Implication of thymoquinone as a remedy for polycystic ovary in rat.
BACKGROUND
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-κB) 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.


METHODS
To validate the effect of TQ (1 µM/ml), NF-κB 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-κB 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.


CONCLUSIONS
Overall, most of the above molecular changes are regulated via NF-κB pathway, thus TQ, due to its modulatory effect on the NF-κB signaling, could elevate normal ovarian phenotype and physiological function in the PCO model, indicating its remarkable potential as a remedy for rat PCO.
a Biochemistry Laboratory, School of Environmental Sciences, Jawaharlal Nehru University , New Delhi , India and.|b Reproductive Toxicology Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia , New Delhi , India.
Mohammed
M
Arif
b Reproductive Toxicology Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia , New Delhi , India.
Sonu Chand
SC
Thakur
a Biochemistry Laboratory, School of Environmental Sciences, Jawaharlal Nehru University , New Delhi , India and.
Kasturi
K
Datta
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D016227:Benzoquinones; D018836:Inflammation Mediators; D016328:NF-kappa B; C003466:thymoquinone
COX2; NF-κB; hyaluronan-binding protein 1; matrix metalloproteinase