Protease-activated receptor 2 (PAR2) is a member of G-protein-coupled receptors and affects ligan... more Protease-activated receptor 2 (PAR2) is a member of G-protein-coupled receptors and affects ligand-modulated calcium signaling. Although PAR2 signaling promotes obesity and adipose tissue inflammation in high fat- (HF-) fed conditions, its role in adipocyte differentiation under nonobesogenic conditions needs to be elucidated. Here, we used several tissues and primary-cultured adipocytes of mice lacking PAR2 to study its role in the development of adipose tissues. C57BL/6J mice with PAR2 deficiency exhibited a mild lipodystrophy-like phenotype in a chow diet-fed condition. When adipocyte differentiation was examined using primary-cultured preadipocytes, PAR2 deficiency led to a notable decrease in adipocyte differentiation and related protein expression, and PAR2 agonist treatment elevated adipocyte differentiation. Regarding the mechanism, PAR2-deficient preadipocytes exhibited impaired mitochondrial energy consumption. Further studies indicated that calcium-related signaling pathw...
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome c... more The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. ...
Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its... more Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its underlying mechanisms of action and constituents have not yet been completely elucidated. Previously, we have confirmed that AVE treatment significantly reduces the viral replication of green fluorescent protein-labeled influenza A virus in Madin-Darby canine kidney (MDCK) cells. In addition, post-treatment with AVE inhibited viral matrix protein 1 (M1), matrix protein 2 (M2), and hemagglutinin (HA) mRNA synthesis and viral protein (M1, M2, and HA) expressions. In this study, we demonstrated that AVE inhibited autophagy induced by influenza A virus in MDCK cells and also identified quercetin, catechin hydrate, and kaempferol as the active antiviral components of AVE. We also found that post-treatment with quercetin, catechin hydrate, and kaempferol markedly inhibited M2 viral mRNA synthesis and M2 protein expression. A docking simulation suggested that the binding affinity of quercetin,...
Objectives Sargassum serratifolium, a marine brown alga consumed in Asian countries, has shown an... more Objectives Sargassum serratifolium, a marine brown alga consumed in Asian countries, has shown anti-obesity effect by stimulating white adipose tissue browning. Therefore, the purpose of this study was to investigate lipid catabolic effects of sargahydroquinoic acid (SHQA), which is one of the major bioactive compounds of S. serratifolium by white adipocyte browning effect. Methods Isolated and purified SHQA from S. serratifolium was used to treat 3T3-L1 preadipocytes to see the effects of lipid catabolism and white adipocyte browning. Glycerol concentration measurement, Oil Red O lipid staining, and triglyceride quantification were conducted to examine the lipid catabolism by SHQA in the 3T3-L1 cells. In addition, real-time PCR and Western Blot assays were used to examine the expressions of genes related with lipid catabolic pathway, mitochondria biogenesis and white adipocyte browning. Results SHQA significantly upregulated non-shivering thermogenic gene expressions in 3T3-L1 cell...
Although enzymatic browning is important for the beneficial coloration of some foods, it also cau... more Although enzymatic browning is important for the beneficial coloration of some foods, it also causes negative effects on safety, quality, and nutritional values of fruit and vegetable. Thus, anti-browning natural compounds have gained attention in the food industry. Xanthone-related compounds have been well-known for its biological activities, but their roles in enzymatic browning are unclear. We screened xanthone-related natural compounds for their anti-polyphenol oxidase (PPO) activity and maclurin was selected for further experiments due to stronger PPO-inhibitory activity. Maclurin suppressed enzymatic browning in potato supernatant for long-term partly through direct binding to and inactivating PPO presumably by forming multiple hydrogen bonds and aromatic interactions with the binding pocket. In addition, maclurin elevated antioxidant capacity when added to potato supernatant. Considering the diverse health-promoting effects of antioxidants, maclurin can be applied as a functi...
The intestine plays an essential role in integrating immunity and nutrient digestion and absorpti... more The intestine plays an essential role in integrating immunity and nutrient digestion and absorption. Adjacent intestinal epithelia form tight junctions (TJs) that are essential to the function of the physical intestinal barrier, regulating the paracellular movement of various substances including ions, solutes, and water across the intestinal epithelium. Studies have shown that TJ dysfunction is highly associated with metabolic and inflammatory diseases. Thus, molecular and nutritional factors that improve TJ activity have gained attention in the pharmaceutical and medicinal fields. This review focuses on the association between TJ and diverse pathological conditions, as well as various molecular and nutritional interventions designed to boost TJ integrity.
Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction... more Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of . Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARβ/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARβ/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARβ/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-indu...
Enzymatic browning is a major issue that needs to be solved in the food industry. Although swerti... more Enzymatic browning is a major issue that needs to be solved in the food industry. Although swertiajaponin is a flavonoid rich in the whole herb of Swertia japonica that has been clinically used, its biological functions and application in the foods have not been fully elucidated. Here, we showed that swertiajaponin efficiently blocked enzymatic browning in potatoes possibly by direct binding to and inactivating polyphenol oxidase. Furthermore, swertiajaponin showed potent antioxidant activity proven by markedly suppressed reactive oxygen species. Swertiajaponin significantly increased antioxidant properties of potato extract when it is added since it additively elevated total flavonoid content. Considering numerous beneficial effects of antioxidants, swertiajaponin may be used as a functional food additive to suppress enzymatic browning and elevate the antioxidant capacity of foods including beverages and soups by fortification of flavonoids.
Gleditsia sinensis Lam. (G. sinensis) has been used in Oriental medicine for tumor, thrombosis, i... more Gleditsia sinensis Lam. (G. sinensis) has been used in Oriental medicine for tumor, thrombosis, inflammation-related disease, and obesity. The pharmacological inhibitory effects of fruits of G. sinensis (GFE) on hyperlipidemia have been reported, but its inhibitory effects on adipogenesis and underlying mechanisms have not been elucidated. Herein we evaluated the anti-adipogenic effects of GFE and described the underlying mechanisms. The effects of ethanol extracts of GFE on adipocyte differentiation were examined in 3T3-L1 cells using biochemical and molecular analyses of lipid accumulation and adipogenic protein and mRNA expression. During the differentiation of 3T3-L1 cells, GFE significantly reduced lipid accumulation and downregulated master adipogenic transcription factors, including CCAAT/enhancer-binding protein-α and peroxisome proliferator-activated receptor-γ, at mRNA and protein levels. These changes led to the suppression of several adipogenic-specific genes and protein...
Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Pe... more Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, includin...
Bioorganic & medicinal chemistry letters, Feb 15, 2018
The NAD-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndro... more The NAD-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720. We performed an in vitro SIRT1 activity assay to identify the strongest SIRT1 activator. The assay confirmed MHY2233 to be the strongest SIRT1 activator (1.5-fold more potent than resveratrol), and docking simulation showed that the binding affinity of MHY2233 was higher than that of resveratrol and SRT1720. To investigate its beneficial effects, db/db mice were orally administered MHY2233 for 1 month, and various metabolic parameters were assessed in the serum and liver tissues. MHY2233 markedly ameliorate...
Age-associated renal fibrosis is related with renal function decline during aging. Imbalance betw... more Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein-protein interaction (PPI). Both mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore, the interaction between MMP2 and A2M was verified by immunoprecipitation and immunohistochemistry. MMP2 activity was further measured under the presence or absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the absence of A2M-MMP2 interaction, was significantly decreased under the presence of interactions in aged kidney. We furthe...
Liver inflammation is closely associated with metabolic syndrome. Oxidative stress plays a synerg... more Liver inflammation is closely associated with metabolic syndrome. Oxidative stress plays a synergistic role in inflammation by activating nuclear factor kappa B (NF-κB) signaling in the liver. Therefore, substantial efforts have been made to develop compounds that inhibit the generation of oxidative stress and activation of NF-κB. We synthesized twenty-six novel 5-(substituted benzyl)-2-oxo- and 5-(substituted benzyl)-2-thioxo-dihydropyrimidine-4,6(1H,5H)-dione derivatives for the development of potential antioxidants and examined their biological activities in vitro and in vivo. Thio-barbiturate-derived compounds 5-[4-hydroxy-3-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]-dione (2d) and 5-[4-hydroxy-3,5-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]-dione (2l) had the strongest inhibitory effect on reactive oxygen species and peroxynitrite generation in vitro. Furthermore, oral administration of compounds 2d and 2l in mice notably suppressed lipopolysaccharide (LPS)-induc...
Protease-activated receptor 2 (PAR2) is a member of G-protein-coupled receptors and affects ligan... more Protease-activated receptor 2 (PAR2) is a member of G-protein-coupled receptors and affects ligand-modulated calcium signaling. Although PAR2 signaling promotes obesity and adipose tissue inflammation in high fat- (HF-) fed conditions, its role in adipocyte differentiation under nonobesogenic conditions needs to be elucidated. Here, we used several tissues and primary-cultured adipocytes of mice lacking PAR2 to study its role in the development of adipose tissues. C57BL/6J mice with PAR2 deficiency exhibited a mild lipodystrophy-like phenotype in a chow diet-fed condition. When adipocyte differentiation was examined using primary-cultured preadipocytes, PAR2 deficiency led to a notable decrease in adipocyte differentiation and related protein expression, and PAR2 agonist treatment elevated adipocyte differentiation. Regarding the mechanism, PAR2-deficient preadipocytes exhibited impaired mitochondrial energy consumption. Further studies indicated that calcium-related signaling pathw...
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome c... more The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. ...
Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its... more Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its underlying mechanisms of action and constituents have not yet been completely elucidated. Previously, we have confirmed that AVE treatment significantly reduces the viral replication of green fluorescent protein-labeled influenza A virus in Madin-Darby canine kidney (MDCK) cells. In addition, post-treatment with AVE inhibited viral matrix protein 1 (M1), matrix protein 2 (M2), and hemagglutinin (HA) mRNA synthesis and viral protein (M1, M2, and HA) expressions. In this study, we demonstrated that AVE inhibited autophagy induced by influenza A virus in MDCK cells and also identified quercetin, catechin hydrate, and kaempferol as the active antiviral components of AVE. We also found that post-treatment with quercetin, catechin hydrate, and kaempferol markedly inhibited M2 viral mRNA synthesis and M2 protein expression. A docking simulation suggested that the binding affinity of quercetin,...
Objectives Sargassum serratifolium, a marine brown alga consumed in Asian countries, has shown an... more Objectives Sargassum serratifolium, a marine brown alga consumed in Asian countries, has shown anti-obesity effect by stimulating white adipose tissue browning. Therefore, the purpose of this study was to investigate lipid catabolic effects of sargahydroquinoic acid (SHQA), which is one of the major bioactive compounds of S. serratifolium by white adipocyte browning effect. Methods Isolated and purified SHQA from S. serratifolium was used to treat 3T3-L1 preadipocytes to see the effects of lipid catabolism and white adipocyte browning. Glycerol concentration measurement, Oil Red O lipid staining, and triglyceride quantification were conducted to examine the lipid catabolism by SHQA in the 3T3-L1 cells. In addition, real-time PCR and Western Blot assays were used to examine the expressions of genes related with lipid catabolic pathway, mitochondria biogenesis and white adipocyte browning. Results SHQA significantly upregulated non-shivering thermogenic gene expressions in 3T3-L1 cell...
Although enzymatic browning is important for the beneficial coloration of some foods, it also cau... more Although enzymatic browning is important for the beneficial coloration of some foods, it also causes negative effects on safety, quality, and nutritional values of fruit and vegetable. Thus, anti-browning natural compounds have gained attention in the food industry. Xanthone-related compounds have been well-known for its biological activities, but their roles in enzymatic browning are unclear. We screened xanthone-related natural compounds for their anti-polyphenol oxidase (PPO) activity and maclurin was selected for further experiments due to stronger PPO-inhibitory activity. Maclurin suppressed enzymatic browning in potato supernatant for long-term partly through direct binding to and inactivating PPO presumably by forming multiple hydrogen bonds and aromatic interactions with the binding pocket. In addition, maclurin elevated antioxidant capacity when added to potato supernatant. Considering the diverse health-promoting effects of antioxidants, maclurin can be applied as a functi...
The intestine plays an essential role in integrating immunity and nutrient digestion and absorpti... more The intestine plays an essential role in integrating immunity and nutrient digestion and absorption. Adjacent intestinal epithelia form tight junctions (TJs) that are essential to the function of the physical intestinal barrier, regulating the paracellular movement of various substances including ions, solutes, and water across the intestinal epithelium. Studies have shown that TJ dysfunction is highly associated with metabolic and inflammatory diseases. Thus, molecular and nutritional factors that improve TJ activity have gained attention in the pharmaceutical and medicinal fields. This review focuses on the association between TJ and diverse pathological conditions, as well as various molecular and nutritional interventions designed to boost TJ integrity.
Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction... more Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of . Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARβ/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARβ/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARβ/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-indu...
Enzymatic browning is a major issue that needs to be solved in the food industry. Although swerti... more Enzymatic browning is a major issue that needs to be solved in the food industry. Although swertiajaponin is a flavonoid rich in the whole herb of Swertia japonica that has been clinically used, its biological functions and application in the foods have not been fully elucidated. Here, we showed that swertiajaponin efficiently blocked enzymatic browning in potatoes possibly by direct binding to and inactivating polyphenol oxidase. Furthermore, swertiajaponin showed potent antioxidant activity proven by markedly suppressed reactive oxygen species. Swertiajaponin significantly increased antioxidant properties of potato extract when it is added since it additively elevated total flavonoid content. Considering numerous beneficial effects of antioxidants, swertiajaponin may be used as a functional food additive to suppress enzymatic browning and elevate the antioxidant capacity of foods including beverages and soups by fortification of flavonoids.
Gleditsia sinensis Lam. (G. sinensis) has been used in Oriental medicine for tumor, thrombosis, i... more Gleditsia sinensis Lam. (G. sinensis) has been used in Oriental medicine for tumor, thrombosis, inflammation-related disease, and obesity. The pharmacological inhibitory effects of fruits of G. sinensis (GFE) on hyperlipidemia have been reported, but its inhibitory effects on adipogenesis and underlying mechanisms have not been elucidated. Herein we evaluated the anti-adipogenic effects of GFE and described the underlying mechanisms. The effects of ethanol extracts of GFE on adipocyte differentiation were examined in 3T3-L1 cells using biochemical and molecular analyses of lipid accumulation and adipogenic protein and mRNA expression. During the differentiation of 3T3-L1 cells, GFE significantly reduced lipid accumulation and downregulated master adipogenic transcription factors, including CCAAT/enhancer-binding protein-α and peroxisome proliferator-activated receptor-γ, at mRNA and protein levels. These changes led to the suppression of several adipogenic-specific genes and protein...
Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Pe... more Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, includin...
Bioorganic & medicinal chemistry letters, Feb 15, 2018
The NAD-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndro... more The NAD-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720. We performed an in vitro SIRT1 activity assay to identify the strongest SIRT1 activator. The assay confirmed MHY2233 to be the strongest SIRT1 activator (1.5-fold more potent than resveratrol), and docking simulation showed that the binding affinity of MHY2233 was higher than that of resveratrol and SRT1720. To investigate its beneficial effects, db/db mice were orally administered MHY2233 for 1 month, and various metabolic parameters were assessed in the serum and liver tissues. MHY2233 markedly ameliorate...
Age-associated renal fibrosis is related with renal function decline during aging. Imbalance betw... more Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein-protein interaction (PPI). Both mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore, the interaction between MMP2 and A2M was verified by immunoprecipitation and immunohistochemistry. MMP2 activity was further measured under the presence or absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the absence of A2M-MMP2 interaction, was significantly decreased under the presence of interactions in aged kidney. We furthe...
Liver inflammation is closely associated with metabolic syndrome. Oxidative stress plays a synerg... more Liver inflammation is closely associated with metabolic syndrome. Oxidative stress plays a synergistic role in inflammation by activating nuclear factor kappa B (NF-κB) signaling in the liver. Therefore, substantial efforts have been made to develop compounds that inhibit the generation of oxidative stress and activation of NF-κB. We synthesized twenty-six novel 5-(substituted benzyl)-2-oxo- and 5-(substituted benzyl)-2-thioxo-dihydropyrimidine-4,6(1H,5H)-dione derivatives for the development of potential antioxidants and examined their biological activities in vitro and in vivo. Thio-barbiturate-derived compounds 5-[4-hydroxy-3-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]-dione (2d) and 5-[4-hydroxy-3,5-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]-dione (2l) had the strongest inhibitory effect on reactive oxygen species and peroxynitrite generation in vitro. Furthermore, oral administration of compounds 2d and 2l in mice notably suppressed lipopolysaccharide (LPS)-induc...
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