Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring
Safaa I. Khater,
Taghreed N. Almanaa,
Doaa M. Abdel Fattah,
Tarek Khamis,
Mona M. Seif,
Naief Dahran,
Leena S. Alqahtani,
Mohamed M. M. Metwally,
Mahmoud Mostafa,
Raghad A. Albedair,
Azza I. Helal,
Manal Alosaimi,
Amany Abdel-Rahman Mohamed
Affiliations
Safaa I. Khater
Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Taghreed N. Almanaa
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Doaa M. Abdel Fattah
Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Tarek Khamis
Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
Mona M. Seif
Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Naief Dahran
Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah 80203, Saudi Arabia
Leena S. Alqahtani
Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia
Mohamed M. M. Metwally
Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Mahmoud Mostafa
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
Raghad A. Albedair
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
Azza I. Helal
Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
Manal Alosaimi
Department of Basic Medical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Amany Abdel-Rahman Mohamed
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
In the advanced stages of type 2 diabetes mellitus (T2DM), diabetic liver damage is a common complication that can devastate a patient’s quality of life. The present study investigated the ability of liposomal berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM) and the possible pathways by which it does so. Liver tissue microarchitectures and immunohistochemical staining were applied during the study. The rats were divided into a control non-diabetic group and four diabetic groups, which are the T2DM, T2DM-Lip-BBR (10 mg/kg b.wt), T2DM-Vildagliptin (Vild) (10 mg/kg b.wt), and T2DM-BBR-Vild (10 mg/kg b.wt + Vild (5 mg/kg b.wt) groups. The findings demonstrated that Lip-BBR treatment could restore liver tissue microarchitectures, reduce steatosis and liver function, and regulate lipid metabolism. Moreover, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats. Lip-BBR also activated the GLP-1 expression, which stimulated insulin biosynthesis. It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation. Collectively, Lip-BBR ameliorated diabetic liver injury in a T2DM rat model with its promotion activity of AMPK/mTOR-mediated autophagy and limiting ER stress.
