Diminished Lipid Raft SNAP23 Increases Blood Pressure by Inhibiting the Membrane Fluidity of Vascular Smooth-Muscle Cells.

Synaptosomal-associated protein 23 (SNAP23) is involved in microvesicle trafficking and exocytosis in various cell types, but its functional role in blood pressure (BP) regulation has not yet been defined. Here, we found that lipid raft SNAP23 expression was much lower in vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) than in those from normotensive Wistar-Kyoto (WKY) rats. This led us to investigate the hypothesis that this lower expression may be linked to the spontaneous hypertension found in SHR. The expression level of lipid raft SNAP23 and the fluidity in the plasma membrane of VSMCs were lower in SHR than in WKY rats. Cholesterol content in the VSMC membrane was higher, but the secreted cholesterols found in VSMC-conditioned medium and in the blood serum were lower in SHR than in WKY rats. SNAP23 knockdown in WKY rat VSMCs reduced the membrane fluidity and increased the membrane cholesterol level. Systemic overexpression of SNAP23 in SHR resulted in an increase of cholesterol content in their serum, a decrease in cholesterol in their aorta and the reduction of their BP. Our findings suggest that the low expression of the lipid raft SNAP23 in VSMCs might be a potential cause for the characteristic hypertension of SHR.

Chrysanthemum boreale flower floral water inhibits platelet-derived growth factor-stimulated migration and proliferation in vascular smooth muscle cells.

CONTEXT: Chrysanthemum boreale Makino (Compositae) (CBM) is a traditional medicine that has been used for the prevention or treatment of various disorders; it has various properties including antioxidation, anti-inflammation, and antitumor. OBJECTIVE: The present study was designed to explore the in vitro effect of CBM flower floral water (CBMFF) on atherosclerosis-related responses in rat aortic smooth muscle cells (RASMCs). MATERIALS AND METHODS: CBMFF was extracted from CBM flower by steam distillation and analyzed using gas chromatography-mass spectrometry. The anti-atherosclerosis activity of CBMFF was tested by estimating platelet-derived growth factor (PDGF)-BB (10 ng/mL)-induced proliferation and migration levels and intracellular kinase pathways in RASMCs at CBMFF concentrations of 0.01-100 µM and analyzing ex vivo aortic ring assay. RESULTS: Gas chromatography-mass spectrometry showed that the CBMFF contained a total of seven components. The CBMFF inhibits PDGF-BB-stimulated RASMC migration and proliferation (IC50: 0.010 µg/mL). Treatment of RASMCs with PDGF-BB induced PDGFR-ß phosphorylation and increased the phosphorylations of MAPK p38 and ERK1/2. CBMFF addition prevented PDGF-BB-induced phosphorylation of these kinases (IC50: 008 and 0.018 µg/mL, for p38 MAPK and ERK1/2, respectively), as well as PDGFR-ß (IC50: 0.046 µg/mL). Treatment with inhibitors of PDGFR, P38 MAPK, and ERK1/2 decreased PDGF-BB-increased migration and proliferation in RASMCs. Moreover, the CBMFF suppressed PDGF-BB-increased sprout outgrowth of aortic rings (IC50: 0.047 µg/mL). DISCUSSION AND CONCLUSION: These results demonstrate that CBMFF may inhibit PDGF-BB-induced vascular migration and proliferation, most likely through inhibition of the PDGFR-ß-mediated MAPK pathway; therefore, the CBMFF may be promising candidate for the development of herbal remedies for vascular disorders.

Chrysanthemum boreale Makino essential oil induces keratinocyte proliferation and skin regeneration.

We investigated the effect of essential oil from the flower of Chrysanthemum boreale Makino (CBMEO) on growth of human keratinocytes (HaCaTs) and explored a possible mechanism for this response. CBMEO was extracted using the steam distillation method. CBMEO contained a total of 33 compounds. CBMEO stimulated HaCaT proliferation (EC50, 0.028 µg/mL) and also induced phosphorylation of Akt and ERK1/2 in HaCaTs (EC50, 0.007 and 0.005 µg/mL, for phosphorylated Akt and ERK1/2, respectively). Moreover, CBMEO promoted wound closure in the dorsal side skin of rat tail. This study demonstrated that CBMEO can stimulate growth of human skin keratinocytes, probably through the Akt and ERK1/2 pathways. Therefore, CBMEO may be helpful in skin regeneration and wound healing in human skin, and may also be a possible cosmetic material for skin beauty.

Skin regeneration effect and chemical composition of essential oil from Artemisia Montana.

Artemisia montana Pampan (Compositae) (AMP) contains various compounds, including phenolic acids, alkaloids, and essential oil. It has been widely used in oriental medicine due to a variety of biological effects. However, the biological activity of the essential oil from AMP (AMPEO) on skin has not been investigated. In the present study, AMPEO was evaluated for its composition and its effect on cellular events (migration and proliferation) related to skin regeneration using normal human keratinocytes (HaCats). AMPEO, which was extracted by steam distillation, contained 42 components. AMPEO increased proliferation in HaCats in a dose-dependent manner (EC 50, 8.5 ng/mL) and did not affect migration. AMPEO also enhanced the phosphorylation of Akt and ERK 1/2 and induced the synthesis of type IV collagen, but not type I collagen in HaCats. In addition, AMPEO promoted wound closure in the dorsal side skin of rat tail. These results demonstrated that AMPEO extracted by steam distillation induced proliferation and synthesis of type IV collagen in human skin keratinocytes, and may thereby exert positive effects on skin regeneration and wound healing in human skin.