Environmental Science and Pollution Research Pub Date : 2021-02-09 , DOI: 10.1007/s11356-021-12716-0 Manar G Helal 1 , Ahmed G Abd Elhameed 1, 2
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In this study, we elucidated the potential protective effects of graviola leaves, compared with sulfasalazine, against acetic acid (AA)–induced ulcerative colitis (UC) in rats. Twenty-eight mature male rats were divided into four groups, Sham, Colitis, Colitis/Sulfa, and Colitis/Graviola, and were treated orally with either saline, saline, sulfasalazine (100 mg/kg/day), or graviola (100 mg/kg/day), respectively, for 7 days. On the 4th day, UC was induced by transrectal administration of 4% AA. Colon tissues were excised for macroscopic and histopathological evaluation and immunohistochemical analysis of caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax). Also, levels of oxidative mediators, Wnt family member1 (Wnt1), smoothened (Smo), and glioblastoma-1 (Gli1) were evaluated. Macroscopic and histopathological examination revealed that both graviola and sulfasalazine significantly mitigated colonic damage. Besides, both treatments significantly alleviated AA-induced oxidative stress, as evidenced by reduced nitric oxide (No) and malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity and raised reduced glutathione (GSH) content. Both treatments significantly attenuated AA-induced apoptosis via downregulating the expression of Bax and caspase-3 and upregulating the expression of the anti-apoptotic protein, Bcl-2. Furthermore, downregulation of mRNA expression of Wnt1 with concomitant upregulation of Smo and Gli1 was observed in rats treated with either sulfasalazine or graviola. Based on these observations, graviola may attenuate AA-induced UC, at least partially, by modulating apoptosis and Wingless/Int1 (Wnt) and hedgehog (Hh) signaling crosstalk.
Graphical abstract
中文翻译：
Graviola 减轻乙酸诱导的大鼠溃疡性结肠炎：深入了解细胞凋亡和 Wnt/Hh 信号串扰
在这项研究中，我们阐明了与柳氮磺吡啶相比，番荔枝叶对乙酸（AA）诱导的大鼠溃疡性结肠炎（UC）的潜在保护作用。将 28 只成年雄性大鼠分为四组：假手术组、结肠炎组、结肠炎/磺胺组和结肠炎/Graviola 组，并口服盐水、盐水、柳氮磺吡啶（100 mg/kg/天）或 Graviola（100 mg）进行口服治疗。 /kg/天），分别持续7天。第4天，经直肠给予4%AA诱导UC。切除结肠组织进行宏观和组织病理学评估以及 caspase-3、B 细胞淋巴瘤 2 (Bcl-2) 和 Bcl-2 相关 X 蛋白 (Bax) 的免疫组织化学分析。此外，还评估了氧化介质、Wnt 家族成员 1 (Wnt1)、smoothened (Smo) 和胶质母细胞瘤-1 (Gli1) 的水平。肉眼观察和组织病理学检查显示，graviola 和柳氮磺吡啶均显着减轻了结肠损伤。此外，两种治疗均显着减轻了 AA 诱导的氧化应激，一氧化氮 (No) 和丙二醛 (MDA) 水平降低以及髓过氧化物酶 (MPO) 活性降低以及还原型谷胱甘肽 (GSH) 含量升高就证明了这一点。两种治疗均通过下调 Bax 和 caspase-3 的表达以及上调抗凋亡蛋白 Bcl-2 的表达来显着减弱 AA 诱导的细胞凋亡。此外，在用柳氮磺吡啶或番石榴治疗的大鼠中观察到 Wnt1 mRNA 表达下调，同时 Smo 和 Gli1 上调。基于这些观察，graviola 可能通过调节细胞凋亡以及 Wingless/Int1 (Wnt) 和刺猬 (Hh) 信号串扰来至少部分减弱 AA 诱导的 UC。
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