Prevention of Disuse Muscle Atrophy by Dietary Ingestion of 8-Prenylnaringenin in Denervated Mice

Flavonoids have attracted considerable attention in relation to their effects upon health. 8-Prenylnaringenin (8-PN) is found in the common hop (Humulus lupulus) and assumed to be responsible for the health impact of beer consumption. We wanted to clarify the effects of prenylation on the physiological functions of dietary flavonoids by comparing the effects of 8-PN with that of intact naringenin in the prevention of disuse muscle atrophy using a model of denervation in mice. Consumption of 8-PN (but not naringenin) prevented loss of weight in the gastrocnemius muscle further supported by the lack of induction of the protein content of a key ubiquitin ligase involved in muscle atrophy, atrogin-1, and by the activation of Akt phosphorylation. 8-PN content in the gastrocnemius muscle was tenfold higher than that of naringenin. These results suggested that, compared with naringenin, 8-PN was effectively concentrated into skeletal muscle to exert its preventive effects upon disuse muscle atrophy. It is likely that prenylation generates novel functions for 8-PN by enhancing its accumulation into muscle tissue through dietary intake

Bioavailability of prenyl quercetin

Prenyl flavonoids are widely distributed in plant foods and have attracted appreciable attention in relation to their potential benefits for human health. Prenylation may enhance the biological functions of flavonoids by introducing hydrophobic properties in their basic structures. Previously, we found that 8-prenyl naringenin exerted a greater preventive effect on muscle atrophy than nonprenylated naringenin in a mouse model. Here, we aimed to estimate the effect of prenylation on the bioavailability of dietary quercetin (Q). The cellular uptake of 8-prenyl quercetin (PQ) and Q in Caco-2 cells and C2C12 myotube cells was examined. Prenylation significantly enhanced the cellular uptake by increasing the lipophilicity in both cell types. In Caco-2 cells, efflux of PQ to the basolateral side was <15% of that of Q, suggesting that prenylation attenuates transport from the intestine to the circulation. After intragastric administration of PQ or Q to mice or rats, the area under the concentration-time curve for PQ in plasma and lymph was 52.5% and 37.5% lower than that of Q, respectively. PQ and its O-methylated form (MePQ) accumulated at much higher amounts than Q and O-methylated Q in the liver (Q: 3400%; MePQ: 7570%) and kidney (Q: 385%; MePQ: 736%) of mice after 18 d of feeding. These data suggest that prenylation enhances the accumulation of Q in tissues during long-term feeding, even though prenylation per se lowers its intestinal absorption from the diet

C/Cフクゴウザイリョウ ノ チョウコウオンカ ニオケル キョウドジンセイ

Mechanical properties of carbon fiber reinforced carbon (C/C) composites, fabricated by the preformed yarn method, were studied at elevated temperature up to 2300℃ in vacuum. Various mechanical tests including tensile, flexural, interlamina shear and fracture toughness tests were carried out to evaluate temperature dependence of strength, Young\u27s modulus and fracture toughness for three kinds of laminate C/C composites with uni-directional, 0°/90° and O°/90°/±45° fiber orientations. The failure processes of C/C composites were examined mainly focused on the influence of "transverse-cracks", which bad introduced during processing

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens\u27 antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents.Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S.aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S.pneumoniae were 1.1% and 0.0%, respectively. Among H.influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively.Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis

Prevention of disuse muscle atrophy by dietary ingestion of 8-prenylnaringenin in denervated mice.

Flavonoids have attracted considerable attention in relation to their effects upon health. 8-Prenylnaringenin (8-PN) is found in the common hop (Humulus lupulus) and assumed to be responsible for the health impact of beer consumption. We wanted to clarify the effects of prenylation on the physiological functions of dietary flavonoids by comparing the effects of 8-PN with that of intact naringenin in the prevention of disuse muscle atrophy using a model of denervation in mice. Consumption of 8-PN (but not naringenin) prevented loss of weight in the gastrocnemius muscle further supported by the lack of induction of the protein content of a key ubiquitin ligase involved in muscle atrophy, atrogin-1, and by the activation of Akt phosphorylation. 8-PN content in the gastrocnemius muscle was tenfold higher than that of naringenin. These results suggested that, compared with naringenin, 8-PN was effectively concentrated into skeletal muscle to exert its preventive effects upon disuse muscle atrophy. It is likely that prenylation generates novel functions for 8-PN by enhancing its accumulation into muscle tissue through dietary intake

8-PN can prevent disuse muscle atrophy by enhancing Akt phosphorylation.

<p>(a) Muscle atrophy induced by denervation. The weight of the GM was measured after denervation for the indicated period. Open bar: sham leg (left); closed bar: denervated leg (right). Data are the mean ± S.E (n = 4). Asterisks indicate significant differences between sham and the denervated leg (Student’s <i>t</i>-test, <i>p</i><0.007). (b) Effect of dietary intake of 8-PN or naringenin on muscle atrophy. Mice consumed each flavonoid-mixed diet for 18 days, and denervation was then carried out. After 4 (black bar) or 6 (white bar) days, the level of atrophy in the GM was calculated as the ratio of the weight of denervated muscle to the weight of sham muscle in each mouse. Data are the mean ± S.E (n = 4). C: control-diet group, 8-PN: 8-PN-containing diet group. Asterisks indicate significant differences to the control diet, which was analyzed by the Tukey multiple comparison test with one-way ANOVA (day 4: <i>p</i> = 0.0034; day 6: <i>p</i> = 0.041). (c) Phosphorylation of Akt and atrogin-1 in the GM (which was collected on the 6th day after denervation) was detected by western blotting (upper) and the density of each image analyzed (bottom). The black bar and white bar in left graph denote phosphorylated Akt and total Akt, respectively. Data are the mean ± S.E (n = 4). C: control-diet group, 8-PN: 8-PN-containing diet group. *Significant differences to the control diet-denervation group (<i>p</i>0.05). #Significant differences to the control diet-sham group.</p

Pharmacokinetic parameters of flavonoids after oral administration of 8-PN and naringenin (50 mg/kg body weight) in a single dose in mice.

<p>C_max: maximum concentration in plasma; AUC: area under the plasma concentration–time curve; Tmax: time to maximum plasma concentration; T_1/2: half-life of flavonoid in the elimination phase.</p><p>Each flavonoid (50 mg/kg bw) was administered to mice once by stomach intubation. Plasma concentration was analyzed by HPLC–UV. Data are the mean ± S.E (n = 4). Asterisks indicate significant differences between two groups (C_max: <i>p</i> = 0.026; AUC: <i>p</i> = 0.0039, Student’s <i>t-</i>test).</p

Accumulation of 8-PN in the GM. (a)–(e): HPLC chromatograms for quantitative analyses of 8-PN or naringenin in the GM.

<p>Chromatograms from mice fed an 8-PN-containing diet (a) and control diet (b). Chromatograms from mice fed a naringenin-containing diet (c) and control diet (d). (a) and (b) were obtained by the analytical condition for 8-PN. (c) and (d) were obtained by the analytical condition for naringenin. These analyses were undertaken by HPLC with electrochemical detection. (e) Contents of these flavonoids in the GM as determined by HPLC analysis. Data are the mean ± S.E (n = 4). Different letters indicate significant differences analyzed by the Tukey multiple comparison test with two-way ANOVA (<i>p</i> = 0.00043).</p

Preventive effect of <i>Humulus lupulus</i> on disuse muscle atrophy.

<p>Mice consumed a <i>Humulus lupulus</i>-mixed diet for 14 days, after which denervation was carried out. After 4 days, the weight of the GM was measured. The level of atrophy was calculated to be the ratio of the weight of denervated muscle to the weight of sham muscle in each mouse. Data are the mean ± S.E (n = 3). Asterisks indicate significant differences analyzed by the Student’s <i>t</i>-test (P = 0.0046).</p