Investigation of the effect of onion, flaxseeds and turmeric on the development or regression of the endometriotic focus in the treatment of surgical induced endometriosis in rat models

Introduction and Aim: Endometriosis is disorder in growth of tissue outside uterus, in which it lines inside uterus under normal conditions and 10-15% of the women in reproductive age and 30-50% of infertile women suffers from it. The most common symptoms are chronic pelvic pain, dysmenorrhea (painful periods), dyspareunia (painful intercourse) and infertility. Although the pathogenesis of endometriosis is still unknown, it has been thought that the immunological factors, mediators of inflammation, some related genes and oxidative stress could be effectors. The current medical treatments unfortunately give limited and short-term solution due to negative side effects in long term. In fact, the relapse of the disease is seen in common and frequent after completing of treatment. Therefore, these limitations encourage researchers to look for a long-term and safer treatments and keeps the field in hot agenda. Of note, it has been showed that non-pharmacological approaches such as changes in lifestyle and diet may contribute the recovery of the symptoms and disease. Nowadays the tendency to search in an alternative medicine such as phytoherapy in endometriosis has been increased in our country like all over the world due to the limitations of current treatments in endometriosis and also increased interest in phytoherapy in many disease such as cancer to support treatment and/or treat the disease. In literature some studies have been already reported the positive effect of turmeric (Curcuma longa) in the treatment of endometriosis, in which it might possess antioxidant, anti-inflammatory, anti-tumoral, anti-mutagenic and anti-metastatic properties and hormonal regulator. Moreover, an onion (Allium cepa L.) and flax seeds (Linum usitatissimum L.) have been used commonly as antioxidant and anti-inflammatory. Due to all reasons above, we purposed in this case-control study that we observed the effects of commonly used onion, turmeric and flax seeds used in our country as alternative medicine on rats with experimentally induced endometriosis and compared the macroscopic and microscopic results. Our study was the first study using and showing the effects of the onion and flax seeds in endometriosis. Materials and Methods: This study is a case-control study and has been conducted in SUDETAM (Experimental Medical Practices and Research Center, Faculty of Medicine, University of Sakarya) and Department of Biochemistry at SUEAH and Laboratory of Histology and Embryology, Faculty of Medicine, University of Sakarya. In this research mature (3- 6 months old) Sprague Dawley female rats were used in which their weights were between 250-300 and their age. Firstly, we formed endometriotic implants by laparotomy and then waited for 4 weeks. After that we checked whether or not the endometriotic implants were successful. After confirmation of success, we numerated the rats for randomization, and we formed 4 different random group by lottery. The subjects have been fed daily by same person at same time by oral gavage during following two weeks with 3 cc/day of onion water or curcumin or lignan. We also fed the control groups (Sham Group) with same amount of distilled water to provide the same external disturbances and conditions. While we performed the histopathological and immunological experiments on the cysts, we did biochemical experiments with some parameters such as cas3, TGFα, TGF β and VEGF on the blood withdrawn from the subjects and control groups. Results: Weights of the subjects and average values of the maximum and minimum endometriotic implants s after and before treatment were compared. We could not observe any significant differences in maximum values of endometriotic implants before treatment (p>0.05). That values were significantly different after phytoherapy (p<0.05). After treatment the maximum difference,4.17±1.69 mm in endometriotic implants was in group fed by turmeric, followed by sham, flax seeds and onion extraction, respectively. The changes in MMP-2 and caspase 3 expression were not significant (p>0.05). Although the values of TGFα in flax seed, TGFβ in turmeric and VEGF in sham groups were high, there were no significant changes in all three parameters between groups (p>0.05). However, the differences in epithelialization averages were significantly changed between groups (p<0.05). The levels of fibrosis were highest in group fed by onion extraction with 2.43±0.53 averagely, followed by flax seed, turmeric and sham, respectively. According to variation analyses, the differences between groups fed by sham and onion extraction was significant (p=0.016<0.05). Nonetheless there were no significant correlation between epithelialization and fibrosis with other parameters (p>0.05). Conclusion: Endometriosis is disorder growth disease of tissue out of uterus with limited medical treatments, followed by side effects with long term use. This also causes increase in use of herbs with properties such as antioxidant, anti-inflammation and anti-angiogenesis in endometriosis. In our study we observed that in the group fed with onion extraction (Allium cepa) the size of endometriotic implants were significantly reduced and there was a marked increase in epithelialization and fibrosis. It might be concluded that the onion (Allium cepa) extraction may influence the regression of endometriotic implants. Nevertheless, more prospective randomized control case reports are needed to understand the effect of traditional use of herbs on endometriosis. Keywords: Endometriosis, Phytoherapy, Onion, Turmeric, Curcumin, Flax seeds, Lignan, Endometriosis induced rat models and Rats.