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

Yokozawa, Takako; Park, Chan Hum; Matsumoto, Kinzo

doi:10.5582/ddt.2016.01069

Cited by 4 publications

(7 citation statements)

References 38 publications

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“…Kangen-karyu (KK) is a formula in traditional Kampo and Chinese medicine that has been used in treating neuro-degenerative diseases, diabetes, and various symptoms related to blood circulation. A handful of studies have reported the clinical relevance of using the KK extract such as for cognitive dysfunctions in type 2 diabetic patients by attenuating central cholinergic dysfunction [ 24 ], for age-related memory deficit by normalizing neuroplasticity-related signaling, and the VEGF system in the brain [ 25 ] against oxidative tissue damage in a mouse model [ 26 ], for diabetes and diabetic complications [ 27 ], for a neuroprotective effect [ 28 ], and for a renoprotective effect against diabetic nephropathy in type 2 diabetic mice [ 29 ]. However, there are no reports of GSK-3β inhibition by KK or its components.…”

Section: Introductionmentioning

confidence: 99%

Rosmarinic Acid Derivatives’ Inhibition of Glycogen Synthase Kinase-3β Is the Pharmacological Basis of Kangen-Karyu in Alzheimer’s Disease

et al. 2018

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Inhibition of glycogen synthase kinase 3β (GSK-3β) is considered to be the central therapeutic approach against Alzheimer’s disease (AD). In the present study, boiled water extracts of the Kangen-karyu (KK) herbal mixture and its constituents were screened for GSK-3β inhibitory activity. KK is used in traditional Kampo and Chinese medicines for improving cognitive function. The GSK-3β inhibition potential was evaluated by using the Kinase-Glo luminescent kinase assay platform. Furthermore, enzyme kinetics and in silico modeling were performed by using AutoDockTools to demonstrate the mechanism of enzyme inhibition. KK extract significantly inhibited GSK-3β in a concentration-dependent manner (IC50: 17.05 ± 1.14 μg/mL) when compared with the reference drug luteolin (IC50: 2.18 ± 0.13 μM). Among the six components of KK, extracts of Cyperi Rhizoma and Salviae Miltiorrhizae Radix significantly inhibited GSK-3β with IC50 values of 20.68 ± 2.50 and 7.77 ± 1.38 μg/mL, respectively. Among the constituents of the roots of S. miltiorrhiza water extract, rosmarinic acid, magnesium lithospermate B, salvianolic acid A, salvianolic acid B, and salvianolic acid C inhibited GSK-3β with IC50 values ranging from 6.97 to 135.5 μM. Salvianolic acid B was found to be an ATP-competitive inhibitor of GSK-3β and showed the lowest IC50 value (6.97 ± 0.96 µM). In silico modeling suggested a mechanism of action by which the hydrophobic, π–cation, and hydrophilic interactions of salvianolic acid B at ATP and substrate sites are critical for the observed GSK-3β inhibition. Therefore, one of the mechanisms of action of KK against AD may be the inhibition of GSK-3β and one of the active components of KK is the root of S. miltiorrhiza and its constituents: rosmarinic acid, magnesium lithospermate B, and salvianolic acids A, B, and C. Our results demonstrate the pharmacological basis for the use of KK against AD.

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Section: Introductionmentioning

confidence: 99%

Rosmarinic Acid Derivatives’ Inhibition of Glycogen Synthase Kinase-3β Is the Pharmacological Basis of Kangen-Karyu in Alzheimer’s Disease

et al. 2018

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“…Kangen-karyu has received much attention as a source of new therapeutic agents based on pre-clinical animal experiments related to various human diseases [14][15][16][17][18][19][20][21]. To add to these findings, we reported evidence supporting its preventive and/or therapeutic potential against diabetes-induced renal damage [22][23][24][25]. The administration of Kangen-karyu reduced the increased serum glucose level in type 2 diabetic mice, and decreased the elevated oxidative and inflammatory biomarkers in the serum and kidney.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies demonstrated that Kangen-karyu exhibited favorable biological activity such as anti-aging effects, platelet aggregation inhibition, hypertension suppression, anti-dyslipidemia, aiding the recovery of learning and memory impairment induced by senescence, neuroprotection, and an anti-dementia effect in animal experiments [14][15][16][17][18][19][20][21]. Although studies have proposed the pharmacological functions of Kangen-karyu to treat various diseases, we previously reported evidence supporting its preventive and/or therapeutic potential against diabetes-induced renal damage using db/db mice, a type 2 diabetic animal model [22][23][24][25]. The results of our previous study provide important evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

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

Hiratani¹,

Shoji²,

Osanai³

et al. 2019

Arch Clin Med Case Rep

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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 sideeffects, 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 m 2 . 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.

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“…Kangen-karyu has received much attention as a source of new therapeutic agents based on pre-clinical animal experiments related to various human diseases (10)(11)(12)(13)(14)(15)(16)(17). To add to these findings, we report evidence supporting its preventive and/or therapeutic potential against diabetes-induced renal damage (18)(19)(20). The administration of Kangenkaryu reduced the increased serum glucose level in type 2 diabetic mice, and decreased the elevated oxidative and inflammatory biomarkers in the serum and kidney.…”

Section: Clinical Characteristicsmentioning

confidence: 91%

“…Many studies demonstrated that Kangen-karyu exhibits favorable biological activity such as anti-aging effects, platelet aggregation inhibition, hypertension suppression, anti-dyslipidemia, aiding the recovery of learning and memory impairment induced by senescence, neuroprotection, and an anti-dementia effect in animal experiments (10)(11)(12)(13)(14)(15)(16)(17). Although studies have proposed the pharmacological functions of Kangen-karyu to treat various diseases, we previously reported evidence supporting its preventive and/or therapeutic potential against diabetes-induced renal damage using db/db mice, a type 2 diabetic animal model (18)(19)(20). The results of our previous study provide important evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of Chinese prescription Kangen-karyu in patients with diabetic nephropathy

Park

Hiratani

Natazuka

et al. 2020

DD&T

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diabetic nephropathy, traditional Chinese medicine, Kangen-karyu, case report Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. A number of new therapies have been developed based on the pathogenic factors of diabetic nephropathy such as intensive glycemic control, precise hypertension control, lifestyle modifications including exercise and an energy-restricted diet, and numerous novel agents. The utilization of traditional Chinese medicine for patients with diabetic nephropathy has also 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 patients with diabetic nephropathy, stage 2 or 3. Kangen-karyu extract (7.5 g/day) was administered three times per day for 6 months. The estimated glomerular filtration rate was increased at the 6-month follow-up. The serum creatinine level decreased following administration. At that time, somatic and subjective symptoms had partially disappeared. Here, we present evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.

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

Cited by 4 publications

References 38 publications

Rosmarinic Acid Derivatives’ Inhibition of Glycogen Synthase Kinase-3β Is the Pharmacological Basis of Kangen-Karyu in Alzheimer’s Disease

Rosmarinic Acid Derivatives’ Inhibition of Glycogen Synthase Kinase-3β Is the Pharmacological Basis of Kangen-Karyu in Alzheimer’s Disease

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

Therapeutic effect of Chinese prescription Kangen-karyu in patients with diabetic nephropathy

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