Hideki Hokazono

Effects of Single and Combined Administration of Fermented Barley Extract and γ-Aminobutyric Acid on the Development of Atopic Dermatitis in NC/Nga Mice

We examined the effects single and combined administration of fermented barley extract P (FBEP), prepared from barley-shochu distillery by-products, and γ-aminobutyric acid (GABA) on the development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice. Single administration of FBEP and GABA dose-dependently reduced the development of AD-like skin lesions in mice. GABA reduced the development of AD-like skin lesions by suppressing serum immunoglobulin E (IgE) and splenocyte interleukin (IL)-4 production, while FBEP reduced skin lesions without affecting the IgE or cytokine production. However, in mice with induced AD-like skin lesions, combined administration of FBEP and GABA decreased serum IgE levels and splenic cell IL-4 production, and increased splenic cell interferon-γ production. These results suggest that combined administration of FBEP and GABA alleviated AD-like skin lesions in the NC/Nga mice by adjusting the Th1/Th2 balance to a Th1-predominant immune response.

Fermented barley extract supplementation maintained antioxidative defense suppressing lipopolysaccharide-induced inflammatory liver injury in rats.

Utilizing phytochemicals in treating inflammation is becoming a viable alternative to pharmacological treatment. We have reported that fermented barley extract (FBE) effectively suppresses oxidative stress in chronically ethanol-fed rats. Here we report that FBE suppressed acute increases in oxidative stress as a response to lipopolysaccharide (LPS)-induced inflammation. Rats supplemented with FBE for 10 d showed decreases in plasma interleukin (IL)-1β, IL-6, and tumor necrosis factor-α by 25%, 34%, and 35% respectively after LPS challenge. Liver damage was significantly suppressed, as marked by a 44% decrease in plasma alanine aminotransferase. FBE supplementation sustained liver anti-oxidative enzymes, catalase, glutathione peroxidase, and superoxide dismutase, at transcriptional and enzymatic levels, thus suppressing oxidative stress markers such as plasma nitric oxide and 8-hydroxy-2′-deoxyguanosine, by 42% and 23% respectively. We concluded that active compounds in FBE effectively inhibited the propagation of inflammation by suppressing oxidative stress.

Effects of a Fermented Barley Extract on Subjects with Slightly High Serum Uric Acid or Mild Hyperuricemia

The uric acid-lowering effect and safety of a fermented barley extract P (FBEP) prepared from barley-shochu distillery by-products were investigated in a randomized, placebo-controlled, parallel-group, double-blinded study. A total of 111 subjects with serum uric acid levels of 6.0–7.9 mg/dl were provided with either a drink containing 2 g/d of FBEP (test group) or a placebo drink. After 12 weeks, the serum uric acid levels changed by −0.21±0.56 mg/dl in the test group, showing a significant decrease in comparison to those of the placebo group (+0.02±0.54 mg/dl). Additionally, the uric acid clearance in the test group showed a tendency to increase after 12 weeks more than in the placebo group (p=0.054). No abnormalities in the physical and clinical tests were observed, and no adverse diagnostic findings were attributed to the intake of the test meal. These results demonstrated the benefits and safety of the FBEP treatment to subjects with slightly high serum uric acid or mild hyperuricemia.

Effects of GABA on the expression of type I collagen gene in normal human dermal fibroblasts

We examined the effects of GABA on type I collagen gene expression in normal human dermal fibroblasts. Real-time PCR analysis indicated GABA increased the level of type I collagen transcripts, and suppressed the expression of matrix metalloproteinase-1, which is a collagen-degrading enzyme. These results suggest GABA improves the skin elasticity by regulating type I collagen expression.

GABA promotes elastin synthesis and elastin fiber formation in normal human dermal fibroblasts (HDFs)

The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner. Additionally, the expression of fibrillin-1, fibrillin-2, and fibulin-5/DANCE, but not lysyl oxidase and latent transforming factor-β-binding protein 4, were also significantly increased in HDFs. Finally, immunohistochemical analysis confirmed that treatment with GABA dramatically increased the formation of elastic fibers in HDFs. Taken together, our results showed that GABA improves skin elasticity in HDFs by upregulating elastin synthesis and elastin fiber formation.

Fermented barley extract supplementation ameliorates metabolic state in stroke-prone spontaneously hypertensive rats

We studied the effects of fermented barley extract P (FBEP) in stroke-prone spontaneously hypertensive rats (SHRSP). Male 10-week-old SHRSP were divided into three groups that were fed: an AIN-93M diet (control), a low dose of FBEP (4 g/kg; FBEP1), and a high dose of FBEP (20 g/kg; FBEP2) for three weeks. Hypertension was significantly improved by the use of FBEP supplementation. The FBEP diet improved plasma triglyceride, insulin sensitivity, enhanced plasma catalase, and superoxide dismutase activities, and decreased plasma 8-hydroxy-2′-deoxyguanosine levels. In addition, the FBEP diet upregulated hepatic antioxidative genes and modulated Nrf2 protein levels in the liver. Furthermore, a single oral dose of FBEP (2 g/kg body weight) was able to lower blood pressure in SHRSP. In conclusion, our data suggest that increased expression of hepatic antioxidative genes and modulation of Nrf2 may play a role in the regulation of metabolic diseases in SHRSP consuming a FBEP diet. Graphical Abstract Chronic administration of fermented barley extract significantly reduces systolic blood pressure in SHRSP.