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Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) show excessive peristalsis, and antispasmodic agents may be useful therapeutic agents. There are few reports on the use of Kampo medicines for the treatment of IBS-D. Shakuyakukanzoto (SKT) is a Kampo medicine that is effective against abdominal pain. We examined the relationship between SKT and intestinal peristalsis in an animal model and a prospective study. In the animal model, SKT and its components were administered from the serosal side of the colon and colonic peristalsis was evaluated using intraluminal pressure and spatiotemporal mapping before and after the administration of SKT and its components. In this clinical trial, we used abdominal ultrasonography (US) to obtain long-axis images of the sigmoid colon of 11 patients. The frequency of intestinal peristalsis was measured using US in five patients with SKT and six patients without medication after the ingestion of a test meal. The primary outcome was the frequency of peristalsis. The Clinical Trial Registry Website (Trial No. UMIN-CTR; UMIN000051547). In the animal model, peony did not suppress peristalsis frequency, but SKT (p = 0.005) and glycyrrhiza (p = 0.001) significantly suppressed peristalsis frequency compared with saline and peony. Among the glycyrrhiza components, glycycoumarin and isoliquiritigenin suppressed the peristalsis frequency compared to dimethyl sulfoxide (control) (p = 0.001, 0.01, respectively). In a clinical trial, peristalsis was significantly suppressed after oral administration in patients taking SKT (p = 0.03). Administration of SKT was found to inhibit colonic peristalsis, with glycicumarin and isoliquiritigenin being particularly relevant among its components.

Introduction/aims: Muscle cramps are a common and often disabling symptom in amyotrophic lateral sclerosis (ALS), a devastating and incurable neurodegenerative disorder. To date, there are no medications specifically approved for the treatment of muscle cramps. Ameliorating muscle cramps in ALS may improve and sustain quality of life. A widely prescribed traditional Japanese (Kampo) medicine against muscle cramps, shakuyakukanzoto (TJ-68), has been studied in advanced liver disease, spinal stenosis, kidney failure, and diabetic neuropathy. The Japanese ALS Management Guideline mentions TJ-68 for difficult muscle cramps in ALS. Therefore, the rationale of our trial is to investigate the safety and effectiveness of TJ-68 in treating painful and disabling muscle cramps in people with ALS outside of Japan. Accordingly, we are conducting a randomized clinical trial to test the safety and efficacy of TJ-68 in participants with ALS reporting frequent muscle cramps using an innovative, personalized N-of-1 design. If successful, TJ-68 may be used for muscle cramps in a broader population of people with ALS., Methods: This is a two-site, double-blind, randomized personalized N-of-1 early clinical trial with TJ-68. At least 22 participants with ALS and daily muscle cramps will receive drug or placebo for 2 weeks (one treatment period) followed by a 1-week washout in a four-period cross-over design. While the primary objective is to evaluate the safety of TJ-68, the study has 85% power to detect a one-point shift on the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity of the Columbia Muscle Cramp Scale (MCS). Secondary outcomes include the full MCS score, a Cramp Diary, Clinical Global Impression of Changes, Goal Attainment Scale, quality of life scale and ALS functional rating scale-revised (ALSFRS-R)., Discussion: The study is underway. A personalized N-of-1 trial design is an efficient approach to testing medications that alleviate muscle cramps in rare disorders. If TJ-68 proves safe and efficacious then it may be used to treat cramps in ALS, and help to improve and sustain quality of life., Trial Registration: This clinical trial has been registered with ClinicalTrials.gov (NCT04998305), 8/9/2021., (© 2023. The Author(s).)

Background: Muscle soreness after exercise, called delayed-onset muscle soreness (DOMS), may cause significant changes in muscle function and may increase the risk of sports injuries. Therefore, various therapeutic strategies have been studied to help recovery after exercise. Jakyakgamcho-tang (JGT) is a widely prescribed herbal medicine to treat muscle pain and cramps in traditional Eastern medicine. The aim of this study is to evaluate the effect of JGT for reducing pain and improving muscle damage after exercise., Methods: This study is a randomized, double-blind, placebo-controlled, crossover design clinical trial. A total of 30 healthy male adults will be recruited. Subjects who voluntarily wish to participate in this study will be hospitalized for 4 days. On the first day, the subjects will perform a standardized treadmill exercise for 1 h to induce DOMS. After the exercise, the subjects will take either JGT or a placebo for 3 days. After a more than 1 week wash-out period, the subjects will repeat the same process with the other drug. Pain intensity, calf circumference, and pain threshold will be measured as outcome measures. Blood tests and blood pressure will be measured as safety assessments. In addition, blood tests for muscle damage and inflammation markers, such as creatine kinase, interleukin-6, and C-reactive protein, will be analyzed., Discussion: This will be the first trial to assess the effect of JGT on exercise-induced muscle soreness. Our findings will provide valuable data to determine the clinical effects of JGT on DOMS., Trial Registration: Clinical Research Information Sevice, KCT0003457. Registered on 29 January 2019.

Background: In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy., Methods: Paclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay., Results: Addition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn't influence cytotoxicity of paclitaxel in A549 cells., Conclusions: Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel.

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: 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.