Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

Chen, Sufang; Li, Xiang; Wang, Yanling; Mu, Panwei; Chen, Chaojin; Huang, Pinjie; Liu, Dezhao

doi:10.3892/mmr.2019.10018

Cited by 46 publications

(43 citation statements)

References 54 publications

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“…Tissue injuries, including those to liver [ 78 ], brain [ 79 ], heart [ 80 ], and intestine [ 81 ], are related to excessive/aberrant inflammation, oxidative stress, mitochondrial dysfunction, and apoptosis [ 82 ]. Mitochondria are known as the energy factory of cells [ 83 ], and inflammation, ROS generation, mitochondrial dysfunction, and apoptosis are also found in I/R injuries [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53

Almoiliqy

Wen

et al. 2020

Acta Pharmacol Sin

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Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg −1 · d −1 , ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. CA pretreatment dose-dependently ameliorated morphological damage and reduced inflammation evidenced by decreased TNF-α, IL-1β, and IL-6 levels and MPO activity in I/R-treated intestinal tissues. CA pretreatment also attenuated oxidative stress through restoring SOD, GSH, LDH, and MDA levels in I/R-treated intestinal tissues. Furthermore, CA pretreatment significantly reduced the expression of inflammation/apoptosis-related NF-κB p65, IKKβ, IK-α, and NF-κB p50, and downregulated apoptotic protein expression including p53, Bax, caspase-9 and caspase-3, and restoring Bcl-2, in I/R-treated intestinal tissues. We pretreated IEC-6 cells in vitro with CA for 24 h, followed by 4 h hypoxia and 3 h reoxygenation (H/R) incubation. Pretreatment with CA (3.125, 6.25, and 12.5 μmol · L −1 ) significantly reversed H/R-induced reduction of IEC-6 cell viability. CA pretreatment significantly suppressed oxidative stress, NF-κB activation and apoptosis in H/R-treated IEC-6 cells. Moreover, CA pretreatment significantly reversed mitochondrial dysfunction in H/R-treated IEC-6 cells. CA pretreatment inhibited the nuclear translocation of p53 and NF-κB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-κB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-κB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-κB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-κB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-κB and p53 played a key role in ameliorating intestinal I/R injuries. Finally, we used immunoprecipitation assay to demonstrate an interaction between p53 and NF-κB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies.

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Section: Discussionmentioning

confidence: 99%

Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53

Almoiliqy

Wen

et al. 2020

Acta Pharmacol Sin

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“…For instance, Rb1 was documented to possess potential anti-inflammatory and anti-apoptotic properties in human articular chondrocytes [18]. A previous study demonstrated that Rb1 attenuated IIR-induced inflammation and oxidative stress by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B/nuclear factor erythroid 2related factor 2 (Nrf2) pathway [19]. More importantly, it has been proved that Rb1 ameliorated IIR-or LPSinduced lung injury via inhibiting NF-κB-dependent inflammatory response [20,21].…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammatory injury by downregulating miR-222 in WI-38 cells

Wei

Xiao

Jia

et al. 2020

Preprint

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Background Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H.Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Methods Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry analysis, respectively. The production of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-lβ, and IL-6 were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. Results LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. Conclusion Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-κB pathway, contributing to our understanding of the effects and molecular mechanism of Rb1 in pneumonia.

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“…Serum levels of D-lactate and DAO were investigated spectrophotometrically (Sigma-Aldrich, St. Louis, MO, USA; Merck KGaA). Serum levels of endotoxin were determined by a Limulus Amebocyte Lysate Assay kit (Shanghai Biochemical Co., Ltd., Shanghai, China) [ 31 ]. PGE2 ileal tissue expression was determined according to the manufacturer’s instructions (MyBiosource, Bergamo, Italy) [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

Novel Combination of COX-2 Inhibitor and Antioxidant Therapy for Modulating Oxidative Stress Associated with Intestinal Ischemic Reperfusion Injury and Endotoxemia

et al. 2020

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Background: Intestinal ischemic reperfusion (I/R) injury is associated with a high mortality rate; this condition is also related to significant endotoxemia and systemic inflammation. The preservation of tissue perfusion and a sufficient blood flow are required to deliver nutrients and oxygen, preserve metabolic pathways, and eliminate waste products. Oxidative stress plays a fundamental role in intestinal I/R injury and leads to disruption of the mucosal barrier and necrosis, allowing the migration of endotoxins and luminal bacteria into the systemic circulation. In this study, we evaluated the beneficial effects of a cyclooxygenase (COX)-2 inhibitor—firocoxib—plus the antioxidant vitamin C in a rat model of intestinal I/R injury. Methods: We used a rat model of I/R injury in which the superior mesenteric artery was clamped for 30 min by a vascular clamp, and the animals were then allowed 1 h of reperfusion. Results: Our results show the importance of combined anti-inflammatory and antioxidant treatment for the prevention of intestinal I/R injury that leads to reduced systemic endotoxemia. We observed a significantly synergistic effect of firocoxib and vitamin C in reducing intestinal wall damage and oxidative stress, leading to a significant reduction of inflammation and endotoxemia. Conclusions: Our results indicate that this approach could be a new pharmacological protocol for intestinal colic or ischemic injury-induced endotoxemia.

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Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

Cited by 46 publications

References 54 publications

Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53

Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53

Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammatory injury by downregulating miR-222 in WI-38 cells

Novel Combination of COX-2 Inhibitor and Antioxidant Therapy for Modulating Oxidative Stress Associated with Intestinal Ischemic Reperfusion Injury and Endotoxemia

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