PMID- 19000375
OWN - NLM
STAT- MEDLINE
DCOM- 20090127
LR  - 20131121
IS  - 0022-3573 (Print)
IS  - 0022-3573 (Linking)
VI  - 60
IP  - 12
DP  - 2008 Dec
TI  - Total triterpene acids, active ingredients from Fructus Corni, attenuate diabetic 
      cardiomyopathy by normalizing ET pathway and expression of FKBP12.6 and SERCA2a 
      in streptozotocin-rats.
PG  - 1687-94
LID - 10.1211/jpp/60.12.0016 [doi]
AB  - Total triterpene acids (TTAs) isolated from Cornus officinalis Sieb., one of the 
      herbs contained in Liuwei Dihuang decoction, were aimed at alleviating diabetic 
      cardiomyopathy. We hypothesized that the benefits of TTAs may result from 
      suppressing the endothelin-reactive oxidative species (ET-ROS) pathway in the 
      myocardium. Diabetes was produced by a single injection of streptozotocin (STZ, 
      60 mg kg(-1), i.p.) in rats. Assessment of cardiac function, calcium handling 
      proteins, endothelin-1 (ET-1) and redox system was conducted 8 weeks after STZ 
      injection. Medication with TTAs (50 mg kg(-1), i.g.) was installed in the last 4 
      weeks. The compromised cardiac function was characterized by depressed 
      contractility (LVSP and LV+dp/dt(max)) and relaxation (LVEDP and -LVdp/dt(min)) 
      in association with hyperglycaemia (30.2 +/- 2.6 mmol L(-1)) in STZ-injected 
      rats. Down-regulated expression of FKBP12.6 (calstabin 2), sarcoplasmic reticulum 
      Ca(2+)-ATPase 2a (SERCA2a) and phospholamban (PLB) were also found. These changes 
      occurred in connection with an increased ET-1, up-regulated mRNA of propreET-1 
      and endothelin converting enzyme (ECE), and a state of oxidant stress was found 
      by increased malondialdehyde (MDA), decreased superoxide dismutase (SOD) and 
      glutathione peroxidase (GSH-px) activity, and an enhanced activity and expression 
      of inducible nitric oxide synthase (iNOS) in the diabetic myocardium. After 4 
      weeks of treatment with TTAs, these changes were alleviated dramatically despite 
      a mild reduction in hyperglycaemia (26.9 +/- 3.4 mmol L(-1)). In conclusion, 
      TTAs, as active ingredients of Liuwei Dihuang decoction, alleviated diabetic 
      cardiomyopathy by normalizing the abnormality of FKBP12.6 and SERCA2a and ET-ROS 
      pathway in the myocardium rather than by hypoglycaemic activity.
FAU - Qi, Min-You
AU  - Qi MY
AD  - Research Division of Pharmacology, China Pharmaceutical University, Nanjing, 
      Jiangsu 210009, China.
FAU - Liu, Hao-Ran
AU  - Liu HR
FAU - Dai, De-Zai
AU  - Dai DZ
FAU - Li, Na
AU  - Li N
FAU - Dai, Yin
AU  - Dai Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Endothelin-1)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Triterpenes)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - EC 5.2.1.- (tacrolimus binding protein 1B)
SB  - IM
MH  - Animals
MH  - Cardiomyopathies/*drug therapy/etiology
MH  - Cornus/*chemistry
MH  - Diabetes Complications/*drug therapy
MH  - Diabetes Mellitus, Experimental/complications
MH  - Endothelin-1/drug effects/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Myocardium/pathology
MH  - Oxidation-Reduction/drug effects
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/drug effects/metabolism
MH  - Streptozocin
MH  - Tacrolimus Binding Proteins/drug effects/metabolism
MH  - Triterpenes/isolation & purification/*pharmacology
EDAT- 2008/11/13 09:00
MHDA- 2009/01/28 09:00
CRDT- 2008/11/13 09:00
PHST- 2008/11/13 09:00 [pubmed]
PHST- 2009/01/28 09:00 [medline]
PHST- 2008/11/13 09:00 [entrez]
AID - 10.1211/jpp/60.12.0016 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2008 Dec;60(12):1687-94. doi: 10.1211/jpp/60.12.0016.