The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

Abstract

This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.

The anti-inflammatory activity of licorice, a widely used Chinese herb

“…It also significantly reduced the generation of excessive NO, PGE2 and ROS, inhibited the protein and mRNA levels of iNOS and COX-2 and suppressed the release of LPS-induced TNF-a, IL-6 and IL-1b in a dose-dependent manner (Wang et al 2011;Ishida et al 2013). It has been studied in indomethacin-induced small intestinal damage (Ishida et al 2013), LPS-induced macrophages (Wang et al 2011) in vitro and neuronal damage caused by global cerebral ischaemia/reperfusion in C57BL/J6 mouse models (Oztanir et al 2014) in vivo, and the anti-inflammatory actions were significantly affirmed.…”

The Pharmacological Activities of Licorice

“…The mechanisms of the anti-inflammatory activity of licorice have been explored deeply. It has been widely accepted that GC and 18β-GA suppress proinflammatory cytokine COX-2, iNOS, TNF-α, HMGP 1, PGE2, myeloperoxidase, DPPH radicals, IL-6, IL-10, TGF-β, and NF-κB, inhibit the translocation of toll-like receptor 4 to lipid rafts, and activate ABCA1 [31][32][33][34][35][36][37][38]. GLD and ISL inhibit the release of NO and IL-1β [39], and LID and LIA inhibit the activation of NF-κB p65 and the secretion of IL-6, chemokine (C-C motif) ligand 5, MMP-7, MMP-8, and MMP-9 [40].…”

“…In vivo and clinical studies have shown that GC has been used in the postischemic brain with a middle cerebral artery occlusion mouse model [31], in an LPS-induced acute lung injury mouse model, and in a mastitis mouse model [33,34]. GA has been used to treat oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model [38]. LCA has been used in childhood atopic dermatitis and in a murine model of asthma [44,45].…”

α-Lipoic Acid Promotes Neurological Recovery After Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage

“…Oxidative stress, which plays a vital role in the pathogenesis of cerebral I/R injury [5, 6], is caused by an imbalance between the production of ROS and its effective removal by endogenous scavenger enzymes and protective antioxidants [7]. Oxidative modification of intracellular molecules, such as proteins, lipids, and DNA, by ROS leads to neuronal injury and necrosis [8, 9]. …”