Page 13 - 《中国药房》2024年21期
P. 13
1β, IL-10, myeloperoxidase (MPO),tumor necrosis factor-α (TNF-α)] in colon tissue, and protein expressions of core targets
were detected. RESULTS A total of 39 active ingredients and 232 potential targets of C. deserticola in the treatment of IBD were
obtained. The treatment of IBD with C. deserticola might be related to core components such as quercetin, suchilactone,
β-sitosterol and cistanoside H, and core targets such as TNF, AKT1, STAT3, EGFR and SRC. GO and KEGG pathway analysis
predicted that the biological processes of C. deserticola in the treatment of IBD were mainly related to protein phosphorylation, and
negative regulation of apoptosis, mainly involving PI3K/AKT and EGFR tyrosine kinase inhibitor resistance signaling pathways.
The results of molecular docking showed that the binding energy between the core components and core target of C. deserticola was
less than -4.7 kJ/mol. Animal experiment results showed that after intervention with C. deserticola extract, the body weight and
colon length of mice significantly increased (P<0.05 or P<0.01), while DAI decreased significantly (P<0.05 or P<0.01). The
congestion and edema of colon mucosa were significantly reduced, and the pathological score of colon tissue was significantly
decreased (P<0.05 or P<0.01); the levels of IL-6, IL-1β, MPO and TNF- α, as well as the protein expressions of PI3K,
phosphorylated PI3K (p-PI3K), EGFR, TNF- α, STAT3, phosphorylated STAT3 (p-STAT3), AKT1, phosphorylated AKT1
(p-AKT1) and SRC in colon tissue were reduced significantly (P<0.05 or P<0.01), while the level of IL-10 was significantly
increased in model group (P<0.01). CONCLUSIONS C. deserticola may alleviate IBD by regulating the SRC/EGFR/PI3K/AKT
signaling pathway.
KEYWORDS Cistanche deserticola; inflammatory bowel disease; network pharmacology; molecular docking; experimental
verification
炎症性肠病(inflammatory bowel disease,IBD)是一 靶点和信号通路对IBD起到治疗作用尚未有研究报道。
类胃肠道慢性、非特异性、炎症性疾病的统称,包含克罗 为此,本研究拟通过网络药理学方法结合分子对接技
恩病和溃疡性结肠炎 2 个亚型 。IBD 是我国消化系统 术,对肉苁蓉治疗 IBD 的潜在作用机制进行预测,并对
[1]
常见疑难疾病之一,也是消化系统疾病基础研究和临床 预测结果进行药效学验证,从而系统地阐明肉苁蓉治疗
诊疗的重点、热点和难点。近 20 年,我国 IBD 发病率逐 IBD 的分子机制,以期为其后续开发利用提供理论
[2]
年上升,预计到 2025 年可达 15 万人,居亚洲之首 。目 依据。
前普遍认为,遗传易感性、环境因素、机体免疫功能障 1 材料
碍、肠道菌群改变及肠黏膜屏障功能受损是IBD发生发 1.1 实验动物
[3]
展的主要原因 。IBD 的临床治疗以药物治疗为主,主 本研究所用动物为雄性SPF级C57BL/6小鼠,共48
要包括氨基水杨酸类、抗生素、皮质激素类和免疫抑制 只,购自新疆医科大学动物实验中心,体重18~20 g,实
[4]
剂等 ,但上述药物容易导致多种不良反应,且患者长期 验动物生产许可证号为SCXK(新)2023-0004,实验动物
[5]
使用会产生耐受性,停药后易复发 。 使用许可证号为 SYXK(新)2023-0001。小鼠饲养在温
中药作为我国传统的优势资源,在治疗慢性疾病方 度为(22±2)℃,相对湿度为 50%~70%,循环照明 12 h
面具有疗效明确、复发率低、不良反应少等优势。有 的环境中。本研究严格遵守动物福利和新疆医科大学
“沙漠人参”之称的肉苁蓉来源于列当科植物肉苁蓉 实 验 动 物 伦 理 委 员 会 伦 理 要 求( 审 批 号 为
Cistanche deserticola Y.C. Ma 或管花肉苁蓉 C. tubulosa 20210301-177)。
(Schenk)Wight 的干燥带鳞叶的肉质茎,是新疆特色优 1.2 主要药品与试剂
势药用资源,主要含有苯乙醇苷类、萜类等活性成分,具 肉苁蓉提取物(Cistanche extract,CE;纯度≥85%,
有补肾壮阳、润肠通便的作用,被广泛用于肠道疾病的 其 中 松 果 菊 苷 ≥40%,毛 蕊 花 糖 苷 ≥16%;批 号
治疗 [6―7] 。苯乙醇苷类成分是 2020 年版《中国药典》(一 20230103)购自新疆和田帝辰医药生物科技有限公
部)规定的用于肉苁蓉鉴别和含量测定的指标性成分 司;葡聚糖硫酸钠(DSS,相对分子量 36 000~50 000,
[8]
(主要为松果菊苷和毛蕊花糖苷) 。研究显示,松果菊 批号C16013701)购自上海麦克林生化科技有限公司;粪
苷可通过促进肠上皮细胞增殖而抑制细胞凋亡改善小 便隐血定性检测试剂盒(批号 ml1095013)购自上海酶
[9]
鼠结肠炎 ;毛蕊花糖苷作为自由基清除剂可减缓大鼠 联生物科技有限公司;地塞米松对照品(纯度≥98%,批
结肠炎进展 ;肉苁蓉总苷可通过抑制炎症因子表达防 号 54231207002)购自北京索莱宝科技有限公司;肿瘤
[10]
[11]
治IBD 。但是肉苁蓉中具体是哪些化学成分通过哪些 坏死因子 α(tumor necrosis factor-α,TNF-α)、白细胞介
中国药房 2024年第35卷第21期 China Pharmacy 2024 Vol. 35 No. 21 · 2583 ·