Betulinic acid protects the neuronal damage in new born rats from isoflurane-induced apoptosis in the developing brain by blocking FASL-FAS signaling pathway.

Betulinic acid (BA) is a naturally occurring pentacyclic lupane group triterpenoid, has reported to protect cerebral ischemia. Present study evaluates the protective effect of betulinic acid on the isoflurane-induced neuronal damage in neonatal mice. All the mice of 7days age were exposed to isoflurane (2%; 2h) for the duration of 3day. At the end of protocol cognitive function was evaluated by Morris water maze (MWM) test. However count of apoptotic cells were estimated by TUNEL staining. Concentration of oxidative stress parameters [superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH)], cytokines [tumor necrosis factor (TNF-α); interlukin-6 (IL-6) and IL-1β] and expressions of caspase 3, FAS and FASL were estimated in the neuronal cells. Result of the study suggested that treatment with betulinic acid significantly reduces the escape latency and enhances platform crossing time than negative control group. Count of apoptotic cells were also found to be reduced in BA treated group of mice than negative control group. Moreover treatment with BA significantly attenuates the concentration of inflammatory cytokines and oxidative stress in isoflurane induced neonatal mice. However expressions of caspase-3, FAS/FASL was found to be significantly reduced in BA treated group of mice than negative control group. Present study concludes the neuroprotective effect of betulinic acid in isoflurane-induced brain damage in developing brain by attenuating the apoptosis through Fas/FASL pathway inhibition.