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

Effects of Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) on endothelial function in spontaneously hypertensive rats

We examined the protective effect of Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) (KB) against vascular endothelial disorder in spontaneously hypertensive rats (SHR). We administered KB extract (400 mg/kg/day, p.o.) to SHR for 14 weeks. Blood pressure and plasma viscosity in the KB group were significantly lower than in the SHR control group without KB, and the endothelium-dependent relaxation rate by acetylcholine in the KB group was significantly higher than that in the SHR control group. The rate of endothelium-dependent contraction induced by oxygen-derived free radicals produced by the xanthine-xanthine oxidase system was significantly lower in the KB group than in the SHR control group, and plasma lipid peroxide concentration was also significantly lower in the KB group than in the SHR control group. These results suggest the possibility that KB prevents vascular complications due to hypertension. 自然発症高血圧ラット(SHR)における血管内皮障害に対する桂枝茯苓丸(KB)の保護作用について検討した。KBエキス(400mg/kg/day)は,経口で14週間SHRに投与した。KB群の血圧と血漿粘度は,SHR対照群と比較して有意に低下した。内皮依存性血管弛緩作用はSHR対照群と比較してKB群で有意に増加した。キサンチン-キサンチンオキシダーゼ系による内皮依存性血管収縮作用はSHR対照群と比較してKB群で有意に減少し,血漿過酸化脂質はKB群で有意に低下した。このことから,桂枝茯苓丸が,高血圧症による血管合併症を予防する可能性が示唆された

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 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

Inhibitory effects of Cinnamomi Cortex and cinnamaldehyde on oxygen-derived free radical-induced vasocontraction in isolated aorta of spontaneously hypertensive rats

自然発症高血圧ラット(SHR)摘出胸部大動脈におけるキサンチン-キサンチンオキシダーゼ(XOD)誘発血管収縮反応に対する桂皮エキスおよびケイヒアルデヒド(CA)の収縮抑制作用についてオルガンバス法を用いて検討した。キサンチン-XOD誘発血管収縮反応は,SHR対照群と比較して,桂皮エキス(10^g/ml)前処置群,CA(10^M)前処置群で,有意に抑制されていた。キサンチン-XOD収縮反応時のトロンボキサンB_2(TXB_2)産生量は,SHR対照群と比較して,桂皮エキス(10^g/ml)群,CA(10^M)群で,有意に抑制されていた。CAのTX産生抑制の機序を検討するため,フォスフォリパーゼA_2(PLA_2)誘発血管収縮反応に対する収縮抑制作用について検討したところ,PLA_2誘発血管収縮反応はSHR対照群と比較して,CA(10^M)群で,有意に抑制されていた。PLA_2収縮反応時のTXB_2産生量は,SHR対照群と比較してCA(10^M)群で,有意に抑制されていた。以上のことから,桂皮は,血管収縮因子であるTXA_2抑制作用を持つ生薬である可能性が示唆された。 We examined the inhibiting effect of Cinnamomi Cortex extract (CCE) and cianamaldehyde (CA) against vasocontraction induced by oxygen-derived free radicals produced by the xanthine-xanthine oxidase (XOD) system in the thoracic aortic ring of the spontaneously hypertensive rat (SHR), using the organ bath method in vitro. The vasocontraction induced by xanthine-XOD in the CCE (10^g/ml) and CA (10^M) treatment groups were significantly lower than that in the control group. Further, the amounts of thromboxane B_2 (TXB_2) produced in the vasocontractive response in the CCE (10^g/ml) and CA (10^M) treatment groups were significantly lower than that in the control group. For the purpose of examining the mechanism of the inhibiting effect of CA against thromboxane production, the inhibiting effect of CA against the vasocontraction induced by phospholipase A_2 (PLA_2) was examined. The vasocontraction induced by PLA_2 in the CA (10^M) treatment group was significantly lower than that in the control group. Moreover, the amount of TXB_2 produced by the vasocontractive response in the CA (10^M) treatment group was significantly lower than that in the control group. From the above findings, it is suggested that Cinnamomi Cortex is an agent which exerts an inhibitory effect on the vasocontractive factor (TXA_2) in vitro

The effect of interleukin-15 on the expression of killer-cell immunoglobulin-like receptors on peripheral natural killer cells in human.

Interleukin (IL)-15 has emerged as a key regulator of both natural killer (NK) cell differentiation and activation. The aim of the present study was to investigate the expansion of the population of cells expressing killer-cell immunoglobulin-like receptors (CD158a and CD158b) in human peripheral lymphocytes by treatment with IL-15. One million peripheral lymphocytes were cultured in RPMI1640 medium alone or in medium containing IL-2 at 100 U/ml or IL-15 at 0.1, 1.0, or 10.0 ng/ml for 48 h. After each incubation, we assessed the natural killing activity and the population of CD16(+)CD158a(+)/b(+) cells and CD8(+)CD158a(+)/b(+) cells. IL-15 increased the NK activity and expanded the populations of CD16(+)CD158a(+)/b(+) cells and CD8(+)CD158a(+)/b(+) cells. These actions were dose dependent, and the effects of IL-15 at 1.0 ng/ml were close to those of IL-2 at 100 U/ml. These findings suggest that IL-15 induces the effector functions of resting NK cells throughout the body, and thereby plays a critical role in the activation of tissue-associated immune responses

A case of rheumatoid arthritis complicated by bucillamine-induced nephropathy satisfactorily treated with Kampo medicines

We reported a case of rheumatoid arthritis complicated by bucillamine-induced nephropathy satisfactorily treated with Kampo (Chinese/Japanese traditional) medicines. The patient was a 56-year-old male, who suffered from polyarthralgia from December 1996. In February 1997, he was diagnosed with RA in another hospital and treated with loxoprofen sodium, bucillamine and prednisolone. He visited our hospital in May 1997, and we began to treat him with a combination of modern Western and Kampo medicines. During his clinical course, proteinuria induced by bucillamine developed. After bucillamine was discontinued, his polyarthralgia and inflammatory parameters became worse. However, Kampo formulations, Keishi-bukuryo-gan mixed with Toki-shakuyaku-san and Dai-bofu-to, were effective for reducing the activity of RA. The clinical course of this case suggests that Kampo medicines might be useful for the treatment of RA patients, especially for those who have adverse reaction to disease-modifying antirheumatic drugs (DMARDs).　ブシラミン腎症を併発した慢性関節リウマチ(RA)に対して,漢方治療が奏功した1例を報告した。症例は56歳,男性。1996年12月,多関節痛出現。1997年2月,他院にてRAの診断のもと,ロキソプロフェン,プレドニゾロン,ブシラミンにて加療を受けた。1997年5月,当科初診以来,現代西洋医学的治療に漢方治療を併用して加療にあたった。経過中,ブシラミンによる蛋白尿が出現。ブシラミンを中止したところ,多関節痛と炎症反応が悪化した。しかし,桂枝茯苓丸合当帰芍薬散および大防風湯が奏功し,RAの活動性が低下し蛋白尿も消失した。このことから,副作用によりDMARDsが使用困難なRAの治療に対して,漢方治療が有効である可能性が示唆された

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

Endothelium-dependent vasodilator effect of tannin extract from Cinnamonomi Cortex on isolated rat aorta

Cinnamonomi Cortex (the bark of Cinnamomum cassia BLUME) is a crude drug that is widely used in spices and medical products. Although improvement of blood flow by this plant component has long been known, there have been no reports concerning the mechanism involved. We studied the vasodilator actions of this drug especially focusing on the role of endothelium in the isolated vascular bed. Tannin from Cinnamonomi Cortex (TCC) relaxed prostaglandin F_-precontracted ring preparations of rat aorta with intact endothelium. TCC did not cause relaxation of specimens without endothelium, and TCC-induced relaxation was inhibited by pretreatment with 10^M N^G-nitro-l-arginine methyl ester. Dimer, trimer, tetramer, and pentamer components of TCC also produced endothelium-dependent vasodilatation. Stronger relaxation was caused by higher molecular weight tannins, and endothelium-dependent vasodilation even appeared at low concentrations. In conclusion, we found that TCC exhibits an endothelium-dependent vasodilatation in the isolated rat aorta mainly via endothelium derived NO. NO mediated endothelium-dependent relaxation seems to be more potent for TCC with higher molecular weight than that with lower molecular weight. 桂皮の血流改善作用については古くから知られており,これに関連した報告はあるものの,その詳細な検討はなされていない。今回我々はマグヌス法を用いて,ラット胸部大動脈輪状標本における桂皮含有クンニンの血管作動性について検討した。桂皮含有タンニンは,プロスタグランディンF_(PGF_)の血管収縮に対し,内皮保存血管において濃度依存性に血管弛緩作用が認められた。しかし,内皮除去血管及ぴN^G-nitro-l-argininemethyl ester(L-NAME)前処置内皮保存血管においては,血管弛緩作用はほぼ消失した。以上より,桂皮含有タンニンの血管弛緩作用は内皮依存性であることが明らかとなった。桂皮含有タンニンをさらに二量体から五量体までのタンニン画分に分取し検討したところ,二量体以上の重合したタンニンにおいて血管弛緩作用が認められた。また,重合度が増すに従い血管弛緩作用はより低い濃度で発揮され,作用も増強されることが明らかとなった

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