A case of mediastinal lymphangioma successfully treated with Kampo medicine.

OBJECTIVE: The authors report a case of mediastinal lymphangioma successfully treated with Kampo medicine. METHODS: A 2-year-old boy with an axillary soft mass consulted our clinic. Physical examination findings were normal except for axillary elastic swelling. The neck and chest magnetic resonance imaging scan (MRI) showed a multilocular mass starting from a cervical lesion and extending above the carina. RESULTS: After 9 months of Kampo administration, MRI showed marked regression of mediastinal lymphangioma. CONCLUSIONS: It was found that Kampo medicine might be safe and effective as an alternative choice of treatment for lymphangiomas.

A suspected case of somatoform disorder successfully treated with an herbal medicine.

OBJECTIVE: Subjective physical symptoms, irrespective of whether they are psychosomatic or not, do not always show obvious or reasonable signs in examinations, which often makes the differential diagnosis between somatoform disorders and actual physical disease difficult for psychiatrists. In addition, psychiatrists have few clues as to how to treat diverse "medically unexplained" symptoms. This difficulty has highlighted the need for alternative treatments for somatoform disorders. SUBJECT: A 16-year-old high school baseball player was suffering from coxalgia and was unable to walk without crutches over 6 months. No painkiller was effective, the orthopedist found no remarkable signs in any examinations, and the patient was psychiatrically diagnosed with undifferentiated somatoform disorder. However, conventional therapies such as psychotherapy and selective serotonin reuptake inhibitors were ineffective. INTERVENTIONS AND OUTCOME: The therapeutic strategy was reevaluated from the perspective of Kampo diagnostics and keishikajutsubuto, a traditional Japanese herbal (Kampo) medicine, was chosen to be prescribed, which had a remarkable effect. His leg function improved within 2 weeks, and his pain and need for crutches disappeared in 6 weeks. CONCLUSIONS: Keishikajutsubuto has a different pain-relieving effect from conventional therapies. Kampo medicine thus provides an alternative approach for treating medically unexplained symptoms without strictly distinguishing between physically existing illness and psychologically caused somatoform disorders. Although details regarding the therapeutic mechanisms of Kampo medicine remain unclear and further studies are needed to increase its usefulness in clinical practice, Kampo medicine should be considered as an alternative treatment, especially for somatoform disorders.

Three Cases of Chemotherapy-induced Peripheral Neuropathy Successfully Treated With Therapy Based on Kampo Diagnosis.

Patients undergoing chemotherapy often develop symptoms of neurological side effects such as numbness, pain, and weakness in a stocking-and-glove pattern. Yet few therapies are available to treat this condition. We examined the efficacy of therapy based on Kampo diagnosis in three cases of chemotherapy-induced peripheral neuropathy (CIPN). These patients all had severe cases, and the symptoms of CIPN interfered with their daily lives even after the cessation of the offending drugs. Early cessation of the drug therapy would be ideal, but in some cases where chemotherapies were effective against cancer, CIPN was worsened by prolonged administration. With the initiation of therapy based on Kampo diagnosis, the subjects of these case reports showed marked improvement in their daily activities. The Kampo diagnosis of CIPN is not only Jinkyo, as Tankaku, Kiutsu, and other Kampo clinical conditions can be candidates. We consider that the traditional way of Kampo diagnosis can provide options for the treatment of CIPN.

Evidence-based efficacy of Kampo formulas in a model of non alcoholic fatty liver.

Data on the efficacy of herbal compounds are often burdened by the lack of appropriate controls or a limited statistical power. Treatments to prevent the progression of non alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain unsatisfactory. A total of 56 rabbits were arrayed into 7 groups fed with standard rabbit chow (SRC), SRC with 1% cholesterol, or each of the five experimental treatments (Kampo formulas 1% keishibukuryogan [KBG], 1% orengedokuto [OGT], and 1% shosaikoto [SST]; vitamin E [VE]; or pioglitazone [PG]) in a 1% cholesterol SRC. We analyzed changes after 12 weeks in plasma and liver lipid profiles, glucose metabolism, adipocytokines, oxidative stress, and liver fibrosis. Data demonstrated that all five treatments were associated with significant amelioration of lipid profiles, oxidative stress, and liver fibrosis compared to no supplementation. KBG was superior to VE and PG in the reduction of liver total cholesterol (P < 0.01) and lipid peroxidase levels (P < 0.05), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.05), hepatic alpha-smooth muscle actin positive areas (P < 0.01) and activated stellate cells (P < 0.01). In conclusion, there was a statistically significant benefit of Kampo formulas (KBG in particular) on a dietary model of NAFLD/NASH. Future studies need to be directed at the mechanisms in the treatment of NASH.

Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis.

BACKGROUND: The number of patients suffering from metabolic syndrome is increasing rapidly. Metabolic syndrome causes severe pathological changes in various organs, including the liver, and its main phenotype is nonalcoholic fatty liver disease (NAFLD). NAFLD has a broad spectrum ranging from simple fatty change to severe steatohepatitis with marked fibrosis. Recently, several experimental animal models for NAFLD have been proposed. However, most were established by rather artificial conditions such as genetic alteration. In the present study, we tried to establish a unique animal model mimicking some of the physiopathological features of NAFLD using high-cholesterol-fed rabbits. METHODS: Male rabbits fed with standard rabbit food containing 1% cholesterol for 8 weeks and 12 weeks were compared to controls (six rabbits/group). The weight of food was strictly restricted to 100 g/rabbit per day. RESULTS: Body weights and fasting plasma insulin levels showed no significant differences among the groups. In contrast, characteristic fine fibrosis was extended from perivenular to pericellular areas, and microvesicular fatty change with ballooning degeneration was observed in perivenular areas in livers of the cholesterol-fed rabbits. Increase of serum cholesterol level, activation of hepatic stellate cells, and exposure to oxidative stress were also recognized. CONCLUSIONS: Cholesterol-fed rabbits share several physiopathological features of NAFLD. Because this model did not show insulin resistance or obesity, it may be useful for elucidating the mechanism of NAFLD related mainly to hyperlipidemia.

[A case of pulmonary Mycobacterium fortuitum infection successfully treated with Kampo treatments].

A 72-year-old male was referred to our hospital in August 2001 for his pulmonary M. fortuitum infection. His symptoms were coughing, pyrexia, hemoptysis, general malaise, and insomnia. He had been suffering from these symptoms since 1982, though the intensive anti-mycobacterial chemotherapy such as three-drug (RFP, SM, and INH), twice two-drug (KM and SM and cycloserine and enviomycin) and four-drug (CAM, EB, RFP, and KM) regimens were administered for 26 months from July 1999. His symptoms tentatively improved after chemotherapy, but soon recurred with smear positive sputum. We decided to withdraw all antibacterial agents to treat him with decoction of Ninjinyoueito according to the diagnostics Kampo medical science in September 2001. After this prescription, his subjective symptoms gradually improved, and ten months later his sputum converted to smear negative. Because of recurrence of his general malaise in August 2002, we replaced the Ninjinyoueito by Seishoekkito, based on the Kampo diagnostics. His physical conditions remained good until 2005. In addition, the sputum smear examination maintain the level below +/-. We evaluate that Kampo (Chinese traditional medicine) treatment resulted in favorable response. Though it is not common to prescribe Kampo-medicine for intractable infectious diseases, we believe that Kampo-medicine is effective in some cases associated with host defense mechanisms.

Reduction of perception of chronic fatigue in an observational study of patients receiving 12 weeks of Kampo therapy.

OBJECTIVE: The aim of this study was to observe the influence of Kampo therapy on latent chronic fatigue of patients with chronic diseases. SUBJECTS: One hundred and seventy-three (173) consecutive patients with chronic diseases came to our department for the first time. DESIGN: This was a prospective study. Patients were divided into two groups: a chronic fatigue group (CFG) and a nonchronic fatigue group (NCFG). Based on Kampo diagnosis, both groups were prescribed Kampo formulae as an extract or decoction for 12 weeks. OUTCOME MEASURES: By using questionnaires, patients were assessed concerning their physical and mental types of fatigue, their sleep situation, and their attitude toward work or housekeeping, both before and after 12 weeks of treatment, according to Kampo diagnosis. RESULTS: The mental fatigue, physical fatigue, and sleep scores of both groups, and the work score of CFG, were decreased. The rate of reduction of the fatigue score was significantly greater in CFG than in NCFG. The factor responsible for this difference in fatigue score was physical fatigue. CONCLUSIONS: A reduction of the perception of chronic fatigue was observed in patients receiving 12 weeks of Kampo therapy.

Inhibitory effects of triterpenes isolated from Chuling (Polyporus umbellatus Fries) on free radical-induced lysis of red blood cells.

Chuling, sclerotia of Polyporus umbellatus FRIES, has long been used for urological disorders in traditional medicine. In this study, we demonstrated that Chuling in vitro protects red blood cells from 2,2-azo-bis(2-amidinopropane)dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 50 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of Chuling with scavenging effect on free radicals. Triterpene carboxylic acids isolated from the methanol extract of Chuling, namely, polyporusterone A and polyporusterone B, were found to have inhibitory activities against AAPH-induced lysis of red blood cells. The anti-hemolytic effect was significantly stronger in polyporusterone B compared with polyporusterone A. Furthermore, the ingestion of 150 mg of Chuling was associated with a significant increase in free-radical scavenging effect of plasma in rats.

Inhibitory effects of Stephania tetrandra S. Moore on free radical-induced lysis of rat red blood cells.

Crude preparations of Stephania tetrandra S. MOORE (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. In this study, we demonstrated that ST in vitro protects red blood cells from 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 10 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of ST that exerts a scavenging effect on free-radicals. Three representative alkaloids, tetrandrine, fangchinoline, and cyclanoline, isolated from ST, were found to have inhibitory activities against AAPH-induced lysis of red blood cells (RBC). Furthermore, the ingestion of 200 mg of ST extract was associated with a significant increase in free-radical scavenging effect of plasma in rats. These results suggest that ST as antioxidant inhibits AAPH-induced hemolysis of RBC both in vitro and in vivo.

Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits.

In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol and 1% KBG, and the vitamin E group was fed standard rabbit chow containing 1% cholesterol and vitamin E (450 mg/1000 g). All four groups were kept on these diets for 8 weeks. At the end of the experiments, the percentage of surface area of the total thoracic aorta with visible plaque was significantly reduced in the OGT and KBG groups. The serum thiobarbituric acid reactive substances of the vitamin E group showed a significantly low value compared with the control group, whereas the serum lipid peroxide levels of the OGT and KBG groups were considerably lower than that of the control groups as well as that of the vitamin E group. Furthermore, the urinary 8-hydroxydeoxyguanosine levels of the OGT and KBG groups were considerably lower than that of the vitamin E group. These results suggest that OGT and KBG prevent the progression of atheromatous plaque by creating a sounder antioxidant defense system than vitamin E.

Effects of Choto-san and hooks and stems of Uncaria sinensis on antioxidant enzyme activities in the gerbil brain after transient forebrain ischemia.

Previously, we revealed that oral administrations of Choto-san, a Kampo formula, and the hooks and stems of Uncaria sinensis Haviland (Rubiaceae), a medicinal plant comprising Choto-san, enhanced superoxide anion and hydroxyl radical scavenging activities in the hippocampus, and prevented delayed neuronal death of pyramidal cells in the hippocampal CA1 region in a transient forebrain ischemia gerbil model. In the present study, for the purpose of clarifying whether the endogenous antioxidant enzymes contribute to these mechanisms, we investigated the effects of Choto-san extract (CSE) and Uncaria sinensis extract (USE) on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the brain by using the same experimental model. 1.0% CSE or 3.0% USE were dissolved in water and provided to gerbils ad libitum from 7 days prior to ischemia/reperfusion (i/rp). Seven days of continuous administrations of CSE or USE without i/rp procedure enhanced CAT activity but not SOD and GSH-Px activities in both the hippocampus and cortex. CSE elevated CAT activity in the hippocampus at 7 days and in the cortex at 3h after i/rp. USE raised CAT activity in both the hippocampus and cortex at 3 h and 7 days after i/rp. These results suggest that one of the mechanisms of the protective effects of CSE and USE against transient brain ischemia-induced neuronal damage may be their enhancing effect on CAT activity in the brain.

Protective effects of Choto-san and hooks and stems of Uncaria sinensis against delayed neuronal death after transient forebrain ischemia in gerbil.

Previously, we revealed that Choto-san (Diao-teng-san in Chinese), a Kampo formula, is effective on vascular dementia clinically, and the hooks and stems of Uncaria sinensis (Oliv.) Havil., a medicinal plant comprising Chotosan, has a neuroprotective effect in vitro. In the present study, for the purpose of clarifying their effects in vivo, we investigated whether the oral administration of Choto-san extract (CSE) or U. sinensis extract (USE) reduces delayed neuronal death following ischemia/reperfusion (i/rp) in gerbils. Transient forebrain ischemia was induced by bilateral carotid artery occlusion for 4 min, and two doses (1.0% and 3.0%) of CSE or USE were dissolved in drinking water and provided to the gerbils ad libitum from 7 days prior to i/rp until 7 days after i/rp. It was found that 1.0% and 3.0% CSE treatments significantly reduced pyramidal cell death in the hippocampal CA1 region at 7 days post i/rp. Three percent USE treatment also inhibited pyramidal cell death significantly at 7 days after i/rp. Superoxide anion and hydroxyl radical scavenging activities of the homogenized hippocampus at 7 days after i/rp in the 1.0% CSE- and 3.0% USE-treated groups were significantly enhanced compared to those of control. Further, lipid peroxide and NO2-/NO3- levels of the homogenized hippocampus at 48h after i/rp in the 1.0% CSE- and 3.0% USE-treated groups were significantly lower than those of control. These results suggest that the oral administration of CSE or USE provides a protective effect against transient ischemia-induced delayed neuronal death by reducing oxidative damage to neurons.

Suppressive effects of Stephania tetrandra on the neutrophil function in patients with rheumatoid arthritis.

Crude preparations of Stephania tetrandra (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. The concentration of granulocyte elastase - alpha 1 protease inhibitor complex in plasma is enhanced in inflammatory processes, e.g. in septicaemia and rheumatoid arthritis (RA), being an expression of granulocyte activation during inflammatory response. It has previously been reported that ST showed beneficial and immunomodulatory effects in the treatment of relatively mild RA. After the administration of ST for 12 weeks, the proportion of granulocytes and the granulocyte count in peripheral blood decreased significantly. The lipid peroxide and human granulocyte elastase levels of stored plasma declined significantly. Furthermore, both the leukocyte/elastase ratio and granulocyte/elastase ratio increased significantly. The findings of this study suggest that the suppressive effect of ST administration on excessive granulocyte activation resulted in the improvement of inflammation with rheumatoid arthritis.

Choto-san prevents occurrence of stroke and prolongs life span in stroke-prone spontaneously hypertensive rats.

The effects of long-term oral administration of choto-san (diao-teng-san in Chinese) extract on the occurrence of stroke and life span were investigated in stroke-prone spontaneously hypertensive rats (SHR-SPs). Twenty-four rats were ramdomized into three groups. From 8 weeks of age, 0.1% and 0.3% choto-san groups were given water containing 0.1% (150 mg/kg/day) and 0.3% (450 mg/kg/day) choto-san extract, respectively. A control group was given only water. The mean survival times of the control group, 0.1% and 0.3% choto-san groups were 122.1, 159.8 and 176.8 days, respectively. The percent survivals of both the 0.1% and 0.3% choto-san groups were significantly enhanced compared to the control (Kaplan-Meier analysis followed by log-rank test; 0.1% choto-san: p < 0.05; 0.3% choto-san: p < 0.05). Furthermore, the cumulative percent occurrence of neurological and behavioral signs accompying stroke in the 0.3% choto-san group was significantly inhibited compared to the control (p < 0.05). These results suggested that choto-san prevents the occurrence of stroke and prolongs the life span of SHR-SPs.

Effects of goshajinkigan on corneal sensitivity, superficial punctate keratopathy and tear secretion in patients with insulin-dependent diabetes mellitus.

Goshajinkigan (niu-che-shen-qi-wan in Chinese), a traditional herbal medicine, has been used in Japan to treat clinical symptoms of diabetic neuropathy. A double-masked study was performed to evaluate its effects on corneal sensitivity, superficial punctate keratopathy and tear production in patients with insulin-dependent diabetes mellitus. Fifty diabetic patients were randomized into two groups: Group A, in which 25 patients received goshajinkigan orally, 7.5 g/day for 3 months; Group B, in which 25 patients were orally administered placebo, 6.0 g/day for 3 months; and in Group C, 25 non-diabetic subjects were orally administered goshajinkigan, 7.5 g/day for 3 months. Corneal sensitivity was measured with an aesthesiometer. The area of superficial punctate keratopathy was expressed as a fluorescein staining score. Reflex tearing was determined with a Schirmer test without anesthesia goshajinkigan was analyzed by high-performance liquid chromatography. Corneal thresholds after treatment with goshajinkigan (2.03 g/mm2) in Group A were significantly lower than those before treatment (2.47 g/mm2). Those in Groups B and C did not change after treatment. Fluorescein staining scores after administration of Goshajinkigan (0.64) in Group A were significantly lower than those before treatment (1.32). Those in Groups B and C did not change after treatment. Schirmer test results after goshajinkigan administration (11.0 mm/5 min) in Group A were significantly higher than those before treatment (9.3 mm/5 min). Those in Groups B and C did not change after treatment. Hemoglobin A1c levels in Groups A, B,and C did not change after treatment. Several components in goshajinkigan were found on high performance liquid chromatography. In conclusion, goshajinkigan improved ocular surface disorders in patients with insulin-dependent diabetes mellitus.

Inhibitory effects of Oren-Gedoku-To (Huanglian-Jie-Du-Tang) on free radical-induced lysis of human red blood cells.

Oren-gedoku-to (Huanglian-Jie-Du-Tang, OGT) has been used for the treatment of cerebrovascular disease, hypertension, gastritis and liver disease in Japan. The present study was to test our hypothesis that ingestion of Oren-gedoku-to extract (TJ-15) would protect red blood cell (RBC) membrane from free radical-induced oxidation if antioxidants in OGT could be absorbed and circulated in blood. When incubated with RBC suspension, OGT and its four constituting herbs provided strong protection for RBC membrane to hemolysis induced by 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH), an azo free radical initiator. The inhibitory effect was in a dose-dependent manner at concentrations of 5 microgram/ml to 500 microgram/ml. Furthermore, the ingestion of 7.5 g of OGT (daily dose) was associated with a significant decrease in susceptibility of RBC to hemolysis in humans. The direct protection of RBC membrane from free-radical attack as observed in the present study could provide an important pathophysiological basis for making use of the favorable hemorheological effect of OGT.

Inhibitory effects of triterpenes isolated from Hoelen on free radical-induced lysis of red blood cells.

Hoelen, sclederma of Poria cocos Wolf, has long been used as a sedative and diuretic in traditional medicine. Formerly, we demonstrated that Hoelen in vitro protects red blood cells from AAPH-induced hemolysis. In this study, tests were carried out to identify the main ingredient of Hoelen that has the scavenging effect on free-radicals. Triterpene carboxylic acids isolated from the methanol extract of Hoelen, i.e. pachymic acid, polyporenic acid, 3-epidehydrotumulosic acid, 3beta-hydroxylanosta-7,9(11), 24-trien-21-oic acid and 3-o-acetyl-16 alpha -hydroxytrametenolic acid, were found to have inhibitory activities against AAPH-induced lysis of red blood cells.

Keishi-bukuryo-gan preserves the endothelium dependent relaxation of thoracic aorta in cholesterol-fed rabbit by limiting superoxide generation.

Formerly, we have reported that keishi-bukuryo-gan prevents the progression of atherosclerosis in cholesterol-fed rabbits and inhibits the free radical-induced RBC haemolysis in rats. The present study was performed to investigate how keishi-bukuryo-gan (KBG) inhibits the early stage of atherosclerosis. Plasma lipid concentration and hydroxyl radical generation during respiratory burst in neutrophils were evaluated at the start and end of the study. The protective effect of KBG against endothelium disorder due to hypercholesterolaemia was examined. Twelve male Japanese white rabbits (2 kg body weight) were divided into two groups. Group A (n = 6) was fed standard rabbit chow containing 1% cholesterol for 4 weeks. Group B (n = 6) was fed standard rabbit chow containing 1% cholesterol and 1% KBG for 4 weeks. In the plasma lipid concentration, only the lipid peroxide concentration of group A was significantly higher than that of group B. At the end of the study, DMPO-OH, the spin-trapped adduct of hydroxyl radicals generated by neutrophils, was increased in both groups, and this increase was marked in group B. Endothelium-dependent vasodilatation by acetylcholine increased significantly in group B compared with group A. Thus, KBG protects the vascular endothelium function by its antioxidative effect and by inhibiting the release of free radicals from neutrophils in vivo.

Inhibitory effects of Keishi-bukuryo-gan on free radical induced lysis of rat red blood cells.

Keishi-bukuryo-gan (KBG) prevents the progression of atherosclerosis in cholesterol-fed rabbits by its antioxidative effect. The present study was to test our hypothesis that ingestion of KBG would protect red blood cell (RBC) membranes from free radical induced oxidation if polyphenolic antioxidants in KBG could be absorbed and circulated in the blood. When incubated with a RBC suspension, KBG and four of five herb medicines constituting KBG provided strong protection for RBC membranes against haemolysis induced by 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH), an azo free radical initiator. The inhibitory effect was dose dependent at concentrations of 100-1000 microg/mL. Furthermore, the ingestion of 200 mg of KBG was associated with a significant decrease in susceptibility of RBC to haemolysis in rats.