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Case Shakuyakukanzoto (SKT) has long been used for the treatment of muscle cramps. A typical and well-known adverse effect of SKT is licorice-induced pseudoaldosteronism with symptoms of hypokalemia and hypertension. Outcome Herein, we report two cases of severe hypokalemia due to SKT-induced pseudoaldosteronism. Both patients were female, over 80 years old and with a history of prolonged SKT usage. Symptoms related to pseudoaldosteronism resolved soon after SKT stoppage with spironolactone. Conclusion SKT-induced pseudoaldosteronism should be considered in elderly patients with hypokalemia and hypertension.

Aim The influence of angiotensin II receptor blockers (ARB) on licorice-induced pseudoaldosteronism remains unclear and the antihypertensive drug selection of prescribers, when they encounter hypokalemia and hypertension in licorice-treated patients, has not been surveyed. Methods We examined the occurrence of hypokalemia, concomitant drugs, and treatment for hypokalemia and hypertension in 42, 26 and 27 patients prescribed the licorice-containing traditional Japanese kampo medicines shakuyakukanzoto (SKT; containing 6 g licorice/day), rikkunshito (RKT; 1 g licorice/day), and goshajinkigan (GJG; without licorice), respectively. Results Seven (16.7%; P

Case A 74-year-old man developed tetanus 3 days after working with cow and poultry manure. Kakkonto and shakuyakukanzoto, traditional Japanese herbal medicines that are effective for the relief of pain primarily related to muscle contraction, were given to control the trismus and painful contracture of the neck. Generalized convulsions were controlled without the use of muscle relaxants. Outcome After 30 days, the patient was discharged from the hospital without any sequelae. Conclusion Kakkonto and shakuyakukanzoto may be useful for the control of muscle spasms resulting from generalized tetanus.

Shakuyakukanzoto (SKT) is a kampo medicine composed of equal proportions of Glycyrrhizae radix (G. radix) and Paeoniae radix (P. radix). A double-blind study reported that SKT significantly ameliorated painful muscle cramp in cirrhosis patients without the typical severe side effects of muscle weakness and central nervous system (CNS) depression. Previous basic studies reported that SKT and its active components induced relaxation by a direct action on skeletal muscle and that SKT did not depress CNS functions; however, why SKT has a lower incidence of muscle weakness remains unknown. In the present study, we investigated which components are absorbed into the blood of rats after a single oral administration of SKT to identify the active components of SKT. We also investigated the effects of SKT and its components on the twitch contraction induced by physiological Ca(2+) release. Our study demonstrated that SKT and five G. radix isolates, which are responsible for the antispasmodic effect of SKT, did not inhibit the twitch contraction in contrast to dantrolene sodium, a direct-acting peripheral muscle relaxant, indicating that the mechanisms of muscle contraction of SKT and dantrolene in skeletal muscle differ. These findings suggest that SKT does not reduce the contractile force in skeletal muscle under physiological conditions, i.e., SKT may have a low risk of causing muscle weakness in clinical use. Considering that most muscle relaxants and anticonvulsants cause various harmful side effects such as weakness and CNS depression, SKT appears to have a benign safety profile.

芍薬甘草湯が無効で，疎経活血湯が奏効したこむら返りの4例を経験した。症例1は73歳，男性。以前からあったこむら返りが1ヵ月くらい前から増強し，当科を初診。芍薬甘草湯7.5g／日を投与したが不変のため，疎経活血湯7.5g／日に変更したところ，速やかに軽減した。症例2は67歳女性。肩こり，腰痛などで通院中。夜間にこむら返りが出現するようになり，芍薬甘草湯7.5g／日を投与したが不変。疎経活血湯2.5g／眠前投与に変更したところ，こむら返りは速やかに軽減した。症例3は66歳女性。腰痛にて当科治療中。こむら返りが出現したため，芍薬甘草附子湯3.0g／日を投与したが，効果が少なく，疎経活血湯7.5g／日に変更したところ，速やかに消失した。症例4は75歳男性。左の下肢冷感で加療中。こむら返りが出現したため，芍薬甘草附子湯1.5g／日投与したが，変化は一時的で，疎経活血湯2.5g／日に変更したところ，速やかに消失した。血流を改善し，鎮痛効果の期待できる疎経活血湯は，芍薬甘草湯無効のこむら返りに試みられてよい方剤と考えられる。

体外受精-胚移植は難治性不妊に対して広く行われている治療である。しかし, 胚移植時の子宮収縮が治療効果に悪影響を与えるという報告がある。そこで今回われわれは, 平滑筋収縮抑制効果が期待できる芍薬甘草湯を胚移植時に併用し, 体外受精-胚移植の成績が向上するかどうかを検討した。体外受精を行った186症例のうち, 体外受精を行った順に1番目～94番目に対し芍薬甘草湯を胚移植後4日間投与し, 95番目～186番目に対しては何も投与しなかった。また二つの群において年齢や移植胚数および胚質, 黄体機能など臨床的背景に有意な差はなかった。芍薬甘草湯を投与した群と非投与群とで胚移植あたりの妊娠率を比較したところ投与群は33.0%だったのに対し非投与群は20.7%となり, 両群間に有意な差が認められた。しかし, 本研究結果を説明する正確なメカニズムは不明である。したがって, さらに症例数を増やし, 胚移植時の芍薬甘草湯の効果を検討していく必要がある。

Oxaliplatin-induced peripheral neuropathy characterized especially as cold dysesthesia is a major dose-limiting side effect of the drug and is very difficult to control. In the present study, we examined whether the traditional herbal formulation Shakuyakukanzoto (SKT: 芍藥甘草湯Sháo Yào Gān Cǎo Tāng) could relieve oxaliplatin-induced cold dysesthesia in mice. The inhibitory mechanisms were also investigated. Repetitive administration of SKT (0.1–1.0 g/kg) starting from the day after oxaliplatin injection inhibited cold dysesthesia in a dose-dependent manner. Our previous report has shown that the mRNA expression of transient receptor potential melastatin 8 (TRPM8), characterized as a cold-sensing cation channel, is increased in the dorsal root ganglia of mice treated with oxaliplatin. In addition, TRPM8 antagonist TC-I 2014 (10 and 30 mg/kg) also attenuated cold dysesthesia in oxaliplatin-treated mice. Taken together, it is suggested that TRPM8 is involved in the cold dysesthesia induced by oxaliplatin. Repetitive administration of SKT inhibited the mRNA expression of TRPM8 induced by oxaliplatin in the dorsal root ganglia. These results suggested that prophylactic repetitive administration of SKT is effective in preventing the exacerbation of oxaliplatin-induced cold dysesthesia by inhibiting the mRNA expression of TRPM8 in the dorsal root ganglia., Graphical abstract

Background/Aims: Topical epinephrine application to the duodenal papilla reduces spasm of the sphincter of Oddi and prevents acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). Shakuyakukanzoto (TJ-68) has an inhibitory effect on muscle contraction. Therefore, TJ-68 potentially allows the relaxation of the sphincter of Oddi, which can aid in the prevention of post-ERCP pancreatitis. Methods: Thirty-six patients planned for ERCP were divided into TJ-68 (n = 17) and control groups (n = 19). In the TJ-68 group, the TJ-68 solution was endoscopically sprayed directly onto the duodenal papilla of patients. To assess the effects of TJ-68, serum amylase levels were measured at 1 h and 1 day after ERCP and symptoms were evaluated. Results: The serum amylase levels at 1 h after ERCP were 273.6 ± 212.0 IU/l in the TJ-68 group and 428.7 ± 281.6 IU/l in the control group, showing a statistically significant difference (p = 0.036). The serum amylase levels at 24 h after ERCP were 230.0 ± 182.7 IU/l in the TJ-68 group and 497.4 ± 514.0 IU/l in the control group (p = 0.011). Post-ERCP pancreatitis was observed in 0 and 4 patients (21.1%) in the TJ-68 and control groups, respectively, which was not statistically significant (p = 0.11). Conclusion: Direct TJ-68 solution application to the duodenal papilla significantly inhibited the elevation of serum amylase levels. However, the preventive effect regarding post-ERCP pancreatitis was not confirmed in this study.

Shakuyakukanzoto (shao-yao-gan-cao-tang) is a commonly used Chinese traditional herbal medicine for the treatment of acute pain with muscle cramp. However, its mechanism of action is unclear. We previously reported that a low concentration of Kanzo (licorice) and isoliquiritigenin, a component of licorice, inhibited the potassium (K(+)) current in H9c2 cells. Therefore, in the present study, we examined the effects of Shakuyakukanzoto, Shakuyaku or Kanzo on the K(+) current (IKur) in H9c2 cells. Shakuyakukanzoto inhibited IKur in a concentration-dependent manner. The half-maximal concentration of Shakuyakukanzoto was approximately 1.3 mg/mL and the Hill coefficient was 1.2. The order of potency of inhibiting IKur was Kanzo>Shakuyakukanzoto>Shakuyaku. Glycyrrhizin, a major component of licorice, had no inhibitory effect on IKur. A small interfering RNA experiment indicated that IKur was most likely to be Kv2.1 in H9c2 cells. Our results suggest that Shakuyakukanzoto may normalize intracellular and extracellular K(+) balance by inhibiting IKur and reducing K(+) efflux, while the Na(+)-K(+) pump promotes K(+) influx into myofibers. Consequently, excess K(+) may be reduced from external space of myofibers. This may be a part of the Shakuyakukanzoto mechanism for improving muscle pain.

Herbal medicine in Japan is termed as Kampo medicine, which is derived from traditional Chinese medicine. Shakuyakukanzoto (Shao-Yao-Gan-Cao-Tang) as a kind of Kampo formulations is composed of just two components; Paeoniae Radix and Glycyrrhizae Radix, which produced marked relaxation of intestinal tract. Mokuboito (Mu-Fang-Ji-Tang) inhibited cardiac ionic channel currents, and as a mixture also produced great vasodilatation. Sinomenine (a main ingredient of Mokuboito) as a single compound also caused the vasodilatation, but decreased it along with ageing. Gypsum containing in Mokuboito and Chotosan (Diao-Teng-San) caused more marked effects, as compared with those without Gypsum. On the other hand, Rokumigan (Liu-Wei-Wan), Hachimijiogan (Ba-Wei-Di-Huang-Wan) and Goshajinkigan (Niu-Che-Shen-Qi-Wan) increase in order the number of contained ingredients. The formulations with more herbs (ingredients) produced much more effective actions on rat aorta, presumably due to compensation of the decline of pharmacological sensitivity with ageing. Thus, there are some important differences between single chemical drugs and mixture drugs with many ingredients. The effects of Kampo medicine (mixture) are never just a sum of each effect induced by a lot of ingredients. For elder persons, furthermore, Kampo medicine exerts more effective actions.