Implication of thymoquinone as a remedy for polycystic ovary in rat

Abstract

Context: Thymoquinone (TQ), an active component of Nigella sativa L. (Ranunculaceae), possesses anti-inflammatory and anti-oxidative properties. Polycystic ovary syndrome exhibits chronic inflammatory behavior, thus might involve nuclear factor kappa B (NF-B) signaling and related molecular factors. Objective: The objective of the present study is to investigate and validate the effect of TQ in polycystic ovary (PCO) rat. Materials and methods: To validate the effect of TQ (1 μM/ml), NF-Bκ activation, COX2 (cyclooxygenase-2) expression and reactive oxygen species (ROS) induction were studied in the KK1 cell line. To evaluate the effect of TQ (2 mg/200 μl olive oil/rat; sc) with an in vivo system, ovulation rate, levels of key ovulation mediators, and ovarian gelatinases activity were compared in superovulated, PCO, and RU486 + TQ-treated Wistar rats. Results: In vitro studies showed that NF-Bκ nuclear translocation, COX2, and ROS expression were repressed via TQ supplementation in RU486-treated KK1 cells. Pretreatment of TQ in the PCO rat model induced significant restoration of normal physio-molecular behavior of ovary, such as reduced cysts formation, increased ovulation rate, and normalization of key ovarian factors [like TNF-α-stimulated gene/protein 6, hyaluronan, hyaluronan-binding protein 1, COX2, matrix metalloproteinases (membrane type 1-matrix metalloproteinase, MMP9 and MMP2)], tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2), and gelatinases (like MMP9 and -2) activity during follicular maturation. Discussion and conclusion: Overall, most of the above molecular changes are regulated via NF-Bκ pathway, thus TQ, due to its modulatory effect on the NF-Bκ signaling, could elevate normal ovarian phenotype and physiological function in the PCO model, indicating its remarkable potential as a remedy for rat PCO.