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

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

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

Protective effect of the hooks and stems of Uncaria sinensis against nitric oxide donor-induced neuronal death in cultured cerebellar granule cells

We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (O_.) H_., Uncariae Uncus Cum Ramulus, protects against glutamate-induced neuronal death in vitro. Nitric oxide (NO) free radicals are also implicated in the process of neuronal death. In this study, we investigated the protective effects of Uncaria sinensis extract (USE) and its phenolic and alkaloid fractions against NO donors, sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), -induced neuronal death in cultured rat cerebellar granule cells. MTT assay showed cell viability to be significantly increased by the addition of USE (10, 30 and 100 μg/ml) compared with exposure (6, 12 and 24 h) to SNP (30 μM) only, and by the addition of USE (10 and 30 μg/mi) compared with exposure (6, 12 and 24 h) to SIN-1 (300μM) only. Phenolic fraction of USE (10 and 30μg/ml) significantly protected against SNP (30 μM, 24 hr)-induced cell death, and 3 and 10 μg/ml of this fraction significantly protected against SIN-1 (300 μM, 24 hr)-induced cell death. Alkaloid fraction of USE (30 and 100 μg/ml) significantly protected against SNP (30 μM, 24 hr) and SIN-1 (300 μM, 24 hr)-induced cell death. These results appear to indicate that Uncaria sinensis has a protective effect against NO-mediated neuronal death in cultured cerebellar granule cells and that its active components are included in phenolic and alkaloid fractions. 培養ラット小脳顆粒細胞を用いて,NO donor誘導神経細胞死に対する釣藤鈎エキスの保護作用を検討した。NO donorにはsodium nitroprusside(SNP) と 3-morpholinosydnonimine (SIN-1)を用い,細胞生存率の評価にはMTT法を用いた。釣藤鈎エキス(10,30,100μg/ml)は,SNP(30μM)6,12,24時間添加による神経細胞死を有意に抑制した。釣藤鈎エキス(10,30μg/ml)は,SIN-1(300μM)6,12,24時間添加による神経細胞死を有意に抑制した。釣藤鈎エキスのフェノール画分は,10,30μg/mlの濃度でSNP(30μM,24時間)添加による神経細胞死を有意に抑制し,同じく3,10μg/mlの濃度でSIN-1(300μM,24時間)添加による神経細胞死を有意に抑制した。釣藤鈎エキスのアルカロイド画分(30,100g/ml)は,SNP(30μM,24時間)およびSIN-1(300μM,24時間)添加による神経細胞死を有意に抑制した。以上より,釣藤鈎エキスはNO donorによって誘導される神経細胞死に対して保護作用を有し,その活性は釣藤鈎のフェノール画分およびアルカロイド画分にあることが示唆された

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