Two-step inhibitory effect of kanzo on oxytocin-induced and prostaglandin F2α-induced uterine myometrial contractions

Sumi, Genichiro; Yasuda, Katsuhiko; Kanamori, Chiharu; Kajimoto, Megumi; Nishigaki, Akemi; Tsuzuki, Tomoko; Cho, Hisayuu; Okada, Hidetaka; Kanzaki, Hideharu

doi:10.1007/s11418-014-0835-y

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…It has been reported to have an anticontraction effect, by suppressing the increase of intracellular calcium ion concentration, and anti-inflammatory effects, by inhibiting the production of prostaglandin E2, leukotriene B4, and nitric oxide [ 31 ]. However, some studies found that the isolated crude drug did not act as an anticontraction agent on uterine smooth muscle [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study

Yoshino

Katayama

Horiba

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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In Kampo medicine, two different formulas are effective for treating dysmenorrhea—tokishakuyakusan and keishibukuryogan; however, the criteria by which specialists select the appropriate formula for each patient are not clear. We compared patients treated with tokishakuyakusan and those with keishibukuryogan and proposed a predictive model. The study included 168 primary and secondary dysmenorrhea patients who visited the Kampo Clinic at Keio University Hospital. We collected clinical data from 128 dysmenorrhea patients, compared the two patient groups and selected significantly different factors as potential predictors, and used logistic regression to establish a model. An external validation was performed using 40 dysmenorrhea patients. Lightheadedness, BMI < 18.5, and a weak abdomen were significantly more frequent in the tokishakuyakusan group; tendency to sweat, heat intolerance, leg numbness, a cold sensation in the lower back, a strong abdomen, and paraumbilical tenderness and resistance were more frequent in the keishibukuryogan group. The final model fitted the data well. Internally estimated accuracy was 81.2%, and a leave-one-out cross-validation estimate of accuracy was 80.5%. External validation accuracy was 85.0%. We proposed a model for predicting the use of two Kampo formulas for dysmenorrhea, which should be validated in prospective trials.

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Section: Discussionmentioning

confidence: 99%

The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study

Yoshino

Katayama

Horiba

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…SKT has been reported to inhibit acetylcholine‐induced and neurogenic contractions of the gastrointestinal tract and to decrease unfavorable smooth muscle contractions during upper and lower gastrointestinal endoscopy . SKT also inhibits oxytocin‐induced myometrial contractions of uterine tissue in pregnant women in a dose‐dependent manner . In addition to ameliorating muscle symptoms, SKT has been found to improve extrapyramidal symptoms while exerting no significant effect on psychiatric symptoms .…”

Section: Discussionmentioning

confidence: 99%

Effect of Shakuyaku‐kanzo‐to in patients with muscle cramps: A systematic literature review

Ota

Fukui

Nakamura

et al. 2020

J of Gen and Family Med

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Background Previous clinical studies have reported that Shakuyaku‐kanzo‐to (SKT) has a therapeutic effect on muscle cramps, but few studies have clarified how SKT acts to treat muscle cramps. The aim of this study was to perform an updated systematic review of clinical trials for SKT in patients with muscle cramps. Methods The literature was systematically reviewed to assess the effects of SKT in patients with muscle cramps. PubMed, Web of Science, Cochrane Library, Google Scholar, and Ichushi‐Web were searched using the terms “Shakuyaku‐kanzo‐to” (“shakuyakukanzoto”, etc), “clinical trials” and “muscle cramps”. Two quality assessments were conducted independently by three authors. Data were extracted using a standardized extraction tool, and a qualitative synthesis of evidence was performed. Results Three randomized controlled articles were identified and enrolled in this study. A systematic review, but not a meta‐analysis, was performed because of the high heterogeneity and limited number of studies. In patients with liver cirrhosis, the odds ratio (OR) for improvement with SKT compared to placebo was 1.27 (95% confidence interval [CI], 0.445‐2.086) and compared to Goshajinkigan was 0.81 (95%CI, −1.734‐0.114). The OR for improvement with SKT compared with eperisone hydrochloride in patients with lumbar spinal stenosis was 2.86 (95%CI, 0.980‐4.744). Conclusions Current evidence appears insufficient to allow a meta‐analysis of the effects of SKT, but SKT might show efficacy in treating muscle cramps in patients with cirrhosis or lumbar spinal stenosis.

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“…The increase of these pro-inflammatory cytokines favors the stimulation of uterine contractions and induces the onset of labor [34]. This inflammatory response provokes the release of uterotonic agents, such as PGF2α that stimulates the uterine contraction and is a well-recognized smooth muscle motility inducer [5]. On the contrary, many of the uterus relaxant mechanisms involve the second messenger cyclic adenosine monophosphate (cAMP); in fact, cAMP is responsible for the signal transduction that stimulates the cAMP-dependent pathway, such as the activation cAMP-dependent protein kinase (PKA) that, in turn, phosphorylates and inhibits key proteins which cause uterine contractions [6].…”

Section: Introductionmentioning

confidence: 99%

Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4 inhibitors in pregnant rat uterus

Muñoz-Pérez

Fernández-Martínez

Ponce‐Monter

et al. 2017

Korean J Physiol Pharmacol

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The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy. Uterine samples were used in functional studies to evaluate the inhibitory effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-F2α (PGF2α)-induced phasic, K+-induced tonic, and Ca2+-induced contractions. Accumulation of cAMP was quantified in uterine homogenates by ELISA. Anti-inflammatory effect was assessed by using ELISA for determination of the pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, and anti-inflammatory IL-10, from uterine explants stimulated with lipopolysaccharide (LPS). Nifedipine, forskolin and rolipram were used as positive controls where required. Both thalidomide analogs induced a significant inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. Nifedipine and forskolin were more potent than the analogs to inhibit the uterine contractility, but these were more potent than rolipram, and 4APDPMe was equieffective to nifedipine. Thalidomide analogs increased uterine cAMP-levels in a concentration-dependent manner. The LPS-induced TNFα and IL-1β uterine secretion was diminished in a concentration-dependent fashion by both analogs, whereas IL-10 secretion was increased significantly. The thalidomide analogs induced utero-relaxant and anti-inflammatory effects, which were associated with the increased cAMP levels as PDE-4 inhibitors in the pregnant rat uterus. Such properties place these thalidomide analogs as potentially safe and effective tocolytic agents in a field that urgently needs improved pharmacological treatments, as in cases of preterm labor.

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Two-step inhibitory effect of kanzo on oxytocin-induced and prostaglandin F2α-induced uterine myometrial contractions

Cited by 8 publications

References 25 publications

The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study

The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study

Effect of Shakuyaku‐kanzo‐to in patients with muscle cramps: A systematic literature review

Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4 inhibitors in pregnant rat uterus

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