Chinese Prescription Kangen-karyu Research Articles

Chinese Prescription Kangen-karyu as Potential Anti-Alzheimer’s Disease Therapeutic: Analyses of BACE1 and GSK-3b Inhibitory Activities

Inhibition of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) or glycogen synthase kinase-3β (GSK-3β) is estimated to be the central therapeutic approach for Alzheimer’s disease (AD). In this study, water extract of Kangenkaryu, its crude drug and chemical composition used in oriental medicine were evaluated regarding their BACE1 and GSK-3β inhibitory activities.Fluorescence resonance energy transfer was used to characterize the BACE1 inhibitory effect of Kangen-karyu, its crude drug and chemical composition.GSK-3β activity was determined using the Kinase-Glo Luminescent Kinase Assay Platform. The water extract of Kangen-karyu inhibited BACE1 and GSK-3β in concentration-dependent manners when compared with reference drugs, quercetin and luteolin. Among six components of Kangen-karyu, the water extracts of Salviae Miltiorrhizae Radix or Cyperi Rhizoma exhibited significant inhibitory effects on BACE1 and GSK-3β. Among the constituents of Salviae Miltiorrhizae Radix extract, salvianolic acid C, salvianolic acid A, rosmarinic acid, and magnesium lithospermate B significantly inhibited BACE1. In addition, they inhibited GSK-3β with an IC50 value range of 6.97 to 135.35 μM. From these results, one of the effectiveness and its mechanisms of action of Kangen-karyu against AD may be the inhibition of BACE1 and GSK-3β, and one of the active ingredients of Kangen-karyu is Salviae Miltiorrhizae Radix and its constituents.

Chinese Prescription Kangen-karyu against Metabolic Syndrome: Successful Treatment of Three Patients

Metabolic syndrome is the cluster of diseases, which is manifested by central obesity, impaired glucose tolerance, lipodystrophy, and high blood pressure. These metabolic syndrome-related traits significantly increase the risk of type 2 diabetes, adverse cardiac events, stroke, and hepatic steatosis. In the past decade, several organizations have proposed different diagnostic criteria. The use of traditional Chinese medicine to treat metabolic syndrome has received increasing attention due to its wide availability. In this paper, we report a case of three patients with metabolic syndrome with improved administration of 7.5 g of Kangen-karyu extract per day for 6 months. We present and discuss evidence supporting the possibility of using Kangenkaryu for metabolic syndrome.

Chinese Prescription Kangen-karyu in Treatment of Metabolic Syndrome

Metabolic syndrome is defined as a disease state complicated by multiple metabolic diseases such as hyperlipidemia, hypertension, and diabetes. Even when each individual component disease is mild, the risk of metabolic syndrome is high. Over the past decade, different organizations have been proposed various diagnostic criteria. The use of traditional Chinese medicine for the treatment of metabolic syndrome is becoming increasingly popular due to its wide availability. In this paper, we report a case of metabolic syndrome improved when a 64-year-old woman with hypertension, hypercholesterolemia, and obesity administered 7.5 g of Kangen-karyu extract per day. After 6 months, serum lipid levels were improved. The abdominal circumference, body weight, and blood pressure were decreased following administration. At that time, the physical and subjective symptoms had partially disappeared. On tongue diagnosis, there was a notable improvement in vessels below the tongue. Herein, we present evidence supporting the use of Kangen-karyu extract against metabolic syndrome.

Chinese prescription Kangen-karyu ameliorates the development of diabetic renal damage using LLC-PK1 cells and db/db mice

Chinese prescription Kangen-karyu ameliorates the development of diabetic renal damage using LLC-PK1 cells and db/db mice

Treatment of Patient with Diabetic Nephropathy using Chinese Prescription Kangen-karyu

Diabetic nephropathy is among the main causes of end-stage renal disease worldwide. The mainstay of diabetic nephropathy has been the management of hyperglycemia, blood pressure, and proteinuria using hypoglycemic agents, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. The utilization of traditional Chinese medicine to diabetic nephropathy has received increasing attention due to its wide availability, weak side-effects, and proven therapeutic mechanisms and benefits. In this paper, we report the case of a 54-year-old patient with a 10-year history of diabetes, who showed a marked improvement in diabetic nephropathy on the administration of 7.5 g of Kangen-karyu extract per day. After 6 months, estimated glomerular filtration rate had increased from 95.8 to 104.2 ml/min/1.73 m2. Urinary protein and albumin levels decreased following administration. At that time, the somatic and subjective symptoms had partially disappeared. Herein, we present and discuss the evidence supporting the use and mechanism of Kangen-karyu extract against diabetic nephropathy based on the patient.

Scientific evidence for therapeutic effects of Chinese prescription Kangen-karyu from pre-clinical animal experiments.

Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study reports therapeutic evidence for Kangen-karyu from pre-clinical animal experiments related to human diseases. Kangen-karyu showed beneficial effects on type 1 diabetes and related complications through the suppression of protein expression related to advanced glycation endproducts and oxidative stress. Kangen-karyu reduced oxidative stress via the regulation of dyslipidemia, and also exerted a renoprotective effect mainly through its antioxidant properties during the development of diabetic nephropathy in type 2 diabetes. In addition, Kangen-karyu showed neuroprotective effects by attenuating the spatial memory impairment and neuronal death induced by diabetes. Kangen-karyu counteracted oxidative stress and ameliorated tissue damage possibly associated with aging. These findings provide scientific evidence to explain the efficacy of Kangen-karyu based on its underlying therapeutic effects.

Chinese prescription Kangen-karyu and Salviae Miltiorrhizae Radix improve age-related oxidative stress and inflammatory response through the PI3K/Akt or MAPK pathways.

This study examined whether Kangen-karyu and its crude drug, Salviae Miltiorrhizae Radix, have a reno-protective effect on the age-related oxidative stress and inflammatory response through the phosphoinositide 3-kinase (PI3K)/Akt or mitogen-activated protein kinase (MAPK) pathways in aged rats. Kangen-karyu or Salviae Miltiorrhizae Radix (20 mg/kg body weight/day) was administered orally to old groups of rats for 16 days, and their effects were compared with the vehicle-treated old and young rats. The administration of Kangen-karyu caused a slight decrease in the serum glucose level and a significant decrease in the serum insulin level in the old rats. The increased levels of serum renal functional parameter (urea-nitrogen) and oxidative parameter were significantly reduced by both Kangen-karyu and Salviae Miltiorrhizae Radix. The old rats exhibited a dysregulation of the protein expression related to insulin resistance, oxidative stress, and inflammation in the kidneys, but Kangen-karyu administration significantly reduced the expression of the inflammatory proteins through the PI3K/Akt pathway. On the other hand, the Salviae Miltiorrhizae Radix-treated old rats showed a decrease in the inflammatory cytokines through the MAPK pathway. These results provide important evidence that Kangen-karyu and Salviae Miltiorrhizae Radix have a pleiotropic effect on the PI3K/Akt and MAPK pathways, showing renoprotective effects against the development of inflammation in old rats. This study provides scientific evidence that Kangen-karyu and Salviae Miltiorrhizae Radix improve the inflammatory responses via the PI3K/Akt or MAPK pathways in the kidney of old rats.

Effectiveness of Chinese prescription Kangen-karyu for dyslipi-demia, using 3T3-L1 adipocytes and type 2 diabetic mice.

The Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study was conducted to examine whether Kangen-karyu has an ameliorative effect on dyslipidemia. The effect of Kangen-karyu was evaluated using 3T3-L1 adipocytes, and also db/db mice as an experimental model for diabetic dyslipidemia. Kangen-karyu significantly inhibited adipocyte differentiation and lipid accumulation. Kangen-karyu also down-regulated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ, sterol regulatory element-binding protein (SREBP)-1c, and fatty acid synthase, and the protein levels of aP2 and PPARγ, which indicates that Kangen-karyu inhibited adipogenesis during adipocyte differentiation, and may have potential anti-dyslipidemia effects. In addition, the administration of Kangen-karyu reduced hyperlipidemia in db/db type 2 diabetic mice through a decline in the serum levels of lipids, and an improvement of lipoprotein profiles. The enhanced hepatic triglyceride level of the db/db mice was significantly reduced by Kangen-karyu administration through the down-regulation of SREBP-1 and lipogenic enzymes in the liver. These findings indicate that Kangen-karyu exerts anti-dyslipidemia effects in adipocytes and type 2 diabetic db/db mice.

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

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

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. 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 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)-β1, fibronectin and collagen IV were down-regulated by Kangen-karyu administration. 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.

Chinese prescription Kangen-karyu prevents dyslipidaemia and oxidative stress in mouse model of type 2 diabetes

We have investigated the effects of Kangen-karyu, a Chinese prescription, on the lipid metabolism and oxidative stress in a type 2 diabetes model. Male db/db mice were divided into three groups: control (vehicle), Kangen-karyu 100 or 200 mg/kg body weight/day orally administered mice. Age-matched non-diabetic m/m mice were used as a normal group. The administration of Kangen-karyu reduced hyperglycaemia and hyperlipidaemia in db/db type 2 diabetic mice through a decline in the serum levels of glucose and lipids, and an improvement of lipoprotein profiles. The increased oxidative stress in db/db mice was attenuated by the administration of Kangen-karyu through inhibiting the generation of reactive oxygen species and lipid peroxidation. The enhanced hepatic triglyceride and total cholesterol levels of the db/db mice were significantly reduced by Kangen-karyu administration through down-regulation of sterol regulatory element-binding protein-1 and lipogenic enzymes in liver. Furthermore, the expressions of hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 and inducible nitric oxide synthase protein levels were also augmented in db/db mice. However, Kangen-karyu reduced the expressions of these inflammatory proteins by inhibiting NF-κB activation in db/db type 2 diabetes. This study suggests that Kangen-karyu may improve oxidative stress via the regulation of dyslipidaemia in type 2 diabetes.

Effect of Chinese prescription Kangen-karyu on lipid metabolism in type 2 diabetic db/ db mice

Aim of the study Chinese prescription Kangen-karyu is clinically used as a treatment for cardiovascular diseases, and we have reported the beneficial effects on chemically induced hyperlipidemic animal models. The present study was investigated to evaluate the hypolipidemic effect of Kangen-karyu in type 2 diabetic db/ db mice which has not been explored yet. Materials and methods Male db/ db mice were divided into three groups, vehicle (control), Kangen-karyu 100, or 200 mg/kg body weight/day, and orally administered for 5 weeks every day. Age-matched non-diabetic m/ m mice were used as a normal group. Results Serum triglyceride (TG) and total cholesterol levels in db/ db mice were increased compared with those of m/ m mice. However, the administration of Kangen-karyu reduced hyperlipidemia in db/ db mice through a decline in the serum levels of TG and total cholesterol. The hepatic TG and total cholesterol levels of db/ db mice were markedly higher than those of m/ m mice, but these elevated lipid levels were significantly reduced by 200 mg/kg Kangen-karyu administration. Also, oil red O staining showed that the increased lipid deposition level in the liver of db/ db control mice was improved by Kangen-karyu administration. The expression of sterol regulatory element-binding protein-1 in the liver of db/ db mice was significantly down-regulated by the administration of Kangen-karyu at a dose of 200 mg/kg body weight. Kangen-karyu caused a slight elevation in the expression of peroxisome proliferator-activated receptor α in the liver of db/ db mice. Conclusions This study provides scientific evidence that Kangen-karyu improves hyperlipidemia and lipid deposition via the regulation of hepatic SREBP-1 expression in type 2 diabetic db/ db mice.

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

Abstract 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 (H2O2)-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 H2O2 treatment and inhibited senescence-associated β-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-κB) translocation in response to oxidative stress suggested that Kangen-karyu exerted its anti-aging effect through NF-κB modulation and prevention of H2O2-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.

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.

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 200 mg/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 ɛ-(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-κB, 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 (200 mg/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.

Contribution of Chinese prescription Kangen-karyu in the oxidative stress-related aging process

Contribution of Chinese prescription Kangen-karyu in the oxidative stress-related aging process

Protective effect of the Chinese prescription Kangen-karyu against high glucose-induced oxidative stress in LLC-PK 1 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 (30 mM) treatment induced LLC-PK 1 cell death, but Kangen-karyu, at a concentration of 5, 10 or 50 μg/ml, significantly inhibited high glucose-induced cytotoxicity. In addition, the intracellular reactive oxygen species level was increased by 30 mM glucose treatment, but it was concentration-dependently inhibited by Kangen-karyu treatment. Moreover, 30 mM 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 50 μg/ml, inhibited the nuclear translocation of nuclear factor-kappa B induced by 30 mM 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.