Inngjerdingen Kari T, Kiyohara Hiroaki, Matsumoto Tsukasa, Petersen Dirk, Michaelsen Terje E, Diallo Drissa, Inngjerdingen Marit, Yamada Haruki, Paulsen Berit S
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, Norway.
Phytochemistry. 2007 Apr;68(7):1046-58. doi: 10.1016/j.phytochem.2007.01.011. Epub 2007 Mar 6.
An immunomodulating pectic polymer, GOA1, obtained from the aerial parts of the Malian medicinal plant Glinus oppositifolius (L.) Aug. DC. (Aizoaceae) has previously been reported to consist of arabinogalactans type I and II, probably linked to a rhamnogalacturonan backbone. To further elucidate the structure of the polymer GOA1, enzymatic degradation studies and weak acid hydrolysis were performed. Five different glycosidases were used, endo-alpha-D-(1-->4)-polygalacturonase, exo-alpha-L-arabinofuranosidase, endo-alpha-L-(1-->5)-arabinanase, endo-beta-D-(1-->4)-galactanase and exo-beta-D-galactosidase. It appears that GOA1 may contain a structural moiety consisting of a 1,3-linked galactopyranosyl (Galp) main chain with 1,6-linked Galp side chains attached to position 6 of the main chain. The 1,6-linked Galp side chain may be branched in position 3 with arabinofuranosyl (Araf) side chains. A 1,4-linked Galp backbone which might carry side chains or glycosyl units attached to position 3 is also a structural element in the polymer. We further show that GOA1 induce proliferation of B cells and the secretion of IL-1beta by macrophages, in addition to a marked increase of mRNA for IFN-gamma in NK-cells. To elucidate structure-activity relations the native polymer and the digested fractions were tested for complement fixing activity and intestinal immune stimulating activity. The partial removal of Araf residues after enzymatic degradations did not affect the bioactivities, while the acid hydrolysed fraction showed reduced complement fixing activity. A decrease in Araf units, 1,3,6-linked Galp units and a partial hydrolysed rhamnogalacturonan backbone, in addition to a reduction in molecular weight are factors that might have contributed to reduced bioactivity.
一种从马里药用植物反叶银胶菊(Glinus oppositifolius (L.) Aug. DC.,番杏科)地上部分获得的免疫调节性果胶聚合物GOA1,此前据报道由I型和II型阿拉伯半乳聚糖组成,可能与鼠李半乳糖醛酸聚糖主链相连。为了进一步阐明聚合物GOA1的结构,进行了酶促降解研究和弱酸水解。使用了五种不同的糖苷酶,内切α-D-(1→4)-聚半乳糖醛酸酶、外切α-L-阿拉伯呋喃糖苷酶、内切α-L-(1→5)-阿拉伯聚糖酶、内切β-D-(1→4)-半乳聚糖酶和外切β-D-半乳糖苷酶。似乎GOA1可能含有一个结构部分,该部分由1,3-连接的吡喃半乳糖基(Galp)主链和连接在主链6位的1,6-连接的Galp侧链组成。1,6-连接的Galp侧链可能在3位被阿拉伯呋喃糖基(Araf)侧链分支。一个1,4-连接的Galp主链,其可能携带连接在3位的侧链或糖基单元,也是该聚合物中的一个结构元素。我们还表明,GOA1除了显著增加NK细胞中IFN-γ的mRNA水平外,还能诱导B细胞增殖和巨噬细胞分泌IL-1β。为了阐明结构-活性关系,对天然聚合物和消化后的组分进行了补体固定活性和肠道免疫刺激活性测试。酶促降解后Araf残基的部分去除不影响生物活性,而酸水解组分的补体固定活性降低。Araf单元、1,3,6-连接的Galp单元的减少以及部分水解的鼠李半乳糖醛酸聚糖主链,再加上分子量的降低,可能是导致生物活性降低的因素。