Keishibukuryogan Research Articles

Responder analysis of keishibukuryogan for the symptoms of Yusho certified patients

AbstractBackgroundYusho is a 1968 mass food poisoning that was caused by the ingestion of rice oil contaminated with dioxins and related organochlorines. We previously reported that keishibukuryogan (KBG) administration was effective for improvement of the symptoms of Yusho patients. This study used responder analysis to more deeply elucidate the effectiveness of KBG.MethodThe data analyzed in the study were collected from our previous clinical study done to predict response to KBG treatment. The patients were divided into responders and non‐responders based on whether their symptoms improved after taking KBG. We assessed baseline patient characteristics and the intensity of general fatigue and dermatological, neurological, and respiratory symptoms. Further, we used SF‐36 to evaluate Quality of Life (QOL).ResultsOf the 42 patients who completed the previous study, 27 were responders and 15 non‐responders, with no significant differences in the patient characteristics. The general fatigue, dermatological symptoms, and respiratory symptoms of responders were significantly improved at month 3 of treatment. Analysis of the eight QOL domain profiles of SF‐36 showed that the general health of responders was significantly improved from baseline to month 3 compared with non‐responders, as was vitality from baseline to month 1. Moreover, the mental health of responders significantly improved from baseline to months 1 and 3.ConclusionsKeishibukuryogan was not only effective for symptoms such as general fatigue, dermatological symptoms, and respiratory symptoms, but also for the mental health of Yusho patients, which indicates that it would be a good first‐choice Kampo medicine for the treatment of these patients.

Recent applications of Kampo treatment for neurological diseases

AbstractBackgroundAlthough various new drugs have been developed for neurological diseases, many diseases have no effective treatment or only inadequate efficacy. Here we introduce some examples of effective Kampo treatment.Key Findings(1) Parasomnia in the elderly is preceded by the onset of diffuse Lewy body disease, with symptoms such as nightmares and loud screaming in the middle of the night. Keishikaryukotsuboreito (KSTRB), indicated in the classics for treating parasomnia, was effective in alleviating the symptoms. KSTRB is also used for enuresis that persists into adulthood. (2) Chronic subdural hematomas (CSDHs), treated by hematoma removal with burr‐hole surgery, recur at a rate of up to 20%. Goreisan (GRS) reduces hematoma volume and prevents postoperative CSDH recurrence. Homogeneous CSDH was most responsive to GRS in preventing recurrence. (3) Migraine frequently interferes with daily life. Keishibukuryogan (KBG), which alleviates blood stasis, was effective for patients with both menstruation‐associated migraine and scintillating scotomas. (4) Many traditional herbal medicines are listed in the Korean Medicine Clinical Practice Guideline for Stroke in Korea. Chunghyuldan, a related formula of Orengedokuto (OGT), is mainly used to prevent stroke.ConclusionKampo medicine is being applied in new and effective ways to treat various neurological diseases. Hopefully, more clinicians will recognize the usefulness of such Kampo medicines and utilize them in their daily practice.

Japanese herbal Kampo medicine, Keishibukuryogan, for chronic subdural hematoma - Prospective observational study.

Background: Pharmacological treatment for chronic subdural hematoma (CSDH) recurrence prevention after surgery is under debate. CSDH may be related to suidoku (fluid disturbance) from the Japanese herbal kampo perspective. Goreisan (GRS) treats suidoku and is used to prevent a postoperative recurrence. However, not all CSDHs are liquid, and some have structures such as trabecula, hematoma, and clots, suggesting oketsu (blood stasis). Therefore, we prospectively investigated the keishibukuryogan (KBG) effectiveness, which treats oketsu, for CSDH recurrence prevention and hematoma resolution compared to GRS.Methods: We prospectively prescribed KBG 7.5 g/day for 12 CSDH patients after burr-hole surgery. As a control cohort, we retrospectively collected 48 patients treated by GRS 7.5 g/day. The recurrence within 1 month and the hematoma thickness after 1 month were evaluated.Results: The median age was 84 years old. All the patients’ symptoms improved after surgery. The median preoperative midline shift and mean hematoma thicknesses were 6.0 mm and 23.75 mm. Those at 1 month were 2.0 mm and 11.43 mm. The recurrence rate was not significantly different between the KBG cohort (1 of 12) and the GRS cohort (4 of 48) (P = 0.999). The KBG’s noninferiority to GRS regarding the hematoma thickness at 1 month was statistically proven; KBG (12.26 mm) and GRS (11.20 mm).Conclusion: The recurrence rate at 1 month was not different between the KBG and GRS cohorts. The hematoma thickness at 1 month in the KBG cohort was not statistically inferior to that in the GRS cohort.

Live-Imaging Analysis of Target Vessels and Nitric Oxide Production Associated with Gosha-Jinki-Gan and Keishi-Bukuryo-Gan: Two Herbal Preparations with Clinically Proven Blood Flow-Improving Effects but with Different Traditional Clinical Indicative Patterns.

Gosha-jinki-gan (GJG) and Keishi-bukuryo-gan (KBG) are Kampo traditional herbal prescriptions used for different clinical patterns (sho) that improve blood flow. The pharmacological basis of the therapeutic choice remains unclear, although the clinical reliance of this pattern-based therapy is widely proven. We aimed to investigate their effects on microcirculation and nitric oxide (NO) kinetics using a live-imaging system to provide evidence for this. Live-imaging was performed in murine subcutaneous vessels and rat mesentery. In the subcutaneous vessels, we analyzed the effects of both drugs on the vessel diameter, blood flow velocity, and volume in the arteries, arterioles, and capillaries. In the rat mesentery, we induced the “oketsu” blood stasis using a stack of thin vinylidene chloride films and examined the effect on NO production using a fluorescent diaminofluorescein-2 diacetate. Following dissolution in hot water, 300 mg/kg of both drugs were administered intragastrically via a transesophageal catheter. Live-imaging analysis of subcutaneous blood flow revealed the different effects of GJG and KBG on their target vessels and effect onset. GJG targeted the capillaries and progressively increased the blood flow velocity and rate at 30–120 min after administration. No vasodilation or increased blood flow in the arteries and arterioles occurred. In contrast, KBG increased the diameter of the arterioles and arteries at 30–90 min after administration, and increased blood flow velocity and rate in arteries and arterioles. In a model of oketsu blood stasis in the mesenteric arteries, KBG increased the NO production from the vascular endothelial cells with dilatation of the arteriolar diameter. GJG improved blood flow mainly in the capillaries. Endothelial NO production decreased after GJG administration. The empirical treatment choice between GJG and KBG is based on the difference in target vessels and NO action and provides a pharmacological basis for therapy based on traditional medicine.

A Review on the Mechanism and Application of Keishibukuryogan.

The concept of “blood stasis” – called yū xiě in Chinese, Oketsu in Japanese – is one of the unique pathophysiology of traditional medicine that originated in China and inherited in Korea and Japan. This concept is related to the multiple aspects of hemodynamic disorders brought on by quantitative and qualitative changes. It theorizes that the quantitative changes of “blood stasis” are related to peripheral circulatory insufficiency. When chronic qualitative changes of “blood stasis” produce stagnant blood that turns into a pathological product, it could cause inflammation and lead to organic changes. Trauma induced hematomas, that are considered to be a quantitative change of blood, are also a form of blood stasis. The basic medicine research on Keishibukuryogan (KBG)–a Japanese name in Traditional Japanese Medicine (Kampo) for one of the most common anti- “blood stasis” prescriptions, also known as gui-zhi-fu-ling-wan (GFW) in Chinese in Traditional Chinese Medicine (TCM)–indicated that the initiation of quantitative changes was closely related to loss of redox balances on endothelial function induced by oxidative stress. The following qualitative changes were related to coagulopathy, hyper viscosity; anti-platelet aggregation, lipid metabolism; a regulation of systemic leptin level and/or lipid metabolism, inflammatory factor; cyclooxygenase-1,2 (COX-1, 2), interleukin-6, 8 tumor necrosis factor-α, macrophage infiltration, hyperplasia, tissue fibrosis and sclerosis caused by transforming growth factor-β1 and fibronectin, the dysfunction of regulated cell deaths, such as, apoptosis, autophagy, ferroptosis and ovarian hormone imbalance. Clinically, KBG was often used for diseases related to Obstetrics and Gynecology, Endocrine Metabolism, Rheumatology and Dermatology. In this review, we give an overview of the mechanism and its current clinical application of KBG through a summary of the basic and clinical research and discuss future perspective.

Clinical and genetic characteristics of Keishi-Bukuryo-Gan syndrome: an analysis of 5 cases.

: To analyze the clinical and genetic characteristics of children with Keishi-Bukuryo-Gan (KBG) syndrome. The clinical and genetic data of 5 children with KBG syndrome admitted in Children's Hospital Affiliated of Zhengzhou University from November 2018 to September 2020 were retrospectively analyzed. Five children were all males who came from four different families. All children presented triangular face, bushy eyebrows, thin upper lip, large or delayed closure of anterior fontanel, and abnormal bone development. Four cases had growth retardation, large ears, thick ear lips; 3 cases had large central incisors; 2 cases had congenital heart disease; 2 cases had abnormal skin changes; 2 cases had genital changes; and 2 cases became grumpy. Liver and kidney function,thyroid function, blood gas analysis and electrolyte of the children were all in the normal range. Three children received bone age examination, and all showed bone age lag. Two cases showed backward myelination of white matter in MRI. Whole exome sequencing revealed that all 5 children had heterozygous mutations in the gene, among which c.6836_6837delTG, c.5866C>T, and c.6270delT were newly discovered mutation sites. None of the parents of probands were found to carry the mutations in gene. Two cases achieved height catch-up and cognitive improvement after treatment with recombinant human growth hormone. KBG syndrome is characterized by a wide spectrum of phenotypes, and large or delayed closure of the anterior fontanel, large ears and thick ear lips may be the main manifestations of the disease in infants and young children. gene mostly presents spontaneous mutations, and early application of growth hormone therapy can achieve height catch-up and cognitive improvement without obvious adverse reactions.

Safety and Efficacy of Keishi-Bukuryo-Gan in Patients with Spontaneous Intracerebral Hemorrhage during the Acute Period:CT Image-Based Analysis of the Clearance of Hematoma

Keishi-Bukuryo-Gan(KBG)is a traditional Japanese(Kampo)formula used to improve microcirculation and a congestive condition called "Oketsu". KBG is also used to prevent the development of atherosclerosis. Many patients with intracerebral hemorrhage(ICH)have comorbid diseases related to atherosclerosis;thus, KBG may be a treatment option for ICH. The aim of this study was to investigate whether the administration of KBG in patients with ICH during the acute phase affects the course of absorption of ICH, detected using computed tomography(CT). We identified 308 patients with ICH who were diagnosed and treated at our institution from April 2013 to June 2016. Among them, 53 patients were chosen based on the accessibility of CT images, patient background, and past history. The volume and CT value of the hematoma were analyzed at admission, one week(six to eight days)after admission, and two weeks(thirteen to sixteen days)after admission. There were no significant differences between KBG and non-KBG patients in terms of the background parameters, hematoma volume, or CT value at admission. However, there were significant differences in both the volume reduction ratio(non-KBG=64.3±8.4%, KBG=48.5±14.5%, p=0.03)and CT value(non-KBG=48.5±4.6HU, KBG=44.0±7.0HU, p=0.04)two weeks after admission. Significant improvement in the absorption of ICH was observed in KBG patients. To our knowledge, this is the first report that shows the facilitative effect of KBG on intracranial hematoma clearance during the acute phase.

Traditional Japanese formulas tokishakuyakusan and ogikenchuto suppress dermal sclerosis in bleomycin‐induced murine scleroderma

ABSTRACTAimSystemic scleroderma is a connective tissue disease of unknown etiology characterized by fibrosis of the skin and internal organs. There are few effective treatments for this disease. In this study, we examined the effectiveness of the traditional Japanese medicines keishibukuryogan (KBG), tokishakuyakusan (TSS), and ogikenchuto (OKT) in treating systemic scleroderma.MethodsDermal sclerosis was induced in mice by daily injection of bleomycin. The mice were randomly divided into five groups based on treatment: KBG, TSS, and OKT groups (250 mg/kg/day), and two groups given water only (the sham and control groups). The sham group received local phosphate‐buffered saline injections (without bleomycin), and the control group received local bleomycin injections (without treatment). Kampo treatment groups also received local bleomycin injections. A daily dose of 0.01 mL of either kampo solution or water/g·bodyweight was given orally (through a stomach tube) for 4 weeks.ResultsOn histology at week 4, significantly fewer mast cells had infiltrated into the dermis in the TSS and OKT groups than in the control group; dermal sclerosis was also less severe in these groups. Furthermore, at week 1, the KBG, TSS, and OKT groups had significantly reduced serum transforming growth factor β1 (TGF‐β1). OKT and TSS had significantly reduced the level of malondialdehyde in the skin tissue.Conclusion OKT and TSS suppressed the progression of dermal sclerosis by inhibiting mast cell infiltration, as well as by decreasing TGF‐β1 and oxidative stress.

Traumatic lateral abdominal wall hematoma treated with Kampo medicines

ABSTRACTCaseA 62‐year‐old woman presented with whiplash, bruised chest, and lateral abdominal wall hematoma with an arterial rupture. Keishibukuryogan (KBG), a traditional Japanese Kampo medicine, was administered for treatment of oketsu syndrome. Five days after the injury, cervical and chest pain were still present, and the subcutaneous hematoma had increased tremendously in size. KBG was discontinued and jidabokuippo (JDI) was administered. The subcutaneous hematoma improved dramatically.OutcomeSymptoms improved after treatment with JDI.Conclusion JDI can be used for the management of pain and swelling following abdominal wall hematoma as an alternative to non‐steroidal anti‐inflammatory drugs.

Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood.

Effects of keishibukuryogan (KBG) on platelet aggregation were investigated. To ensure the specificity of KBG, tokishakuyakusan (TSS) and kamisyoyosan (KSS), which are known to have platelet aggregation-inhibiting effects, and rikkunshito (RKT) and shakuyakukanzoto (SKT), which are considered to be devoid of such effects, were used for comparison. The platelet aggregation of each test drug was measured by the screen filtration pressure method using whole blood of guinea pigs and expressed as a collagen-induced pressure rate (%) or a collagen concentration required for 50% increase in the pressure rate (PATI value). KBG suppressed the collagen-induced whole blood pressure rate increase and increased the PATI value, like TSS and KSS. Neither RKT nor SKT showed these effects. The Moutan cortex and Cinnamomi cortex, the constituent crude drugs of KBG, showed KBG-like pressure rate suppression and PATI-increasing effects. Furthermore, paeonol, a representative component of Moutan cortex, and aspirin which is known to have platelet aggregation-inhibiting activity (COX-1 inhibitor) also showed similar effects. These results suggest that the platelet aggregation-inhibiting activity of the constituent crude drugs Moutan cortex and Cinnamomi cortex is involved in the improving effects of KBG on impaired microcirculation and that paeonol plays a role in these effects.

In vitro Cytokine Expression by Peripheral Mononuclear Cells in Herbal Drug-induced Skin Eruption

Herbal medicine is widely used worldwide and is associated with side-effects such as skin eruptions. Herbal drugs are often produced by combining multiple crude drugs, mostly of plant origin. Determining which medi-cinal plants are associated with the herbal drugs that induce skin eruptions can therefore be difficult. This study investigated mRNA expression of several cytokines in peripheral mononuclear cells (PBMCs) from two patients with herbal drug-induced skin eruptions; one reacted to keishi-bukuryo-gan (KBG), composed of 5 medicinal plants, and the other patient reacted to senna. PBMCs (1×106) from the 2 patients were cultured for 24 h with the supernatant from the medicinal plants from KBG or senna in various concentrations, and a reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. A high mRNA level of interleukin (IL)-4 and IL-5 was detected in PBMCs stimulated by KBG and two of its components. Senna stimulated a high level of IL-4 and IL-5 mRNA levels in PBMCs from patient with senna-induced drug reaction.

Effectiveness of Keishibukuryogan on Chronic-Stage Lichenification Associated with Atopic Dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. Keishibukuryogan (KBG) is a traditional herbal medicine, composed of five kinds of medical plants and has been administered to patients with blood stagnation in Japan. This study investigated the effect of KBG on the disease activity in AD (n = 45) patients. AD patients were administered KBG for 4 to 6 weeks in addition to their prescribed medications. The results showed that the SCORAD index and VAS score were significantly decreased after the administration of KBG (P < 0.01). KBG also decreased the serum LDH level significantly (P < 0.01). The global assessment of the clinical response in SCORAD index showed that 88.5% of the patients with moderate improvement to excellent response (n = 26) had a high lichenification score (lichenification score ≥2 in SCORAD). On the other hand, only 42.1% of the patients with no improvement to mild improvement (n = 19) had a high lichenification score. Furthermore, long-term administration of KBG for 9–67 weeks showed a marked improvement in patients with a high lichenification score. Therefore, KBG was found to be effective against AD, particularly in cases presenting with lichenified lesions.

The Traditional Japanese Formula Keishibukuryogan Inhibits the Production of Inflammatory Cytokines by Dermal Endothelial Cells

Keishibukuryogan (KBG) is one of the traditional herbal formulations widely administered to patients with blood stagnation for improving blood circulation; currently, it is the most frequently prescribed medicine in Japan. KBG has been reported to improve conjunctional microcirculation. The aim of this study was to evaluate the role of KBG and paeoniflorin, a bioactive compound of KBG, in inhibiting the production of inflammatory cytokines using human dermal microvessel endothelial cells (HDMECs). The authors observed that lipopolysaccharide (LPS; 1 μg/mL) stimulated the secretion of proinflammatory cytokines in HDMECs. KBG treatment (10 mg/mL) significantly suppressed the mRNA levels of migration inhibitory factor (MIF), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated cultured HDMECs. Similarly, paeoniflorin significantly suppressed the mRNA levels of these cytokines in LPS-stimulated cultured HDMECs. ELISA showed that KBG and paeoniflorin suppressed the production of MIF, IL-6, IL-8, and TNF-α in LPS-stimulated HDMECs. Moreover, KBG and paeoniflorin decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) in these cells. These results suggest that KBG may be useful for improving microvascular inflammation in patients with skin diseases.

ECAM: Integrative Genomics and Fecundity

<i>eCAM</i>: Integrative Genomics and Fecundity

Effect of Keishibukuryogan on Silent Brain Infarction over 3 Years

The purpose of this study was to evaluate the effect of keishibukuryogan (KB) against the cognitive symptoms associated with silent brain infarction in a prospective cohort study. The subjects were 93 patients with silent brain infarcts who visited the Department of Japanese Oriental Medicine, University of Toyama, and its allied hospitals. They consisted of 24 males and 69 females, mean age (± S.E.) 70.0±0.8.Group SK (n=51) consisted of patients who used KB extract for more than6months per year. Group SC (n=42) consisted of patients who did not use Kampo formulas. The NS group (n=44) consisted of elderly subjects who had no silent brain infarction, 21 males and 23 females, with a mean age (± S.E.) of 70.7±0.7 years. Among the three groups, the revised version of Hasegawa's dementia scale, apathy scale and self-rating depression scale were compared between the study start and after three years. In the SK and SC groups, these scores, and the subjective symptom levels (head heaviness, headache, dizziness or vertigo, stiff shoulder) were also studied. The results showed that the self-rating depression scales at study start for the SK and SC groups were significantly higher compared to the NS group. In spite of the scores for the NS group increasing after three years, the SK group scores were significantly decreased compared to the SC and NS groups. KB was effective against head heaviness, which often complicates silent brain infarction. In the above mentioned, KB was effective in treating cognitive disorders and subjective symptoms related to silent brain infarction.

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 (Hpα1). Conclusion: Hpα1 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.

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.

Rediscovery of natural products using genomic tools

A screening methodology called ‘genomic screening’ was established to identify natural products that can regulate cellular gene expression. Application of genomic screening to Keishi-bukuryo-gan (KBG), a Japanese herbal medicine formulation, identified a previously unnoticed transcriptional effect by linoleic acid, a known KBG component. The approach opens up a possibility to develop cell-permeable molecular tools for functional genomics research and sets a stage to evaluate the potential of natural products for transcription therapies.

Keishibukuryogan (Gui‐Zhi‐Fu‐Ling‐Wan), a Kampo Formula, Decreases Disease Activity and Soluble Vascular Adhesion Molecule‐1 in Patients with Rheumatoid Arthritis

An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS28). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1β, IL-6 and TNF-α) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS28 decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients.

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.