A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice.

Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE-/-) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE-/- mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE-/- mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.

Potential mechanisms underlying cardiovascular protection by polyphenols: Role of the endothelium.

Epidemiological studies have indicated that regular intake of polyphenol-rich diets such as red wine and tea, are associated with a reduced risk of cardiovascular diseases. The beneficial effect of polyphenol-rich products has been attributable, at least in part, to their direct action on the endothelial function. Indeed, polyphenols from tea, grapes, cacao, berries, and plants have been shown to activate endothelial cells to increase the formation of potent vasoprotective factors including nitric oxide (NO) and to delay endothelial ageing. Moreover, intake of such polyphenol-rich products has been associated with the prevention and/or the improvement of an established endothelial dysfunction in several experimental models of cardiovascular diseases and in Humans with cardiovascular diseases. This review will discuss both experimental and clinical evidences indicating that polyphenols are able to promote endothelial and vascular health, as well as the underlying mechanisms.

Cacao Polyphenols Potentiate Anti-Platelet Effect of Endothelial Cells and Ameliorate Hypercoagulatory States Associated with Hypercholesterolemia.

Platelets are related to the formation of blood clots that play a crucial role in thrombosis and other cardiovascular diseases. Cocoa, derived from Theobroma cocoa, has been widely used as functional food for improving cardiovascular health. In the present study, the direct and indirect effects of cacao polyphenols (CPs) were investigated on human platelet aggregation associated with endothelial cells (ECs) senescence. In addition, the effect of CPs on high-fat diet- (HFD-) induced hypercoagulatory states in rats was evaluated. CPs directly inhibited the human platelet aggregation induced by thromboxane analogue, U46619, and treatment of CPs on senescent endothelial cells markedly restored inhibitory effect of ECs on platelet aggregation. Nitric oxide (NO) from ECs is known as modulator of platelet aggregation and CPs increased eNOS activity in ECs and coronary artery. In animal model, increased TG level induced by high fat diet (HFD) was significantly decreased by CPs administration. In addition, the HFD animal had shorter bleeding time, and CPs administration attenuated the HFD-induced changes. Taken together, the present study indicates that CPs have potent anti-platelet effects most likely by direct and indirect effect via ECs and have the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia.

The Effect of Quercus salicina Leaf Extracts on Vascular Endothelial Function: Role of Nitric Oxide.

Dysfunction of the vascular endothelium is reported as a hallmark of cardiovascular diseases. Many evidences suggest that polyphenols are associated with a decreased global mortality and might be involved in protection against cardiovascular risk. This beneficial effect of polyphenol may be due to many actions as antioxidant that increases bioavailability of nitric oxide, vasodilation or anti-hypertensive properties. To identify new natural medicine candidate for cardiovascular protection, plant extracts used in traditional medicine were evaluated by vascular reactivity system. Porcine coronary artery rings were suspended in organ chambers for the measurement of changes in isometric tension. Screening results indicated that the ethanolic extract of leaf from Quercus salicina (QSE) has been found to exhibit potent vasorelaxant activity. QSE dose-dependently induced endothelium-dependent relaxations, which were abolished by inhibitors of nitric oxide synthase (Nomega-nitro-L-arginine). In addition, QSE strongly and dose-dependently activate endothelial nitric oxide synthase (eNOS) in porcine coronary artery endothelial cell. Taken together, the present study has demonstrated that QSE is a powerful endothelium-dependentvasodilator and that this effect involves increased nitric oxide bioavailability. In conclusion, QSE could be a cardiovascular protective herbal medicine candidate associated with cardiovascular diseases and endothelial dysfunction.

Protective Effect of Salicornia europaea Extracts on High Salt Intake-Induced Vascular Dysfunction and Hypertension.

High salt intake causes and aggravates arterial hypertension and vascular dysfunction. We investigated the effect of Salicornia europaea extracts (SE) on vascular function and blood pressure. SE constituents were analyzed using high performance liquid chromatography, and SE's effect on vascular function was evaluated in isolated porcine coronary arteries. SE's vascular protective effect was also evaluated in vivo using normotensive and spontaneous hypertensive rats (SHRs). SE mainly contained sodium chloride (55.6%), 5-(hydroxymethyl)furfural, p-coumaric acid, and trans-ferulic acid. High sodium (160 mmol/L) induced vascular dysfunction; however, SE containing the same quantity of sodium did not cause vascular dysfunction. Among the compounds in SE, trans-ferulic acid accounts for the vascular protective effect. Normotensive rats fed a high-salt diet showed significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), which decreased significantly in the SE-treated groups. In SHRs, high edible salt intake significantly increased SBP, DBP, and MAP, but SE intake was associated with a significantly lower MAP. Thus, SE did not induce vascular dysfunction, and trans-ferulic acid might be at least partly responsible for the vasoprotective effect of SE. Taken together, SE could be used as an alternative to purified salt to prevent and ameliorate hypertension.

Vascular Protective Effect of an Ethanol Extract of Camellia japonica Fruit: Endothelium-Dependent Relaxation of Coronary Artery and Reduction of Smooth Muscle Cell Migration.

Camellia japonica is a popular garden plant in Asia and widely used as cosmetic sources and traditional medicine. However, the possibility that C. japonica affects cardiovascular system remains unclear. The aim of the present study was to evaluate vascular effects of an extract of C. japonica. Vascular reactivity was assessed in organ baths using porcine coronary arteries and inhibition of proliferation and migration were assessed using human vascular smooth muscle cells (VSMCs). All four different parts, leaf, stem, flower, and fruits, caused concentration-dependent relaxations and C. japonica fruit (CJF) extract showed the strongest vasorelaxation and its effect was endothelium dependent. Relaxations to CJF were markedly reduced by inhibitor of endothelial nitric oxide synthase (eNOS) and inhibitor of PI3-kinase, but not affected by inhibitor of cyclooxygenase and endothelium-derived hyperpolarizing factor-mediated response. CJF induced activated a time- and concentration-dependent phosphorylation of eNOS in endothelial cells. Altogether, these studies have demonstrated that CJF is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, PI3K-eNOS-NO pathway. Moreover, CJF attenuated TNF-α induced proliferation and PDGF-BB induced migration of VSMCs. The present findings indicate that CJF could be a valuable candidate of herbal medicine for cardiovascular diseases associated with endothelial dysfunction and atherosclerosis.

Coriander leaf extract exerts antioxidant activity and protects against UVB-induced photoaging of skin by regulation of procollagen type I and MMP-1 expression.

Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging.