Eprosartan Mesylate

Eprosartan is an effective blood pressure medication that blocks the Angiotensin Type 1 (AT1) receptor. The studies conducted on Eprosartan showed anti-oxidative stress effects and modulating inflammatory mechanisms. The current research is designed to clarify and examine the possible advantageous impacts of Eprosartan against chronic ethanol-induced hepatic damage.

Twenty-four male Sprague-Dawley rats were haphazardly separated into four groups. The control group received normal saline 1 g/kg for 35 days (group 1). The EtOH group received 7 g/kg of 40% ethanol orally for 35 days (group 2). The EtOH+ EP group was pretreated with 60 mg/kg of Eprosartan dissolved in normal saline orally and, after 60 minutes, received 7 g/kg of 40% ethanol orally for 35 days (group 3). The EP group received only Eprosartan 60 mg/kg dissolved in normal saline for 35 days (group 4). The levels of biochemical parameters, oxidative stress markers, pro-inflammatory cytokines, and histopathological staining were evaluated in serum and liver tissue. The interactive behavior of Eprosartan with Tumor Necrosis Factor-α (TNF-α) protein was also explained by molecular docking.

Pre-treatment with Eprosartan (60 mg/kg) notably diminished the elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Gamma-Glutamyl Transferase (GGT) enzymes, total triglyceride, cholesterol, total bilirubin, and inflammatory cytokines including TNF-α, Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) levels, which were induced by alcohol administration (P-value ≤ 0.05). In the Eprosartan pre-treated group, malondialdehyde and protein carbonyl content of liver tissue were remarkably diminished, as compared to the ethanol-induced rats. In addition, histopathological results approved the indicated finding. Molecular docking research gives insights into potential interactions of Eprosartan with TNF-α protein.

Our results revealed that the pre-treatment with Eprosartan (60 mg/kg) preserves against chronic alcohol-induced hepatic damage.

Despite growing evidence for the renin-angiotensin system (RAS) involvement in Parkinson's disease (PD), its role in microglial polarization during disease progression remains unclear. This study explored the ability of modulating RAS using eprosartan, an AT1R antagonist, and xanthenone, an ACE2 activator, to support microglial M2 polarization in rats with PD highlighting the roles of miR-155, protein phosphatase 2 A (PP2A), and mitogen-activated protein kinase phosphatase 1 (MKP-1). Rotenone (1.5 mg/kg) was administered to Wistar rats to induce PD, with concurrent treatments of eprosartan (60 mg/kg/day) or xanthenone (2 mg/kg/day) for 28 days. Both agents improved motor function and neuronal damage, as evidenced by behavioral, histopathological, and immunohistochemical analyses. Eprosartan and xanthenone enhanced tyrosine hydroxylase activity and reduced α-synuclein accumulation in the substantia nigra. Eprosartan and xanthenone modulated the RAS axis by reducing angiotensin II level and increasing ACE2 activity and Ang 1-7 concentration in the striatum. Importantly, these agents induced a shift in microglial polarization from the M1 proinflammatory phenotype (marked by reduced IL-1β, iNOS, and CD86) to the M2 anti-inflammatory phenotype (marked by enhanced arginase1, Ym1, Fizz1 and CD163). This shift was associated with altered STAT signaling pathways, including decreased p-STAT1 and increased p-STAT6. Additionally, levels of miR-155 were decreased, and levels of SOCS1, MKP-1, and PP2A were increased. These findings address a critical gap in understanding how RAS modulation can influence neuroinflammation through microglial polarization via regulating the interplay between MKP-1/ miR-155 /SOCS1 and PP2A, offering a promising therapeutic strategy to mitigate neurodegeneration and inflammation in PD.