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Song X.,University of South China | Song X.,Suzhou Academy of Wumen Chinese Medicine | Liu Y.,University of South China | Ma J.,Soochow University of China | And 5 more authors.
Medicinal Chemistry Research | Year: 2015

Abstract Two series of amino acid derivatives containing chrysin were prepared from 7-O-carboxymethyl chrysin (4a) and 7-O-carboxypropyl chrysin (4b) and amino acid methyl esters by treatment with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxybenzotriazole as coupling reagents. The anti-proliferative activities of these derivatives in vitro against human gastric carcinoma MGC-803 cells were evaluated by the standard MTT method. The results showed that among these derivatives tested, compound N-[4-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)butyryl]-l-isoleucine methyl ester (7c) exhibited the most potent inhibitory activity against the growth of MGC-803 cells with IC50 value of 3.78 μmol/L, comparable to the positive control cisplatin. The preliminary apoptotic mechanism of compound 7c was also investigated by flow cytometry (FCM) and Western blot analysis. Results form the FCM assay demonstrated that compound 7c could induce the apoptosis of MGC-803 cells in a dose-dependent manner. And further Western blot assay indicated that 7c could induce the apoptosis through increasing protein expression of Bax and decreasing protein expression of Bcl-xl. In summary, these results suggest that compound 7c may serve as an effective chemotherapeutic candidate. © 2014 Springer Science+Business Media New York.


Liang G.,Suzhou Academy of Wumen Chinese Medicine | Song X.,Suzhou Academy of Wumen Chinese Medicine | Xu H.,Suzhou Academy of Wumen Chinese Medicine | Wang F.,Suzhou Academy of Wumen Chinese Medicine | And 3 more authors.
Experimental and Clinical Endocrinology and Diabetes | Year: 2015

A recent study found an increased level of 3DG during oral glucose load in healthy individuals, which redirects our attention to the effect of high plasma 3DG level in the pathophysiology of type 2 diabetes mellitus. We found previously that abnormally elevated plasma 3DG was significantly associated with the impaired glucose regulation in non-diabetic seniors. The current study aimed to investigate the acute effects of exogenous 3DG on plasma 3DG levels, glucose tolerance and insulin levels. A significant increase in the plasma level of 3DG was observed in rats administrated 50 mg/kg 3DG i. v. even 2 h after. With the acute elevation of circulating 3DG, intravenous glucose tolerance of normal rats was impaired, whereas plasma insulin levels were higher. The 3DG-mediated impairment in glucose tolerance was associated with the attenuated insulin-stimulated glucose uptake in the adipose and liver tissues and the decreased glucose-stimulated insulin secretion in the pancreas tissue. In rats treated with 50 mg/kg 3DG i. v., a reduced phosphorylation of p85-PI3K was observed in both the liver and pancreas tissues. The increase in plasma levels of 3DG and the deleterious effects of 3DG were attenuated by aminoguanidine pretreatment. Our results indicated a close association of 3DG with diabetes through participating in inducing acute glucose intolerance involvement of PI3K signaling in healthy individuals. By such a mechanism, a 3DG-targeted intervention to attenuation of the acute elevation of circulating 3DG is promising new therapeutic and prevention strategies for diabetes and its complications. Copyright © 2015, Georg Thieme Verlag KG. All rights reserved.


Wang F.,Suzhou Academy of Wumen Chinese Medicine | Zhou L.,Suzhou Academy of Wumen Chinese Medicine | Song X.,Suzhou Academy of Wumen Chinese Medicine | Liang G.,Suzhou Academy of Wumen Chinese Medicine | And 3 more authors.
Experimental and Clinical Endocrinology and Diabetes | Year: 2016

Secretion of glucagon-like peptide-1 has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. 3-Deoxyglucosone, a dietary composition, has been suggested as an independent factor for the development of prediabetes. A-pathophysiological very high condition of 3DG concentrations administered i. v. induced acute glucose intolerance in rats. In this study, to examine the acute effects of single intragastric administration of 3DG at dose of potentially single-meal intake on plasma glucose, insulin, glucagon, total GLP-1 and total GIP levels in response to a glucose load, OGTT was performed immediately in normal Kunming mice or Sprague-Dawleys rats after 3DG administration. GLP-1 secretion, intracellular cAMP levels and 2-NBDG uptake were examined in STC-1 cells exposured to 3DG. In rats, 20 mg/kg 3DG i.g. (3DG-20 i.g.) impaired glucose tolerance (P<0.05) with increased AUC (1 070±105.2 vs. 918.0±91.20, P<0.05). The mice treated with 3DG-20 i.g. exhibited a similar effect, independent of the effect of plasma 3DG concentration. 3DG-20 i.g. treatment reduced plasma insulin concentrations with decreased AUC (3 552±300.2 vs. 4 715±420.5, P<0.05) in rats whereas plasma glucagon levels were not significantly different. These changes occurred in conjunction with decreased plasma GLP-1 and GIP levels (P<0.05). Furthermore, non-cytotoxic 3DG concentrations directly reduced GLP-1 secretion in STC-1, at least in part, by decreasing intracellular cAMP level and glucose uptake. We demonstrated for the first time that single intragastric administration of 3DG resulted in acute reduction of incretin effect and glucose intolerance, which was associated with a decrease in the biological function of GLP-1 by decreasing GLP-1 secretion. Copyright © 2016, Georg Thieme Verlag KG. All rights reserved.


Jiang G.-R.,Suzhou Academy of Wumen Chinese Medicine | Ge H.-N.,Suzhou Academy of Wumen Chinese Medicine | Liang G.-Q.,Suzhou Academy of Wumen Chinese Medicine | Zhou L.,Suzhou Academy of Wumen Chinese Medicine | Zhang L.-R.,Suzhou Academy of Wumen Chinese Medicine
Asian Pacific Journal of Tropical Medicine | Year: 2016

Objective: To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer. Methods: A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid (24 rats with sham operation served as sham operation group), and were randomly divided into model group (n = 30), western medicine group (n = 30), traditional Chinese medicine (TCM) group (n = 24) and combination group (combined western medicine and TCM group, n = 30). Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon; TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon. Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed. Twenty-eight days after gavage, interleukin (IL)-1β was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group. Results: Compared with model group and western medicine group, treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer, and increase the healing rate and inhibition rate of peptic ulcer. After IL-1β-induced ulcer recurrence, combination group was significantly superior to model group and western medicine group in ulcer recurrent rate [50% (3/6) vs. 100% (6/6)] and severity. Conclusions: Basic acid-suppression therapy combined with Qi-Replenishing and Blood-Activating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence. © 2016 Hainan Medical College.


Liang G.,Suzhou Academy of Wumen Chinese Medicine | Wang F.,Suzhou Academy of Wumen Chinese Medicine | Song X.,Suzhou Academy of Wumen Chinese Medicine | Zhang L.,Suzhou Academy of Wumen Chinese Medicine | And 2 more authors.
Molecular Medicine Reports | Year: 2016

3-Deoxyglucosone (3DG), a highly reactive dicarbonyl intermediate generated during glycation, has been confirmed to be markedly elevated in the plasma of patients with diabetes. Our previous study found that there is an association between increasing accumulation of plasma 3DG and impaired glucose regulation in non-diabetic seniors (females, >50 years old; males, >55 years old). It was also found that 3DG led to impaired plasma glucose homeostasis in healthy mice, however, the mechanisms underlying the deleterious effect of 3DG in diabetes remain to be fully elucidated. The present study aimed to investigate the ability of 3DG to cause hepatic insulin resistance in a cell model by assessing glucose uptake and glycogen content. In addition, the molecular signaling events, including the phosphoinositide 3-kinase (PI3K)/AKT/glucose transporter 2 (GLUT2) and PI3K/AKT/glycogen synthase kinase-3 (GSK-3) pathways, which affect hepatic insulin resistance, were further investigated using Western blot analysis. The results showed that 3DG (10-300 ng/ml) had no significant effect on HepG2 cell viability, however, the viability of the HepG2 cells decreased with exposure to concentrations of 500 and 1,000 ng/ml. Treatment with non-cytotoxic 3DG concentrations resulted in decreased uptake of glucose and glycogen content with insulin stimulation, but not under basal conditions. The insulin-induced expression of GLUT2 and p-GSK-3 were eliminated by 3DG (80 and 300 ng/ml), in addition to inhibiting the phosphorylation of downstream effectors of the insulin signaling pathway, including insulin receptor substrate 1, PI3K and AKT. In conclusion, the findings of the present study indicated that the addition of exogenous 3DG directly contributed to the induction of insulin resistance by impairing insulin signaling in the HepG2 cells, which suggested that 3DG may be involved in worsening of the diabetic condition.


PubMed | Suzhou Academy of Wumen Chinese Medicine
Type: | Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association | Year: 2016

Secretion of glucagon-like peptide-1 has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. 3-Deoxyglucosone, a dietary composition, has been suggested as an independent factor for the development of prediabetes. A-pathophysiological very high condition of 3DG concentrations administered i.v. induced acute glucose intolerance in rats. In this study, to examine the acute effects of single intragastric administration of 3DG at dose of potentially single-meal intake on plasma glucose, insulin, glucagon, total GLP-1 and total GIP levels in response to a glucose load, OGTT was performed immediately in normal Kunming mice or Sprague-Dawleys rats after 3DG administration. GLP-1 secretion, intracellular cAMP levels and 2-NBDG uptake were examined in STC-1 cells exposured to 3DG. In rats, 20mg/kg 3DG i.g. (3DG-20 i.g.) impaired glucose tolerance (


PubMed | Suzhou Academy of Wumen Chinese Medicine
Type: Journal Article | Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association | Year: 2016

A recent study found an increased level of 3DG during oral glucose load in healthy individuals, which redirects our attention to the effect of high plasma 3DG level in the pathophysiology of type 2 diabetes mellitus. We found previously that abnormally elevated plasma 3DG was significantly associated with the impaired glucose regulation in non-diabetic seniors. The current study aimed to investigate the acute effects of exogenous 3DG on plasma 3DG levels, glucose tolerance and insulin levels. A significant increase in the plasma level of 3DG was observed in rats administrated 50mg/kg 3DG i.v. even 2h after. With the acute elevation of circulating 3DG, intravenous glucose tolerance of normal rats was impaired, whereas plasma insulin levels were higher. The 3DG-mediated impairment in glucose tolerance was associated with the attenuated insulin-stimulated glucose uptake in the adipose and liver tissues and the decreased glucose-stimulated insulin secretion in the pancreas tissue. In rats treated with 50mg/kg 3DG i.v., a reduced phosphorylation of p85-PI3K was observed in both the liver and pancreas tissues. The increase in plasma levels of 3DG and the deleterious effects of 3DG were attenuated by aminoguanidine pretreatment. Our results indicated a close association of 3DG with diabetes through participating in inducing acute glucose intolerance involvement of PI3K signaling in healthy individuals. By such a mechanism, a 3DG-targeted intervention to attenuation of the acute elevation of circulating 3DG is promising new therapeutic and prevention strategies for diabetes and its complications.


PubMed | Suzhou Academy of Wumen Chinese Medicine
Type: Journal Article | Journal: Asian Pacific journal of tropical medicine | Year: 2016

To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer.A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid (24 rats with sham operation served as sham operation group), and were randomly divided into model group (n=30), western medicine group (n=30), traditional Chinese medicine (TCM) group (n=24) and combination group (combined western medicine and TCM group, n=30). Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon; TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon. Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed. Twenty-eight days after gavage, interleukin (IL)-1 was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group.Compared with model group and western medicine group, treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer, and increase the healing rate and inhibition rate of peptic ulcer. After IL-1-induced ulcer recurrence, combination group was significantly superior to model group and western medicine group in ulcer recurrent rate [50% (3/6) vs. 100% (6/6)] and severity.Basic acid-suppression therapy combined with Qi-Replenishing and Blood-Activating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence.


PubMed | Suzhou Academy of Wumen Chinese Medicine
Type: | Journal: Diabetology & metabolic syndrome | Year: 2016

Our recent findings support the idea that 3-deoxyglucosone (3DG), a dietary composition, has been suggested as an independent factor for the development of prediabetes. Secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. Since low oral bioavailability of 3DG has been indicated in a single administration study, in the present study we examined if 3DG is capable of accumulating in intestinal tissue of rats after 2-week administration of 3DG, and the 3DG treatment affects GLP-1 secretion and glucose tolerance.Rats were administered by gastric gavage for 2weeks. We measured 3DG contents of intestinal tissues (by HPLC), plasma levels of total GLP-1 (by ELISA), insulin and glucagon (both by radioimmunoassay) and blood glucose concentrations. The expressions of the sweet receptor subunits (TAS1R2, TAS1R3) and its downstream molecule TRPM5 in duodenum and colon tissues of rats were quantified by WB. We examined GLP-1 secretion in enteroendocrine STC-1 cells exposured to 3DG.3DG treatment for 2weeks increased 3DG content of intestinal tissues, fasting blood glucose concentration, and reduced plasma concentrations of GLP-1 and insulin at fasting and 15 and 180min after the glucose load and oral glucose tolerance in conjunction with increased plasma glucagon concentrations. The expressions of TAS1R2, TAS1R3 and TRPM5 were shown to be reduced whereas 3DG treatment did not affect plasma dipeptidyl peptidase-4 activity, indicating an impaired GLP-1 secretion in 3DG-treated rats. This idea was further supported by the fact that exposure to 3DG directly decrease GLP-1 secretion in STC-1.It is the first demonstration that 3DG was capable of accumulating in intestinal tissue and thereby decreased secretion of GLP-1 and insulin in a similar manner. 3DG-treated rats developed impaired glucose regulation (IGR) with obviously pancreatic islet cell dysfunction. It is further concluded that a decrease in the biological function of GLP-1 resulting from the decreased GLP-1 secretion is the most likely mechanism for the impaired insulin secretion, whichultimately promoted the development of IGR. These results will also contribute to a better understanding of the significance for restoring physiological GLP-1 secretion.


PubMed | Suzhou Academy of Wumen Chinese Medicine
Type: Journal Article | Journal: Molecular medicine reports | Year: 2016

3-Deoxyglucosone (3DG), a highly reactive dicarbonyl intermediate generated during glycation, has been confirmed to be markedly elevated in the plasma of patients with diabetes. Our previous study found that there is an association between increasing accumulation of plasma 3DG and impaired glucose regulation in non-diabetic seniors (females,>50 years old; males, >55 years old). It was also found that 3DG led to impaired plasma glucose homeostasis in healthy mice, however, the mechanisms underlying the deleterious effect of 3DG in diabetes remain to be fully elucidated. The present study aimed to investigate the ability of 3DG to cause hepatic insulin resistance in a cell model by assessing glucose uptake and glycogen content. In addition, the molecular signaling events, including the phosphoinositide 3kinase (PI3K)/AKT/glucose transporter2 (GLUT2) and PI3K/AKT/glycogen synthase kinase3 (GSK3) pathways, which affect hepatic insulin resistance, were further investigated using Western blot analysis. The results showed that 3DG (10300ng/ml) had no significant effect on HepG2 cell viability, however, the viability of the HepG2 cells decreased with exposure to concentrations of 500 and 1,000ng/ml. Treatment with noncytotoxic 3DG concentrations resulted in decreased uptake of glucose and glycogen content with insulin stimulation, but not under basal conditions. The insulininduced expression of GLUT2 and pGSK3 were eliminated by 3DG (80 and 300ng/ml), in addition to inhibiting the phosphorylation of downstream effectors of the insulin signaling pathway, including insulin receptor substrate1, PI3K and AKT. In conclusion, the findings of the present study indicated that the addition of exogenous 3DG directly contributed to the induction of insulin resistance by impairing insulin signaling in the HepG2 cells, which suggested that 3DG may be involved in worsening of the diabetic condition.

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