Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis

Danlou tablet (DLT), a commercial Chinese patent medicine, has been widely used to treat cardiovascular diseases for many years. Atherosclerosis (AS) is the leading cause of cardiovascular disease. Increasing evidence indicates that autophagy plays a vital role in the development of AS. Here we investigated whether DLT could activate autophagy to improve AS and further clarified its underlying mechanisms. In an ApoE−/− mice model, the results of Oil red O, Masson’s trichrome, and H&E staining techniques showed that DLT significantly inhibited lipid accumulation and fibrosis formation in atherosclerotic plaque tissue. DLT also inhibited serum triglyceride, cholesterol, and low-density lipoprotein levels and suppressed serum levels of inflammatory factors interleukin-6 and tumor necrosis factor-α in ApoE−/− mice. Moreover, DLT suppressed proliferation, migration, and invasion of human vascular adventitial fibroblasts (HVAFs) by inhibiting the PI3K/Akt/mTOR pathway. In addition, western blot analysis showed that Danlou tablet treatment decreased the expression of p62 and increased Beclin 1 and LC3 I -to-LC3 II ratios in HVAFs. The role of autophagy in treating atherosclerosis by DLT is confirmed by 3-methyladenine (autophagy inhibitor) and rapamycin (autophagy activator) in HVAFs. In summary, DLT activated PI3K/Akt/mTOR-mediated autophagy of vascular adventitial fibroblasts to protect cells from damage caused by atherosclerosis.

Effective Components-Targets-Mechanism-Chinese Prescription Strategy (ETMC), A New Strategy for Chinese Prescription Development: A Case Study in Danlou Tablet

Background: Chinese prescription is a combination medicine used by Chinese medical workers to treat various diseases and has saved countless human lives. By studying the effective substances, therapeutic targets, and mechanism of Chinese prescription, Western researchers can better understand the great value of Chinese prescription. Methods: In this study, a new strategy was proposed for the development of Chinese prescription: the effective components (E)-targets (T)-mechanism (M)-Chinese prescription (C) strategy, namely the ETMC strategy. Results: The proposed strategy used the chemical compositions of the Chinese prescription as the source of ligands to predict the corresponding targets for discovering the mechanism of Chinese prescription, which was helpful to further screen out effective substances from the chemical compositions of Chinese prescription. Here an example on development of Danlou tablet was performed to introduce the application of ETMC. Conclusions: A novel strategy for Chinese prescription development, ETMC, along with its application was provided in the current study, which contributed to the further development, wider application and internationalization of Chinese prescription.

Efficacy of Danlou Tablet in Patients with Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from a Multicentre, Placebo-Controlled, Randomized Trial

This study seeks to investigate potential cardioprotection of Danlou Tablets in patients undergoing PCI with non-ST elevation acute coronary syndrome (NSTE-ACS). 219 patients with NSTE-ACS were randomised to Danlou Tablet pretreatment (n=109) or placebo (n=110). No patients received statins prior to PCI and all patients were given atorvastatin (10 mg/day) after procedure. The main endpoint was the composite incidence of major adverse cardiac events (MACEs) within 30 days after PCI. The proportion of patients with elevated levels of cTn I>5 × 99% of upper reference limit was significantly lower in the Danlou Tablet group at 8 h (22.0% versus 34.5%, p=0.04) and 24 h (23.9% versus 38.2%, p=0.02) after PCI. The 30-day MACEs occurred in 22.0% of the Danlou Tablet group and 33.6% in the placebo group (p=0.06). The incidence of MACE at 90-day follow-up was significantly decreased in the Danlou Tablet group compared to the placebo group (23.9% versus 37.3%, p=0.03). The difference between the groups at 90 days was the incidence of nonfatal myocardial infarction (22% versus 34.5%, p=0.04). These findings might support that treatment with Danlou Tablet could reduce the incidence of periprocedural myocardial infarction in patients with ACS undergoing PCI.