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1.
Pharm Biol ; 58(1): 845-853, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32870741

ABSTRACT

CONTEXT: Cryptotanshinone (CT) is a diterpene quinone compound from Salvia miltiorrhiza Bge. Labiatae has been widely used in cardio-cerebral vascular diseases, which could be potentially effective in treating diabetic wounds. OBJECTIVE: This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice. MATERIALS AND METHODS: Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with sodium carboxymethyl cellulose (CMC-Na) or 300 mg/kg/d CT for 16 days. Wound closure was measured every two days. Body weight, fasting blood glucose, re-epithelialization, granulation, leukocyte infiltration, capillary density, collagen deposition and expressions of CXCL1, CXCL2, VEGF, Ang-1, p-eNOS, eNOS, α-SMA, MMP2 and MMP9 were analysed. Expression of VEGF and tube formation was measured in vitro with human umbilical vein endothelial cells (HUVECs). RESULTS: CT significantly accelerated rate of wound closure, as the contraction ratio increased from 68% (non-treated group) to 83% (CT-treated group) at days 16 post-injury. A significant increase was observed in re-epithelialization and granulation tissue formation. Mechanistically, CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression. CT treatment also increased blood vessel density and expression level of VEGF, Ang-1 and p-eNOS. In vitro, CT boosted expression of VEGF and tube formation of endothelial cells. Moreover, extracellular matrix (ECM) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9. CONCLUSIONS: Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Phenanthrenes/pharmacology , Wound Healing/drug effects , Animals , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 2/complications , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Fibroblasts/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Inflammation/drug therapy , Inflammation/pathology , Male , Mice , Neovascularization, Physiologic/drug effects , Time Factors
2.
Arch Pharm Res ; 43(8): 863-874, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32720163

ABSTRACT

Acute myocardial infarction (AMI) results in irreversible cardiac cell damage or death because of decreased blood flow to the heart. Apoptosis plays an important role in the process of tissue damage after myocardial infarction (MI), which has pathological and therapeutic implications. Ferulic acid (FA) is a phenolic acid endowed with strong antioxidative and cytoprotective activities. The present study aimed to investigate whether FA protects cardiomyocytes from apoptosis by regulating autophagy, which is a cellular self-digestion process, and one of the first lines of defense against oxidative stress. Apoptosis was induced by TNF-α (10 ng/mL) and cycloheximide (CHX, 5 µg/mL) in rat H9c2 cardiomyocytes. FA-inhibited TNF-α/CHX-induced apoptosis was determined by the quantification of TUNEL-positive cells, and the effect was associated with decreased ROS production and inhibited caspase3 activation. FA treatment enhanced autophagy and increased autophagy-associated protein expression, leading to an inhibition of mTOR signaling. When co-treated with 3-methyladenine (3-MA), an autophagy inhibitor, the anti-apoptotic effect of FA was attenuated. In an in vivo mouse MI model, FA treatment decreased the apoptotic cell number, reduced infarct size, and improved cardiac performance, as determined by histological and echocardiographic assessments. Taken collectively, these results suggest that FA could protect cardiomyocytes from apoptosis by enhancing autophagy.


Subject(s)
Apoptosis/drug effects , Coumaric Acids/pharmacology , Myocardial Infarction/drug therapy , Myocytes, Cardiac/drug effects , Adenine/analogs & derivatives , Adenine/pharmacology , Animals , Autophagy/drug effects , Cell Line , Cycloheximide/administration & dosage , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Myocardial Infarction/physiopathology , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Rats , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/administration & dosage
3.
Pharm Biol ; 58(1): 165-175, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32608342

ABSTRACT

Context: Astragali Radix (AR) and Angelica sinensis Radix (ASR) combinations are used to treat cardiovascular disorders.Objectives: This study investigates the protective effects of different compatibility proportions of AR and ASR on cardiac dysfunction in a C57BL/6 mouse model of myocardial infarction (MI).Materials and methods: MI mice were induced by ligation of the left coronary artery and divided into six groups: sham, vehicle, 10 mg/kg/d simvastatin and combinations of AR and ASR at different ratios, including 1:1 (AR 2.5 g/kg + ASR 2.5 g/kg), 3:1 (AR 3.75 g/kg + ASR 1.25 g/kg) and 5:1 (AR 4.17 g/kg + ASR 0.83 g/kg). Both AR-ASR combinations and simvastatin were dissolved in saline solution and given daily by gavage. The left ventricle function, infarct size, heart tissue injury, apoptosis of cardiomyocytes, leukocyte infiltrates, capillary density and expression of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, Bad, IL-1ß, IL-6, VEGF, p-Akt and p-eNOS were analysed.Results: Different combinations of AR and ASR improve cardiac function and reduce infarct size (61.15% vs. 39.3%, 42.65% and 45.5%) and tissue injury through different mechanisms. When AR was combined with ASR at ratio of 1:1, the inflammation and cardiomyocyte apoptosis were suppressed (p < 0.05, p < 0.01). The combination ratio of 3:1 exerted effect in promoting angiogensis (p < 0.05). In the combination of AR and ASR at 5:1 ratio, angiogenesis was significantly improved (p < 0.01) and the apoptosis was inhibited (p < 0.05).Conclusions: Our results reflect the regulation of multiple targets and links in herb pairs and provide an important basis for the use of AR and ASR combinations in the treatment of MI.


Subject(s)
Angelica sinensis , Astragalus Plant , Cardiotonic Agents/therapeutic use , Myocardial Infarction/drug therapy , Plant Extracts/therapeutic use , Plant Roots , Animals , Cardiotonic Agents/isolation & purification , Male , Mice , Mice, Inbred C57BL , Myocardial Infarction/metabolism , Plant Extracts/isolation & purification
4.
Cardiol Res Pract ; 2020: 4375127, 2020.
Article in English | MEDLINE | ID: mdl-32377427

ABSTRACT

Heart diseases remain the major cause of death worldwide. Advances in pharmacological and biomedical management have resulted in an increasing proportion of patients surviving acute heart failure (HF). However, many survivors of HF in the early stages end up increasing the disease to chronic HF (CHF). HF is an established frequent complication of myocardial infarction (MI), and numerous influences including persistent myocardial ischemia, shocked myocardium, ventricular remodeling, infarct size, and mechanical impairments, as well as hibernating myocardium trigger the development of left ventricular systolic dysfunction following MI. Macrophage population is active in inflammatory process, yet the clear understanding of the causative roles for these macrophage cells in HF development and progression is actually incomplete. Long ago, it was thought that macrophages are of importance in the heart after MI. Also, though inflammation is as a result of adverse HF in patients, but despite the fact that broad immunosuppression therapeutic target has been used in various clinical trials, no positive results have showed up, but rather, the focus on proinflammatory cytokines has proved more benefits in patients with HF. Therefore, in this review, we discuss the recent findings and new development about macrophage activations in HF, its role in the healthy heart, and some therapeutic targets for myocardial repair. We have a strong believe that there is a need to give maximum attention to cardiac resident macrophages due to the fact that they perform various tasks in wound healing, self-renewal of the heart, and tissue remodeling. Currently, it has been discovered that the study of macrophages goes far beyond its phagocytotic roles. If researchers in future confirm that macrophages play a vital role in the heart, they can be therapeutically targeted for cardiac healing.

5.
J Steroid Biochem Mol Biol ; 172: 149-159, 2017 09.
Article in English | MEDLINE | ID: mdl-28711487

ABSTRACT

Aucubin (AU) is an iridoid glycoside that has been shown to display estrogenic properties and has various pharmacological effects. Herein, we described the angiogenic properties of AU. In the study, hindlimb ischemia was induced by ligation of femoral artery on the right leg of ovariectomized mice. AU treatment significantly accelerated perfusion recovery and reduced tissue injury in mice muscle. Quantification of CD31-positive vessels in hindlimb muscles provided evidences that AU promoted angiogenesis in peripheral ischemia. In addition, results from quantitative PCR and western blot suggested AU induced angiogenesis via vascular endothelial cell growth factor (VEGF)/Akt/endothelial nitric oxide synthase (eNOS) signaling pathway. More interestingly, AU's angiogenic effects could be completely abolished in estrogen receptor beta (ERß) knockout mice. In conclusion, the underlying mechanisms were elucidated that AU produced pro-angiogenic effects through ERß-mediated VEGF signaling pathways. These results expand knowledge about the beneficial effects of AU in angiogenesis and blood flow recovery. It might provide insight into the ERß regulating neovascularisation in hindlimb ischemia and identify AU as a potent new compound used for the treatment of peripheral vascular disease.


Subject(s)
Angiogenesis Inducing Agents/pharmacology , Estrogen Receptor beta/genetics , Iridoid Glucosides/pharmacology , Ischemia/drug therapy , Neovascularization, Physiologic/drug effects , Phytoestrogens/pharmacology , Animals , Disease Models, Animal , Estrogen Receptor beta/deficiency , Female , Femoral Artery/surgery , Gene Expression Regulation , Hindlimb , Ischemia/genetics , Ischemia/pathology , Ischemia/surgery , Ligation , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Ovariectomy , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Recovery of Function/drug effects , Signal Transduction , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
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