Objective: Berberine (BBR) is a known alkaloid that has verified its protective effects against ischemia/reperfusion
(I/RN) lesion in multiple organs but its poor oral bioavailability limited its use. Despite the previous works, its
possible impact on the warm hepatic I/RN-induced lesion is not clear. Accordingly, a nanostructured lipid carrier
of BBR (NLC BBR) was developed for enhancing its efficiency and to inspect its protective mechanistic against
warm hepatic I/RN.
Methods: NLC BBR formula was evaluated pharmaceutically. Wistar rats were orally pre-treated with either BBR
or NLC BBR (100 mg/kg) for 2 weeks followed by hepatic I/RN (30 min/24 h). Biochemical, ELISA, qPCR,
western blot, histopathological, and immunohistochemical studies were performed.
Key findings: Optimized NLC BBR was prepared with a particle size of 130 ± 8.3 nm. NLC BBR divulged its
aptitude to safeguard the hepatic tissues partly due to anti-inflammatory capacity through downsizing the
HMGB1/TLR4/NF-κB trajectory with concomitant rebating of TNF-α, iNOS, COX-2, and MPO content. Furthermore,
NLC BBR antiapoptotic trait was confirmed by boosting the prosurvival protein (Bcl-2) and cutting down
the pro-apoptotic marker (Bax). Moreover, its antioxidant nature was confirmed by TAC uplifting besides MDA
subsiding. On the other hand, NLC BBR action embroiled autophagy flux spiking merit exemplified in Beclin-1
and LC3-II enhancement. Finally, NLC BBR administration ascertained its hepatocyte guarding action by
recovering the histopathological ailment and diminishing serum transaminases.
Conclusion: NLC BBR purveyed reasonable shielding mechanisms and subsided incidents contemporaneous to
warm hepatic I/RN lesion in part, by moderating HMGB1/TLR4/NF-κB inflammatory signaling, autophagy, and
apoptosis. |
