Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.
Animals ; Oxytocin/pharmacology* ; Gyrus Cinguli/drug effects* ; Male ; Female ; Corticosterone/pharmacology* ; Empathy/drug effects* ; Sex Characteristics ; Receptors, Oxytocin/antagonists & inhibitors* ; Pain/psychology* ; Rats ; Rats, Sprague-Dawley ; Neurons/metabolism*

One of the core symptoms in anxiety disorders is dysregulated fear response. It is crucial for psychologists and neuroscientists to understand how fear responses are enhanced and inhibited. Although oxytocin (OXT) was initially conceived as a prosocial molecule and mammalian neuropeptide that enhances cooperation and trust, later studies showed that it produces modulatory influence on fear responses. Therefore, OXT is now regarded as a promising pharmacological agent to boost treatment response in anxiety disorders. However, the effect of OXT on fear responses have been somewhat complex, and there are some contradictions among animal experiments and human studies. In this article, we summarize recent studies that employed animal models, brain region-specific manipulations and preclinical studies to explore the role of OXT in the acquisition and processing of fear response. We also discuss the methodological differences among these studies and review the potential factors that may contribute to the complicated effect of OXT on fear response. This review will help to promote the potential clinical application of OXT.
Animals ; Brain ; drug effects ; Fear ; drug effects ; Humans ; Oxytocics ; pharmacology ; Oxytocin ; pharmacology

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.
Animals ; Blood Flow Velocity ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Dysmenorrhea ; drug therapy ; physiopathology ; Female ; Humans ; Mice ; Mice, Inbred ICR ; Oxytocin ; adverse effects ; Uterine Contraction ; drug effects ; Uterus ; blood supply ; drug effects ; physiopathology

To study preliminarily the effect of Jiawei Bazhen decoction combined with oxytocin in promoting cervical ripening of full-term pregnancy women who were in the deficiency of qi and blood type through the syndrome differentiation of traditional Chinese medicine (TCM). 180 patients that met the inclusion criteria of the study were randomly divided into three groups: the control group(oxytocin group), the treatment group (Jiawei Bazhen decoction combined with oxytocin group), the blank control group (expected and observation group). Cervical maturity score (Bishop score), vaginal and cervical secretions fetal fibronectin (FFN), the result of induced labor, the result of mother and baby were observed in each group before and after treatment. The result comes out that the cervical Bishop score of pregnant women for treatment group were significantly higher than the control group and blank control group after treatment (P < 0.05). The FFN of pregnant women for the treatment group were significantly different from the control group and blank control group after treatment (P < 0.05). The pregnancy outcome of the three groups: the labor rate and rate of vaginal delivery of the treatment group were higher than the other two groups, and the difference was statistically significant (P < 0.05). The cesarean section rate of the treatment group was significantly lower than the other two groups, the difference was also statistically significant (P < 0.05). The three groups did not appear the phenomenon of neonatal asphyxia. Jiawei Bazhen decoction combined with oxytocin is effective in producing cervical ripening and induce labor. It is convenient, safe and reliable, for it is no obvious adverse effects on mother and fetus, but effective in reducing the rate of cesarean section, and playing a positive role in promoting natural delivery.
Adult ; Cervical Ripening ; drug effects ; metabolism ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Fibronectins ; secretion ; Humans ; Labor, Induced ; Oxytocin ; administration & dosage ; Pregnancy ; Pregnancy Complications ; drug therapy ; metabolism ; physiopathology ; Pregnancy Outcome ; Qi ; Vagina ; drug effects ; secretion ; Young Adult

Human ; Female ; Pregnancy ; Carboprost ; Uterine Inertia ; Postpartum Hemorrhage ; Oxytocin ; Maternal Mortality ; Cesarean Section ; Drug-related Side Effects And Adverse Reactions

BACKGROUND: Oxytocin is a drug widely used for induction of labor. Despite its widespread use, data on the benefit from continuous oxytocin infusion for labor induction beyond the onset of active phase of labor are scarce. To address this, a single-blind randomized clinical trial was done comparing the course and outcome of labor of patients given continuous oxytocin versus those whose oxytocin were discontinued during the active phase of labor.

METHOD: Term, singleton primigravid patients admitted in a tertiary hospital from January 1 to May 31, 2013 were included in the study. After careful assessment, 64 primigravids who fulfilled the inclusion criteria, (32 per group), were randomized to 2 groups, Group 1 (received continuous oxytocin infusion) and Group 2 oxytocin was discontinued during the active phase of labor). Analysis of data collected was done using SPSS software version 17, student T test, Chi square tests, z test of proportion were used.

RESULTS: There was no statistically significant difference found between the two groups with regards to the outcome during the latent phase of labor as well as the second stage of labor. However, there was significant difference in the duration of the active phase of labor among patients from Group 1 (those given continuous oxytocin). In terms of mode of delivery, there was no statistically significant difference between 2 groups. Some of the patients from both groups eventually required abdominal delivery, this outcome was found to be not statistically significant. The neonatal outcome in terms of APGAR score, clearance given to be roomed-in immediately and the need for antibiotics were also found to be not statistically significant.

CONCLUSION: In this study, results show that discontinuing oxytocin during active phase of labor does not increase the abdominal delivery rate, affect labor and fetal outcomes.

Human ; Female ; Adult ; Young Adult ; Oxytocin-drug effects ; Pregnancy ; Labor Presentation

The objective of this study was to investigate the effects of oxytocin infusion on corpus luteum (CL) function during early to mid-diestrus by measuring luteal size (LS) and luteal blood flow (LBF) along with plasma levels of progesterone (P4) and prostaglandin metabolites (13,14-dihydro-15-keto-prostaglandin F2alpha, PGFM). On day (D) 7 of the estrus cycle (D1 = ovulation), seven cows received 100 IU of oxytocin (OXY) or placebo (PL) following a Latin square design. LS and LBF increased in both groups over time and no differences were observed between the groups. PGFM did not differ either within the groups over time or between the groups at any time point. P4 of the OXY group was higher compared to that of the the PL group 360 min after the infusion (p = 0.01) and tended to be higher at the time points 450 min, 48 h, and 72 h (all p = 0.08). Results from this study support the hypothesis that OXY is not directly involved in the mechanism(s) governing blood flow of the CL and has no remarkable effects either on luteal size or P4 and PGFM plasma levels. Further investigation is needed to elucidate the role of OXY in CL blood flow during early and late luteal phases.
Animals ; Cattle/*physiology ; Corpus Luteum/blood supply/*drug effects/secretion/ultrasonography ; Dinoprost/analogs & derivatives/blood ; Estrous Cycle/*drug effects/physiology ; Female ; Immunoenzyme Techniques/veterinary ; Organ Size/physiology ; Oxytocin/*pharmacology ; Progesterone/blood/*secretion ; Random Allocation ; Ultrasonography, Doppler, Color/veterinary

OBJECTIVETo observe effects of Shujing Ketong soft capsules (SJKTSC) on activities of the uterine of the rat in vitro and in vivo.

METHODThe isolated rat uterine were mounted in the improved Genell solution with a final content of 0. 96, 1.92, 3.84 microg x g(-1) of SJKTSC at 37 degrees C; and 9. 6, 19. 2, 38.4 mg x kg(-1) of SJKTSC and 2 g x kg(-1) of Tongjingbao granules were given to the rat through the duodenum respectively. Their effects on frequency, amplitude and activity of contraction of rat uterus in vitro and in vivo were investigated.

RESULTSJKTSC could significantly inhibit the frequency, amplitude and activity of contraction of the normal rat uterus in vitro and decrease the oxytocin-induced increase of contraction of the rat uterus in vitro; lowered the frequency, amplitude and activity of the oxytocin-induced contraction of the rat uterus in vivo and inhibit the oxytocin-induced the strengthening of contraction of the rat uterus in vivo.

CONCLUSIONShujing Ketong soft capsules maybe used for treatment of dysmenorrhea induced by spasm of uterine smooth muscle.

Animals ; Capsules ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Dysmenorrhea ; drug therapy ; physiopathology ; Female ; In Vitro Techniques ; Muscle, Smooth ; drug effects ; physiology ; Oxytocin ; adverse effects ; Rats ; Rats, Wistar ; Time Factors ; Uterine Contraction ; drug effects ; Uterus ; drug effects ; physiology

OBJECTIVETo observe effects of Fufang Xiaojingtong capsules (FXJTC) on activities of the uterine smooth muscle of the rat in vitro and the uterus of the rabbit in vivo.

METHODThe isolated rat uterine smooth muscle strips were mounted in a Magnus bath containing Locke's solution with a final content of 12.48, 6.24 or 3.12 mg x mL(-1) of FXJTC at 37 degrees C; and 2.0, 1.0 and 0.5 g x kg(-1) of FXJTC and 2.0 g x kg(-1) of Tianqi Tongjing capsules were respectively given to the rabbits through the duodenum, respectively. Their effects on frequency, amplitude and activity of contraction of the rat uterus in vitro and the rabbit uterus in vivo were investigated.

RESULTFXJTC could significantly inhibit the frequency, amplitude and activity of contraction of the normal rat uterus in vitro and decrease the oxytocin-induced increase of contraction of the rabbit uterus in vitro; lowered the frequency, amplitude and activity of contraction of the rabbit uterus in vivo and inhibit the oxytocin-induced the strengthening of contraction of the rabbit uterus in vivo.

CONCLUSIONFufang Xiaojingtong capsules maybe used for treatment of dysmenorrhea induced by spasm of uterine smooth muscle.

Animals ; Capsules ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; In Vitro Techniques ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Oxytocin ; antagonists & inhibitors ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uterus ; drug effects ; physiology