Berberine-loaded nanostructured lipid carriers mitigate warm hepatic ischemia/reperfusion-induced lesion through modulation of HMGB1/TLR4/NF-κB signaling and autophagy
| Autor: | Mohamed R. Elnagar, Abdallah M. Gendy, Alaadin E. El-Haddad, Shereen S. El-Mancy, Sahar M. Fayez, Mohamed R. Mousa, Mona M. Allam, Osama S. Elnahas, Ahmed E. Khodir |
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| Rok vydání: | 2022 |
| Předmět: |
Cell death
Male Programmed cell death Berberine Anti-Inflammatory Agents Apoptosis RM1-950 Liver injury Pharmacology HMGB1 Lesion chemistry.chemical_compound Autophagy medicine Animals HMGB1 Protein Particle Size Rats Wistar Inflammation Drug Carriers Nano strategy biology Chemistry Liver Diseases NF-kappa B General Medicine medicine.disease Lipids Nanostructures Rats Toll-Like Receptor 4 Reperfusion Injury biology.protein TLR4 Therapeutics. Pharmacology medicine.symptom Signal Transduction |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 145, Iss, Pp 112122-(2022) |
| ISSN: | 0753-3322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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