Objective: The present study was conducted to elucidate the underlying molecular mechanism
as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/
reperfusion (IR) injury.
Methods: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia
and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ
(200 mg/kg P.O.). The experiment lasted for 28 days.
Results: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of
serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation
of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of
Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked
histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment
with RJ significantly improved hepatic functions along with the alleviation of histopathological
changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf-
2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response
by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression.
Conclusion: The present results revealed that RJ has successfully protected the liver against hepatic
IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-
α signaling pathways.