A report of three cases of diabetic nephropathy satisfactorily treated with traditional herbal medicine

We reported that three cases of diabetic nephropathy, who had overt proteinuria, were treated satisfactorily not only for their symptoms but also renal nephropathy with traditional herbal medicine over the long term. In Case 1, the level of S-Cr had changed from 1.2 to 2.0 mg/dl over 98 months, in Case 2 from 0.9 to 1.9 mg/dl over 70 months, and in Case 3 from 1.1 to 2.9 mg/dl over 81 months, acceptably moderate increases, meaning that the progression of their renal insufficiency was controlled over the long term. At the same time, the symptoms of hotness, numbness and edema were improved. Diabetic nephropathy with overt proteinuria is known to develop into renal failure after several years. In these cases, traditional herbal medicine was considered responsible for improving their QOL and prolonging the pre-dialysis period of diabetic nephropathy. 顕性蛋白尿期にある糖尿病性腎症の患者に漢方治療を施行した。その結果,随伴する諸症状の改善のみならず長期問,腎機能低下の進行を抑制した3症例を経験したので報告した。症例lでは,98ケ月の観察でS-Cr値はl.2から2.0mg/dl,症例2では70ケ月の観察で,S-Cr値は0.9から1.9mg/dl,症例3では81ケ月の観察で,S-Cr値は1.1から2.9mg/dl,と長期間腎機能低下の進行を抑制した。同時に,手足の火照りやしぴれ感,下肢の浮腫などの症状の軽快も認めた。持続的に蛋白尿を認める顕牲腎症期に至った糖尿病性腎症は数年の経過で,末期腎不全から血液透析に至ると言われている。今回の症例から和漢薬は,糖尿病性腎症における腎機能障害に対して腎機能障害の進行抑制作用を有する可能性が示唆された。このことから,和漢薬は糖尿病に随伴する諸症状を緩和し,QOLを改善するのみでなく,血液透析導人までの期間を延長し,予後を改善したと考えられた

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 (DAS(28)). 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 DAS(28) 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

Effect of Keishi-bukuryo-gan on autonomic nervous activity

桂枝茯苓丸の自律神経活動に対する効果を明らかとするために,レーザードプラ血流計,R-R間隔および収縮期血圧のスペクトル解析を用いて検討した。健常者8名を対象とし,自律神経活動の変化を桂枝茯苓丸料と微温湯において統計学的に解析した。桂枝茯苓丸により,皮膚血流量(SBF)は前値に比較して一旦15分後に減少し,90分後に有意に増加した。収縮期血圧低周波成分(SBP-LF)・収縮期血圧成分比(SBP-L/H)は前値に比較して一旦15分後に増加し,60及び90分後に有意に減少した。微温湯では有意な変化はみられなかった。SBFは交感神経活動にともない変化し,SBP-LF及びSBP-L/Hは交感神経活動と関連するとされている。今回の結果は,桂枝茯苓丸が交感神経活動に対する作用を有していることを示唆するものである。 In order to confirm any effects of Keishi-bukuryo-gan (KBG) on the autonomic nervous system, 8 healthy volunteers were evaluated with laser Doppler flowmetry and spectral analysis of the R-R intervals (RR) and systolic blood pressure (SBP). After evaluation of the "oketsu" score and measurement of the electrophysiological parameters (PRE), each subject was administered KBG or hot water. The same parameters were re-measured at 15, 30, 45, 60 and 90 minutes after their administration to each subject. Changes in the parameters after the administration of KBG or hot water were investigated compared with PRE. In the experiment with KBG, skin blood flow (SBF) was increased at 90 min, although it had been significantly decreased at 15 min. By spectral analysis, SBP-low frequency (LF) and SBP-low to high frequency ratio (L/H) were initially increased at 15 min, and then were significantly decreased at 60 and 90 min. As for hot water, there were no significant changes in any of the parameters. It is known that SBF changes with sympathetic nervous activity, and SBP-LF and SBP-L/H reflect sympathetic nervous activity. These results suggest that KBG has certain effects on sympathetic nervous activity

Pharmacokinetic study of Paeoniflorin Paeonimetabolin-I and Glycyrrhetic acid in humans after oral administration of Paeony Root, Glycyrrhiza and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang)

The pharmacokinetics of Paeoniflorin (PF) , Paeonimetabolin-I (PM-I) and Glycyrrhetic acid (GA) after oral administration of the decoction of Paeony Root (PR) and Glycyrrhiza (GR) and Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang ; SK) were studied using human subjects. Concerning the intra- and inter-individual variability of PF and PM-I after oral administration of SK, each inter-individual coefficient of variation (CV) of the pharmacokinetic parameters was larger than its intra-individual CV. There was no significant correlation between each pharmacokinetic parameter and each subject\u27s physiques. These results suggested that a large inter-individual variability were not caused by differences in the subjects\u27 physiques. Regarding a comparison of the pharmacokinetic parameters, AUC and Cmax of PF of PR were significantly higher than those of SK, and MRT and Tmax of PM-I of SK were significantly longer than those of PR. AUC of GA of SK was significantly higher than those of GR. There is the possibility that PR would be better than SK when a stronger efficacy of PR is expected in a short time, and SK would be beter than PR when a longer efficacy of PR or a stronger efficacy of GR is expected. ヒト健常人において芍薬・甘草・芍薬甘草湯経口投与時のペオニフロリン(PF),ペオニメタボリン-I(PM-I),グリチルレチン酸(GA)の葉物動態の研究を施行した。芍薬甘草湯投与後のPF,PMIの個体内・個体間変動については,各々の個体問変動係数が個体内変動係数よりも大きく,また,全ての薬物動態の各パラメータと被験者の体格との間には相関はみられなかった。芍薬・甘草と芍薬甘草湯との比較では,芍薬のPFのAUC,Cmaxが芍薬甘草湯のものに比較して有意に高値を示し,芍薬甘草湯のPM-IのMRT,Tmaxが芍薬に比較して有意に長かった。また,芍薬甘草湯のGAのAUCは甘革単独投与のものに比較して有意に高値を示した。このことから,短時間に芍薬のより強い効果を期待する際には芍薬単独で用い,芍薬成分のより長い効果や甘草成分のより強い効果を期待する際には芍薬甘草湯として投与する方がよい可能性がある

Correlation between "oketsu" syndrome and autonomic nervous activity : a diachronic study on the same subjects

In order to confirm that autonomic nervous activity changes with the change in the "oketsu" state using a diachronic study with the same subjects, 20 patients were evaluated by laser Doppler flowmetry and spectral analyses of the R-R intervals (RRs) and systolic blood pressure (SBP). According to the diagnostic criteria of "oketsu", the "oketsu" score (OS) was evaluated. After evaluation of OS and measurement of the parameters, each subject underwent his own Kampo treatment. Twelve weeks later, OS and the parameters were re-evaluated for each subject. The changes in OS and the parameters between week 0 and 12 weeks later were investigated, with the quantity of each change being calculated as Δ-. Δ-SBF showed a significant negative correlation with Δ-OS, and Δ-RR-L/H, Δ-SBP-LF and Δ-. SBP-L/H revealed significant positive correlations with Δ-OS. It is known that SBF changes with sympathetic nervous activity, and SBP-LF and SBP-L/H reflect α-sympathetic nervous activity. These results suggest that the significant relationship between OS and sympathetic nervous activity was maintained even after change in the "oketsu" state in the same subjects. 瘀血病態の経時的変化と自律神経活動の変化との関連性を明らかとするために,レーザードプラ血流計,R-R間隔および収縮期血圧のスペクトル解析を用いて検討した。患者20名を対象とし,瘀血スコアの変化と自律神経活動の変化との関連について統計学的に解析した。結果として,皮膚血流量(SBF)の変化量は瘀血スコアと負の相関を示し,R-R間隔成分比(RR-L/H)・収縮期血圧低周波成分(SBP-LF)・収縮期血圧成分比(SBP-L/H)は瘀血スコアと正の相関を示した。CVRR,・R-R間隔高周波成分(RR-HF)・収縮期血圧高周波成分(SBP-HF)については瘀血スコアとの間に有意な相関を認めなかった。SBFは交感神経活動にともない変化し,SBP-LFはα作動性交感神経活動と関連するとされている。今回の結果は,血病態がα作動性交感神経活動と密接に関連していることを示唆するものである

Effect of Keishi-bukuryo-gan on asymptomatic cerebral infarction for short term

無症候性脳梗塞患者に対する桂枝茯苓丸の効果を検討した。142例(男性32例,女性110例,平均年齢68.9才)を対象とし,副作用のため内服を中止した3例を除く139例に対して,桂枝茯苓丸エキス1日量7.5gを12週間投与した。投与開始時と比較して,改訂長谷川式簡易知能評価スケール,Apathyスケール(やる気スケール),SDS(うつ状態スケール)は有意に改善した。また,頭重感,頭痛,めまいの自覚症状も桂枝茯苓丸の投与により改善し,拡張期血圧は投与前に比べ有意に低下した。これらの結果から,桂枝茯苓丸が無症候性脳梗塞に伴う認知機能の低下,精神症状や自覚症状の悪化に対して有効である可能性が示唆された。 The efficacy of Keishi-bukuryo-gan in patients suffering from asymptomatic cerebral infarction was studied. 142 patients, 32 males and 110 females, with a mean age of 68.9 years, were enrolled and analyzed, and 139 completed the study. They were given Keishi-bukuryo-gan extract (7.5g/day) three times a day for 12 weeks. In comparison to the beginning of the study, Keishi-bukuryo-gan showed improvement with statistical significance in the mean revised version of Hasegawa\u27s dementia scale, Apathy scale and Self-rating depression scale. The number of patients with subjective symptoms as headdullness, headache and dizziness decreased by the treatment with Keishi-bukuryo-gan, and diastolic blood pressure was decreased with statistical significance as compared to the beginning of the study. These results suggest that Keishi-bukuryo-gan is effective against dysfunction of acknowledgment, emotional disorder and subjective symptoms with asymptomatic cerebral infarction

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-β1 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