Abstract
Compound Danshen dripping pills (CDDP) is widely used for the treatment of coronary arteriosclerosis and ischemic heart diseases for decades of years. In our study, we interestingly discovered the effects and mechanism of CDDP on insulin resistance that increase the risk factor of cardiovascular diseases. Effects of CDDP on fasting blood glucose, the insulin tolerance test (ITT), the oral glucose tolerance test (OGTT), hepatic function, and underlying mechanism were analyzed in ob/ob mice. CDDP was found improving the impaired insulin signal sensitivity of ob/ob mice by ameliorating insulin and glucose tolerance, improving hepatic phosphorylation of the insulin receptor substrate-1 on Ser 307 (pIRS1) of ob/ob mice, and restoring hepatic function by decreasing serum ALT and AST, which increased in ob/ob mice serum. Decreasing hepatic phosphorylation of pancreatic ER kinase (PERK) and inositol-requiring enzyme-1 (IRE1) regulating hepatic ER stress in the liver of ob/ob mice were increased by CDDP. Furthermore, CDDP was also found stimulating ob/ob mice hepatic autophagy by increasing the expression of Beclin1 and LC3B, while decreasing P62 expression. Our study discovered an important role of CDDP on improving ob/ob mice insulin resistance and liver function probably through relieving hepatic ER stress and stimulating hepatic autophagy, which would broaden the application value and provide more benefits for treating cardiovascular patients. This trial is registered with NCT01659580.
Highlights
Introduction® Dantonic ) launched in 1995 by the China Food and Drug
Compound Danshen dripping pills (CDDP, known as® Dantonic ) launched in 1995 by the China Food and DrugAdministration (CFDA) for the treatment of angina pectoris (AP) has a rich clinical history for the past 24 years with an estimated more than 450 million patients in China [1], and it has been approved to enter the phase III (NCT01659580) clinical trial by the US Food and Drug Administration in 2016 [2]
Male ob/ob mice of 6 weeks maintained a higher level of blood glucose within 2 hours after intraperitoneal injection of insulin (Figure 1(a)) and a significant increase of the serum ALT and AST level (Figure 1(b)). e result of the insulin tolerance test showed a significantly lower blood glucose level at 30, 60, and 90 minute time points after an intraperitoneal injection of insulin in mice which received CDDP compared to the control group (Figure 1(c))
Summary
® Dantonic ) launched in 1995 by the China Food and Drug. Administration (CFDA) for the treatment of angina pectoris (AP) has a rich clinical history for the past 24 years with an estimated more than 450 million patients in China [1], and it has been approved to enter the phase III (NCT01659580) clinical trial by the US Food and Drug Administration in 2016 [2]. CDDP is widely applied for the treatment of cardiovascular events such as AP, ischemic heart diseases, and coronary arteriosclerosis in China [3, 4], and CDDP is marketed as a prescription or nonprescription drug for the prevention and treatment of ischemic heart diseases in Singapore, Canada, South Korea, Mongolia, and Vietnam [5]. S. miltiorrhiza extracts have positive effects on antiperoxidative damage, myocardial protection, myocardial energy metabolism improvement, and antiplatelet aggregation activities [3, 6]. CDDP was used and researched mainly based on cardiovascular protection
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