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Objective To explore the effect of Dingkun pill on the PI3K/AKT/mTOR signaling pathway in rats with endometriosis(EM).Methods EM rat models were established by heterotopic transplantation of endometrial tissue and randomly divided into five groups:model group(M group),Dingkun pill low(1.13 g/kg)dose group(DKP-L group),Dingkun pill medium(2.26 g/kg)dose group(DKP-M group),Dingkun pill high(4.52 g/kg)dose group(DKP-H group)and gestrinone(60 mg/kg)group(GES group)with 12 rats in each group.The abdomen was opened without transplantation of ectopic endometrial tissue in another 12 normal SD rats as sham operation group(Sham group).The rats were sacrificed after drug treatments,The mass and volume of ectopic endometrium were measured.The microvessel density(CD31-positive rate)and expression of VEGF and MMP-9 in rat ectopic endometrial tissue were assessed by immunohistochemical staining.Rat serum VEGF,MMP-9,iNOS and TNF-α levels were measured by enzyme-linked immunosorbent assays.Expression of PI3K/AKT/mTOR pathway-related proteins in rat ectopic endometrial tissue was detected by Western blot.Results Compared with those in the sham group,the microvessel density,VEGF and MMP-9 expression,serum VEGF,MMP-9,iNOS and TNF-α levels,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR in ectopic endometrial tissue were significantly increased in the M group(P<0.05).Compared with the findings in the M group,the ectopic endometrial volume,weight of the ectopic lesion,microvessel density of the ectopic endometrial tissue,VEGF and MMP-9 expression,serum VEGF,MMP-9,iNOS and TNF-α levels,p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR in ectopic endometrial tissue were all decreased in the DKP-L,DKP-M,DKP-H groups,and dose-dependent effects were observed in Dingkun pill low dose,Dingkun pill medium dose,and Dingkun pill high dose groups(P<0.05).Compared with DKP-H group and GES group,no significant difference was found in the indicators(P>0.05).Conclusions Dingkun Dan reduces inflammation and inhibits ectopic endometrial growth in EM rats,which may be achieved by blocking the PI3K/AKT/mTOR signal pathway.
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OBJECTIVE@#To evaluate the effects of Chinese medicine Dingkun Pill () alone or in combination with Diane-35 on patients with polycystic ovary syndrome (PCOS).@*METHODS@#This is a prospective randomized controlled trial conducted at Peking Union Medical College Hospital Beijing, China, from December 2016 to September 2017. Totally 117 PCOS patients were randomly assigned to the Dingkun Pill group (38 cases), Diane-35 group (40 cases), or combined group (39 cases). Patients in the Dingkun Pill group or Diane-35 group took daily 7 g of oral Dingkun Pill or 1 tablet of oral Diane-35, respectively, for 21 consecutive days followed by 7 drug-free days. And the combined group received a combination of Dingkun Pill and Diane-35. The treatment course was 3 months. Fasting plasma glucose and insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), free fatty acids (FFA) and sex hormones were analyzed, quantitative insulin sensitivity check index (QUICKI) was calculated, and menstruation and acne scores were recorded at baseline and after 3-month treatment.@*RESULTS@#Compared with before treatment, QUICKI decreased significantly in the Dingkun Pill and combined groups after 3-month treatment (P0.05).@*CONCLUSIONS@#Dingkun Pill showed better effects than Diane-35 in improving insulin sensitivity, lowering TC and FFA. Diane-35 was more efficient in regulating menstruation and lowering androgen than Dingkun Pill. Combination of Dingkun Pill and Diane-35 may be a better choice to regulate menstruation, lower androgens while improve glucose metabolism in PCOS patients. (Registered on ClinicalTrials.gov, registration No. NCT03264638).
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OBJECTIVE@#To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS).@*METHODS@#A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated.@*RESULTS@#Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05).@*CONCLUSION@#DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).