Evaluation of the In Vivo Therapeutic Effects of Radix Paeoniae Rubra Ethanol Extract with the Hypoglycemic Activities Measured from Multiple Cell‐Based Assays
Abstract:Background. Radix Paeoniae Rubra (Chi Shao) contains several phytochemicals with hypoglycemic actions. Current research aims to explore potential insulinotropic effects and long-term therapeutic efficacy of such herb against type 2 diabetes. Methods. Composition analysis for the ethanol extract (PRExt) was executed by high performance liquid chromatography. Polyphenol-enriched fraction was characterized by high pressure size exclusion chromatography. Multiple cell platforms were employed to evaluate hypoglycem… Show more
“…Recently, studies have demonstrated that traditional Chinese medicine may be effective in the prevention and treatment of myocardial I/R injury ( 7 , 8 ). According to traditional Chinese medicine, Radix Paeoniae Rubra, the dried root of Paeonia lactiflora Pall, is able to reduce heat and cool blood, disperse stasis and relieve pain ( 9 – 11 ). Total paeony glycoside (TPG) is a major component of Radix Paeoniae Rubra, and the effective component of TPG is a monoterpene compound ( 12 ).…”
Section: Introductionmentioning
confidence: 99%
“…Total paeony glycoside (TPG) is a major component of Radix Paeoniae Rubra, and the effective component of TPG is a monoterpene compound ( 12 ). Modern pharmacological studies have demonstrated that Radix Paeoniae Rubra has various pharmacological functions that mainly produce effects on the cardiovascular system ( 9 , 13 , 14 ). In addition, it exerts antitumor and anti-endotoxin effects, as well as other functions ( 9 , 13 , 14 ).…”
Section: Introductionmentioning
confidence: 99%
“…Modern pharmacological studies have demonstrated that Radix Paeoniae Rubra has various pharmacological functions that mainly produce effects on the cardiovascular system ( 9 , 13 , 14 ). In addition, it exerts antitumor and anti-endotoxin effects, as well as other functions ( 9 , 13 , 14 ). Furthermore, TPG has been used to treat cancer, atherosclerosis and ischemic cerebrovascular disease in China ( 15 , 16 ).…”
At present, cardiovascular disease is the global leading cause of mortality. Total paeony glycoside (TPG) is a traditional Chinese medicine, which serves a pivotal role in the cardiovascular system. In the present study, the effects and underlying mechanisms of TPG on ischemia/reperfusion (I/R) injury-induced apoptosis of cardiomyocytes were investigated in vitro. Cell Counting kit-8 and flow cytometry were used to assess the viability, reactive oxygen species (ROS) content and apoptosis of H9C2 cells. The activities of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were analyzed by commercial detection kits. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to evaluate the expression levels of various factors. The results demonstrated that the viability of H9C2 cells was not significantly altered in response to various concentrations of TPG. However, following I/R injury, TPG markedly enhanced cell viability in a time- and dose-dependent manner. Furthermore, TPG decreased the rate of apoptosis and ROS levels, and reduced the activities of MDA and LDH. Conversely, TPG increased SOD and GPX activities. In addition, TPG upregulated the expression levels of pro-caspase-3 and B-cell lymphoma2 (Bcl-2), whereas it downregulated cleaved-caspase-3, poly (ADP-ribose) polymerase 1, Bcl-2-associated X protein, phosphorylated (p)-phosphatidylinositol 3 kinase (PI3K) and p-protein kinase B (Akt) expression. Treatment with insulin-like growth factor-1 increased the apoptosis of H9C2 cells, thus suggesting that activation of the PI3K/Akt signaling pathway reversed the protective effects of TPG. Taken together, TPG may suppress I/R-induced apoptosis and oxidative stress of H9C2 cells possibly by inhibiting the PI3K/Akt signaling pathway; such a phenomenon may have a therapeutic effect on cardiovascular disease.
“…Recently, studies have demonstrated that traditional Chinese medicine may be effective in the prevention and treatment of myocardial I/R injury ( 7 , 8 ). According to traditional Chinese medicine, Radix Paeoniae Rubra, the dried root of Paeonia lactiflora Pall, is able to reduce heat and cool blood, disperse stasis and relieve pain ( 9 – 11 ). Total paeony glycoside (TPG) is a major component of Radix Paeoniae Rubra, and the effective component of TPG is a monoterpene compound ( 12 ).…”
Section: Introductionmentioning
confidence: 99%
“…Total paeony glycoside (TPG) is a major component of Radix Paeoniae Rubra, and the effective component of TPG is a monoterpene compound ( 12 ). Modern pharmacological studies have demonstrated that Radix Paeoniae Rubra has various pharmacological functions that mainly produce effects on the cardiovascular system ( 9 , 13 , 14 ). In addition, it exerts antitumor and anti-endotoxin effects, as well as other functions ( 9 , 13 , 14 ).…”
Section: Introductionmentioning
confidence: 99%
“…Modern pharmacological studies have demonstrated that Radix Paeoniae Rubra has various pharmacological functions that mainly produce effects on the cardiovascular system ( 9 , 13 , 14 ). In addition, it exerts antitumor and anti-endotoxin effects, as well as other functions ( 9 , 13 , 14 ). Furthermore, TPG has been used to treat cancer, atherosclerosis and ischemic cerebrovascular disease in China ( 15 , 16 ).…”
At present, cardiovascular disease is the global leading cause of mortality. Total paeony glycoside (TPG) is a traditional Chinese medicine, which serves a pivotal role in the cardiovascular system. In the present study, the effects and underlying mechanisms of TPG on ischemia/reperfusion (I/R) injury-induced apoptosis of cardiomyocytes were investigated in vitro. Cell Counting kit-8 and flow cytometry were used to assess the viability, reactive oxygen species (ROS) content and apoptosis of H9C2 cells. The activities of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were analyzed by commercial detection kits. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to evaluate the expression levels of various factors. The results demonstrated that the viability of H9C2 cells was not significantly altered in response to various concentrations of TPG. However, following I/R injury, TPG markedly enhanced cell viability in a time- and dose-dependent manner. Furthermore, TPG decreased the rate of apoptosis and ROS levels, and reduced the activities of MDA and LDH. Conversely, TPG increased SOD and GPX activities. In addition, TPG upregulated the expression levels of pro-caspase-3 and B-cell lymphoma2 (Bcl-2), whereas it downregulated cleaved-caspase-3, poly (ADP-ribose) polymerase 1, Bcl-2-associated X protein, phosphorylated (p)-phosphatidylinositol 3 kinase (PI3K) and p-protein kinase B (Akt) expression. Treatment with insulin-like growth factor-1 increased the apoptosis of H9C2 cells, thus suggesting that activation of the PI3K/Akt signaling pathway reversed the protective effects of TPG. Taken together, TPG may suppress I/R-induced apoptosis and oxidative stress of H9C2 cells possibly by inhibiting the PI3K/Akt signaling pathway; such a phenomenon may have a therapeutic effect on cardiovascular disease.
“…These two anomers of pentagalloyl glucose prevented the conversion of preadipocytes to mature adipocytes (Ren, Himmeldirk, & Chen, 2006). When the activity of penta‐ O ‐galloyl‐D‐glucopyranose on BRIN‐BD11 cells, which are responsible for the releasing of the insulin, was investigated, it was shown that penta‐ O ‐galloyl‐D‐glucopyranose showed the insulinotropic effect in a dose‐dependent manner (Chang et al., 2016). The activities of α and β anomers of penta‐ O ‐galloyl‐D‐glucopyranose on stimulation of glucose transport were investigated, so the EC50 value of α and β pentagalloyl glucose was found to be 17 and 18 µM, respectively (Klein, Kim, Himmeldirk, Cao, & Chen, 2007).…”
The leaves and fruits of Rhus coriaria are traditionally used in Turkey for the treatment of diabetes. The aim of the present study is to determine α-amylase, α-glucosidase, and pancreatic lipase inhibitory activities of R. coriaria leaf and fruit ethanol extracts (80%), and to isolate active compounds against these enzymes. As a result of the activity-guided isolation, the active compounds were determined as the amentoflavone, agathisflavone, and 1,2,3,4,6-penta-O-galloyl-βglucopyranose. Agathisflavone, amentoflavone, and penta-O-galloyl-β-glucopyranose inhibited α-glucosidase with 11.4 ± 0.9, 11.3 ± 0.7, and 4.1 ± 0.1 μM IC 50 values, respectively. Furthermore, penta-O-galloyl-β-glucopyranose inhibited αamylase with 6.32 ± 0.18 μM IC 50. These three compounds also significantly inhibited (P < 0.05) pancreatic lipase. The results of high-performance liquid chromatography analysis showed that penta-O-galloyl-β-D-glycopyranose was one of the main compounds in both fruit and leaf extracts. Therefore, it may be considered that R. coriaria fruit and leaf extracts can be standardized on this substance and used in the development of both medicinal products and functional food for diabetes.
“…This fact was not a surprise because many papers describing heat damage to polyphenols availability have been published. Losses of between 16 and 28% of polyphenol levels after pasteurization have been previously reported in grape and watermelon juice and strawberry puree [ 41 , 42 , 43 , 44 ]. The really important fact is that this loss is not considered relevant, since the remaining polyphenols are sufficient to induce healthy in vivo effects [ 45 ].…”
Neurodegenerative diseases pose a major health problem for developed countries. Stress, which induces oxidation in the brain, has been identified as the main risk factor for these disorders. We have developed an antioxidant-enriched drink and have examined its protective properties against acute oxidative stress. We found that addition of red grape polyphenols and MecobalActive® to grape juice did not provoke changes in juice organoleptic characteristics, and that the pasteurization process did not greatly affect the levels of flavonoids and vitamin B12. Out of all combinations, grape juice with red grape polyphenols was selected by expert judges (28.6% selected it as their first choice). In vivo, oral administration of grape juice supplemented with red grape polyphenols exerted an antioxidant effect in the brain of stressed mice reducing two-fold the expression of genes involved in inflammation and oxidation mechanisms and increasing three-fold the expression of genes related to protection against oxidative stress. In addition, we found that this drink augmented antioxidant enzyme activity (17.8 vs. 8.2 nmol/mg), and prevented lipid peroxidation in the brain (49.7 vs. 96.5 nmol/mg). Therefore, we propose supporting the use of this drink by the general population as a new and global strategy for the prevention of neurodegeneration.
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