":"<p><p>Lactic acid bacteria are known to have various effects on the immune system. The type and extent of the effect differ, depending on the type of lactic acid bacteria. This study aimed to investigate the effects of Lactobacillus johnsonii bacterin on mouse-derived immune cells. Treating splenocytes with <i>L. johnsonii</i> bacterin slightly increased the metabolic activity. Additionally, the expression of the activation marker CD25 and production of the Th1-type inflammatory cytokine interferon (IFN)- gamma increased. We confirmed that the increase in IFN-gamma production due to <i>L. johnsonii</i> stimulation was mainly due to T and B cells among splenocytes. Treating dendritic cells (DCs) with <i>L. johnsonii</i> bacterin at concentrations of 10<sup>6</sup> and 10<sup>7</sup> cfu/ ml significantly increased tumor necrosis factor-alpha, a pro-inflammatory cytokine, and interleukin-12, a cell-mediated immunity cytokine. Additionally, the expression of surface markers increased. Allogeneic mixed lymphocyte reactions showed that <i>L. johnsonii</i> reduced the antigen-presenting ability of DCs. In cocultures of DCs and splenocytes, <i>L. johnsonii</i> decreased cellular metabolic activity and increased cell death. <i>L. johnsonii</i> upregulated the expression of programmed death ligand 1 on DCs. The findings of this study indicate that <i>L. johnsonii</i> bacterin has immunomodulatory and immunostimulatory effects. While <i>L. johnsonii</i> increased the expression of cytokines and surface markers of immune cells, it modulated DC-mediated immune response. Further studies are needed to determine the effects of <i>L. johnsonii</i> bacterin on DCs and related immune cells.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.4196/kjpp.2024.28.6.503
Hami Yu, Yujin Jin, Hyesu Jeon, Lila Kim, Kyung-Sun Heo
Macrophages play a central role in cardiovascular diseases, like atherosclerosis, by accumulating in vessel walls and inducing sustained local inflammation marked by the release of chemokines, cytokines, and matrix-degrading enzymes. Recent studies indicate that 6'-sialyllactose (6'-SL) may mitigate inflammation by modulating the immune system. Here, we examined the impact of 6'-SL on lipopolysaccharide (LPS)-induced acute inflammation using RAW 264.7 cells and a mouse model. In vivo, ICR mice received pretreatment with 100 mg/kg 6'-SL for 2 h, followed by intraperitoneal LPS injection (10 mg/kg) for 6 h. In vitro, RAW 264.7 cells were preincubated with 6'-SL before LPS stimulation. Mechanistic insights were gained though Western blotting, qRT-PCR, and immunofluorescence analysis, while reactive oxygen species (ROS) production was assessed via DHE assay. 6'-SL effectively attenuated LPS-induced p38 MAPK and Akt phosphorylation, as well as p65 nuclear translocation. Additionally, 6'-SL inhibited LPS-induced expression of tissue damage marker MMP9, IL-1β, and MCP-1 by modulating NF-κB activation. It also reduced ROS levels, mediated by p38 MAPK and Akt pathways. Moreover, 6'-SL restored LPS-suppressed Nrf2 and HO-1 akin to specific inhibitors SB203580 and LY294002. Consistent with in vitro results, 6'-SL decreased oxidative stress, MMP9, and MCP-1 expression in mouse endothelium following LPS-induced macrophage activation. In summary, our findings suggest that 6'-SL holds promise in mitigating atherosclerosis by dampening LPS-induced acute macrophage inflammation.
{"title":"Protective effect of 6'-Sialyllactose on LPS-induced macrophage inflammation <i>via</i> regulating Nrf2-mediated oxidative stress and inflammatory signaling pathways.","authors":"Hami Yu, Yujin Jin, Hyesu Jeon, Lila Kim, Kyung-Sun Heo","doi":"10.4196/kjpp.2024.28.6.503","DOIUrl":"10.4196/kjpp.2024.28.6.503","url":null,"abstract":"<p><p>Macrophages play a central role in cardiovascular diseases, like atherosclerosis, by accumulating in vessel walls and inducing sustained local inflammation marked by the release of chemokines, cytokines, and matrix-degrading enzymes. Recent studies indicate that 6'-sialyllactose (6'-SL) may mitigate inflammation by modulating the immune system. Here, we examined the impact of 6'-SL on lipopolysaccharide (LPS)-induced acute inflammation using RAW 264.7 cells and a mouse model. <i>In vivo</i>, ICR mice received pretreatment with 100 mg/kg 6'-SL for 2 h, followed by intraperitoneal LPS injection (10 mg/kg) for 6 h. <i>In vitro</i>, RAW 264.7 cells were preincubated with 6'-SL before LPS stimulation. Mechanistic insights were gained though Western blotting, qRT-PCR, and immunofluorescence analysis, while reactive oxygen species (ROS) production was assessed via DHE assay. 6'-SL effectively attenuated LPS-induced p38 MAPK and Akt phosphorylation, as well as p65 nuclear translocation. Additionally, 6'-SL inhibited LPS-induced expression of tissue damage marker MMP9, IL-1β, and MCP-1 by modulating NF-κB activation. It also reduced ROS levels, mediated by p38 MAPK and Akt pathways. Moreover, 6'-SL restored LPS-suppressed Nrf2 and HO-1 akin to specific inhibitors SB203580 and LY294002. Consistent with <i>in vitro</i> results, 6'-SL decreased oxidative stress, MMP9, and MCP-1 expression in mouse endothelium following LPS-induced macrophage activation. In summary, our findings suggest that 6'-SL holds promise in mitigating atherosclerosis by dampening LPS-induced acute macrophage inflammation.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"503-513"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM). HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.
{"title":"Norepinephrine triggers glutamatergic long-term potentiation in hypothalamic paraventricular nucleus magnocellular neuroendocrine cells through postsynaptic β1-AR/PKA signaling pathway <i>in vitro</i> in rats.","authors":"Jing-Ri Jin, Zhao-Yi Zhang, Chun-Ping Chu, Yu-Zi Li, De-Lai Qiu","doi":"10.4196/kjpp.2024.28.6.569","DOIUrl":"10.4196/kjpp.2024.28.6.569","url":null,"abstract":"<p><p>Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs <i>in vitro</i>, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM). HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway <i>in vitro</i> in rats.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"569-576"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.4196/kjpp.2024.28.6.549
Lingling Zhen, Mingtong Hou, Shengbao Wang
Sepsis triggers a systemic inflammatory response that can lead to acute lung injury (ALI). Salidroside (SAL) has many pharmacological activities such as antiinflammatory and anti-oxidation. The objective of the study was to explore the mechanism of SAL on ALI caused by sepsis. A model of ALI in septic mice was established by cecal ligation and puncture. Following SAL treatment, the effect of SAL on the ferroptosis pathway in mice was analyzed. The pathological damage of lung tissue, the levels of inflammatory factors and apoptosis in bronchoalveolar lavage fluid (BALF) of mice were evaluated, and the changes of gene expression level and metabolite content abundance were explored by combining transcriptomics and metabolomics analysis. The effect of SAL on ferroptosis in mice with lung injury was observed by intraperitoneal injection of ferroptosis activator Erastin or ferroptosis inhibitor Ferrostatin-1 to promote or inhibit ferroptosis in mice. SAL significantly alleviated the pathological damage of lung tissue, decreased the number of TUNEL positive cells and the levels of TNF-α, IL-1β, IL-6 in BALF, and increased the level of IL- 10 in lung injury mice. Moreover, the Fe2+ content and malondialdehyde decreased significantly, the reactive oxygen species and glutathione content increased significantly, and the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20- HETE), (5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid (12-OxOETE), (5Z, 8Z, 10E, 14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE), (5Z, 8Z, 14Z)-11,12-Dihydroxyeicosa-5,8,14-trienoic acid (11,12-DHET), (5Z, 11Z, 14Z)-8,9- Dihydroxyeicosa-5,11,14-trienoic acid, Leukotriene B4, Leukotriene D4 were significantly up-regulated after SAL treatment. Salidroside alleviates ALI caused by sepsis by inhibiting ferroptosis.
败血症会引发全身炎症反应,导致急性肺损伤(ALI)。皂苷(SAL)具有抗炎和抗氧化等多种药理活性。本研究的目的是探索水杨甙对脓毒症引起的急性肺损伤(ALI)的作用机制。研究人员通过盲肠结扎和穿刺建立了败血症小鼠 ALI 模型。在 SAL 治疗后,分析了 SAL 对小鼠铁蛋白沉积途径的影响。通过转录组学和代谢组学分析,评估了小鼠肺组织的病理损伤、支气管肺泡灌洗液(BALF)中炎症因子和细胞凋亡的水平,并探讨了基因表达水平和代谢物含量丰度的变化。通过腹腔注射铁蛋白激活剂Erastin或铁蛋白抑制剂Ferrostatin-1来促进或抑制小鼠的铁蛋白沉积,观察了SAL对肺损伤小鼠铁蛋白沉积的影响。SAL 能明显减轻肺损伤小鼠肺组织的病理损伤,减少 TUNEL 阳性细胞的数量,降低 BALF 中 TNF-α、IL-1β、IL-6 的水平,提高 IL- 10 的水平。此外,Fe2+ 含量和丙二醛含量显著下降,活性氧和谷胱甘肽含量显著增加,花生四烯酸代谢物 20-hydroxyeicosatetraenoic acid(20-HETE)、(5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid(12-OxOETE)、(5Z,8Z,10E,14Z)-(12S)-12-羟基-5,8,10,14-四烯酸(12(S)-HETE)、(5Z,8Z,14Z)-11,12-二羟基-5,8,14-三烯酸(11、12-DHET)、(5Z, 11Z, 14Z)-8,9- 二羟基二十二碳-5,11,14-三烯酸、白三烯 B4、白三烯 D4 在 SAL 处理后显著上调。皂苷能通过抑制铁变态反应减轻败血症引起的急性呼吸道感染。
{"title":"Salidroside attenuates sepsis-induced acute lung injury by inhibiting ferroptosis-dependent pathway.","authors":"Lingling Zhen, Mingtong Hou, Shengbao Wang","doi":"10.4196/kjpp.2024.28.6.549","DOIUrl":"10.4196/kjpp.2024.28.6.549","url":null,"abstract":"<p><p>Sepsis triggers a systemic inflammatory response that can lead to acute lung injury (ALI). Salidroside (SAL) has many pharmacological activities such as antiinflammatory and anti-oxidation. The objective of the study was to explore the mechanism of SAL on ALI caused by sepsis. A model of ALI in septic mice was established by cecal ligation and puncture. Following SAL treatment, the effect of SAL on the ferroptosis pathway in mice was analyzed. The pathological damage of lung tissue, the levels of inflammatory factors and apoptosis in bronchoalveolar lavage fluid (BALF) of mice were evaluated, and the changes of gene expression level and metabolite content abundance were explored by combining transcriptomics and metabolomics analysis. The effect of SAL on ferroptosis in mice with lung injury was observed by intraperitoneal injection of ferroptosis activator Erastin or ferroptosis inhibitor Ferrostatin-1 to promote or inhibit ferroptosis in mice. SAL significantly alleviated the pathological damage of lung tissue, decreased the number of TUNEL positive cells and the levels of TNF-α, IL-1β, IL-6 in BALF, and increased the level of IL- 10 in lung injury mice. Moreover, the Fe<sup>2+</sup> content and malondialdehyde decreased significantly, the reactive oxygen species and glutathione content increased significantly, and the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20- HETE), (5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid (12-OxOETE), (5Z, 8Z, 10E, 14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE), (5Z, 8Z, 14Z)-11,12-Dihydroxyeicosa-5,8,14-trienoic acid (11,12-DHET), (5Z, 11Z, 14Z)-8,9- Dihydroxyeicosa-5,11,14-trienoic acid, Leukotriene B4, Leukotriene D4 were significantly up-regulated after SAL treatment. Salidroside alleviates ALI caused by sepsis by inhibiting ferroptosis.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"549-558"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.4196/kjpp.2024.28.6.495
Han Byeol Kim, Kwang-Eun Kim
Recent research underscores the pivotal role of cellular organelles, such as mitochondria, the endoplasmic reticulum, and lysosomes, in maintaining cellular homeostasis. Their dynamic interactions are critical for metabolic regulation and stress response. Analysis of organelle proteomes offers valuable insights into their functions in both physiology and disease. Traditional proteomic approaches to studying isolated organelles are now complemented by innovative methodologies focusing on inter-organelle interactions. This review examines the integration of advanced proximity labeling technologies, including TurboID and split-TurboID, which address the inherent limitations of traditional techniques and enable precision proteomics of suborganelle compartments and inter-organellar contact sites. These innovations have led to discoveries regarding organelle interconnections, revealing mechanisms underlying metabolic processes such as cholesterol metabolism, glucose metabolism, and lysosomal repair. In addition to highlighting the advancements in TurboID applications, this review delineates the evolving trends in organelle research, underscoring the transformative potential of these techniques to significantly enhance organelle-specific proteomic investigations.
{"title":"Precision proteomics with TurboID: mapping the suborganelle landscape.","authors":"Han Byeol Kim, Kwang-Eun Kim","doi":"10.4196/kjpp.2024.28.6.495","DOIUrl":"10.4196/kjpp.2024.28.6.495","url":null,"abstract":"<p><p>Recent research underscores the pivotal role of cellular organelles, such as mitochondria, the endoplasmic reticulum, and lysosomes, in maintaining cellular homeostasis. Their dynamic interactions are critical for metabolic regulation and stress response. Analysis of organelle proteomes offers valuable insights into their functions in both physiology and disease. Traditional proteomic approaches to studying isolated organelles are now complemented by innovative methodologies focusing on inter-organelle interactions. This review examines the integration of advanced proximity labeling technologies, including TurboID and split-TurboID, which address the inherent limitations of traditional techniques and enable precision proteomics of suborganelle compartments and inter-organellar contact sites. These innovations have led to discoveries regarding organelle interconnections, revealing mechanisms underlying metabolic processes such as cholesterol metabolism, glucose metabolism, and lysosomal repair. In addition to highlighting the advancements in TurboID applications, this review delineates the evolving trends in organelle research, underscoring the transformative potential of these techniques to significantly enhance organelle-specific proteomic investigations.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"495-501"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.4196/kjpp.2024.28.6.539
Jie Li, Dong Zhan, Cui Chen, Rongfu Li, Fang-Qing Zhu
Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/ AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer.
肝癌是最致命的癌症,在全世界都有很高的死亡风险。Goniothalamin(GTN)是一种苯乙烯内酯,具有抗增殖和细胞凋亡活性。GTN 的分子作用尚未得到充分评估。因此,我们的研究旨在评估二乙基亚硝胺(DEN)诱导的大鼠肝细胞癌(HCC)的化学预防和细胞凋亡活性。大鼠被分为 4 组:对照组、仅 DEN 组、DEN + GTN(30 毫克/千克体重)组和仅 GTN(30 毫克/千克体重)组。我们对大鼠的体重、肝脏重量、肿瘤发病率、肝脏毒性标记物、抗氧化剂、炎症细胞因子、组织病理学、免疫组化和 Western 印迹进行了评估。DEN降低了体重、抗氧化剂和细胞凋亡,而提高了肿瘤发病率、毒性标志物、细胞因子和Bcl-2的表达。GTN 治疗可维持体重、肝脏重量和抗氧化剂水平,还能防止肿瘤发生、氧化应激、毒性标志物、促炎细胞因子和组织学变化。它通过抑制 Bcl-2 和提高 caspase-3 水平来触发细胞凋亡。GTN 还能减弱 P13K/ AKT 信号传导,从而增强细胞凋亡。这些研究结果表明,GTN 可抑制 P13K/AKT 通路,对 DEN 诱导的 HCC 具有良好的化学预防和细胞凋亡作用。因此,GTN可作为肝癌自然疗法的一种新药。
{"title":"Chemopreventive potential of goniothalamin in diethylnitrosamine-induced hepatocellular carcinoma through the suppression of P13K/AKT signalling pathway.","authors":"Jie Li, Dong Zhan, Cui Chen, Rongfu Li, Fang-Qing Zhu","doi":"10.4196/kjpp.2024.28.6.539","DOIUrl":"10.4196/kjpp.2024.28.6.539","url":null,"abstract":"<p><p>Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/ AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"539-547"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.4196/kjpp.2024.28.6.515
Yu Gu, Dong-Hun Seong, Wenduo Liu, Zilin Wang, Yong Whi Jeong, Jae-Cheol Kim, Dae Ryong Kang, Rose Ji Eun Lee, Jin-Ho Koh, Sang Hyun Kim
We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.
{"title":"Exercise improves muscle mitochondrial dysfunction-associated lipid profile under circadian rhythm disturbance.","authors":"Yu Gu, Dong-Hun Seong, Wenduo Liu, Zilin Wang, Yong Whi Jeong, Jae-Cheol Kim, Dae Ryong Kang, Rose Ji Eun Lee, Jin-Ho Koh, Sang Hyun Kim","doi":"10.4196/kjpp.2024.28.6.515","DOIUrl":"10.4196/kjpp.2024.28.6.515","url":null,"abstract":"<p><p>We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"515-526"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.4196/kjpp.2024.28.6.527
Jinwoo Jung, Jeon-Ok Moon, Song Ih Ahn, Haeseung Lee
Oxidative stress is a well-established risk factor for numerous chronic diseases, emphasizing the need for efficient identification of potent antioxidants. Conventional methods for assessing antioxidant properties are often time-consuming and resource-intensive, typically relying on laborious biochemical assays. In this study, we investigated the applicability of machine learning (ML) algorithms for predicting the antioxidant activity of compounds based solely on their molecular structure. We evaluated the performance of five ML algorithms, Support Vector Machine (SVM), Logistic Regression (LR), XGBoost, Random Forest (RF), and Deep Neural Network (DNN), using a dataset of over 1,900 compounds with experimentally determined antioxidant activity. Both RF and SVM achieved the best overall performance, exhibiting high accuracy (> 0.9) and effectively distinguishing active and inactive compounds with high structural similarity. External validation using natural product data from the BATMAN database confirmed the generalizability of the RF and SVM models. Our results suggest that ML models serve as powerful tools to expedite the discovery of novel antioxidant candidates, potentially streamlining the development of future therapeutic interventions.
氧化应激是众多慢性疾病的既定风险因素,因此需要有效地识别强效抗氧化剂。评估抗氧化剂特性的传统方法往往耗费时间和资源,通常依赖于费力的生化试验。在本研究中,我们研究了机器学习(ML)算法在仅根据化合物分子结构预测其抗氧化活性方面的适用性。我们使用由 1900 多种经实验确定具有抗氧化活性的化合物组成的数据集,评估了支持向量机(SVM)、逻辑回归(LR)、XGBoost、随机森林(RF)和深度神经网络(DNN)这五种 ML 算法的性能。RF 和 SVM 的总体性能最佳,表现出较高的准确性(> 0.9),并能有效区分结构相似度较高的活性和非活性化合物。利用 BATMAN 数据库中的天然产品数据进行的外部验证证实了 RF 和 SVM 模型的通用性。我们的研究结果表明,ML 模型是加快发现新型抗氧化候选化合物的有力工具,有可能简化未来治疗干预措施的开发。
{"title":"Predicting antioxidant activity of compounds based on chemical structure using machine learning methods.","authors":"Jinwoo Jung, Jeon-Ok Moon, Song Ih Ahn, Haeseung Lee","doi":"10.4196/kjpp.2024.28.6.527","DOIUrl":"10.4196/kjpp.2024.28.6.527","url":null,"abstract":"<p><p>Oxidative stress is a well-established risk factor for numerous chronic diseases, emphasizing the need for efficient identification of potent antioxidants. Conventional methods for assessing antioxidant properties are often time-consuming and resource-intensive, typically relying on laborious biochemical assays. In this study, we investigated the applicability of machine learning (ML) algorithms for predicting the antioxidant activity of compounds based solely on their molecular structure. We evaluated the performance of five ML algorithms, Support Vector Machine (SVM), Logistic Regression (LR), XGBoost, Random Forest (RF), and Deep Neural Network (DNN), using a dataset of over 1,900 compounds with experimentally determined antioxidant activity. Both RF and SVM achieved the best overall performance, exhibiting high accuracy (> 0.9) and effectively distinguishing active and inactive compounds with high structural similarity. External validation using natural product data from the BATMAN database confirmed the generalizability of the RF and SVM models. Our results suggest that ML models serve as powerful tools to expedite the discovery of novel antioxidant candidates, potentially streamlining the development of future therapeutic interventions.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 6","pages":"527-537"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}