Haarberg Kelley Mk, Wymore Brand Meghan J, Overstreet Anne-Marie C, Hauck Catherine C, Murphy Patricia A, Hostetter Jesse M, Ramer-Tait Amanda E, Wannemuehler Michael J
Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
World J Gastrointest Pharmacol Ther. 2015 Nov 6;6(4):223-37. doi: 10.4292/wjgpt.v6.i4.223.
To investigate the ability of a Prunella vulgaris (P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a(-/-) mice.
Vehicle (5% ethanol) or P. vulgaris ethanolic extract (2.4 mg/d) were administered daily by oral gavage to mdr1a(-/-) or wild type FVB(WT) mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencing weight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity.
Administration of P. vulgaris extracts to mdr1a(-/-) mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a(-/-) mice. Oral administration of the P. vulgaris extract resulted in reduced (P < 0.05) serum levels of IL-10 (4.6 ± 2 vs 19.4 ± 4), CXCL9 (1319.0 ± 277 vs 3901.0 ± 858), and TNFα (9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a(-/-) mice compared to vehicle-treated mdr1a(-/-) mice. Histologically, several microscopic parameters were reduced (P < 0.05) in P. vulgaris-treated mdr1a(-/-) mice, as was myeloperoxidase activity in the colon (2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4(+) T cells (2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells (2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a(-/-) were significantly reduced (P < 0.05) from vehicle-treated mdr1a(-/-) mice. Vehicle-treated mdr1a(-/-) mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a(-/-) mice.
The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a(-/-) mice.
研究夏枯草乙醇提取物减轻mdr1a(-/-)小鼠自发性盲肠炎的能力。
从6周龄至20周龄，每天通过口服灌胃法给mdr1a(-/-)或野生型FVB(WT)小鼠施用溶剂（5%乙醇）或夏枯草乙醇提取物（2.4毫克/天）。通过监测体重减轻来记录疾病的临床症状。体重减轻超过15%的小鼠被排除在研究之外。在将小鼠从研究中排除时，收集血液和结肠组织进行分析，包括病变的组织学评估、炎性细胞因子水平和髓过氧化物酶活性。
与溶剂处理的mdr1a(-/-)小鼠相比，给mdr1a(-/-)小鼠施用夏枯草提取物可延迟结肠炎的发作并减轻粘膜炎症的严重程度。口服夏枯草提取物导致血清中IL-10（4.6±2对19.4±4）、CXCL9（1319.0±277对3901.0±858）和TNFα（9.9±3对14.8±1）水平降低（P<0.05），并且与溶剂处理的mdr1a(-/-)小鼠相比，mdr1a(-/-)小鼠结肠粘膜中Ccl2、Ccl20、Cxcl1、Cxcl9、IL-1α、Mmp10、VCAM-1、ICAM、IL-2和TNFα的基因表达降低了两倍以上。组织学上，夏枯草处理过的mdr1a(-/-)小鼠的几个微观参数降低（P<0.05），结肠中的髓过氧化物酶活性也降低（2.49±0.16对3.36±0.06，P<0.05）。在夏枯草处理过的mdr1a(-/-)小鼠盲肠扁桃体中观察到的CD4(+)T细胞（2031.9±412.1对5054.5±809.5）和生发中心B细胞（2749.6±473.7对4934.0±645.9）数量与溶剂处理的mdr1a(-/-)小鼠相比显著减少（P<0.05）。发现溶剂处理的mdr1a(-/-)小鼠产生针对源自肠道微生物群成员的抗原的血清抗体，这表明存在严重结肠炎以及对微生物群成员的适应性耐受性丧失。在夏枯草处理过的mdr1a(-/-)小鼠中，这些血清抗体大大减少或不存在。
夏枯草乙醇提取物的抗炎活性有效减轻了mdr1a(-/-)小鼠肠道炎症的严重程度。
