Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Background/Aims: The use of 1-L polyethylene glycol with ascorbate (PEG/Asc) and oral sulfate tablets (OST) as low-volume bowel preparation agents has gradually increased. However, these agents may induce acute gastropathy during bowel preparation, particularly in elderly populations. This study aimed to compare the incidence of acute gastropathy of 1-L PEG/Asc and OST according to age, as well as efficacy and safety. Methods: This retrospective study included patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for screening on the same day and underwent bowel preparation using OST or 1-L PEG/Asc. We collected EGD findings related to acute gastropathy, bowel-cleansing score using the Boston Bowel Preparation Scale (BBPS), polyp or adenoma detection rate (ADR), and laboratory parameters. Results: Of 4,711 patients, 1,758, 2,241, and 712 were in the younger (18–49 years), middle-aged (50–64 years), and older (≥65 years) groups, respectively. In all age groups, the OST group had higher rates of acute gastropathy than the 1-L PEG/Asc group. The younger-, middle-, and older-aged groups had OST and 1-L PEG/Asc usage rates of 42.9% and 11.6%, 41.2% and 16.0%, and 41.5% and 16.4%, respectively. Notably, in the younger group, the total BBPS and ADR scores were significantly higher in the OST group than in the 1-L PEG/Asc group; however, these did not differ in the other age groups. Conclusions Acute gastropathy was more strongly associated with OST than with 1-L PEG/Asc in all age groups. Therefore, physicians should consider acute gastropathy associated with low-volume agents in all age groups when performing bowel preparation.

Background/Aims: The use of 1-L polyethylene glycol with ascorbate (PEG/Asc) and oral sulfate tablets (OST) as low-volume bowel preparation agents has gradually increased. However, these agents may induce acute gastropathy during bowel preparation, particularly in elderly populations. This study aimed to compare the incidence of acute gastropathy of 1-L PEG/Asc and OST according to age, as well as efficacy and safety. Methods: This retrospective study included patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for screening on the same day and underwent bowel preparation using OST or 1-L PEG/Asc. We collected EGD findings related to acute gastropathy, bowel-cleansing score using the Boston Bowel Preparation Scale (BBPS), polyp or adenoma detection rate (ADR), and laboratory parameters. Results: Of 4,711 patients, 1,758, 2,241, and 712 were in the younger (18–49 years), middle-aged (50–64 years), and older (≥65 years) groups, respectively. In all age groups, the OST group had higher rates of acute gastropathy than the 1-L PEG/Asc group. The younger-, middle-, and older-aged groups had OST and 1-L PEG/Asc usage rates of 42.9% and 11.6%, 41.2% and 16.0%, and 41.5% and 16.4%, respectively. Notably, in the younger group, the total BBPS and ADR scores were significantly higher in the OST group than in the 1-L PEG/Asc group; however, these did not differ in the other age groups. Conclusions Acute gastropathy was more strongly associated with OST than with 1-L PEG/Asc in all age groups. Therefore, physicians should consider acute gastropathy associated with low-volume agents in all age groups when performing bowel preparation.

Background/Aims: The use of 1-L polyethylene glycol with ascorbate (PEG/Asc) and oral sulfate tablets (OST) as low-volume bowel preparation agents has gradually increased. However, these agents may induce acute gastropathy during bowel preparation, particularly in elderly populations. This study aimed to compare the incidence of acute gastropathy of 1-L PEG/Asc and OST according to age, as well as efficacy and safety. Methods: This retrospective study included patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for screening on the same day and underwent bowel preparation using OST or 1-L PEG/Asc. We collected EGD findings related to acute gastropathy, bowel-cleansing score using the Boston Bowel Preparation Scale (BBPS), polyp or adenoma detection rate (ADR), and laboratory parameters. Results: Of 4,711 patients, 1,758, 2,241, and 712 were in the younger (18–49 years), middle-aged (50–64 years), and older (≥65 years) groups, respectively. In all age groups, the OST group had higher rates of acute gastropathy than the 1-L PEG/Asc group. The younger-, middle-, and older-aged groups had OST and 1-L PEG/Asc usage rates of 42.9% and 11.6%, 41.2% and 16.0%, and 41.5% and 16.4%, respectively. Notably, in the younger group, the total BBPS and ADR scores were significantly higher in the OST group than in the 1-L PEG/Asc group; however, these did not differ in the other age groups. Conclusions Acute gastropathy was more strongly associated with OST than with 1-L PEG/Asc in all age groups. Therefore, physicians should consider acute gastropathy associated with low-volume agents in all age groups when performing bowel preparation.

Background/Aims: The use of 1-L polyethylene glycol with ascorbate (PEG/Asc) and oral sulfate tablets (OST) as low-volume bowel preparation agents has gradually increased. However, these agents may induce acute gastropathy during bowel preparation, particularly in elderly populations. This study aimed to compare the incidence of acute gastropathy of 1-L PEG/Asc and OST according to age, as well as efficacy and safety. Methods: This retrospective study included patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for screening on the same day and underwent bowel preparation using OST or 1-L PEG/Asc. We collected EGD findings related to acute gastropathy, bowel-cleansing score using the Boston Bowel Preparation Scale (BBPS), polyp or adenoma detection rate (ADR), and laboratory parameters. Results: Of 4,711 patients, 1,758, 2,241, and 712 were in the younger (18–49 years), middle-aged (50–64 years), and older (≥65 years) groups, respectively. In all age groups, the OST group had higher rates of acute gastropathy than the 1-L PEG/Asc group. The younger-, middle-, and older-aged groups had OST and 1-L PEG/Asc usage rates of 42.9% and 11.6%, 41.2% and 16.0%, and 41.5% and 16.4%, respectively. Notably, in the younger group, the total BBPS and ADR scores were significantly higher in the OST group than in the 1-L PEG/Asc group; however, these did not differ in the other age groups. Conclusions Acute gastropathy was more strongly associated with OST than with 1-L PEG/Asc in all age groups. Therefore, physicians should consider acute gastropathy associated with low-volume agents in all age groups when performing bowel preparation.