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Phytomedicine ; 17(8-9): 626-34, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20096551

ABSTRACT

The antidiabetic actions of Paeoniae Radix involve stimulating glucose uptake and reducing glucose absorption. However, the importance of this herb in the transcriptional regulation of hepatic gluconeogenesis has not previously been investigated, although hepatic gluconeogenesis contributes the most to fasting hyperglycemia. Using rats with streptozotocin-induced diabetes and db/db mice, the dose- and time-dependent suppressive effects of the ethanol extract of Paeoniae Radix (PR-Et) on diabetic hyperglycemia and phosphoenopyruvate carboxykinase (PEPCK) transcription are first demonstrated. Second, by employing H4IIE cells, the inhibitory action of PR-Et on both dexamethasone- and 8-bromo-cAMP-induced-PEPCK expression was also confirmed without causing any cytotoxicity. In addition, this inhibitory effect could be sustained for over 24 h with repeated treatment. Most importantly, PR-Et's action was unaffected by either insulin desensitization or palmitate stimulation. Finally, paeonol and paeoniflorin, two well-known constituents in Paeoniae Radix, did not suppress PEPCK expression at testing concentration. In conclusion, it was clearly demonstrated that transcriptional inhibition of gluconeogenesis is one of the important antidiabetic actions of Paeoniae Radix. Future development of this herb as a dietary supplement or drug should bring substantial benefits for the diabetic population.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Drugs, Chinese Herbal/therapeutic use , Gluconeogenesis/drug effects , Hypoglycemic Agents/therapeutic use , Liver/drug effects , Paeonia/chemistry , Phosphoenolpyruvate Carboxykinase (GTP)/metabolism , 8-Bromo Cyclic Adenosine Monophosphate , Acetophenones/isolation & purification , Acetophenones/pharmacology , Acetophenones/therapeutic use , Animals , Benzoates/isolation & purification , Benzoates/pharmacology , Benzoates/therapeutic use , Bridged-Ring Compounds/isolation & purification , Bridged-Ring Compounds/pharmacology , Bridged-Ring Compounds/therapeutic use , Cell Line , Dexamethasone , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Gene Expression/drug effects , Gluconeogenesis/genetics , Glucosides/isolation & purification , Glucosides/pharmacology , Glucosides/therapeutic use , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Monoterpenes , Palmitic Acid/metabolism , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Phytotherapy , Plant Roots , Rats , Rats, Sprague-Dawley
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