Effect of Korean Magnolia obovata Extract on Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells.

OBJECTIVE: To investigate the effects of Korean Magnolia obovata crude extract (KME) on plateletderived growth factor (PDGF)-BB-induced proliferation and migration of vascular smooth muscle cells (VSMCs). METHODS: KME composition was analyzed by high-performance liquid chromatography (HPLC). VSMCs were isolated from the aorta of a Sprague-Dawley rat, incubated in serum free-Dulbecco's modified Eagle's medium in the presence or absence of KME (10, 30, 100, and 300 µg/mL), then further treated with PDGF-BB (10 ng/mL). VSMC proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and VSMC migration was determined using the Boyden chamber and scratch wound healing assays. Western blot analysis was used to detect phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2), protein kinase B (p-Akt), and stress-activated protein kinase/c-Jun NH2-terminal kinase (p-SAPK/JNK). The antimigration and proliferation effects of KME were tested using aortic sprout outgrowth. RESULTS: The HPLC analysis identified honokiol (0.45 mg/g) and magnolol (0.34 mg/g) as the major components of KME. KME (30, 100, and 300 µg/mL) significantly decreased the proliferation and migration of PDGF-BB-stimulated (10 ng/mL) VSMCs and the PDGF-BB-induced phosphorylation of EKR1/2, Akt, and SAPK/JNK (P<0.05). Furthermore, PDGF-BBinduced VSMCs treated with 300 µg/mL of KME showed reduction in aortic sprout outgrowth. CONCLUSION: KME could inhibit abnormal proliferation and migration of VSMCs by down-regulating the phosphorylation of EKR1/2 and Akt. Thus, KME might be a functional food for preventing vascular disorders.

Gintonin, a ginseng-derived exogenous lysophosphatidic acid receptor ligand, enhances blood-brain barrier permeability and brain delivery.

Gintonin is a ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin induces [Ca2+]i transient and biological effects through LPA receptor and increases the permeability of the blood-brain barrier (BBB). However, little is known about its mechanisms on the BBB. We examined the in vitro effects of gintonin using primary human brain microvascular endothelial cells (HBMECs) and the in vivo effects of gintonin on brain delivery. Fluorescent-labeled gintonin bound to HBMECs and co-localized with the LPA1 receptor. Gintonin caused morphological changes, increased junctional spaces, and induced differential effects on junctional protein levels such as vascular endothelial-cadherin, occludin, zonula occludens 1, and claudin-5, in HBMECs. Gintonin led to the opening of gap junctions between HBMECs, and allowed Texas red-dextran to enter the cells, which was blocked by Ki16425, an LPA1/3 receptor antagonist, and Y27632, a Rho-associated kinase inhibitor. Intravenous administration of gintonin in rodents also increased the delivery of fluorescein isothiocyanate-dextran or erythropoietin to the brain. Furthermore, fluorescent-labeled gintonin bound to endothelial cells, neurons, and glia in the brain following its entry. Our findings show that gintonin facilitates entry to the brain through the paracellular pathway. Thus, gintonin may be an herbal medicine-derived candidate to overcome the BBB in drug delivery.

The effects of light-emitting diode irradiation at 610 nm and 710 nm on murine T-cell subset populations.

OBJECTIVE: The aim of this study was to investigate the effects of light-emitting diode (LED) irradiation (radiant power, 0.047 mW; irradiation area, 1.13 cm(2)) at 610 nm and 710 nm on T-lymphocyte subset populations and cytokine expression using an in vivo rat model. BACKGROUND DATA: The proliferation of CD4+ T lymphocytes was induced by polychromatic visible polarized light at the range of 540-780 nm in a previous study, but the specific target wavelength for this effect has not yet been identified. METHODS: Before and after 4 weeks of LED phototherapy, whole blood samples were collected from 610 nm, 710 nm, and control groups. The percentages of CD4+ and CD8+ T lymphocyte populations were determined by flow cytometry. The transcript levels of representative cytokines of CD4+ T-cell (interleukin [IL]-4, interferon [IFN]gamma) and proinflammatory cytokines (IL-1beta, IL-6) were assessed with the reverse transcriptase-polymerase chain reaction. RESULTS: The population of CD4+ T cells increased significantly in 710 nm group on day 28 (p < 0.05), but it did not increase in the 610 nm or control group. The population of CD8+ T cells did not show any significant change after irradiation in all groups. The mRNA expression of IL-4 increased in both the 610 nm and 710 nm groups compared to the control group, but IFNgamma was not detected in any group. The transcripts of IL-1beta and IL-6 were slightly induced in the 710 nm group. CONCLUSION: The in vivo irradiation of 710 nm wavelength LED significantly increases the population of murine CD4+ T cells, which suggests that this new phototherapeutic regimen might be promising for CD4+ T lymphocyte-mediated immune modulation therapy.