Effect of DLBS3233, Metformin, and Their Combination on the Expressions of VEGF and Endometriosis Implants in Endometriosis Mice (A Mouse Model in Endometriosis Study)

Abstract Background: Endometriosis is a gynaecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. The process of angiogenesis is regulated by VEGF which plays an important role in the development of endometriosis implants. Metformin is an insulin sensitizer that is known to have a beneficial effect in the treatment of endometriosis and DLBS3233 is a PPARγ agonist, it is hoped that it can reduce VEGF and reduce endometrial implants..Objective: To explore the effect of DLBS3233, metformin, and combination on VEGF expression and endometrial implant area of endometriosis-induced mice.Methods: This experimental study used 3-months old 28 BALB/c mice of endometriosis that were randomly and equally divided into four groups (K, P1, P2, and P3). On the 15th day, the K group was given a placebo, the P1 group was given DLBS3233 0.25 mg/day for 14 days, the P2 group was given metformin 4 mg/day for 14 days and the P3 group was given a combination. The immunohistochemistry of VEGF expression was performed from the abdominal cavity and pelvic peritoneal tissues of the mice and measured by the Remmele Scale Index, while the extracted mice's endometrial implants were analyzed with a computer tracing method. All data normality tests were calculated with the Shapiro-Wilk test. The mean difference test of all groups was analyzed using the one-way ANOVA test and the Kruskal-Wallis test.Results: There were significant differences in the expressions of VEGF (p=0.005) and endometrial implants (p=0.001). Expression of VEGF in the P3 group was significantly lower compared to others and endometrial implant area in the P2 group was significantly lower compared to others.Conclusion: DLBS3233 and Metformin may be a potentially effective drug treatments for endometriosis by decreasing VEGF expression and endometrial implants. Keywords: DLBS3233, Endometriosis, Metformin, VEG

Effect of Probiotic Supplementation on FSH, LH Levels and Folliculogenesis

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that often occurs in women of reproductive age. The main therapy currently used to treat PCOS patients is insulin sensitizer. In PCOS, there is an imbalance in the intestinal flora which causes activation of the immune system and an inflammatory response that leads to insulin resistance. The effect of probiotic supplementation on insulin resistance can have an impact on changes in reproductive hormone levels in PCOS women. Objective: Analyze the effect of probiotic supplementation on levels of FSH, LH, and folliculogenesis in a study of PCOS Wistar rats. Methods: Experimental research with a post-test only controlled group design. The research sample was 35 Wistar rats which were divided into 5 groups, (K-) were healthy rats, (K+) were PCOS rats without treatment, (P1) were PCOS rats received Metformin, (P2) were PCOS rats received Probiotics, and (P3) were PCOS rats that received Metformin + Probiotics. The intervention was carried out for 14 days. The dependent variables were levels of FSH, LH and folliculogenesis. Research data were analyzed using one-way ANOVA test, Fisher Exact test. Differences between groups and controls were tested with Dunnett's post hoc test. Significant p<0.05Results: Metformin + probiotic supplementation resulted in increased FSH levels, decreased LH levels and increased folliculogenesis when compared to the PCOS rats without treatment (K+).Conclusion: Metformin + probiotic supplementation causes levels of FSH, LH and folliculogenesis activity in PCOS rats to resemble healthy rats