Ko Nishimura

Traditional Japanese Kampo Medicine: Clinical Research between Modernity and Traditional Medicine—The State of Research and Methodological Suggestions for the Future

The Japanese traditional herbal medicine, Kampo, has gradually reemerged and 148 different formulations (mainly herbal extracts) can be prescribed within the national health insurance system. The objective of this article is to introduce Kampo and to present information from previous clinical studies that tested Kampo formulae. In addition, suggestions on the design of future research will be stated. The literature search was based on a summary, up until January 2009, by the Japanese Society of Oriental Medicine and included only those trials which were also available in either Pubmed or ICHUSHI (Japan Medical Abstracts Society). We included 135 studies, half of these studies (n = 68) used a standard control and 28 a placebo control. Thirty-seven trials were published in English [all randomized controlled trials (RCTs)] and the remaining articles were in Japanese only. The sample size for most studies was small (two-third of the studies included less than 100 patients) and the overall methodological quality appeared to be low. None of the studies used Kampo diagnosis as the basis for the treatment. In order to evaluate Kampo as a whole treatment system, certain aspects should be taken into account while designing studies. RCTs are the appropriate study design to test efficacy or effectiveness; however, within the trial the treatment could be individualized according to the Kampo diagnosis. Kampo is a complex and individualized treatment with a long tradition, and it would be appropriate for further research on Kampo medicine to take this into account.

Prolonged Survival of Fully Mismatched Cardiac Allografts and Generation of Regulatory Cells by Sairei-to, a Japanese Herbal Medicine

Sairei-to (TJ114), a 12-component Japanese herbal medicine, is used to treat immune-related diseases. We investigated the effects of oral administration of TJ114 in a murine model of cardiac transplantation with fully mismatched allografts. Untreated CBA mice rejected C57BL/6 hearts acutely (median survival time [MST], 7 days), whereas survival of allografts from mice given TJ114 was significantly prolonged (MST >100 days). Secondary CBA recipients of C57BL/6 hearts also had prolonged allograft survival (MST >100 days) after adoptive transfer of whole or CD4+ splenocytes from primary CBA allograft recipients given TJ114. None of the individual components of TJ114 prolonged allograft survival, suggesting that its effects require administration of the combination agent. In mixed leukocyte cultures, proliferation of splenocytes from TJ114-treated CBA recipients was markedly suppressed compared with that of splenocytes from untreated mice, and interferon-&ggr; production was significantly reduced. Thus, in our model, TJ114 treatment induced hyporesponsiveness to cardiac allografts and generated CD4+ regulatory cells.

Maternal stress affects postnatal growth and the pituitary expression of prolactin in mouse offspring

Maternal stress exerts long‐lasting psychiatric and somatic on offspring, which persist into adulthood. However, the effect of maternal stress on the postnatal growth of pups has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight of male mouse offspring, which persisted after weaning. Despite free access to chow, IS induced maternal malnutrition and decreased the serum insulin‐like growth factor‐1 (IGF‐1) levels in the mothers and in the pups. mRNA expression analysis of anterior pituitary hormones in the pups revealed that growth hormone (GH) and prolactin (PRL), but no other hormones, were decreased by IS. Expression of the pituitary transcription factor PIT1 and isoforms of PITX2, which are essential for the development and function of GH‐producing somatotropes and PRL‐producing lactotropes, was decreased, whereas that of PROP1, which is critical for the earlier stages of pituitary development, was unchanged. Immunohistochemistry also showed a decrease in pituitary PRL protein expression. These results suggest that stress in a postpartum mother has persistent effects on the body weight of the offspring. Reduced PRL expression in the offsprings pituitary gland may play a role in these effects.

Evaluation of Oxygen Radical Absorbance Capacity in Kampo Medicine

Antioxidant capacity of food has come to be shown in terms of oxygen radical absorbance capacity (ORAC) mainly on vegetables or fruit. However, the evaluation of Kampo in terms of ORAC has not yet been accomplished. It is important that such an investigation is also conducted for Kampo medicine. We measured the ORAC value of almost all the available Kampo formulas used in the Japanese National health insurance system and examined the ORAC value both for the daily prescription, and also the crude herb ingredients. The ORAC value of Kampo medicine ranged 4.65–5913 units/day. The ORAC value was high in Kampo formulas including Rhei Rhizoma, and was relatively high in Kampo formulas including anti-inflammatory herbs other than Rhei Rhizoma. The ORAC value was also high in Kampo formulas including crude herbs that have relaxation effects. The ORAC value of a crude herb would seem to not be fixed but be dependent on combination with other crude herbs from the comparison of different herbs added to the basic Kampo medicine. These results suggest variability and complexity of the antioxidant capacity of Kampo medicine within the similar range of food. On the other hand, investigation of the compound changes of various crude herbs with ORAC may lead to the elucidation of the action mechanism of Kampo medicine.

Complete Recovery from Tension-Type Headache Through Kampo Medicine

OBJECTIVE We administered Kampo medicine for tension-type headache with extremely effective results. The objective is to demonstrate the effect of Kampo medicine. SUBJECT The case was 13 year-old-girl who had been suffering from headaches from the age of 11 years. As general and neurologic examinations (blood tests, urine analysis, head computed tomography, and electroencephalography) showed no abnormal findings, we diagnosed her as suffering from tension-type headache. Accompanying signs and symptoms included fatigue, shoulder stiffness, and a lot of stress in a private supplementary school and from ballet lessons. INTERVENTIONS AND OUTCOME Kampo medicine was chosen to address the necessity for a comprehensive treatment. We prescribed saikokaryukotsuboreito, with clear positive effect. Although headaches re-appeared when she later forgot to take the formula, the symptom disappeared by taking it again. Treatment was discontinued after 11 months, and the headache has not recurred for 3 years. CONCLUSIONS Kampo medicine was able to improve her overall symptom pattern, as Kampo formulas are selected not only by paying attention to the primary symptom (in this case headache) but also by checking the other characteristics (additional symptoms, constitution, etc). This case showed that Kampo treatment is an effective therapeutic option for tension-type headaches accompanied by various other symptoms.

Current Problems of the Compound Fee for Herbal Medicine

2006年度に改定された漢方生薬の調剤である湯薬調剤料が適正であるか否かを検討した。調剤時間を指標に湯薬調剤と一般調剤を比較した。1～15日処方で一般調剤が平均4．4分／枚のところ湯薬調剤は平均13．4分／枚と約3倍の時間を要し，30日を超過する処方では一般調剤に比べ約7倍の時間を要した。次に調剤業務1分間あたりの調剤報酬を湯薬調剤と一般調剤で比較検討した。1～15日処方では大きな差はなかったが，15日を超える処方日数の湯薬調剤では一般調剤に比べ，調剤報酬が約1／3から1／5ほど低い結果となった。大学病院における処方日数の変移の調査では，30日を超過する処方件数は2003年度では全体の2．7％であったが，2008年度の件数は約14倍に増えて全体の42％であった。長期投薬が増えつつある現状を考慮すると，湯薬調剤料も内服調剤料同様，処方日数に応じた調剤報酬にする必要がある。