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| 两种维药材阿里红和沙枣花化学成分及生物活性的研究 | |
| 其他题名 | Studies on the chemical constituents and bioactivity of Uygur medicine of Fomes Officinalis and Elaeagnus angustifolia |
| 韩建欣 | |
| 出版年 | 2017 |
| 学位类型 | 博士 |
| 导师 | 袁涛 |
| 学位授予单位 | 中国科学院大学 |
| 中文摘要 | 维吾尔医药学是一门历史悠久、具有完整理论体系和丰富临床经验的民族医药学。作为我国传统医药学的一个重要组成部分，它也在不断的汲取现代科学技术方法，在疾病预防、保健和治疗方面不断探索创新。近年来，国家加大了对民族医药的扶持，维吾尔药在如白癜风、抗肿瘤、糖尿病等疾病的治疗方面的优势越来越受到重视，然而大部分维药材的研究基础相对薄弱，这就促使我们应该加大对维药材的基础研究尤其是药效物质基础的研究。本论文对两种常用维药材阿里红和沙枣花的化学成分和生物活性进行了研究，为阐明它们的药效物质奠定了基础。阿里红Fomes officinalis (Vill. Ex Fr.) Ames 为多孔菌科（Polyporaceace）层孔菌属（Fomes）真菌，是维吾尔医常用药材，具有消炎、化痰、活血、利尿等功效，主要分布在我国的西北和东北地区。本论文运用各种色谱技术和波谱学手段（包括1H, 13C NMR, 1H-1H COSY, HMBC, HSQC, NOSEY，MS 等）从阿里红子实体的甲醇提取物中共分离鉴定了34个化合物，包括31 个三萜（1-31），2 个木脂素（32-33）和1 个倍半萜（34）：officimalonic acids A-P （1-16），12,15-dihydroxy-24-methyl-3,23-dioxo-lanosta-7,9(11)-dien-26-oic acid（17），3,12-dihydroxy-24-methyl-7,23-dioxo-lanosta-8-en-26-oic acid （ 18 ） ，3-keto-dehydrosulfurenic acid（19），去氢硫色多孔菌酸（20），硫色多孔菌酸（21），fomitopsin （22），阿里红酸G（23），阿里红酸F（24），阿里红酸D（25），阿里红酸C（26），阿里红酸B（27），Quercinic acid（28），3α,23-dihydroxy-24-methyl-γ-lactone-Lanosta-8,24-dien-26-oic acid（29），齿孔酸（30），carbomethoxyacetylquercinic acid（31），2-[(4-hydroxy-3,5-dimethoxyphenyl)-methyl]-3-[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butanediol（32），lariciresinolacetate（33），落叶松脂酸（34），其中化合物1-18 为未见文献报道的新化合物。对阿里红甲醇提取物的行为学实验考察结果表明，阿里红甲醇提取物对Aβ诱导的AD 小鼠在新事物辨别能力损伤、学习记忆能力损伤和空间学习记忆能力损伤均具有明显保护作用。免疫组化实验表明阿里红甲醇提取物可以显著减轻Aβ 诱导的小鼠脑内神经元损伤以及抑制小胶质细胞的活化。部分单体化合物的抗炎活性表明化合物4、5、7、22 表现出较强的抑制LPS 诱导RAW264.7细胞NO的产生，其IC50 值在5.1-8.9 μM，抑制效果要明显强于阳性对照地塞米松（IC50 = 22.2 μM）。经过构效关系研究，推测阿里红三萜酸类化合物的抗炎活性可能与C-3 位的丙二酸半酯的结构片断有关。以上实验结果表明阿里红三萜酸可能通过抑制神经炎症反应而达到改善阿兹海默症（AD）的作用。另外，部分单体化合物的细胞毒活性测试显示化合物5、7、8 对3 种人癌细胞（H460,HepG2, BGC-823）均表现出了一定的抑制作用（IC50 值在20-70 μM 之间）。沙枣花为胡颓子科（Elaeagnaceae）胡颓子属（Elaeagnus）沙枣（Elaeagnus angustifolia）的花，生长于半干旱、干旱、半荒漠、荒漠地区。沙枣原产于西亚，地中海沿岸、印度以及前苏联地区也有分布。在我国沙枣主要分布于西北地区。《中国沙漠地区药用植物》和《维吾尔医常用药材》均记载，沙枣花具有止咳平喘的功效，可用于治疗慢性支气管炎。本文运用现代色谱技术和波谱学手段从沙枣花中共分离鉴定了16 个化合物，包括3 个黄酮（1-3），3 个苯乙苷（4-6），4 个糖类（7-10），3 个生物碱（11-13），2 个酚酸衍生物（14-15），1 个苯丙素（ 16 ） ： kaempferol 3-glucoside （ 1 ） ， (Z)-tiliroside （ 2 ） ，kaempferol-3-β-D-(6-O-trans-p-coumaroyl)glucopyranoside （ 3 ） ，2-phenylethyl-6-O-α-L-arabinofuranosyl-β-D-glucopyranoside（4），salidroside（5），2-苯乙基-O-β-D-吡喃葡萄糖苷（6），L-arabinonic acid（7），α-D-ribofuranose（8），L-mannonic acid（9），ethyl β-D-glucopyranoside（10），uridine（11），Thymidine（12），methyl phenylalaninate（13），苯甲醇（14），vanilloloside（15），(Z)-isoconiferin（16）。沙枣花提取物对LPS 诱导RAW 264.7小鼠巨噬细胞产生NO 和PGE2 影响的研究结果表明，其具有很强的抑制NO和PGE2 产生的作用，IC50 值分别为40.4 和59.6 g/mL，单体化合物的生物活性还在测试中。 |
| 英文摘要 | Uygur medicine and pharmacology is a long history of ethnomedicine，which has complete theoretical system and abundant clinical experience. As an important part of traditional medicine of our country, it is also learning from modern science and technology and constantly explore innovate method in disease prevention and treatment.In recent years, Uygur medicine get more attention to treat vitiligo, tumour and diabete thanks to rising investment in minority medicine in our country. However, most of medicinal materials research is weaker comparing with traditional Chinese medicinal materials. So we should increase the basic medicinal materials research, especially, in medicine compound effect research. In this dissertation, we study on the chemical constituents and bioactivities of medicinal fungi fomes officinalis and medicinal plant Elaeagnus angustifolia for laying a medicine compound foundation.Fomes officinalis, a fungus of Fomes genus in Polyporaceace family, is distributed mainly over northwestern and northeastern China. It is traditionnally used in Chinese Uygur prescription to treat anti-inflammatory, dissolve sputum, activating blood and diuretic. In this dissertation, we use modern technology and spectroscopic methods (1H, 13C NMR, 1H-1H COSY, HMBC, HSQC, NOSEY, MS ). Thirty-four compounds were isolated from the methanol extracts of fomes officinalis dried sclerotium, including thirty-two triterpenes (1-31), two lignans (32-33) and 1 sesquiterpenes (34): officimalonic acids A-P （1-16）, 12b, 15a-dihydroxy-24-methyl-3,23-dioxo-lanosta-7,9(11)-dien-26-oic acid（17），3a, 12b-dihydroxy-24-methyl-7,23-dioxo-lanosta-8-en-26-oic acid（18），3-keto-dehydrosulfurenic acid（19），Dehydrosulfurenic acid（20），Sulphurenic acid（21），fomitopsin A（22），fomefficinic acid G（23），fomefficinic acid F（24），fomefficinic acid D（25），fomefficinic acid C（26），fomefficinic acid B（27），Quercinic acid（28），3α,23-dihydroxy-24-methyl-γ-lactone-Lanosta-8,24-dien-26-oic acid（29），Eburicoic acid（30），Carbomethoxyacetylquercinic acid（31），2-[(4-hydroxy-3,5-dimethoxyphenyl) -methyl]-3-[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butanediol（32），Lariciresinol acetate（33），Laricinolic acid（34） of which eighteen were new compounds. Results of praxiology experiment showed: the methanol extracts of Fomes officinalis has protective effect on AD mice injury induced by β-amyloid protein(Aβ) in novel object recognition capability of injury, learning and memory capability of injury and the impairment of the spatial learning and memory. Results of immunohistochemistry showed: methanol extracts of fomes officinalis significantly reduced the injury of neurons in brains of mice and inhibiting the microglial activation. The inhibitory effects of parts of the compounds on NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells were evaluated. Compounds 4, 5, 7 and 22 showed strong activities, with IC50 values in the range of 5.1-8.9 μM; these values were around being 3-4 times more potent in inhibiting NO production than that of the positive control, dexamethasone (IC50 = 22.2 μM). All of the triterpenoids contain a malonate half-ester moiety at C-3, which is related with their anti-inflammatory activity. Given that triterpenes are known to be cytotoxic, the cytotoxicities of some of the compounds were tested against three human cancer cell lines (H460, HepG2, BGC-823). However, only compounds 5, 7 and 8 exhibited moderate activities (IC50 = 20-70 mM).Elaeagnus angustifolia blossoms, a flower of Elaeagnus genus in Elaeagnaceae family, which grows well in arid, semiarid, desert and half-desert areas. Elaeagnus angustifolia is native to west Asia, Mediterranean regions, India and former Soviet areas. In our country, Elaeagnus angustifolia is widely distributed in northern districts. According to Medicinal plants in the desert region of China and Uygur medicine commonly used herbs records, Elaeagnus angustifolia blossoms has the antitussive and antiasthmatic effects, and curing chronic tracheitis. In this dissertation, we use modern technology and spectroscopic methods. Sixteen compounds were isolated from the methanol extracts of Elaeagnus angustifolia blossoms, including three flavone (1-3), three Phenylethanoid glycosides (4-6), four sugars (7-10), three alkaloid (11-13), two Phenolic derivatives (14-15), one phenylpropanoids (16): kaempferol 3-glucoside (1), (Z)-tiliroside (2), kaempferol-3-β-D-(6-O-trans-p-coumaroyl)glucopyranoside (3), 2-phenylethyl-6-O-α-L-arabinofuranosyl-β-D-glucopyranoside (4), salidroside (5), 2-phenylethyl-β-D-glucopyranoside (6), L-arabinonic acid (7), α-D-ribofuranose (8), L-mannonic acid (9), ethyl β-D-glucopyranoside (10), uridine (11), thymidine (12), methyl phenylalaninate (13), phenylcarbinol (14), vanilloloside (15), (Z)-isoconiferin (16). The extracts of Elaeagnus angustifolia were evaluated for their inhibitory effect on LPS-induced NO and PGE2 production in RAW264.7 cells. The results showed that extracts of Elaeagnus angustifolia inhibited LPS-induced NO and PGE2 production with IC50 values of 40.4 and 59.6 mg /mL, respectively. Biological activity test of other single compounds is still being tested. |
| 中文关键词 | 阿里红 ; 三萜酸 ; 阿尔茨海默症 ; 抗炎 ; 沙枣花 |
| 英文关键词 | Fomes officinalis triterpenes Alzheimer’s Disease anti-inflammatory Elaeagnus angustifolia |
| 语种 | 中文 |
| 国家 | 中国 |
| 来源学科分类 | 有机化学 |
| 来源机构 | 中国科学院新疆理化技术研究所 |
| 资源类型 | 学位论文 |
| 条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/287979 |
| 推荐引用方式 GB/T 7714 | 韩建欣. 两种维药材阿里红和沙枣花化学成分及生物活性的研究[D]. 中国科学院大学,2017. |
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