Successful treatment of restless legs syndrome accompanied by headaches for 30 years with herbal prescriptions containing Paeoniae Radix: A case report.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder that causes unpleasant symptoms in the legs when resting, which are relieved by movement. Pharmacotherapy is the standard treatment. However, current treatment provides only symptomatic relief and may result in adverse effects with long-term use. Treatment protocols using herbal medicines have emerged to compensate for this limitation. CASE PRESENTATION: A 70-year-old Asian woman visited our hospital with worsening headaches that had persisted for 30 years. Her headaches were aggravated by night-time lower-extremity discomfort. The patient was diagnosed with RLS based on the 2012 Revised International Restless Leg Syndrome Study Group Diagnostic Criteria (IRIS). The patient was prescribed herbal medicines, Shihogyeji-tang, Gyejibokryeong-hwan, and Jakyakgamcho-tang, all of which contain Paeoniae Radix. Fourteen days after starting herbal medicine treatment, the IRIS score decreased from 30 to 18. The patient experienced less leg discomfort. Moreover, her sleep time increased, and her headaches resolved. After 28 days of herbal treatment, the IRIS score decreased to 9. Importantly, the patient reported no sleep disturbance or headaches. Subsequently, conventional medications were discontinued. The patient remained stable (IRIS score: 9-10). Herbal treatment was discontinued on day 163. At the last follow-up, (day 364), the patient has not reported any symptom recurrence. CONCLUSIONS: We described a female patient with a 30-year history of RLS symptoms and related sleep disturbances that induced chronic uncontrolled headaches, who experienced improvements shortly after using herbal medicines containing Paeoniae Radix. Conventional medications were discontinued and the patient had no recurrence of symptoms. Considering these, herbal medicines containing Paeoniae Radix may be a suitable alternative treatment for RLS and its related symptoms.

Current research and future directions in pattern identification: Results of an international symposium.

A symposium on pattern identification (PI) was held at the Korea Institute of Oriental Medicine (KIOM) on October 2, 2013, in Daejeon, South Korea. This symposium was convened to provide information on the current research in PI as well as suggest future research directions. The participants discussed the nature of PI, possible research questions, strategies and future international collaborations in pattern research. With eight presentations and an extensive panel discussion, the symposium allowed participants to discuss research methods in traditional medicine for PI. One speaker presented the topic, 'Clinical pattern differentiation and contemporary research in PI.' Two speakers presented current trends in research on blood stasis while the remaining five other delegates discussed the research methods and future directions of PI research. The participants engaged in in-depth discussions regarding the nature of PI, potential research questions, strategies and future international collaborations in pattern research.

Blood stasis syndrome in Japan and its molecular biological analysis.

Blood stasis syndrome is one of the pathological concepts of Oriental traditional medicine. In Oriental traditional medicine, blood is thought of as not only blood but also as a living component of the body. In fact, blood stasis syndrome is related to not just circulation disorders but dermatological and gynecological and other diseases. In Japan, the concept of blood stasis syndrome is based on the past literature, for instance, Synopsis of Golden Chamber (Jin Kui Yao Lue), etc. There are many signs of this syndrome, such as a dry mouth, fullness of the abdomen and rough skin. However, the levels of importance of these signs had been unclear. Therefore, in order to determine the levels of seriousness, a scoring system of blood stasis syndrome was made based on multivariate analysis by Dr. Terasawa (Terasawa's Blood Stasis Score). Using the scoring system, we have studied blood stasis syndrome mainly related to blood circulation using modern techniques of analysis. From the results, we found that patients with blood stasis syndrome showed hemorheological abnormalities, and an improvement in these abnormalities was shown after administration of removing-blood stasis formulae. Furthermore, we have studied blood stasis syndrome from the point of view of molecular biology. We searched for the specific protein expression in blood stasis syndrome by proteomic analysis, and found no specific protein expression. However, there may be a possibility of developing a diagnostic algorithm for blood stasis by construction of a decision tree. During the past few years, as one of the molecular biological factors affecting blood stasis syndrome, we have been studying hypoxia inducible factor, which is located in the upstream of many genes. Above all, blood stasis syndrome is more than just circulatory deficit but encompasses the pathological concept of constant multilateral change in the living body.

The long-term effects of a kampo medicine, juzentaihoto, on maintenance of antibody titer in elderly people after influenza vaccination.

We have performed a broad-ranging analysis of the adjuvant effect of a Kampo medicine, juzentaihoto (JTT), on influenza vaccination in a multicenter randomized controlled trial. In this study, the enhancing effect of JTT on antibody titer after influenza vaccination was studied for 28 weeks in elderly people who were in the high-risk group for influenza infection. In total, 91 subjects over 65 years old were recruited from four long-term-care facilities located in Chiba, Gunma, and Toyama prefectures in Japan. Participants were randomly assigned to the JTT and the control groups. Blood samples were taken at 4 weeks before vaccination, at the time of vaccination, and then at 4, 8, 12, and 24 weeks after vaccination. The hemagglutination inhibition (HI) titers against A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 were then manually measured. A significant increase in HI titer against H3N2 was observed at week 8 after vaccination in the JTT group compared with the control group (P = 0.0229), and the HI titer of the JTT group significantly increased from 4 to 24 weeks (P = 0.0468), compared with the control group. In conclusion, our results indicated that JTT increased and prolonged antibody production against A/Victoria/210/2009 (H3N2), in particular, after influenza vaccination.

Effect of keishibukuryogan on endothelial function in patients with at least one component of the diagnostic criteria for metabolic syndrome: a controlled clinical trial with crossover design.

We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan), a traditional Japanese (Kampo) formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000) in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval) or group B (first control, then KBG-treatment). In forty-nine (27, group A; 22, group B) patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI) increased and those of serum nonesterified fatty acid (NEFA), malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors.

Traditional Japanese formula kigikenchuto accelerates healing of pressure-loading skin ulcer in rats.

We evaluated the effect of kigikenchuto (KKT), a traditional Japanese formula, in a modified rat pressure-loading skin ulcer model. Rats were divided into three groups, KKT extract orally administered (250 or 500 mg/kg/day for 35 days) and control. KKT shortened the duration until healing. Immunohistochemically, KKT increased CD-31-positive vessels in early phase and increased α-smooth muscle actin-(α-SMA-) positive fibroblastic cells in early phase and decreased them in late phase of wound healing. By Western blotting, KKT showed the potential to decrease inflammatory cytokines (MCP-1, IL-1ß, and TNF-α) in early phase, decrease vascular endothelial growth factor in early phase and increase it in late phase, and modulate the expression of extracellular protein matrix (α-SMA, TGF-ß1, bFGF, collagen III, and collagen I). These results suggested the possibility that KKT accelerates pressure ulcer healing through decreases of inflammatory cytokines, increase of angiogenesis, and induction of extracellular matrix remodeling.

Effect of Hachimijiogan against Renal Dysfunction and Involvement of Hypoxia-Inducible Factor-1α in the Remnant Kidney Model.

In chronic renal failure, hypoxia of renal tissue is thought to be the common final pathway leading to end-stage renal failure. In this study the effects of hachimijiogan, a Kampo formula, were studied with respect to hypoxia-inducible factor (HIF). Using remnant kidney rats, we studied the effects of hachimijiogan on renal function in comparison with angiotensin II receptor blocker. The result showed that oral administration of hachimijiogan for seven days suppressed urinary protein excretion and urinary 8-OHdG, a marker of antioxidant activity, equally as well as oral administration of candesartan cilexetil. In contrast, the protein volume of HIF-1α in the renal cortex was not increased in the candesartan cilexetil group, but that in the hachimijiogan group was increased. In immunohistochemical studies as well, the expression of HIF-1α of the high-dose hachimijiogan group increased compared to that of the control group. Vascular endothelial growth factor and glucose transporter 1, target genes of HIF-1α, were also increased in the hachimijiogan group. These results suggest that hachimijiogan produces a protective effect by a mechanism different from that of candesartan cilexetil.

Keishibukuryogan reduces renal injury in the early stage of renal failure in the remnant kidney model.

The effects of keishibukuryogan on the early stage of progressive renal failure were examined in rats subjected to 5/6 nephrectomy. Keishibukuryogan, one of the traditional herbal formulations, was given orally at a dose of 1% (w/w) and 3% (w/w) in chow. Administration of keishibukuryogan was started at 1 week after 5/6 nephrectomy and was continued for 4 weeks. At the end of the experiment, Azan staining did not reveal any severe histological changes in the kidneys of the nephrectomized rats. On the other hand, significant increases in mRNA expressions of transforming growth factor-ß(1) and fibronectin related to tissue fibrosis, as examined by Reverse Transcriptase-Polymerase Chain Reaction, were observed in nephrectomized rats, and they were significantly suppressed by 3% keishibukuryogan treatment. Against gene expressions related to macrophage infiltration, 3% keishibukuryogan treatment significantly suppressed osteopontin mRNA levels, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 mRNA levels showed a tendency to decrease, but without statistical significance. It was also observed that 3% keishibukuryogan attenuated serum urea nitrogen and urinary protein excretion levels. From these results, it was suggested that keishibukuryogan exerts beneficial effects that result in slowing the progression of chronic renal failure.

A chinese herbal medicine, tokishakuyakusan, reduces the worsening of impairments and independence after stroke: a 1-year randomized, controlled trial.

In post-stroke patients, the recurrence of stroke and progression of impairments lead to a bedridden state and dementia. As for their treatments, only anti-hypertension and anti-coagulation therapies to prevent the recurrence of stroke are available. In Asia, post-stroke patients with impairments are often treated with herbal medicine. The present study evaluated the effectiveness of tokishakuyakusan (TS) in improving the impairment and independence in post-stroke patients. Thirty-one post-stroke patients (mean age = 81.4 years) were recruited and enrolled. Participants were randomly assigned to the TS group (n = 16) or non-treatment (control) group (n = 15) and treated for 12 months. Impairments were assessed using the Stroke Impairment Assessment Set (SIAS). Independence was evaluated using the functional independence measure (FIM). For each outcome measure, mean change was calculated every 3 months. The results were that impairments according to SIAS did not significantly change in the TS group. In contrast, SIAS significantly worsened in the control group. There was a significant difference between the two groups. In each term of SIAS, affected lower extremity scores, abdominal muscle strength, function of visuospatial perception, and so forth. in the TS group were better than those in the control group. Independence according to FIM did not change significantly in the TS group. In contrast, FIM significantly worsened in the control group. There was also a significant difference between the two groups. In conclusion, TS was considered to suppress the impairments of lower limbs and to exert a favorable effect on cerebral function for post-stroke patients.

The traditional Japanese formula keishibukuryogan reduces liver injury and inflammation in patients with nonalcoholic fatty liver disease.

The Kampo formula keishibukuryogan (KBG, Guizhifulingwan) is frequently used in traditional Japanese and Chinese medicine to treat several symptoms and manifests anti-inflammatory and scavenging effects. Nonalcoholic fatty liver disease (NAFLD) is a common manifestation of the metabolic syndrome and has the potential to evolve to liver cirrhosis through chronic inflammation and steatohepatisis (NASH). We have recently reported the KBG significant effectiveness on liver injury in a NASH animal model that prompted us to prescribe to KBG (TJ-25). We performed a retrospective study and reviewed the charts of outpatients who were prescribed KBG for 8-12 weeks due to non-liver-related symptoms (n= 11) over the past year to evaluate the clinical outcome. In six of these cases, biochemical and ultrasound signs of NAFLD were observed. KBG led to a significant reduction in liver injury tests and blood cholesterol but had no effects on body weight in all NAFLD cases. Further, liver tests and lipid profiles returned to baseline values when KBG treatment was stopped. On the basis of data on a small number of subjects, we suggest that the use of KBG is a safe complementary treatment in patients with NAFLD. While it is unlikely that Kampo formulas may substitute the current nutritional approaches to the metabolic syndrome, future studies should address the possibility of an additive effect, possibly through anti-inflammatory mechanisms.

Identification of candidate genes involved in endogenous protection mechanisms against acute pancreatitis in mice.

We surveyed changes of the gene expression profile in caerulein-exposed pancreas using Affymetrix GeneChip system (39,000 genes). Up-regulation of genes coding for claudin 4, claudin 7, F11 receptor, cadherin 1, integrin beta 4, syndecan 1, heat shock proteins b1/90aa1, Serpinb6a, Serpinb6b, Serpinb9, Bax, Bak1, calpain 2, calpain 5, microtubule-associated protein 1 light chain 3 alpha, S100 calcium-binding proteins A4/A10 were found in mouse pancreas exposed to caerulein for 12h. In contrast, the anti-apoptotic gene Bcl2 was down-regulated. The functions of these genes concern tight junction formation, cell-cell/cell-matrix adhesions, stress response, protease inhibition, apoptosis, autophagy, and regulation of cytoskeletal dynamics. Caerulein-exposed pancreatic acinar cells were immunohistochemically stained for claudin 4, cadherin 1, integrin beta 4, heat shock protein b1, and Serpinb6a. In conclusion, we have newly identified a set of genes that are likely to be involved in endogenous self-protection mechanisms against acute pancreatitis.

A Proteomic Approach for the Diagnosis of 'Oketsu' (blood stasis), a Pathophysiologic Concept of Japanese Traditional (Kampo) Medicine.

'Oketsu' is a pathophysiologic concept in Japanese traditional (Kampo) medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for 'Oketsu'. Sixteen rheumatoid arthritis (RA) patients were treated with keishibukuryogan (KBG), a representative Kampo medicine for improving 'Oketsu'. Plasma samples were diagnosed as either having an 'Oketsu' (n = 19) or 'non-Oketsu' (n = 29) state according to Terasawa's 'Oketsu' scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the 'Oketsu' scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the 'Oketsu' and 'non-Oketsu' states. Hierarchical clustering gave three major clusters (I, II, III). The majority (68.4%) of 'Oketsu' samples were clustered into one cluster as the principal component of cluster I. The remaining 'Oketsu' profiles constituted a minor component of cluster II and were all derived from patients cured of the 'Oketsu' state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for 'Oketsu'. A reduction in measurement/pre-processing conditions (from 55 to 16) gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine 'Oketsu' has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing 'Oketsu' using a combination of proteomic and bioinformatics-based classification methods.

Proteomic identification of haptoglobin as a stroke plasma biomarker in spontaneously hypertensive stroke-prone rats.

AIMS: We investigated changes in the expression of plasma proteins in spontaneously hypertensive stroke-prone rats (SHRSP) to identify stroke biomarkers. MAIN METHODS AND KEY FINDINGS: The present analysis using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) demonstrated that three peaks at mass/charge ratios (m/z) of 9330, 9480 and 9700 decreased in intensity during the development and progression of hypertensive stroke in SHRSPs, but not in age-matched control SHR and Wistar rats. Administration of verapamil, an L-type calcium channel blocker which was effective for hypertension in SHRSP rats, prevented the decrease in plasma protein expression. A candidate biomarker protein (m/z 9330) was identified using LC-MS/MS as haptoglobin (Hp). Immunoblotting with anti-Hp antibody demonstrated the decreased expression of both Hpalpha and Hpbeta chains in SHRSP. In contrast, haptoglobin mRNA expression in the liver of SHRSPs slightly increased as compared with control rats. SIGNIFICANCE: These findings suggest that Hp is a biomarker candidate for discriminating pathogenic alterations of stroke.

Keishibukuryogan ameliorates glucose intolerance and hyperlipidemia in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. In this study, we examined the effects of keishibukuryogan on glucose and lipids metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Forty-five-week-old male OLETF rats were divided into three groups: diabetic control rats given a standard chow; diabetic rats given keishibukuryogan (3%, w/w in chow); diabetic rats given pioglitazone (0.01%, w/w in chow). Oral administration of keishibukuryogan produced significant improvement against impaired glucose tolerance. On the other hand, fasting serum glucose and insulin levels, and the homeostasis index of insulin resistance did not change by keishibukuryogan treatment. Against lipid parameters, keishibukuryogan significantly lowered serum total cholesterol and triglyceride levels, and the hepatic total cholesterol level. Keishibukuryogan treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. Additionally, keishibukuryogan showed significant effects on epididymal adipose tissue by decreasing the size of fat cells and on skeletal muscle by reducing TNF-alpha protein content. From these results, it was suggested that keishibukuryogan exerts beneficial effects on the features associated with type 2 diabetes.

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.

Chotosan enhances macrophage colony-stimulating factor mRNA expression in the ischemic rat brain and C6Bu-1 glioma cells.

Macrophage colony stimulating factor (M-CSF) is a cytokine which has been recently reported to have a neuroprotective effect on ischemic rat brain. In this study, we investigated the effect of chotosan, an oriental medicine, which has been clinically demonstrated to be effective for the treatment of vascular dementia, on M-CSF gene expression in rats with permanent occlusion of bilateral common carotid arteries (P2VO) in vivo and in a C6Bu-1 glioma cell line in vitro. The expression level of M-CSF mRNA in the cerebral cortices of P2VO rats was significantly higher than that in the cerebral cortices of sham-operated animals. Repeated treatment of P2VO rats with chotosan (75 mg/kg per day) for 4 d after P2VO significantly increased the expression level of M-CSF mRNA in the cortex but it had no effect on the expression of beta-actin, granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF) mRNAs. Moreover, the present in vitro studies revealed that chotosan treatment (10-100 mug/ml) of C6Bu-1 glioma cells dose-dependently enhanced M-CSF mRNA expression without affecting the expression of G-CSF, GM-CSF, and inducible nitric oxide synthase mRNAs. The effect of chotosan was reversed by Ro 31-8220 (1 muM), a selective protein kinase C (PKC) inhibitor, but not by H-89 (10 muM), a selective protein kinase A (PKA) inhibitor. These findings suggest that the upregulatory effect of chotosan on M-CSF mRNA expression involves PKC and may play an important role in the anti-vascular dementia action of this formula.

Identification of a predictive biomarker for the beneficial effect of a Kampo (Japanese traditional) medicine keishibukuryogan in rheumatoid arthritis patients.

OBJECTIVES: Kampo (Japanese traditional herbal) medicines are now ethically used in Japan as pharmaceutical grade prescription drugs. However, there are distinct groups of responders and non-responders to Kampo medicines. We searched for biomarker candidates to discriminate responders from non-responders to keishibukuryogan (KBG); one of the most frequently used Kampo medicines. DESIGN AND METHODS: A combination of SELDI technology and a decision tree analysis with proprietary developed bioinformatics tools was applied to 41 (32 for tree construction and 9 for validation test) plasma samples obtained from rheumatoid arthritis (RA) patients. A candidate biomarker protein was identified using LC-MS/MS. RESULTS: The constructed tree with measurable reliability contained only a single peak which was identified as haptoglobin alpha 1 chain (Hpalpha1). CONCLUSION: Hpalpha1 is a biomarker candidate for discriminating responders from non-responders to KBG treatment for RA. The present results may open the way to the establishment of "evidence-based" complementary and alternative medicine.

Effects of keishibukuryogan on vascular function in adjuvant-induced arthritis rats.

It is known that rheumatoid arthritis (RA) accelerates atherosclerosis. Further, the soluble form of vascular adhesion molecule-1 (VCAM-1) is known as a predictive marker of atherosclerosis in RA patients. We reported that keishibukuryogan, one of the Kampo formulas, improved articular symptoms and decreased soluble VCAM-1 in patients with RA. In adjuvant-induced arthritis (AIA) rats, an animal model of RA, it is known that endothelial function is injured by inflammation. So, we investigated the effect of keishibukuryogan on endothelial function in AIA rats. Lewis rats were divided into control, AIA control, and AIA with keishibukuryogan groups. The AIA with keishibukuryogan group was fed 3% keishibukuryogan contained in normal chow. On day 25 after injection of Mycobacterium butyricum, endothelium-dependent relaxation by acetylcholine in the AIA control group was suppressed, but it was improved in the AIA with keishibukuryogan group. The contractions by xanthine/xanthine oxidase in both AIA rats increased, but that in keishibukuryogan decreased compared to the AIA control group. Plasma levels of lipid peroxide increased in the AIA control group, but keishibukuryogan decreased these levels. Plasma levels of nitric oxide (NO) increased in both AIA groups. The expressions of endothelial NO synthase, inducible NO synthase and VCAM-1 of thoracic aorta were investigated by western blotting. These expressions increased in the AIA control group, but were restricted in the AIA with keishibukuryogan group. We considered that keishibukuryogan protected the endothelial function of AIA rats mainly by its anti-oxidative effect.

Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp.

Glucose and lipid metabolic parameters play crucial roles in metabolic syndrome and its major feature of insulin resistance. This study was designed to investigate whether dietary astaxanthin oil (ASX-O) has potential effects on metabolic syndrome features in an SHR/NDmcr-cp (cp/cp) rat model. Oral administration of ASX (50 mg/kg/day) for 22 weeks induced a significant reduction in arterial blood pressure in SHRcp. It also significantly reduced the fasting blood glucose level, homeostasis index of insulin resistance (HOMA-IR), and improved insulin sensitivity. The results also showed an improved adiponectin level, a significant increase in high-density lipoprotein cholesterol, a significant decrease in plasma levels of triglycerides, and non-esterified fatty acids. Additionally, ASX showed significant effects on the white adipose tissue by decreasing the size of the fat cells. These results suggest that ASX ameliorates insulin resistance by mechanisms involving the increase of glucose uptake, and by modulating the level of circulating lipid metabolites and adiponectin.

Protective effects of keishibukuryogan on the kidney of spontaneously diabetic WBN/Kob rats.

Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. It consists of the following five crude drugs: Cinnamomi Cortex, Poria, Moutan Cortex, Persicae Semen and Paeoniae Radix. In this study, the effects of keishibukuryogan against renal damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of keishibukuryogan significantly attenuated urinary protein excretion and serum creatinine levels. It did not affect body weight loss and blood glucose levels, but it suppressed renal and hepatic weights of WBN/Kob rats. Keishibukuryogan also reduced fibronectin and transforming growth factor beta(1) (TGF-beta(1)) protein expression in the renal cortex. Furthermore, lipid peroxidation levels in both kidney and liver were significantly lower than those of untreated control WBN/Kob rats. Urinary excretion of 8-hydroxy-deoxyguanosine was suppressed by keishibukuryogan treatment. These results suggest that keishibukuryogan reduces oxidative stress by hyperglycemia, and that it protects renal function and suppresses fibronectin deposition induced by TGF-beta(1) production in WBN/Kob rats.