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石榴皮提取物对刀豆蛋白 A 诱导的小鼠自身免疫性肝炎的保护作用。

Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice.

机构信息

Division of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China.

Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Biomed Pharmacother. 2018 Apr;100:213-220. doi: 10.1016/j.biopha.2017.12.110. Epub 2018 Feb 9.

Abstract

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of an unknown etiology, glucocorticoid therapy is currently recognized as an effective treatment for AIH, but conventional application and patient compliance are both hindered by its side effects. The exploration of the AIH pathogenesis and the searching for the new candidate drugs that exert potential activity and low toxicity are urgently needed. Pomegranate peel extract (PoPx) is a natural extract of Punica granatum and has been reported to have anti-inflammatory and antioxidative properties. The present study aimed to clarify the effect of PoPx on the concanavalin A (ConA)-induced autoimmune hepatitis in a mouse model that is well established at 12h after tail vein injection with a dose of 20 mg/kg of ConA. C57BL/6 female mice were pretreated with PoPx (250 mg/kg, once daily for 3 days) followed by a ConA challenge. Pretreatment with PoPx significantly alleviated ConA-induced liver injury by down-regulating the levels of plasma alanine transaminase (ALT), aspartate transaminase (AST) and cytokine, including TNF-α, interferon (IFN) -γ and interleukin (IL)-6. Moreover, liver hematoxylin and eosin (H&E) staining displayed a lighter inflammatory infiltration around the portal area in the PoPx-pretreated mice. In addition, the flow cytometry (FCM) data showed that the immune response in the liver was died down in the PoPx-pretreated condition. Specially, pretreatment with PoPx reduced the infiltration of activated CD4 and CD8 T cells in the liver. Taken together, these findings contributed to a better understanding of the actions of PoPx against acute AIH and indicated that PoPx might be a potential compound in treating T cell-mediated autoimmune liver injury.

摘要

自身免疫性肝炎(AIH)是一种病因不明的慢性炎症性肝病,糖皮质激素治疗目前被认为是 AIH 的有效治疗方法,但由于其副作用,常规应用和患者依从性均受到阻碍。迫切需要探索 AIH 的发病机制和寻找具有潜在活性和低毒性的新候选药物。石榴皮提取物(PoPx)是石榴的天然提取物,据报道具有抗炎和抗氧化作用。本研究旨在阐明 PoPx 对尾静脉注射 20mg/kg ConA 后 12 小时建立的小鼠模型中伴刀豆球蛋白 A(ConA)诱导的自身免疫性肝炎的影响。C57BL/6 雌性小鼠用 PoPx(250mg/kg,每日一次,连续 3 天)预处理,然后用 ConA 进行攻击。PoPx 预处理通过下调血浆丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和细胞因子(包括 TNF-α、干扰素(IFN)-γ和白细胞介素(IL)-6)水平,显著缓解 ConA 诱导的肝损伤。此外,肝苏木精和伊红(H&E)染色显示 PoPx 预处理小鼠肝门区周围炎症浸润较轻。此外,流式细胞术(FCM)数据显示,PoPx 预处理条件下肝内免疫反应减弱。特别是,PoPx 预处理减少了肝内活化的 CD4 和 CD8 T 细胞的浸润。综上所述,这些发现有助于更好地了解 PoPx 对抗急性 AIH 的作用,并表明 PoPx 可能是治疗 T 细胞介导的自身免疫性肝损伤的潜在化合物。

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