In the present study, we examined whether shigyakusan extract, a traditional Kampo medicine, attenuates enhanced hepatic neutrophil infiltration and oxidative stress with the progression of α-naphthylisothiocyanate (ANIT)-induced liver injury in rats. Rats were treated once with ANIT (75 mg/kg body weight, i.p.). Liver injury with cholestasis occurred 24 h after ANIT treatment and progressed at 48 h. A spray-dried material of shigyakusan extract (SGS) (0.15, 0.75 or 1.5 g/kg body weight, p.o.) administered at 24 h after ANIT treatment prevented the progression of ANIT-induced liver injury dose-dependently. At 24 h after ANIT treatment, the treated rats showed increases in hepatic lipid peroxide (LPO) and reduced glutathione (GSH) contents and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and decreases in hepatic superoxide dismutase (SOD) and glutathione reductase (GSSG-R) activities. At 48 h after ANIT treatment, the treated rats showed enhanced changes in hepatic LPO content and MPO, SOD, and GSSG-R activities except GSH content and decreases in hepatic catalase, Se-glutathione peroxidase, and glucose-6-phosphate dehydrogenase activities. SGS administered at 24 h after ANIT treatment attenuated the ANIT-induced changes in hepatic LPO and GSH content and MPO, catalase, and Se-glutathione peroxidase activities except SOD, GSSG-R, and glucose-6-phosphate dehydrogenase activities at 48 h dose-dependently. These results indicate that orally administered SGS attenuates enhanced hepatic neutrophil infiltration and oxidative stress with liver injury progression and increased hepatic GSH content at the progressed stage of liver injury in rats treated with ANIT, which could contributes to its therapeutic effect on this liver injury.
Oketsu is one of the important pathological concepts in Kampo medicine, primarily denoting blood stasis/stagnant syndrome. Previously, we reported a correlation between oketsu and the disease activity of rheumatoid arthritis (RA). Shortening of life span due to cardiovascular disease (CVD) in RA patients has been reported. It is considered that endothelial dysfunction, a preclinical stage of arteriosclerosis, is affected by inflammation and is closely related to the CVD complication in RA patients. In this study, we examined the relationship between oketsu and plasma biomarkers that indicate endothelial dysfunction. The subjects were 50 RA patients who had been receiving constant treatment over the preceding 3 months, and they were divided into oketsu group (n=25) and non-oketsu group (n=25) by oketsu score. Disease activity of RA, neutrophil elastase as inflammation marker, and coagulation factors were measured and compared. Endothelial dysfunction was assessed by plasma biomarkers such as soluble thrombomodulin (sTM), von Willebrand factor (vWF), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1). Patient characteristics and disease activity were not significantly different between the two groups, except for the grade of bone deformity. Among biomarkers of endothelial dysfunction, t-PA, sICAM-1 and sVCAM-1 were significantly elevated in RA patients with oketsu. In conclusion, the elevation of biomarkers indicating endothelial dysfunction is assumed to accelerate the progression of arteriosclerosis in RA patients with oketsu.
The aerial part of Ephedra sinica Stapf growing in a natural habitat were cut early in the spring for the purpose of examining the effects of herbivory damage by livestock including sheep and goats. The results showed that the plants never generated new stem afterwards in the same year after cutting the aerial parts and did not make cones. In the next season, the plant became small in size and scarcely made cones. Through this study, it was confirmed experimentally that the herbivoly damage to plant growth of E. sinica by livestock was serious.
Tochu tea products generated from the leaves of Eucommia ulmoides OLIVER are habitually consumed as a health beverage in Japan, China and Korea. Therefore, quality control of these products is important for safety and validity evaluation. A method using high-performance liquid chromatography-diode array detector/electrospray ionization mass spectrometry (HPLC-DAD/ESI-MS) was established to simultaneously determine ten bioactive constituents including 2 iridoids, 2 phenolic acids and 6 flavonoids in E. ulmoides leaves and Tochu tea products. Peaks were unequivocally identified by comparing retention times, on-line electrospray ionization mass (ESI-MS) spectra and UV data with those of reference compounds isolated from E. ulmoides leaves and Tochu tea products. All calibration curves of the ten compounds showed good linear regression (R > 0.9994) within test ranges. The new method provided satisfactory precision and accuracy with overall intra-day and inter-day variations of 1.8 - 3.0% and 3.5 - 5.9%, respectively, and overall recovery ranging from 95.4 - 106.1% with relative standard deviations (RSDs) within 3.6% (n = 3) for the ten compounds analyzed. The exclusive selectivity and excellent sensitivity of HPLC-DAD/ESI-MS provided comprehensive chemical information about the constituents of Tochu tea products and E. ulmoides leaves.
Aggravated hypertension (HT) was observed in a 71-year-old female taking sokeikakketsuto (TJ-53: containing 1g of licorice). Her serum potassium level was normal, but her plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were a lower limit of normal range. Based on these data, she was considered to have pseudoaldosteronism (PsA). Discontinuing sokeikakketsuto intake resulted in the improvement of aggravated HT, as well as the change to middle of normal range for PRA and PAC. Although the ratio of PAC/PRA transiently increased, it decreased to the baseline level after 16 weeks. It is thought that PsA should be considered as a cause of HT without hypokalemia in the administration of licorice, and the serial determination of PAC/PRA may be a useful maker to assess the status of PsA.
We present a case suggesting interactions between Kampo medicine and warfarin. The case was a 37-year-old female who complained of joint pain, headache and depression. She was given shigyakusanryogokeishibukuryoganryo and her condition improved. However, she had already taken warfarin to control anti-phospholipid syndrome and her blood PT-INR decreased from 1.7 to 1.25. After she stopped taking Kampo medicine, PT-INR recovered to the prior value. Caution is essential when prescribing Kampo medicines to patients who are already on warfarin therapy. Further accumulation of the similar cases might help to analyse the mechanism of interaction between Kampo medicines and warfarin in future.