首页|Berberine-loaded nanostructured lipid carriers mitigate warm hepatic ischemia/reperfusion-induced lesion through modulation of HMGB1/TLR4/NF-κB signaling and autophagy
Berberine-loaded nanostructured lipid carriers mitigate warm hepatic ischemia/reperfusion-induced lesion through modulation of HMGB1/TLR4/NF-κB signaling and autophagy
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NSTL
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。
Nano strategyBerberineLiver injuryInflammationCell death
Abdallah M. Gendy、Mohamed R. Elnagar、Mona M. Allam、Mohamed R. Mousa、Ahmed E. Khodir、Alaadin E. El-Haddad、Osama S. Elnahas、Sahar M. Fayez、Shereen S. El-Mancy
展开 >
Pharmacology and Toxicology Department, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt
NSTL
