Anwulignan Ameliorates the Intestinal Ischemia/Reperfusion

超氧化物歧化酶 谷胱甘肽 化学 内分泌学 烟酰胺腺嘌呤二核苷酸磷酸 医学 血红素加氧酶 丙二醛 药理学 内科学 生物化学 氧化应激 生物 氧化酶试验 血红素
作者
Huijiao Lin,Xinyun Zhang,Dan Wang,Jiawei Liu,Liwei Yuan,Jiale Liu,Chunmei Wang,Jinghui Sun,Jianguang Chen,He Li,Shu Jing
出处
期刊:Journal of Pharmacology and Experimental Therapeutics [American Society for Pharmacology and Experimental Therapeutics]
卷期号:378 (3): 222-234 被引量:10
标识
DOI:10.1124/jpet.121.000587
摘要

Anwulignan is one of the monomer compounds in the lignans from Schisandra sphenanthera In this study, we observed the effect of anwulignan on intestinal ischemia/reperfusion (II/R) injury in male Sprague-Dawley rats and explored the underlying mechanisms. The results showed that pretreatment with oral anwulignan could significantly increase the mesenteric blood microcirculatory flow velocity; relieve the congestion and pathologic injury of jejunum; enhance the autonomic tension of jejunum smooth muscle and its reactivity to acetylcholine; increase the activities of superoxide dismutase, catalase, glutathione S-transferase, and choline acetyltransferase; increase the contents of acetylcholine and glutathione in the serum or jejunal tissue; decrease the activities of myeloperoxidase, protein kinase C, and nicotinamide adenine dinucleotide phosphate oxidase; reduce the contents of malondialdehyde, 8-hydroxy-2-deoxyguanosine, nicotinamide adenine, reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β; increase the expression levels of muscarinic receptor 3, PI3K, phosphorylation protein kinase B, p-GSK3β Ser9, Nrf2, p-Nrf2, heme oxygenase (decycling) 1, and b-cell lymphoma 2 in the jejunal tissue; and decrease the expression levels of p-GSK3β Tyr216, kelch-like ECH-associated protein 1, Bax, and cleaved caspase-3, suggesting that anwulignan can ameliorate II/R-induced jejunal tissue injury in rats and that the mechanism may be related to its activating the PI3K/protein kinase B pathway and then regulating the Nrf2/Anti-oxidative Response Element signaling pathway and the expression of apoptosis-related proteins to play antioxidant and antiapoptotic roles. SIGNIFICANCE STATEMENT: Anwulignan can significantly reduce jejunal tissue injury and the production of inflammatory factors in rats with intestinal ischemia-reperfusion injury, improve the antioxidant capacity, and reduce the apoptosis of jejunal tissue, and it has the effect of significantly improving intestinal ischemia-reperfusion injury in rats, suggesting that anwulignan may be used as a potential drug for the prevention and treatment of intestinal ischemia-reperfusion injury or a resource for the development of health food.
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