Effect of Berberine against Cognitive Deficits in Rat Model of Thioacetamide-Induced Liver Cirrhosis and Hepatic Encephalopathy (Behavioral, Biochemical, Molecular and Histological Evaluations)

Abstract

Background: Liver cirrhosis (LC) is one of the chronic liver diseases with high disability and mortality accompanying hepatic encephalopathy (HE) followed by cognitive dysfunctions. In this work, the effect of berberine (Ber) on spatial cognition was studied in a rat model of LC induced by thioacetamide (TAA). Materials and Methods: Male Wistar rats (200–250 g) were divided into six groups: (1) control; (2) TAA, 200 mg/kg/day, i.p.; (3–5) TAA + Ber; received Ber (10, 30, and 60 mg/kg, i.p., daily after last TAA injection); (6) Dizocilpine (MK-801) + TAA, received MK-801 (2 mg/kg/day, i.p.) 30 m before TAA injection. The spatial memory, BBB permeability, brain edema, liver enzymes, urea, serum and brain total bilirubin, oxidative stress and cytokine markers in the hippocampus were measured. Furthermore, a histological examination of the hippocampus was carried out. Results: The BBB permeability, brain edema, liver enzymes, urea, total bilirubin levels in serum and hippocampal MDA and TNF-α increased significantly after TAA injection (p < 0.001); the spatial memory was impaired (p < 0.001), and hippocampal IL-10 decreased (p < 0.001). Ber reversed all the above parameters significantly (p < 0.05, p < 0.01 and p < 0.001). MK-801 prevented the development of LC via TAA (p < 0.001). Conclusion: Results showed that Ber improves spatial learning and memory in TAA-induced LC by improving the BBB function, oxidative stress and neuroinflammation. Ber might be a promising therapeutic agent for cognitive improvement in LC.

Neuroprotective and cognitive enhancing effects of herbecetin against thioacetamide induced hepatic encephalopathy in rats via upregulation of AMPK and SIRT1 signaling pathways

“…Herbacetin might be a promising protective agent for cognitive improvement in HE. Our findings are in line with earlier research which found that Berberine improves spatial learning and memory in TAA-induced liver cirrhosis by improving the blood brain function, oxidative stress and neuro-inflammation 35 .…”

Anti‐inflammatory, antioxidant, and immunomodulatory effects of Berberis vulgaris and its constituent berberine, experimental and clinical, a review

“…Oral administration of the berberine (5, 10, and 15 mg/kg, for 1 week) to rats significantly increased total SOD (T-SOD), CAT, GSH, and reduced MDA and ROS levels in the rat model of liver injury (Han et al, 2019). In thioacetamide-induced liver cirrhosis and hepatic encephalopathy in rats, intraperitoneal administration of the berberine (10, 30, and 60 mg/kg, for 1 week) significantly increased GPx activity and decreased MDA level in the hippocampal tissue (Hajipour et al, 2023).…”