Vascular inflammation plays a crucial role in the progression of various pathologies, including atherosclerosis (AS), and thus it has become an attractive therapeutic target. The protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, is endowed with anti-inflammatory activity, but its formulation into nanocarriers may increase its bioavailability. In this study, we developed and characterized dextran shell‒iron oxide core nanoparticles loaded with PCA (MNP-Dex/PCA) and assessed their cytotoxicity and anti-inflammatory potential on cells acting as key players in the onset and progression of AS, namely, endothelial cells (EC) and monocytes/macrophages. The results showed that MNP-Dex/PCA exert an anti-inflammatory activity at non-cytotoxic and therapeutically relevant concentrations of PCA (350 μM) as supported by the reduced levels of inflammatory molecules such as MCP-1, IL-1β, TNF-α, IL-6, and CCR2 in activated EC and M1-type macrophages and functional monocyte adhesion assay. The anti-inflammatory effect of MNP-Dex/PCA was associated with the reduction in the levels of ERK1/2 and p38-α mitogen-activated protein kinases (MAPKs) and NF-kB transcription factor. Our data support the further development of dextran shell-magnetic core nanoparticles as theranostic nanoparticles for guidance, imaging, and therapy of vascular inflammation using PCA or other anti-inflammatory compounds.

• anti-inflammatory activity
• dextran
• endothelial cells
• macrophages
• magnetic nanoparticles
• protocatechuic acid

• Inflammation
• MAPK
• NFκB
• Petai
• TNF-α

• BAEC
• adhesion
• blood platelets
• endothelium
• inflammation
• silica nanoparticles

• Antioxidant
• Deoxycorticosterone acetate
• Hypertension
• Protocatechuic acid

Endothelial progenitor cells (EPCs) have an important role in the maintenance of vascular integrity and homeostasis. While there are many studies that explain EPCs mechanisms action, there are few studies that demonstrate how they interact with other emerging physiological elements such as Endothelial Microparticles (EMPs). EMPs are membranous structures with a size between 100 and 1000 nm that act as molecular information transporter in biological systems and are known as an important elements in develop different pathologies; moreover a lot of works explains that are novel biomarkers. To elucidate these interactions, we proposed an in vitro model of endothelial damage mediated by TNFalpha, in which damaged EMPs and EPCs are in contact to assess EPCs functional effects. We have observed that damaged EMPs can modulate several EPCs classic factors as colony forming units (CFUs), contribution to repair a physically damaged endothelium (wound healing), binding to mature endothelium, and co-adjuvants to the formation of new vessels in vitro (angiogenesis). All of these in a dose-dependent manner. Damaged EMPs at a concentration of 10³ MPs/ml have an activating effect of these capabilities, while at concentrations of 10⁵ MPs/ml these effects are attenuated or reduced. This in vitro model helps explain that in diseases where there is an imbalance between these two elements (EPCs and damaged EMPs), the key cellular elements in the regeneration and maintenance of vascular homeostasis (EPCs) are not fully functional, and could explain, at least in part, endothelial dysfunction associated in various pathologies.

• HUVECs
• TNFalpha
• angiogenesis
• endothelial microparticles
• endothelial progenitor cells

This paper reviews the reported pharmacological properties of protocatechuic acid (PCA, 3,4-dihydroxy benzoic acid), a type of phenolic acid found in many food plants such as olives and white grapes. PCA is a major metabolite of anthocyanin. The pharmacological actions of PCA have been shown to include strong in vitro and in vivo antioxidant activity. In in vivo experiments using rats and mice, PCA has been shown to exert anti-inflammatory as well as antihyperglycemic and antiapoptotic activities. Furthermore, PCA has been shown to inhibit chemical carcinogenesis and exert proapoptotic and antiproliferative effects in different cancerous tissues. Moreover, in vitro studies have shown PCA to have antimicrobial activities and also to exert synergistic interaction with some antibiotics against resistant pathogens. This review aims to comprehensively summarize the pharmacological properties of PCA reported to date with an emphasis on its biological properties and mechanisms of action which could be therapeutically useful in a clinical setting.

• Animals
• Anthocyanins/metabolism
• Apolipoproteins E/deficiency
• Apolipoproteins E/genetics
• Atherosclerosis/drug therapy
• Atherosclerosis/immunology
• Atherosclerosis/physiopathology
• Atherosclerosis/prevention & control
• Cell Adhesion/drug effects
• Cell Line
• Cells, Cultured
• Disease Models, Animal
• Down-Regulation
• Humans
• Hydroxybenzoates/metabolism
• Hydroxybenzoates/pharmacology
• Intercellular Adhesion Molecule-1/genetics
• Intercellular Adhesion Molecule-1/immunology
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Monocytes/cytology
• Monocytes/drug effects
• Monocytes/immunology

• Apoptosis/drug effects
• Becaplermin
• Blotting, Western
• Cardiovascular Agents/pharmacology
• Cell Proliferation/drug effects
• Cells, Cultured
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal/pharmacology
• Endothelium, Vascular/cytology
• Endothelium, Vascular/drug effects
• Humans
• Intercellular Adhesion Molecule-1/metabolism
• Muscle, Smooth, Vascular/cytology
• Muscle, Smooth, Vascular/drug effects
• Panax/chemistry
• Plant Preparations/pharmacology
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Platelet-Derived Growth Factor/metabolism
• Proto-Oncogene Proteins c-sis
• Salvia miltiorrhiza/chemistry
• Thymidine/metabolism
• Tritium
• Tumor Necrosis Factor-alpha/pharmacology
• Vascular Cell Adhesion Molecule-1/metabolism

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaertn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/reperfusion (I/R) in rats fed ethanol chronically.

METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia.

RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption.

CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

• Intestinal reperfusion injury
• Hepatic microvascular dysfunction
• Cardiotonic Pill
• Ethanol

• Animals
• Central Nervous System Depressants/pharmacology
• Drugs, Chinese Herbal/pharmacology
• Ethanol/pharmacology
• Intestines/blood supply
• Leukostasis/drug therapy
• Liver/blood supply
• Liver/drug effects
• Liver Diseases, Alcoholic/complications
• Liver Diseases, Alcoholic/drug therapy
• Male
• Microcirculation
• Rats
• Rats, Wistar
• Reperfusion Injury/drug therapy
• Reperfusion Injury/etiology
• Reperfusion Injury/prevention & control