Preparation of Red Ginseng Marc-Derived Gintonin and Its Application as a Skin Nutrient.

Ginseng is one of the traditional herbal medicines for tonic. Gintonin is a new material derived from white/red ginseng and its lysophosphatidic acids (LPAs) play as a ligand for G protein-coupled LPA receptors. Korean red ginseng marc (KRGM) is a by-product after the KRG processes. We developed a low-cost/high-efficiency method for KRGM gintonin production. We further studied the KRGM gintonin-mediated anti-skin aging effects under UVB exposure using human dermal fibroblasts (HDFs). KRGM gintonin yield is about 8%. KRGM gintonin contains a high amount of LPA C18:2, lysophosphatidylcholine (LPC), and phosphatidylcholine (PC), which is similar to white ginseng gintonin. KRGM gintonin induced [Ca2+]i transient via LPA1/3 receptors and increased cell viability/proliferation under UVB exposure. The underlying mechanisms of these results are associated with the antioxidant action of KRGM gintonin. KRGM gintonin attenuated UVB-induced cell senescence by inhibiting cellular ß-galactosidase overexpression and facilitated wound healing. These results indicate that KRGM can be a novel bioresource of KRGM gintonin, which can be industrially utilized as new material for skin nutrition and/or skin healthcare.

Neuroprotective effects of bornyl acetate on experimental autoimmune encephalomyelitis via anti-inflammatory effects and maintaining blood-brain-barrier integrity.

BACKGROUND: Bornyl acetate (BA), a chemical component of essential oil in the Pinus family, has yet to be actively studies in terms of its therapeutic effect on numerous diseases, including autoimmune diseases. PURPOSE: This study aimed to investigate the pharmacological effects and molecular mechanisms of BA on myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) mice in an animal model of multiple sclerosis (MS), a representative autoimmune disease in central nervous system. METHODS: BA (100, 200, or 400 mg/kg) was orally treated to EAE mice once daily for 30 days after immunization for the behavioral test and for the 16th-18th days for the histopathological and molecular analyses, from the onset stage (8th day) of EAE symptoms. RESULTS: BA mitigated behavioral dysfunction (motor disability) and demyelination in the spinal cord that were associated with the down-regulation of representative pro-inflammatory cytokines (interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha), enzymes (cyclooxygenase-2 and inducible nitric oxide synthase), and chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, and regulated on activation), and decreased infiltration of microglia (CD11b+/CD45+(low)) and macrophages (CD11b+/CD45+(high)). The anti-inflammatory effect of BA was related to the inhibition of mitogen-activated protein kinases and nuclear factor-kappa B pathways. BA also reduced the recruitment/infiltration rates of CD4+ T, Th1, and Th17 cells into the spinal cords of EAE mice, which was related to reduced blood-spinal cord barrier (BSCB) disruption. CONCLUSION: These findings strongly suggest that BA may alleviate EAE due to its anti-inflammatory and BSCB protective activities. This indicates that BA is a potential therapeutic agent for treating autoimmune demyelinating diseases including MS.

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.