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ObjectiveThis study aims to explore and elucidate the possible mechanism of action of Shakuyakukanzoto (SKT) in improving ulcerative colitis (UC) in mice through regulating energy metabolism and polarization of macrophages. MethodsThe mouse UC model was constructed by administering 3% dextran sulfate sodium salt (DSS), and the mice were treated with SKT intragastrically. In addition, single-cell sequencing and enrichment of metabolic pathways against two datasets, GSE21157 and GSE210415, were conducted first. Second, the extraction and metabolomics of peritoneal macrophages from UC mice were verified. Then, the pathway of differentially abundant metabolite enrichment and the correlation of UC risk were analyzed depending on univariate Mendelian randomization of two samples weighted by standard inverse variance. Finally, the results were verified by qRT-PCR, Western blot, and flow cytometry. ResultsAccording to the HE staining results, SKT can significantly alleviate colon damage caused by DSS. Macrophages, NK cells, T cells, and more than 10 different types of cells, based on single-cell sequencing analysis, are detected in the intestinal wall. In the disease group, we can conclude that the activity of 49 macrophage metabolic pathways, mainly involved in energy metabolism, is significantly upregulated through a comparison of the two datasets. In energy metabolomics, 10 and 18 types of metabolites accompanied by significantly upregulated and downregulated differential expression were identified in the treatment group and the model group, as well as the model group and the blank group, respectively. Meanwhile, these differentially expressed metabolites present an obvious correlation with glycolysis and oxidative phosphorylation. Moreover, it can be inferred that glycolysis and the oxidative phosphorylation-related gene NDUFS1 (OR: 0.56, 95% CI: 0.48-0.98, P=0.000 068) are associated with a reduced risk of UC based on the univariate Mendelian randomization of two samples weighted based on standard inverse variance. By analyzing the difference in transcription levels between the two datasets, the transcription level of NDUFS1 in UC was decreased compared with that in the normal group. The results of qRT-PCR, Western blot, and flow cytometry indicate that SKT can promote the expression of the oxidative phosphorylation protein NDUFS1 in macrophages and inhibit the M1-type polarization of macrophages. Furthermore, knockdown/overexpression of NDUFS1 can affect the effect of SKT on M1-type polarization of macrophages. ConclusionBased on the results of this study, SKT inhibits macrophage polarization toward the M1 phenotype by regulating the level of the oxidatively phosphorylated protein NDUFS1 in macrophages; hence, UC is also relieved in mice. These conclusions not only reveal the therapeutic mechanism of SKT for UC but also provide a new theoretical basis for clinical application.
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We report our experience with two patients who had a previous history of cerebral hemorrhage and presented with persistent hiccups. Hangekobokuto was found to be effective in these patients. Case 1 was a 49-year-old man with a history of cerebral hemorrhage who experienced persistent hiccups as a result of pulmonary aspiration that occurred while he was admitted to the hospital for heat stroke. Abdominal palpation revealed epigastric resistance and tenderness. Metoclopramide and shakuyakukanzoto were administered without any amelioration of the symptoms, but the symptoms disappeared 1 hr after changing the drug regimen to hangekobokuto. Case 2 was a 64-year-old man who experienced persistent hiccups 28 days after suffering a cerebral hemorrhage. Abdominal palpation revealed epigastric resistance and tenderness and a lack of resistance at the lower abdomen. Because a regimen of metoclopramide and shakuyakukanzoto was similarly ineffective, we changed the drug regimen to hangekobokuto, and the symptoms subsequently disappeared 7 hr after administration. The symptoms did not recur in either patient following treatment. Hangekobokuto can be effective in cases of persistent hiccups is worth considering as a treatment option.
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<b>Purpose </b>: Shakuyakukanzoto (SKT ; peony and licorice decoction) is a Japanese herbal medicine that is useful in the treatment of acute pain.<br>We investigated the effects of SKT on pain in patients who visited to an outpatient emergency department for painful conditions such as acute gastroenteritis.<br><b>Methods </b>: Thirty patients were enrolled. All participants received 2.5 grams of SKT powder. Pain intensity was measured at baseline and 30 minutes after SKT administration using a visual analog scale (VAS). Patients were asked to rate their pain on a scale from 0 to 100 (0, no pain ; 100, excruciating pain).<br><b>Results </b>: The overall mean VAS score was 71.03 ± 19.42 at baseline and significantly improved to 34.86 ± 34.89 at 30 minutes after SKT administration (P < 0.01).<br><b>Conclusions </b>: SKT was highly effective in managing pain-related emergencies in an outpatient setting. Patients with acute gastroenteritis and tension headache experienced the greatest pain relief.
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Blepharospasm is classified as a focal dystonia, and involves involuntary contraction of muscles such as the orbicularis oculi muscle and the corrugator muscle, which are associated with eyelid movement. Thus blepharospasm involves difficulties to eyelid opening. A 61-year-old woman came to our hospital complaining of a sense of discomfort of the eyes since a half year earlier. Blepharospasm was diagnosed based on current medical history and neurological examination. Oral saikokaryukotsuboreito was started and the blepharospasm improved gradually. After a week, oral treatment with one-third of the amount of shakuyakukanzoto was added and the blepharospasm further improved. The patient wanted to increase the dose of shakuyakukanzoto and to stop the saikokaryukotsuboreito. Once oral shakuyakukanzoto monotherapy was started, however, the blepharospasm worsened. Oral saikokaryukotsuboreito and low dose shakuyakukanzoto was started again, and her blepharospasm improved again.<br>The mechanism behind a focal dystonia such as blepharospasm is explained as a disorder of the basal ganglia motor loop. Saikokaryukotsuboreito is used for the diseases of the central nervous system. Thus there is the possibility that, here, saikokaryukotsuboreito improved a central nervous system disorder, and the blepharospasm. To our knowledge, this is the first report demonstrating that saikokaryukotsuboreito is effective for blepharospasm. It suggests that saikokaryukotsuboreito is a useful option for the treatment of blepharospasm.
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We treated 5 patients with painful muscle cramp due to heat injury using Shakuyakukanzoto. According to their severities, 4 patients were classified with 1 st degree and 1 patient with 3rd degree heat injury. Painful muscle cramps in 4 patients with 1st degree were cured through a single dose of Shakuyakukanzoto. On the other hand, painful muscle cramps in 1 patient with 3rd degree was managed for 4 days after administration of Shakuyakukanzoto. No Shakuyakukanzoto complications were observed in any patient, nor contribution to rhabdomyolysis in 3 patients. Shakuyakukanzoto may be useful to prevent acute kidney injury due to rhabdomyolysis by controlling painful muscle cramps in heat injury.
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Aim:Shakuyakukanzoto is a Japanese herbal medicine that is known to be useful for the treatment of urinary stone pain. In this study, we investigated the effects of shakuyakukanzoto for acute renal colic.Methods:Twenty-five patients were enrolled in this study. Eleven patients took 5.0 g of shakuyakukanzoto powder, and 14 control patients took non-steroidal anti-inflammatory drugs (NSAIDs) for their acute renal colic. The effects were evaluated before and 15, 30, and 60 minutes after treatment with a numerical rating scale (NRS). We defined scale point zero as not having pain, and scale point ten as having the strongest pain.Results:Mean NRS scores improved from 6.7 ± 2.3 to 3.4 ± 3.5 after 15 minutes (shakuyakukanzoto group), and from 8.3 ± 1.8 to 7.0 ± 1.9 after 15 minutes (control group). NRS scores were improved immediately and significantly in both groups. The NRS score of shakuyakukanzoto group was significantly lower than that of control group at the any time after treatment. No side effects were observed in this study.Conclusion : Shakuyakukanzoto has an immediate effect, and it is more effective than NSAIDs. Shakuyakukanzoto was a useful treatment for acute renal colic.
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We encountered 4 cases of calf cramps in which the herbal mixture shakuyakukanzoto was ineffective but another herbal mixture sokeikakketsuto was effective. In case 1, the patient was a 73-year-old man. He had a history of calf cramps, and started experiencing calf cramps more frequently about1month before he made his first visit to our department. Shakuyakukanzoto (7.5g/day) was initially prescribed, but the frequency of cramps did not change. Then, shakuyakukanzoto was replaced with sokeikakketsuto (7.5g/day), and this resulted in rapid alleviation of the symptom. In case 2, the patient was a 67-year-old woman undergoing outpatient care for shoulder stiffness, low back pain, etc. She started experiencing calf cramps at night and underwent shakuyakukanzoto (7.5g/day) treatment. The frequency of cramps did not change, and hence, shakuyakukanzoto was replaced with sokeikakketsuto (2.5g at bedtime). The symptom was alleviated in response to this therapy. In case 3, the patient was a 66-year-old woman undergoing treatment for low back pain at our department. She experienced calf cramps and was treated with shakuyakukanzobushito (3.0g/day). The response was poor, and the herbal mixture was replaced with sokeikakketsuto (7.5g/day), which resulted in the disappearance of her cramps. In case 4, the patient was a 75-year-old man undergoing treatment for a cold sensation in the left leg. He experienced calf cramps and was treated with shakuyakukanzobushito (1.5g/day). This therapy resulted in only temporary relief from the symptom. After the herbal mixture was replaced with sokeikakketsuto (2.5g/day), the cramps disappeared rapidly. Thus, sokeikakketsuto, which improves blood flow and is thought to manifest analgesic effects, may be used for treating patients with calf cramps who do not respond to shakuyakukanzoto.
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Shakuyakukanzoto is effective for pain primarily related to muscle contractions and the powder works rapidly after oral intake. We successfully treated a patient who presented with spastic convulsions by using shakuyakukanzoto. A 32-year-old man had injury to his left hand from a dog bite, resulting in tetanus. Intravenous propofol was chosen as a sedative at first. On day1, shakuyakukanzoto was also administered to control his spastic convulsions. It was effective in reducing his propofol dose and improving various symptoms such as priapism, abdominal pain, tremor, and insomnia. The patient was discharged from our hospital on day 14. This is the first report we know of tetanus treated with shakuyakukanzoto. And we believe that shakuyakukanzoto may be useful for the control of muscle spasms and the management of dysautonomia caused by generalized tetanus.
الموضوعات
Propofol , Paeonia , Tetanus Toxoidالملخص
In vitro fertilization-embryo transfer (IVF-ET) therapy for subfertile couples has become widespread. However, it has been reported that high frequency uterine contractions at the time of embryo transfer influence adversely IVF-ET outcome. This article focuses on the methods of administration of shakuyakukanzoto combined with ET for subfertile women. 186 patients who underwent IVF-ET were recruited. 94 women undergoing IVF were randomly assigned to ET with shakuyakukanzoto for 4 days or 92 with no treatment. Background characteristics (age, number of embryo transferred, quality, and luteal function) were similar in the two groups. Pregnancy rate was 33.0% in the shakuyakukanzoto group as compared with 20.7% in the nontreated group. The increased pregnancy rate with shakuyakukanzoto compared with no treated was significant. However, the precise mechanism to explain for the results of this investigation remains to be unclear. Therefore, further research might be necessary to evaluate the effect of shakuyakukanzoto, at the time of ET.
الموضوعات
Embryo Transfer , Paeoniaالملخص
A painful muscle cramp caused by diabetic neuropathy is one of most bothersome symptoms of patients with diabetes mellitus. It happens during night time and causes sleep disturbance. In this communication we report on the clinical usefulness of Shakuyaku-kanzo-to on nocturnal leg cramp. Twelve diabetic patients were treated with 2.5 to 7.5g/day of Shakuyaku-kanzo-to for 4 weeks. Eight patients were cured of muscle cramp and clinical usefulness was recognized in all patients. In conclusion, Shakuyaku-kanzo-to is very useful in the treatment of patients with muscle cramp caused by diabetic neuropathy.
الملخص
Two cases in which Shakuyakukanzo-to (extract) was effective for spasms in the lower limbs. The spasms in these two cases were associated with central nervous system disorders affecting the brain or spinal cord.<br>The first case was a 61-year-old woman suffering from myelitis sequela. The spasms in her lower left leg increased in severity in the winter, and she experienced difficulty bending her left knee and walking.<br>The second case was a 29-year-old woman with convulsive cerebral anesthesia. Walking had become difficult with exacerbation of her sciatica and with increased spasms in her feet.<br>In both cases, the various muscle relaxants were not sufficiently effective. Regular administration of Shakuyakukanzo-to, however, had a remarkable immediate effect in decreasing spasms and facilitating walking.
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The effectiveness of Shakuyaku-kanzo-to on myotonia in a 50-year-old female with myotonic dystrophy is reported. Neurological examination showed myogenic distal dominant muscle weakness and myotonia. Treatment with Shakuyaku-kanzo-to improved myotonic time from 12.8 to 6.8 seconds. This effect was equal to phenytoin and mexiletine. The results indicated that Shakuyaku-kanzo-to affected the ion channels of the skeletal muscle membrane. The apaminsensitive K channel was speculated to be the affected site of the ion channel. Glycyrrhizin might play an important role in this mechanism.<br>Five week treatment with Shakuyaku-kanzo-to showed no adverse effects on the myopathy.
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We asked 50 ambulatory patients with cerebrovascular disease whether their sleep had been disturbed due to cramp in the calf while they were sleeping soundly at night. Their age ranged from 32 to 81 years. Eleven patients (22%) gave an affirmative answer, and eight of these answered that they had cramp from one to three times a week or more. These eight patients received Syakuyaku-kanzo-to extract granules (2.5g) daily for two weeks. Those who responded sufficiently remained on the same dose, and those who did not received double the dose for further two weeks before the efficacy was evaluated.<br>All five patients who were able to comply with the treatment for four weeks improved either markedly or slightly. The onset of its action was rapid. These results are comparable to those of muscle relaxants and minor tranquilizers and suggest that Syakuyaku-kanzo-to extract granules are beneficial for spasm of the calf in patients with cerebrovascular disease.<br>With regard to its side-effects, one patients who received the treatment for more than two weeks developed pseudoaldosteronism. This was the only negative point of the treatment, but this disappeared rapidly after treatment was discontinued.
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Although Shakuyakukanzo-to (below Shakkan-to) is most commonly used for abdominal pain, Kanzo-to is equally effective. Among out-patients who come to the clinic for treatment for abdominal pain, the transitory pain associated with acute colds and the accompanying gastrocnteritis are the most frequently seen. Over a period of one year 130 such patients were given either of these two formulas by oral administration or by simply holding it in the mouth.<br>Almost no difference was seen between the four different groups (two formulas x two administration methods). In all groups abdominal pain disappeared between about two to ten minutes.
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In hemodialysis patients, muscle cramps in the lower extremities are frequently seen. In order to prevent the occurrence of these cramps, Shakuyakukanzo-to was administered to five patients that frequently suffered from muscle cramps during dialysis. Before receiving dialysis, a dose of 2.5g was given to each of the five patients. The rates of efficacy were: effective for 2 patients, slightly effective for 2 patients and not effective for 1 patient. No severe side effects such as increases in serum potassium levels were observed. The results therefore suggested that Shakuyakukanzo-to is useful in the prevention of muscle cramps during dialysis.