Differential action of pro-angiogenic and anti-angiogenic components of Danhong injection in ischemic vascular disease or tumor models.

Objective: We investigate the chemical basis and mechanism of angiogenesis regulation by a multicomponent Chinese medicine Danhong injection (DHI).

Methods: DHI was fractionated and screened for angiogenesis activities by in vitro tube formation and migration assays. The composition of DHI components was determined by UPLC.

A Defined Combination of Four Active Principles From the Danhong Injection Is Necessary and Sufficient to Accelerate EPC-Mediated Vascular Repair and Local Angiogenesis.

Many compounds in Chinese medicine formulae, including Danhong injection (DHI) formulae, are capable of stimulating angiogenesis and promoting vascular repair, but their chemical basis and action mechanisms remain poorly defined. The aim of this study is to determine the minimal native chemical composition of DHI for the pro-angiogenesis activity and to evaluate its contribution from local endothelial cells (ECs) and bone marrow-derived endothelial progenitor cells (EPCs). Our study demonstrated that the action of DHI in accelerating the recovery of hindlimb blood flow in a ischemic rat model was attributable to its local CXCR4-mediated pro-angiogenesis activity in mature endothelial cells, as well as to its ability to promote the proliferation, migration, adhesion, and angiogenesis of EPCs integrated activation of SDF-1α/CXCR4, VEGF/KDR, and eNOS/MMP-9 signal pathways.

Targeted delivery of nitric oxide via a 'bump-and-hole'-based enzyme-prodrug pair.

The spatiotemporal generation of nitric oxide (NO), a versatile endogenous messenger, is precisely controlled. Despite its therapeutic potential for a wide range of diseases, NO-based therapies are limited clinically due to a lack of effective strategies for precisely delivering NO to a specific site. In the present study, we developed a novel NO delivery system via modification of an enzyme-prodrug pair of galactosidase-galactosyl-NONOate using a 'bump-and-hole' strategy.

Danhong Injection Reversed Cardiac Abnormality in Brain-Heart Syndrome via Local and Remote β-Adrenergic Receptor Signaling.

Ischemic brain injury impacts cardiac dysfunction depending on the part of the brain affected, with a manifestation of irregular blood pressure, arrhythmia, and heart failure. Generally called brain-heart syndrome in traditional Chinese medicine, few mechanistic understanding and treatment options are available at present. We hypothesize that considering the established efficacy for both ischemic stroke and myocardial infarction (MI), Danhong injection (DHI), a multicomponent Chinese patent medicine, may have a dual pharmacological potential for treating the brain-heart syndrome caused by cerebral ischemic stroke through its multi-targeted mechanisms.

-Mediated Atherosclerosis Signaling and Inflammatory Response as a Common Protection Mechanism of Shuxuening Injection Against Both Myocardial and Cerebral Ischemia-Reperfusion Injuries.

Shuxuening injection (SXNI) is a widely prescribed herbal medicine of Ginkgo biloba extract (EGB) for cerebral and cardiovascular diseases in China. However, its curative effects on ischemic stroke and heart diseases and the underlying mechanisms remain unknown. Taking an integrated approach of RNA-seq and network pharmacology analysis, we compared transcriptome profiles of brain and heart ischemia reperfusion injury in C57BL/6J mice to identify common and differential target genes by SXNI.

Long-term evaluation of vascular grafts with circumferentially aligned microfibers in a rat abdominal aorta replacement model.

Long-term results of implants in small animal models can be used to optimize the design of grafts to further promote tissue regeneration. In previous study, we fabricated a poly(ɛ-caprolactone) (PCL) bi-layered vascular graft consisting of an internal layer with circumferentially aligned microfibers and an external layer with random nanofibers. The circumferentially oriented vascular smooth muscle cells (VSMCs) were successfully regenerated after the grafts were implanted in rat abdominal aorta for 3 months.

Specific Combination of Salvianolic Acids As Core Active Ingredients of Danhong Injection for Treatment of Arterial Thrombosis and Its Derived Dry Gangrene.

Although single-targeting anti-platelet agents are used extensively in clinics, their limitations in resistance and bleeding have started a trend of combination therapy. Danhong injection (DHI) is a widely prescribed injection medicine for cardiovascular and cerebrovascular diseases in China. However, its precise clinical efficacy and functional components remain unexplored.

Functional Modification of Electrospun Poly(ε-caprolactone) Vascular Grafts with the Fusion Protein VEGF-HGFI Enhanced Vascular Regeneration.

Synthetic artificial vascular grafts have exhibited low patency rate and severe neointimal hyperplasia in replacing small-caliber arteries (<6 mm) because of their failure to generate a functional endothelium. In this study, small-caliber (2.0 mm) electrospun poly(ε-caprolactone) (PCL) vascular grafts were modified with a fusion protein VEGF-HGFI which consists of the class I hydrophobin (HGFI) and vascular endothelial growth factor (VEGF), via hydrophobic interactions.

Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice.

Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis.

Safety evaluation of chinese medicine injections with a cell imaging-based multiparametric assay revealed a critical involvement of mitochondrial function in hepatotoxicity.

The safety of herbal medicine products has been a widespread concern due to their complex chemical nature and lack of proper evaluation methods. We have adapted a sensitive and reproducible multiparametric cell-based high-content analysis assay to evaluate the hepatic-safety of four Chinese medicine injections and validated it with classical animal-based toxicity assays. Our results suggested that the reported hepatotoxicity by one of the drugs, Fufangkushen injection, could be attributed at least in part to the interference of mitochondrial function in human HepG2 cells by some of its constituents.