Goji Berry Juice Prevents Tumor Necrosis Factor Alpha-Induced Xerostomia in Human Salivary Gland Cells.

Sjögren's syndrome (SS) is an autoimmune disorder characterized by oral dryness that is primarily attributed to tumor necrosis factor alpha (TNF-α)-mediated reduction in saliva production. In traditional Chinese medicine, goji berries are recognized for their hydrating effect and are considered suitable to address oral dryness associated with Yin deficiency. In the present study, we used goji berry juice (GBJ) to investigate the potential preventive effect of goji berries on oral dryness caused by SS. Pretreatment of human salivary gland cells with GBJ effectively prevented the decrease in aquaporin-5 (AQP-5) mRNA and protein levels induced by TNF-α. GBJ also inhibited histone H4 deacetylation and suppressed the generation of intracellular reactive oxygen species (ROS). Furthermore, GBJ pretreatment reserved mitochondrial membrane potential and suppressed the upregulation of Bax and caspase-3, indicating that GBJ exerted an antiapoptotic effect. These findings suggest that GBJ provides protection against TNF-α in human salivary gland cells and prevents the reduction of AQP-5 expression on the cell membrane. Altogether, these results highlight the potential role of GBJ in preventing oral dryness caused by SS.

Rokumi-jio-gan-Containing Prescriptions Attenuate Oxidative Stress, Inflammation, and Apoptosis in the Remnant Kidney.

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-ß(1), 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.

Evaluation of Effects of Chinese Prescription Kangen-karyu on Diabetes-Induced Alterations such as Oxidative Stress and Apoptosis in the Liver of Type 2 Diabetic db/db Mice.

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.

Hepato-/reno-protective activity of Chinese prescription Kangen-karyu through inhibition of AGE formation and fibrosis-related protein expression in type 2 diabetes.

OBJECTIVES: This study was conducted to examine whether Kangen-karyu, a Chinese prescription, has an ameliorative effect on diabetes-induced alterations such as advanced glycation endproduct (AGE) formation or the fibrotic response in liver and kidney of type 2 diabetic db/db mice. METHODS: 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. KEY FINDINGS: The administration of Kangen-karyu decreased the elevated serum glucose concentration in db/db mice. The increased serum creatinine and urea nitrogen levels, which reflect renal dysfunction in db/db mice, were significantly lowered by Kangen-karyu administration. The db/db mice exhibited the up-regulation of AGEs and its receptor expression in liver and kidney; however, Kangen-karyu treatment significantly reduced expression except for the receptor. Moreover, the augmented expressions of fibrosis-related proteins, transforming growth factor (TGF)-ß1, fibronectin and collagen IV were down-regulated by Kangen-karyu administration. CONCLUSIONS: These results provide important evidence that Kangen-karyu exhibits a pleiotropic effect on AGE formation and fibrosis-related parameters, representing hepatoprotective and renoprotective effects against the development of diabetic complications in type 2 diabetic db/db mice.

Chinese prescription kangen-karyu ameliorates the development of diabetic hepatic damages via regulating oxidative stress and inflammation in the liver of db/db mice.

The prevention and treatment of diabetic complications are considered to be the most important for the general care of diabetic patients. We have been conducting pre-clinical animal experiments related to diabetes using kangen-karyu, a Chinese prescription, to examine its therapeutic potential. In the present study, we further studied the anti-diabetic mechanism of kangen-karyu, especially on the regulation of hyperglycemia-induced hepatic oxidative stress and inflammation in db/db mice. Kangen-karyu (100 or 200 mg/kg body weight/day, per os (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 and hepatic glucose concentration in db/db mice. The elevated expressions of p22(phox) and Nox-4 proteins (reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits) were significantly decreased after kangen-karyu treatments. The oxidative stress-related markers in hepatic tissue (reactive oxygen species, reduced glutathione/oxidized glutathione ratio, and thiobarbituric acid-reactive substance) were also significantly ameliorated by the kangen-karyu treatments. The db/db mice exhibited the up-regulation of nuclear factor-κBp65, cyclooxygenase-2, and inducible nitric oxide synthase levels in the liver; however, kangen-karyu treatment significantly reduced those expressions. Taking these into consideration, our findings support the therapeutic evidence for kangen-karyu ameliorating the development of diabetic hepatic damages via regulating oxidative stress and inflammation.

Efficacy of short-term life-review interviews on the spiritual well-being of terminally ill cancer patients.

CONTEXT: There is a little information about effective psychotherapies to enhance the spiritual well-being of terminally ill cancer patients. OBJECTIVES: The primary aim of the study was to examine the efficacy of a one-week Short-Term Life Review for the enhancement of spiritual well-being, using a randomized controlled trial. The secondary aim was to assess the effect of this therapy on anxiety and depression, suffering, and elements of a good death. METHODS: The subjects were 68 terminally ill cancer patients randomly allocated to a Short-Term Life-Review interview group or a control group. The patients completed questionnaires pre- and post-treatment, including the meaning of life domain from the Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp) scale, the Hospital Anxiety and Depression Scale (HADS), a numeric scale for psychological suffering, and items from the Good Death Inventory (Hope, Burden, Life Completion, and Preparation). RESULTS: The FACIT-Sp, Hope, Life Completion, and Preparation scores in the intervention group showed significantly greater improvement compared with those of the control group (FACIT-Sp, P<0.001; Hope, P<0.001; Life Completion, P<0.001; and Preparation, P<0.001). HADS, Burden, and Suffering scores in the intervention group also had suggested greater alleviation of suffering compared with the control group (HADS, P<0.001; Burden, P<0.007; Suffering, P<0.001). CONCLUSION: We conclude that the Short-Term Life Review is effective in improving the spiritual well-being of terminally ill cancer patients, and alleviating psychosocial distress and promoting a good death.

Ameliorating effects of Kangen-karyu on neuronal damage in rats subjected to repeated cerebral ischemia.

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 x 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 microg/mL) dose-dependently suppressed hippocampal neuronal damage induced by both glutamate (100 microM) and kainate (1 mM). These data suggest neuroprotection with KGKR requires continuous pre-ischemic treatment, and that the mechanisms of protection may be involved in inhibiting the glutamatergic receptors of the post-synaptic neurons.

Value of religious care for relief of psycho-existential suffering in Japanese terminally ill cancer patients: the perspective of bereaved family members.

OBJECTIVE: This study aimed to clarify the experience of bereaved family members of cancer patients regarding the usefulness of religious care (perceived usefulness). The value of this care to palliate psycho-existential suffering in future patients was also examined (predicted usefulness). METHODS: A questionnaire was sent to 592 bereaved family members of cancer patients who were admitted to certified palliative care units in Japan. Responses were obtained from 378 families, indicating whether the patient received religious care, the perceived usefulness of the care, and its predicted usefulness for palliation of psycho-existential suffering. RESULTS: About 25% (N=83) indicated that the patient had received religious care, whereas 75% (N=255) had not received it. Families of patients who had received religious care evaluated pastoral care workers (86%), religious services (82%), and religious music (80%) as 'very useful' or 'useful'. Families predicted usefulness of religious care for future patients: attending a religious service (very useful or useful, 56%; not useful or harmful, 44%), a religious atmosphere (48%, 52%), meeting with a pastoral care worker (50%, 50%), and religious care by physicians (26%, 74%), and nurses (27%, 73%). Families with a religion were significantly more likely to rate religious care as useful for future patients. CONCLUSIONS: Families of patients who received religious care generally evaluated this care to be very useful or useful. For future patients, some families felt that religious care would be useful, but some did not. In Japan, religious care is more likely to provide benefits to patients who have a religion.

Beneficial effects of Chinese prescription Kangen-karyu on diabetes associated with hyperlipidemia, advanced glycation endproducts, and oxidative stress in streptozotocin-induced diabetic rats.

AIM OF THE STUDY: In the present study, we investigated the effects of Kangen-karyu, a traditional Chinese prescription comprising six herbs, on diabetes. MATERIALS AND METHODS: Kangen-karyu extract (50, 100, or 200mg/kg body weight) was administered to streptozotocin (STZ)-induced diabetic rats and serum and hepatic biochemical factors, and protein expressions associated with oxidative stress and advanced glycation endproduct (AGE) formation were measured. RESULTS: The oral administration of Kangen-karyu significantly ameliorated hypertriglyceridemia induced by STZ injection, while serum levels of glucose and total cholesterol were mildly affected. Kangen-karyu also markedly reduced the levels of AGEs and malondialdehyde (MDA), a lipid peroxide product used as an indicator of oxidative stress in both serum and hepatic tissue. In addition, Kangen-karyu dose-dependently lowered the expression levels of N(epsilon)-(carboxymethyl) lysine, one of the major component of AGEs closely associated with the pathogenesis of diabetes and liver cirrhosis, and receptor for AGEs, as well as the expression levels of nuclear factor-kappaB, inducible nitric oxide synthase, and cyclooxygenase-2 (COX-2) associated with oxidative stress. Especially, MDA levels in both serum and hepatic tissue and COX-2 expression increased by STZ were recovered by Kangen-karyu (200mg/kg body weight) to normal levels. CONCLUSIONS: Kangen-karyu showed favorable effects on hypertriglycemia, AGE formation, and oxidative stress in STZ-treated rats, suggesting beneficial effects on diabetes, diabetic hepatopathy, and liver diseases such as cirrhosis, as well as cardiovascular and cerebrovascular diseases.

Neuroprotective effects of Kangen-karyu on spatial memory impairment in an 8-arm radial maze and neuronal death in the hippocampal CA1 region induced by repeated cerebral ischemia in rats.

In the present study, we investigated the neuroprotective effects of Kangen-karyu (KGK) in a repeated cerebral ischemia model (2 x 10 min, 1-h interval). A 21-day pre- and post-ischemic treatment with KGK (10 - 300 mg/kg) and aspirin (5 mg/kg) improved the spatial memory impairment and neuronal death in the hippocampal CA1 region induced by repeated cerebral ischemia. However, a 7-day post-ischemic treatment with KGK did not attenuate the spatial memory impairment and neuronal death in this model. To determine the mechanism of action of KGK, we investigated the effects of a 14-day pre-ischemic treatment with KGK on cerebral blood flow in the hippocampal area of the repeated cerebral ischemia model using laser Doppler flowmetry. The 14-day pre-ischemic treatment with KGK increased the cerebral blood flow during reperfusion. These results suggest that a 21-day pre- and post-ischemic treatment with KGK can protect against brain damage caused by cerebral ischemia by increasing the cerebral blood flow in the hippocampal area.

A pilot study of transformation, attributed meanings to the illness, and spiritual well-being for terminally ill cancer patients.

OBJECTIVE: The present study investigated what types of transformation terminally ill cancer patients experienced from diagnosis until the terminal stage, what meanings terminally ill cancer patients attributed to their illness, and whether or not those who attributed positive meaning to their illness achieved high levels of spiritual well-being as a preliminary study. METHOD: Ten terminally ill cancer patients in the hospice wards of two general hospitals participated. A clinical psychologist conducted a semistructured interview with the patients individually for about 60 min. Patients completed the FACIT-Sp and HADS before the interview and talked about the meanings of cancer experience. The contents of the interviews were analyzed qualitatively. Patients were separated into high and low levels of spiritual-well being by the median of FACIT-Sp scores. RESULTS: Three types of transformation were extracted: "group with peaceful mind," "group with both positive attitude and uneasy feeling," and "groups with uneasy feeling." As attributed meanings to the illness, five categories were extracted: "positive meaning," "natural acceptance," "negative acceptance," "search for meaning," and "regret and sorrow." Patients in the high level spiritual well-being group attributed the meaning of illness to "positive meaning" and "natural acceptance," and those in the low level spiritual well-being group attributed it to "regret and sorrow" and "search for meaning." SIGNIFICANCE OF RESULTS: Some Japanese terminally ill cancer patients experienced positive transformation, and patients who attributed "positive meaning" and "natural acceptance" to their illness experience achieved high levels of spiritual well-being.

Therapeutic efficacy of Kangen-karyu against H2O2-induced premature senescence.

The anti-aging potential of Kangen-karyu extract was investigated using the mechanisms of the cellular aging model of stress-induced premature senescence (SIPS) in TIG-1 human fibroblasts. SIPS was induced by a sublethal dose of H2O2 and chronic oxidative stress with repeat treatment of low-dose H2O2. Reactive oxygen species generation, lipid peroxidation, and senescence-associated beta-galactosidase activity were elevated in TIG-1 cells under SIPS induced by H2O2. However, Kangen-karyu extract led to significant declines in these parameters, suggesting its role in ameliorating oxidative stress-related aging. It was also observed that SIPS due to H2O2 treatment led to the loss of cell viability, whereas Kangen-karyu extract improved cell viability by attenuating H2O2-induced oxidative damage. TIG-1 cells under the condition of SIPS caused by sublethal and chronic low doses of H2O2 showed nuclear factor-kappaB (NF-kappaB) translocation to the nucleus from the cytosol, while Kangen-karyu extract inhibited NF-kappaB nuclear translocation, implying that Kangen-karyu extract could exert an anti-aging effect through NF-kappaB modulation. In addition, treatment with Kangen-karyu extract under H2O2-induced chronic oxidative stress normalized the cell cycle by reducing the number of cells in the G0/G1 phase and elevating the proportion of those in the S phase, indicating the role of Kangen-karyu extract in cell cycle regulation. On the other hand, Kangen-karyu extract did not exert such an effect on cell cycle regulation under acute oxidative stress induced by sublethal H2O2. Furthermore, treatment with Kangen-karyu extract prolonged the lifespan of TIG-1 cells under SIPS. The present study suggests that Kangen-karyu might play a therapeutic role against the aging process caused by oxidative stress.

One-week Short-Term Life Review interview can improve spiritual well-being of terminally ill cancer patients.

PURPOSE: The primary aim of this study was to assess the efficacy of the Short-Term Life Review on the spiritual well-being, as well as anxiety, depression, suffering, and happiness of terminally ill cancer patients. METHOD: Thirty patients reviewed their lives in the first session and they confirmed the contents in the album based on the life review in the second session. Duration of the treatment was one week. Measurement instruments included Functional Assessment Chronic Illness Therapy-Spiritual (FACIT-Sp), Hospital Anxiety and Depression Scale (HADS), Numeric Rating Scales of Suffering (from 0 to 6) and Happiness (from 1 to 7). RESULTS: After the therapy, the mean FACIT-Sp scores increased from 16+/-8.2 to 24+/-7.1, anxiety score significantly decreased from 6.8+/-4.7 to 3.0+/-2.2, depression score significantly decreased from 10.2+/-4.7 to 6.6+/-4.1, suffering score significantly decreased from 3.4+/-1.9 to 1.8+/-1.4, and happiness score significantly increased from 4.6+/-1.9 to 5.6+/-1.6. Total HADS scores significantly decreased from 17+/-8.6 to 9.5+/-5.4. CONCLUSION: The Short-Term Life Review is feasible and may be effective in improving the spiritual and psychosocial well-being of terminally ill cancer patients.

The protective role of Kangen-karyu against fructose-induced metabolic syndrome in a rat model.

The protective effect of Kangen-karyu extract and its mechanisms against fructose-induced metabolic syndrome have been investigated using a rat model. Male Wistar rats were fed a high fructose (65%) diet or standard chow for one week, and for two subsequent weeks were treated with 50 or 100 mg kg(-1) body weight/day Kangen-karyu extract or vehicle. Serum glucose, glycosylated protein, triglyceride (TG), total cholesterol, and blood pressure levels of high-fructose-fed rats were increased compared with those of normal rats. However, Kangen-karyu extract ameliorated the high-fructose-induced metabolic syndrome including hyperglycaemia and hypertriglyceridaemia. In addition, the increase of hepatic TG content in rats given the high fructose diet was significantly inhibited with the regulation of sterol regulatory element-binding protein (SREBP)-1 expression by Kangen-karyu extract. On the other hand, peroxisome proliferator-activated receptor alpha and SREBP-2 protein levels were not affected by the feeding of the high fructose diet or Kangen-karyu extract. Moreover, Kangen-karyu extract administration to high-fructose-fed rats markedly reduced the thiobarbituric acid-reactive substance levels in serum, hepatic homogenate, and mitochondria. Furthermore, it inhibited the increase of cyclooxygenase (COX)-2 with the regulation of nuclear factorkappa B (NF-kappaB) and bcl-2 proteins in the liver, suggesting that the protective potential of Kangenkaryu extract against metabolic syndrome would be attributed to the regulation of COX-2, NF-kappaB, and bcl-2 signalling pathways. This study indicated that Kangen-karyu extract significantly improved high-fructose-induced metabolic syndrome such as hyperglycaemia, hyperlipidaemia, and hypertension through the reductions of TG and cholesterol contents with the regulation of hepatic SREBP-1 protein and the NF-kappaB signalling pathway.

Increase in the free radical scavenging activities of American ginseng by heat processing and its safety evaluation.

We previously reported the increase in free radical scavenging activities of Korean ginseng (KG, Panax ginseng C.A. Meyer) by heat processing. In the United States, American ginseng (AG, Panax quinquefolium L.) is a more commonly used herbal medicine than KG, but heat processing-induced chemical and activity changes of AG are not well known. Therefore, we compared the changes in ginsenosides, total phenolic contents, Maillard reaction product (MRP) levels, and several free radical scavenging activities of AG by heat processing. In addition, a short-term toxicity assessment in rats was also conducted for the identification of certain toxic effects of AG after heat processing. As a result, the ginsenosides were deglycosylated at carbon-20 and their total contents were lowered, but the total phenolic contents and MRP levels of AG were about 2.5 and 9.3 times increased, respectively, by heat processing. In addition, all free radical scavenging activities of AG were significantly increased by heat processing. Moreover, there were no toxic signs or decreases in renal and hepatic function parameters of rats administered heat-processed AG. Therefore, heat processing, as in KG, is a useful method to enhance the free radical scavenging activities of AG by the increases in total phenolic contents and MRP levels.

Protective effect of Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in rats.

We have investigated the effect of the Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in-vivo in a rat model. The serum and hepatic triglyceride levels were remarkably elevated in 12-month-old compared with two-month-old rats. However, the administration of Kangen-karyu and Tanjin extracts significantly decreased these levels. This suggested a protective role against related pathological conditions as well as hyperlipidaemia. On the other hand, the reduction of the levels of adiponectin in serum with ageing did not show significant changes in rats given diets supplemented with Kangen-karyu and Tanjin extracts. Furthermore, the expression of transcription factors in nuclear hepatic tissue related to lipid metabolism was investigated. The decline in the expression of nuclear peroxisome proliferator-activated receptor alpha protein in hepatic tissue with age was ameliorated by the administration of Kangen-karyu and Tanjin supplements. On the other hand, the overexpression of sterol regulatory element-binding proteins (SREBP)-1 and SREBP-2 in old rats compared with young rats showed a tendency to decrease with Kangen-karyu and Tanjin administration. The decline of hepatic function with ageing was attenuated by Kangen-karyu and Tanjin, suggesting the beneficial role of Kangen-karyu and Tanjin on lipid metabolism through the improvement of hepatic function. This study has demonstrated that Kangen-karyu and Tanjin inhibited the accumulation of triglyceride with regulation of related protein expressions and they improved hepatic function. Evidence has been provided for the anti-ageing activity of Kangen-karyu and its crude drug Tanjin against age-related lipidosis.

Protective effect of the Chinese prescription Kangen-karyu against high glucose-induced oxidative stress in LLC-PK1 cells.

We investigated the effects of Chinese prescription Kangen-karyu on high glucose-induced oxidative stress using LLC-PK(1) cells, renal tubular cells, which are the most vulnerable renal tissue to oxidative stress. High-concentration glucose (30mM) treatment induced LLC-PK(1) cell death, but Kangen-karyu, at a concentration of 5, 10 or 50 microg/ml, significantly inhibited high glucose-induced cytotoxicity. In addition, the intracellular reactive oxygen species level was increased by 30mM glucose treatment, but it was concentration-dependently inhibited by Kangen-karyu treatment. Moreover, 30mM glucose treatment induced high levels of superoxide anion, nitric oxide and peroxynitrite. However, Kangen-karyu treatment significantly reduced the radical overproduction induced by high glucose, suggesting Kangen-karyu has radical-scavenging activity that would protect against oxidative stress induced by high glucose. Kangen-karyu also reduced the overexpression of inducible nitric oxide synthase and cyclooxygenase-2 proteins induced by high glucose. Furthermore, treatment with Kangen-karyu, at a concentration of 50mug/ml, inhibited the nuclear translocation of nuclear factor-kappa B induced by 30mM glucose in LLC-PK(1) cells. These findings indicate that Kangen-karyu is a potential therapeutic agent that will reduce the damage caused by hyperglycemia-induced oxidative stress associated with diabetes.

The protective role of Chinese prescription Kangen-karyu extract on diet-induced hypercholesterolemia in rats.

This study was carried out to investigate the protective potential of Chinese prescription Kangen-karyu, comprising six crude drugs, on coronary heart disease which is the principal cause of morbidity and mortality worldwide. The diet-induced hypercholesterolemic rat model, which shows an elevation in low density lipoprotein (LDL) cholesterol and atherosclerosis, was employed. The control rats fed a diet of 1% cholesterol and 0.5% cholic acid showed the highest cholesterol levels in serum and feces relative to those fed a normal diet, however, the rats administered Kangen-karyu extract showed reductions in these levels without changes in liver cholesterol, indicating that the reduction of serum total cholesterol by Kangen-karyu extract probably arises from an increase in cholesterol excretion. Furthermore, the administration of Kangen-karyu extract significantly prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase, known as marker enzymes of liver damage. The elevated serum levels of LDL cholesterol were lowered, however, the high density lipoprotein cholesterol level was significantly elevated by Kangen-karyu extract and these were dose-dependent decreases in the atherogenic index to 15.2, 8.8 and 7.5 at oral doses of 50, 100 and 200 mg from the 19.4 control value, respectively. In addition, Kangen-karyu extract inhibited LDL oxidation in a dose-dependent manner, and the elevated level of thiobarbituric acid-reactive substances in control rats showed a decline by the administration of Kangen-karyu extract. The present study suggests that Kangen-karyu could play a protective role against hypercholesterolemia through the regulation of cholesterol levels and inhibition of lipid peroxidation.

Effects of the Chinese prescription Kangen-karyu and its crude drug Tanjin on ageing process in rats.

The effects of the Chinese prescription Kangen-karyu and its crude drug Tanjin on the ageing process were investigated in rats. Diets supplemented with Kangen-karyu and Tanjin extracts decreased glycosylated protein levels in serum, a risk marker of ageing and ageing-related diseases. In addition, they inhibited the levels of thiobarbituric acid reactive substance in the serum and liver; Kangen-karyu in particular led to a strong decrease in hepatic mitochondrial thiobarbituric acid reactive substance. The decline in the reduced glutathione/oxidized glutathione ratio in the liver observed with ageing was ameliorated by Kangen-karyu and Tanjin, while these groups attenuated the increase in glutathione peroxidase activity of hepatic tissue against ageing. This suggests that Kangen-karyu and Tanjin regulate the glutathione redox cycle that maintains the cellular redox condition against age-related oxidative stress. Moreover, the overexpression of cytoplasmic cytochrome c observed with ageing was attenuated by Kangen-karyu and Tanjin. This provides new evidence that Kangen-karyu and Tanjin inhibit leakage of superoxide in mitochondria and attenuate cellular oxidative damage. Furthermore, Kangen-karyu and Tanjin would maintain mitochondrial function with ageing through the regulation of related protein expression such as bax and bcl-2 proteins. In addition, Kangen-karyu reduced the expression of nuclear factor kappa B; Kangen-karyu and Tanjin did not affect the expression of inhibitor kappa B. The present study demonstrated that Kangenkaryu prevented oxidative damage and mitochondrial dysfunction with ageing. Furthermore, Kangen-karyu showed a stronger protective effect against ageing by oxidative stress than Tanjin, probably through synergistic and/or additive effects.

The mechanisms underlying the anti-aging activity of the Chinese prescription Kangen-karyu in hydrogen peroxide-induced human fibroblasts.

Our previous study showed that Kangen-karyu extract protected against cellular senescence by reducing oxidative damage through the inhibition of reactive oxygen species generation and regulation of the antioxidative status. Although these findings suggest that Kangen-karyu could delay the aging process, the mechanisms responsible for protection against aging have rarely been elucidated. Therefore, this study was focussed on the mechanisms responsible for the anti-aging activity of Kangen-karyu extract using hydrogen peroxide (H(2)O(2))-induced human diploid fibroblasts, a well-established experimental model of cellular aging. Kangen-karyu extract exerted a protective effect against the morphological changes induced by H(2)O(2) treatment and inhibited senescence-associated beta-galactosidase activity. In addition, the beneficial effects of Kangen-karyu extract on cell viability and lifespan indicated that Kangen-karyu extract could delay the cellular aging process. The observation that Kangen-karyu extract prevented nuclear factor kappa B (NF-kappaB) translocation in response to oxidative stress suggested that Kangen-karyu exerted its anti-aging effect through NF-kappaB modulation and prevention of H(2)O(2)-induced overexpression of haem oxygenase-1 protein. Moreover, pretreatment with Kangen-karyu extract reduced overexpression of bax protein and prevented the mitochondrial membrane potential decline, suggesting that Kangen-karyu extract may protect mitochondria from mitochondrial oxidative stress and dysfunction. These findings indicate that Kangen-karyu is a promising potential anti-aging agent that may delay, or normalize, the aging process by virtue of its protective activity against oxidative stress-related conditions.