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Chūō-ku, Japan

Park C.H.,University of Toyama | Noh J.S.,University of Toyama | Okamoto T.,Iskra Industry Co. | Park J.C.,Sunchon National University | Yokozawa T.,University of Toyama
Evidence-based Complementary and Alternative Medicine | Year: 2012

The present study was conducted to examine whether Kangen-karyu has an ameliorative effect on diabetes-induced alterations such as oxidative stress and apoptosis in the liver of type 2 diabetic db/db mice. Kangen-karyu (100 or 200 mg/kg body weight/day, p.o.) was administered every day for 18 weeks to db/db mice and its effect was compared with vehicle-treated db/db and m/m mice. The administration of Kangen-karyu decreased the elevated serum glucose and leptin concentrations in db/db mice, and reduced the increased oxidative biomarkers including the generation of reactive oxygen species and lipid peroxidation in the liver. The db/db mice exhibited the upregulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, NF-E2-related factor 2, heme oxygenase-1, nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase levels in the liver; however, Kangen-karyu treatment significantly reduced those expressions. Moreover, the augmented expressions of apoptosis-related proteins, Bax, cytochrome c, c-Jun N-terminal kinase (JNK), phosphor-JNK, AP-1, and caspase-3, were downregulated by Kangen-karyu administration. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of db/db mice improved by Kangen-karyu administration. Our findings support the therapeutic evidence for Kangen-karyu ameliorating the development of diabetic hepatic complications via regulating oxidative stress and apoptosis. © 2012 Chan Hum Park et al.

Park C.H.,University of Toyama | Park C.H.,Iskra Industry Co. | Lee S.L.,University of Toyama | Okamoto T.,University of Toyama | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2012

Two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) were selected to examine their actions in nephrectomized rats. Each prescription was given orally to rats for 10 weeks after the excision of five-sixths of their kidney volumes, and its effect was compared with non-nephrectomized and normal rats. Rats given Hachimi-jio-gan and Bakumi-jio-gan showed an improvement of renal functional parameters such as serum urea nitrogen, creatinine, creatinine clearance, and urinary protein. The nephrectomized rats exhibited the up-regulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, c-Jun N-terminal kinase (JNK), phosphor-JNK, c-Jun, transforming growth factor-β nuclear factor-kappa B, cyclooxygenase-2, inducible nitric oxide synthase, monocyte chemotactic protein-1, intracellular adhesion molecule-1, Bax, cytochrome c, and caspase-3, and down-regulation of NF-E2-related factor 2, heme oxygenase-1, and survivin; however, Bakumi-jio-gan administration acts as a regulator in inflammatory reactions caused by oxidative stress in renal failure. Moreover, the JNK pathway and apoptosis-related protein expressions, Bax, caspase-3, and survivin, were ameliorated to the normal levels by Hachimi-jio-gan administration. The development of renal lesions, glomerular sclerosis, tubulointerstitial damage, and arteriolar sclerotic lesions, estimated by histopathological evaluation and scoring, was strong in the groups administered Hachimi-jio-gan rather than Bakumi-jio-gan. This study suggests that Rokumi-jio-gan-containing prescriptions play a protective role in the progression of renal failure. © 2012 Chan Hum Park et al.

Hirayama A.,Tsukuba University of Technology | Okamoto T.,Iskra Industry Co. | Kimura S.,Tsukuba University of Technology | Nagano Y.,University of Tsukuba | And 4 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2016

Kangen-karyu, a prescription containing six herbs, has been shown to achieve its pharmacological effect through oxidative stress-dependent pathways in animal models. The aim of this study is to investigate the relationship between the antioxidative effect and pharmacological mechanisms of Kangen-karyu, specifically its body temperature elevating effect in humans. Healthy human volunteers, age 35 ± 15 years old, were enrolled in this study. Surface body temperature, serum nitrite, reactive oxygen species (ROS) scavenging activities, and inflammatory cytokines were investigated before and 120 min after Kangen-karyu oral intake. Kangen-karyu significantly increased the surface-body temperature of the entire body; this effect was more remarkable in the upper body and continued for more than 120 min. Accompanying this therapeutic effect, serum nitrite levels were increased 120 min after oral administration. Serum ROS scavenging activities were enhanced against singlet oxygen and were concomitantly decreased against the alkoxyl radical. Serum nitrite levels and superoxide scavenging activities were positively correlated, suggesting that Kangen-karyu affects the O2 ·l--NO balance in vivo. Kangen-karyu had no effect on IL-6, TNF-α and adiponectin levels. These results indicate that the therapeutic effect of Kangenkaryu is achieved through NO- and ROS-dependent mechanisms. Further, this mechanism is not limited to ROS production, but includes ROS-ROS or ROS-NO interactions. © 2016 JCBN.

Li B.,University of Toyama | Li B.,Nanchang University | Lee J.-B.,University of Toyama | Hayashi K.,University of Toyama | And 5 more authors.
Journal of Natural Medicines | Year: 2010

Two novel monoterpenes, sibiscolacton (1) and sibiraic acid (2), were isolated from the aerial part of Sibiraea angustata RCHD. along with seven known compounds, namely three phenylpropanoids (3-5), two flavonoids (6,7), one glucityl ferulate (8, sibirate), and a monoterpene glucoside (9, sibiskoside). The structures of 1 and 2 were established on the basis of spectroscopic and chemical data. © The Japanese Society of Pharmacognosy and Springer 2009.

Pu F.,Fukuoka University | Kaneko T.,Fukuoka University | Enoki M.,Fukuoka University | Irie K.,Fukuoka University | And 8 more authors.
Journal of Natural Medicines | Year: 2010

We previously reported that 21-day (14-day pre-ischemic and 7-day post-ischemic) treatment with Kangen-karyu (KGKR) improved spatial memory impairment and hippocampal neuronal death induced by repeated cerebral ischemia (2 × 10-min, 1-h interval) in rats. In the present study, we examined the effect of single and 14-day pre-ischemic KGKR treatment on neuronal damage in the same repeated cerebral ischemia model. Additionally, to determine the mechanisms of neuroprotection by KGKR at glutamatergic neurons, we examined the effects of KGKR on glutamate release induced by repeated cerebral ischemia in vivo, and on cell damage induced by both glutamate and kainate in primary cultured hippocampal neurons in vitro. The 14-day pre-ischemic KGKR (300 mg/kg, oral administration (p.o.)) treatment reduced neuronal damage and astrocyte expression induced by repeated cerebral ischemia. No effect was observed after single pre-ischemic KGKR treatment. Both single and 14-day KGKR treatment decreased glutamate release in the hippocampal CA1 region in intact rats; however, neither pre-ischemic KGKR treatment altered glutamate release during cerebral ischemia. In vitro, KGKR (100-1000 μg/mL) dose-dependently suppressed hippocampal neuronal damage induced by both glutamate (100 μM) and kainate (1 mM). These data suggest neuroprotection with KGKR requires continuous preischemic treatment, and that the mechanisms of protection may be involved in inhibiting the glutamatergic receptors of the post-synaptic neurons. © The Japanese Society of Pharmacognosy and Springer 2009.

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