基于利尿作用及肠道菌群结构的巴豆霜与甘草配伍禁忌机制研究
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摘要
该研究基于课题组前期发现的"藻戟遂芫"与甘草配伍致毒增毒特点,以利尿作用和肠道菌群结构为表征指标,拓展性开展功效相似、基原相近、化学成分类型类同的中药巴豆霜与甘草合用可能导致的减效增毒作用研究。结果显示,甘草与高剂量巴豆霜合用,可减缓巴豆霜的快速利尿作用,表现为一定的降效作用趋势;巴豆霜高、低剂量均可显著损伤小鼠小肠组织,并使其肠道菌群组成结构发生显著变化。低剂量巴豆霜合用甘草后可使有害菌属Streptococcus(链球菌属)和Rikenellaceae_ukn的水平显著升高,高剂量巴豆霜和甘草合用后致病菌属Desulfovibrio(脱硫弧菌属)和Streptococcaceae_ukn相对丰度升高,两药合用进一步扰乱了肠道微生物稳态,且提示有引发肝脏及肠道炎症的风险。研究结果从巴豆霜传统功效及其对肠道菌群结构影响方面证实巴豆霜与甘草合用具有一定的降效增毒作用趋势,为巴豆霜临床安全用药提供了数据支持。
Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae_ukn. The relative abundance of Desulfovibrio and Streptococcaceae_ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.
Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae_ukn. The relative abundance of Desulfovibrio and Streptococcaceae_ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.
引文
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[23] Chen G, Xie M, Wan P, et al. Fuzhuan brick tea polysaccharides attenuate metabolic syndrome in high-fat diet induced mice in association with modulation in the gut microbiota[J]. J Agric Food Chem, 2018, 66(11): 2783.
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[2] 陶伟伟, 于金高, 陈艳琰, 等. 基于千金子与甘草对肠道菌群/屏障系统的影响探讨其配伍禁忌机制[J]. 中国中药杂志, 2018, 43(2): 369.
[3] Xu J, Chen H B, Li S L. Understanding the molecular mechanisms of the interplay between herbal medicines and gut microbiota[J]. Med Res Rev, 2017, 37(5): 1140.
[4] 戴新新, 蔡红蝶, 宿树兰, 等. 地黄叶对糖尿病肾病大鼠肠道菌群的调节作用[J]. 药学学报, 2017, 52(11): 1683.
[5] 孙艺凡,张霞,王晓艳,等.长期服用人参提取物对大鼠肠道菌群结构的影响[J].中国中药杂志, 2018, 43(19):3927.
[6] Jiao N, Baker S S, Nugent C A, et al. Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a Meta-analysis[J]. Physiol Genomics, 2018, 50(4): 244.
[7] Alverdy J, Holbrook C, Rocha F, et al. Gut-derived sepsis occurs when the right pathogen with the right virulence genes meets the right host: evidence for in vivo virulence expression in Pseudomonas aeruginosa[J]. Ann Surg, 2000, 232(4): 480.
[8] Evans E A, Kawli T, Tan M W. Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans[J]. PloS Pathog, 2008, 4(10): e1000175.
[9] Tao J H, Duan J A, Jiang S, et al. Polysaccharides from Chrysanthemum morifolium Ramat ameliorate colitis rats by modulating the intestinal microbiota community[J]. Oncotarget, 2017, 8(46):80790.
[10] Zhai S, Zhu L, Qin S, et al. Effect of lactulose intervention on gut microbiota and short chain fatty acid composition of C57BL/6J mice[J]. Microbiologyopen, 2018,doi:10.1002/mbo3.612.
[11] Xiao C, Qiao Z, Hai Y, et al. Lactulose: an indirect antioxidant ameliorating inflammatory bowel disease by increasing hydrogen production[J]. Med Hypotheses, 2011, 76(3): 325.
[12] Hu Y X, Yu L, Liu H J, et al. Changes in the composition of intestinal microbiota in mice with acute liver failure induced by D-galactosamine[J]. Chin J Hepatol, 2017, 25(4): 291.
[13] Yellin A E, Heseltine P N, Berne T V, et al. The role of Pseudomonas species in patients treated with ampicillin and sulbactam for gangrenous and perforated appendicitis[J]. Surg Gynecol Obstet, 1985, 161(4): 303.
[14] 尹有宽, 徐立群, 吴宗宝, 等. 假单胞菌属感染(附194例报告)[J]. 上海医学, 1995, 18(10): 574.
[15] 吴洪巧, 纪明宇, 裴凤艳, 等. 146株链球菌属临床感染特征及耐药性分析[J]. 中华医院感染学杂志, 2011, 21(12): 2607.
[16] 朱翠, 师子彪, 蒋宗勇, 等. 乳酸杆菌在调节肠道屏障功能中的作用[J]. 中国畜牧兽医, 2012, 39(9): 118.
[17] 章文明, 汪海峰, 刘建新. 乳酸杆菌益生作用机制的研究进展[J]. 动物营养学报, 2012, 24(3): 389.
[18] Kushkevych I, Kos J, Kollar P, et al. Activity of ring-substituted 8-hydroxyquinoline-2-carboxanilides against intestinal sulfate-reducing bacteria Desulfovibriopiger[J]. Med Chem Res, 2017, 1(27): 1.
[19] Sawin E A, De Wolfe T J, Aktas B, et al. Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice[J]. Am J Physiol Gastrointest Liver Physiol, 2015, 309(7): G590.
[20] Balamurugan R, Rajendiran E, George S, et al. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer[J]. J Gastroenterol Hepatol, 2008, 23(8pt1): 1298.
[21] Xu J, Lian F, Zhao L, et al. Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula[J]. ISME J, 2015, 9(3): 552.
[22] Zeng H, Ishaq S L, Zhao F Q, et al. Colonic inflammation accompanies an increase of beta-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice[J]. J Nutr Biochem, 2016, 35: 30.
[23] Chen G, Xie M, Wan P, et al. Fuzhuan brick tea polysaccharides attenuate metabolic syndrome in high-fat diet induced mice in association with modulation in the gut microbiota[J]. J Agric Food Chem, 2018, 66(11): 2783.
[24] 彭颖, 李晓波. 脾虚证与肠道微生态[J]. 世界华人消化杂志, 2012, 20(34): 3287.