Sha Haixia, Gu Yu, Shen Weixing, Zhang Li, Qian Fei, Zhao Yudong, Li Haixiao, Zhang Ting, Lu Weimin
Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu Province, China.
Jiangsu Province Hospital of Chinese Medicine (Affiliated Hospital of Nanjing University of Chinese Medicine), No. 155, Hanzhong Road, Nanjing, Jiangsu Province, China.
Genes Genomics. 2019 Aug;41(8):909-917. doi: 10.1007/s13258-019-00824-8. Epub 2019 Apr 29.
Acute radiation enteritis (ARE), a common complication of intestinal caused by abdominal and pelvic radiation therapy. Rheinic acid is a major active ingredient derived from Rhubarb. Rhubarb could suppress inflammation, tumor, fibrosis oxidative damage. However, RA as the main active component and extract monomer of Rhubarb, the pharmacological activity and the underlying molecular mechanism on various diseases has not yet been revealed.
To determine the potential role of rheinic acid (RA) in ameliorating inflammation of rats with acute radiation enteritis (ARE), and explore the underlying mechanism.
ARE rat model was established by irradiated with single-dose 10 Gy X-rays at a rate of 0.62 Gy/min to the abdomen. The rats were executed after orally administered with Rheinic acid 7 days and used in the subsequent experiments. Body weight, fecal characteristics and bloody of rats were used to assess the disease activity index. Histological analysis of the jejunum and colon were evaluated using H&E staining. The pro-inflammatory cytokines levels were measured by immunohistochemistry and ELISA. The levels of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were also determined. The mRNA and protein expression were examined by real-time polymerase chain reaction (qRT-PCR) and western blot, respectively.
Rheinic acid promoted intestinal functional recovery, and ameliorated intestinal damage and bloody stool in ARE rats. Rheinic acid strongly decreased the levels of tumor necrosis factor-α, interleukin-1, interleukin-6, NO, and MDA, whereas increased levels of anti-oxidants, SOD and GSH. Moreover, the expression of apoptosis-related proteins, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), were decreased with RA treatment. Further study indicated that PPAR-γ was activated and thereby NF-κB and p38 MAPK signaling pathway were suppressed after rheinic acid treatment.
Rheinic acid could ameliorate acute radiation enteritis and the underlying molecular mechanism is, at least partially, through PPAR-γ/NF-κB and p38 MAPK/JNK pathways.
急性放射性肠炎（ARE）是腹部和盆腔放射治疗引起的肠道常见并发症。大黄酸是大黄的主要活性成分。大黄可抑制炎症、肿瘤、纤维化及氧化损伤。然而，作为大黄主要活性成分和提取物单体的大黄酸，其对各种疾病的药理活性及潜在分子机制尚未明确。
确定大黄酸（RA）在改善急性放射性肠炎（ARE）大鼠炎症中的潜在作用，并探讨其潜在机制。
以0.62 Gy/min的速度对腹部进行单次10 Gy X射线照射建立ARE大鼠模型。大鼠口服大黄酸7天后处死，用于后续实验。通过大鼠体重、粪便特征和便血情况评估疾病活动指数。采用苏木精-伊红（H&E）染色对空肠和结肠进行组织学分析。通过免疫组化和酶联免疫吸附测定（ELISA）检测促炎细胞因子水平。还测定了一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的水平。分别通过实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测mRNA和蛋白质表达。
大黄酸促进ARE大鼠肠道功能恢复，改善肠道损伤和便血情况。大黄酸显著降低肿瘤坏死因子-α、白细胞介素-1、白细胞介素-6、NO和MDA水平，而抗氧化剂SOD和GSH水平升高。此外，大黄酸处理后凋亡相关蛋白裂解的半胱天冬酶-3和裂解的聚（ADP-核糖）聚合酶（PARP）的表达降低。进一步研究表明，大黄酸处理后过氧化物酶体增殖物激活受体-γ（PPAR-γ）被激活，从而抑制核因子-κB（NF-κB）和p38丝裂原活化蛋白激酶（MAPK）信号通路。
大黄酸可改善急性放射性肠炎，其潜在分子机制至少部分是通过PPAR-γ/NF-κB和p38 MAPK/应激活化蛋白激酶（JNK）通路。
