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目的:将芒果苷分子上的一部分羟基进行酰化衍生,以提高化合物的脂溶性;然后比较芒果苷及其酰化衍生物的抗炎活性。方法:将芒果苷分别与乙酸酐、丙酸酐和丁酸酐反应,反应产物用硅胶柱层析分离出化合物单体,用波谱解析化合物的化学结构。雄性小鼠随机分为空白对照组,地塞米松阳性药组(0.115 mmol.kg-1),芒果苷高、中、低剂量组(1.0,0.5,0.25 mmol.kg-1)和酰化衍生物[乙酰化反应产物(PAM),丙酰化反应产物(HPM),丁酰化反应产物(HBM)]各高、中、低剂量组(0.25,0.125,0.063 mmol.kg-1),每组10只。各组连续经口给药5 d。末次给药45 min后,尾静脉注射伊文思蓝,右耳滴二甲苯致炎,腹腔注射冰醋酸。15 min后处死小鼠,用打孔器沿左、右耳廓相同部位打下两侧耳片,分别称重,计算耳廓肿胀度;另用生理盐水腹腔注射进行清洗,收集腹腔液测定吸光度(A),用以评价腹腔毛细血管通透性。结果:得到3个新结构化合物:(a)7,2’,3’,4’,6’-五乙酰化芒果苷衍生物(PAM),(b)3,6,7,2’,3’,4’,6’-七丙酰化芒果苷衍生物(HPM)和(c)3,6,7,2’,3’,4’-六丁酰化芒果苷衍生物(HBM)。与空白对照组比较,芒果苷高、中剂量组、PAM高、中剂量组、HPM高、中、低剂量组和HBM高、中、低剂量组均能显著抑制小鼠耳廓肿胀(P<0.05),并能显著抑制毛细血管的通透性,减少腹腔液渗出(P<0.01或P<0.05),显示出显著的抗炎作用,并呈现一定的结构-效应关系。结论:PAM,HPM和HBM为首次报道的新结构化合物;芒果苷酰化衍生物只需相当于芒果苷1/4的摩尔剂量,即可显示出与芒果苷相似的抗炎作用,说明其抗炎作用的效价强度高于芒果苷,提示其抗炎活性比芒果苷强。
OBJECTIVE: To acylate some hydroxyl groups of mangiferin molecules to improve the fat-solubility of the compounds. Then, the anti-inflammatory activity of mangiferin and its acylated derivatives was compared. Methods: Mangiferin was reacted with acetic anhydride, propionic anhydride and butyric anhydride, respectively. The reaction products were separated by silica gel column chromatography and their chemical structures were elucidated by spectroscopy. Male mice were randomly divided into blank control group, dexamethasone positive group (0.115 mmol.kg-1), mangiferin high, medium and low dose groups (1.0, 0.5 and 0.25 mmol.kg-1) (0.25,0.125,0.063 mmol.kg-1) in each of the high, middle and low dose groups [(acetylation reaction product (PAM), propionylation reaction product (HPM) and butyrylation reaction product (HBM) Group of 10. Each group continuously administered orally for 5 days. 45 min after the last administration, the Evans blue tail vein injection, the right ear drops of xylene inflammation, intraperitoneal injection of glacial acetic acid. After 15 min, the mice were sacrificed, and the ears were punched along the left and right auricles at the same site. The ears were weighed to calculate the degree of auricle swelling. The animals were peritoneally injected with saline for washing, and the peritoneal fluid was collected for determination of absorbance (A ) To evaluate peritoneal capillary permeability. Results: Three novel structural compounds were obtained: (a) 7,2 ’, 3’, 4 ’, 6’-pentaacetylated mangiferin derivatives (PAM), (b) 3,6,7,2’, 3 ’, 4’, 6’-heptapionylated mangiferin derivatives (HPM) and (c) 3,6,7,2 ’, 3’, 4’-hexbutyrylated mangiferin derivatives (HBM). Compared with the blank control group, the mangrove glycosides high and middle dose groups, PAM high and middle dose groups, HPM high, medium and low dose groups and HBM high, medium and low dose groups could significantly inhibit the auricle swelling of mice (P < 0.05), and could significantly inhibit capillary permeability and reduce peritoneal effusion (P <0.01 or P <0.05), showing a significant anti-inflammatory effect, and showed a certain structure-effect relationship. Conclusions: PAM, HPM and HBM were the first reported new structural compounds. Mangiferin acylated derivatives showed a similar anti-inflammatory effect to that of mangiferin with a molar dose equivalent to 1/4 of that of mangiferin. The potency of inflammation is higher than that of mangiferin, suggesting that its anti-inflammatory activity is stronger than that of mangiferin.