Effects of Gintonin-Enriched Fraction in an Atopic Dermatitis Animal Model: Involvement of Autotaxin Regulation

Abstract

Ginseng extract has been used for prevention of atopic dermatitis (AD) in experimental animal models. However, little is known about its active ingredients and the molecular mechanisms underlying its anti-AD effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin, from ginseng. Gintonin, the glycolipoprotein fraction of ginseng, contains LPAs, mainly LPA C with other minor lysophospholipid components. A line of evidence showed that serum autotaxin (ATX) activity and level are significantly elevated in human AD patients compared to those in normal controls, which indicates that ATX may be involved in human AD. In a previous study, we demonstrated that gintonin exerted anti-inflammatory effects via inhibition of microglial activation and proinflammatory cytokine production by immune cells and that it strongly inhibited ATX activity. In this study, we investigated whether oral administration of the gintonin-enriched fraction (GEF) could ameliorate the symptoms of 2,4-dinitrofluorobenzene (DNFB)-induced AD in NC/Nga mice. We found that oral administration of GEF to DNFB-induced AD mice for 2 weeks reduced ear swelling and AD skin index. In addition, oral administration of GEF reduced the serum levels of immunoglobulin E, histamine, interleukin-4, and interferon-γ. Histological examination showed that oral administration of GEF attenuated skin inflammation and significantly reduced eosinophil and mast cell infiltration into the skin. Moreover, oral administration of GEF not only decreased serum ATX level but also reduced serum ATX activity. The present study shows that the anti-AD effects of ginseng might be attributed to GEF-induced anti-inflammatory activity and ATX regulation.

Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway

“…Lysophosphatidic acid (LPA) is a small bioactive phospholipid that regulates numerous cellular responses, such as proliferation, survival, and migration, mediated through six G-protein-coupled receptors (GPCRs; LPA receptors 1–6) in various cell types [ 19 , 20 ]. Recently, LPA has been reported to be involved in the manifestation of skin symptoms and skin diseases, such as itch [ 21 ], atopic dermatitis [ 22 ], scleroderma [ 23 ], and allergic skin inflammation [ 24 ]. Moreover, LPA levels are elevated in skin lesion and plasma of psoriasis patients and IMQ-induced psoriasis-like disease mice [ 16 , 18 , 25 ].…”

Bioactive lipids in gintonin-enriched fraction from ginseng

“…Interestingly, ginseng contains an extraordinarily high concentration of LPAs, especially LPA C18:2, about 10-fold greater than that in other herbal medicines and foodstuffs [9]. We previously developed a simple method for mass production of gintonin-enriched fraction (GEF) from ginseng using ethanol and water, and demonstrated that GEF exhibits various in vitro and in vivo physiological and pharmacological effects [10], [11], [12], [13], [14]. However, although we obtained qualitative evidence that GEF contains other lipid components along with LPAs [10], until now these bioactive lipids related to LPAs and other PL components of GEF have not been identified and quantified.

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Gintonin-enriched fraction improves sarcopenia by maintaining immune homeostasis in 20- to 24-month-old C57BL/6J mice

“…Mice received oral GEF (50 mg/kg/day or 150 mg/kg/day) daily for 5 weeks. Daily dosage of GEF was established referring to several studies demonstrating the bioactive effectiveness of GEF [ 22 , 29 , 30 ], and derived from the human dose (0.25 g/60 kg/day and 0.75 g/60 kg/day) in mathematical table, as described [ 31 ]. During the oral administration period, body weight and grip strength were measured weekly.…”