<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

Abstract

These authors contributed equally to this workObjective: Hepatic ischemia reperfusion (IR) limits the development of liver transplantation technology. The aim of this study was to explore the protective effects of Bergenin on hepatic IR, particularly the elimination of reactive oxygen species (ROS) and activation of the peroxisome proliferators activated receptor γ (PPAR-γ) pathway. Methods: Initial experiments were performed to confirm the non-toxicity of Bergenin. Mice were randomly divided into sham, IR, and IR + Bergenin (10, 20 and 40 mg/kg) groups, and serum and tissue samples were obtained at 2, 8 and 24 h for detection of liver enzymes (ALT and AST), inflammatory factors (TNF-α, IL-6 and IL-1β), ROS, cell death markers (Bcl-2, Bax, Beclin-1 and LC3) and related important pathways (PPAR-γ, P38 MAPK, NF-κB p65 and JAK2/STAT1). Results: Bergenin reduced the release of ROS, down-regulated inflammatory factors, and inhibited apoptosis and autophagy. Additionally, expression of PPAR-γ-related genes was increased and phosphorylation of P38 MAPK, NF-κB p65 and JAK2/STAT1-related proteins was decreased in Bergenin pre-treatment groups in a dose-dependent manner. Conclusion: Bergenin exerts hepatic protection by eliminating ROS, affecting the release of inflammatory factors, and influencing apoptosis-and autophagy-related genes via the PPAR-γ pathway in this model of hepatic IR injury.

Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System

“…The treatment with bergenin effectively reduced the increased levels of TNF-α and IL-1β both in the sciatic nerve and in the spinal cord of neuropathic mice. These results agree with previous reports that bergenin diminishes the release of these cytokines under different inflammatory conditions [ 12 , 17 , 18 , 20 , 33 , 52 ]. Mechanistic hypotheses have been proposed to explain the roles of TNF-α and IL-1β in the pathophysiology of DN.…”

“…The surplus of electrons is then transferred to oxygen molecules, generating superoxide (O 2 - ), which in turn activates damaging pathways and gives rise to other ROS in a chain reaction [ 32 ]. Previous studies have shown that bergenin diminishes intracellular levels of superoxide and other ROS by increasing the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) [ 12 , 16 , 25 , 26 ]. In this work, the antioxidant activity of bergenin was confirmed both in vitro, by the inhibition of NO production by J774 macrophages and in vivo, by the reduction of MDA and nitrite levels in neuropathic mice’s sciatic nerve and spinal cord.…”

“…Bergenin ( Figure 1 ) is a naturally occurring C-glucoside of 4-O-methylgallic acid found in many plant species. Several therapeutic applications of bergenin have been proposed in the literature, e.g., anti-ulcerative [ 10 ], hepatoprotective [ 11 , 12 ], anticancer [ 13 ], neuroprotective [ 14 , 15 ], antidiabetic [ 16 ], anti-inflammatory [ 17 , 18 , 19 , 20 , 21 , 22 ], antinociceptive [ 17 , 23 ], and antioxidant [ 12 , 16 , 24 , 25 , 26 , 27 ]. Considering that oxidative stress and neuroinflammation play key roles in the pathophysiology of DN [ 28 ], the above-mentioned properties of bergenin may contribute to the effective control of painful DN.…”

Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells

“…Two-day treatment of INS-1E cells with inflammatory cytokines reduced mitochondrial membrane potential, which was completely restored by the addition of beregnin with an EC 50 value of 2.27 μM ( Table 1 ). Generally, cellular ROS are in dynamic equilibrium, but increased ROS production due to inflammatory factors, may induce NF-κB, JAK/STAT, and MAPK pathways resulting in beta cell apoptosis [ 46 ]. Bergenin contains five hydoxyl groups, which play important role in its antioxidant activity.…”

Bergenin Attenuates Hepatic Fibrosis by Regulating Autophagy Mediated by the PPAR-γ/TGF-β Pathway

“…This may be because autophagy-mediated lipid degradation provides energy for HSC activation, thereby promoting ECM formation and the progression of liver fibrosis. However, PPAR- γ activation has been linked to autophagy [ 13 , 14 ], but whether PPAR- γ plays an important role in the occurrence and development of liver fibrosis requires further investigation.…”