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睡莲属植物化学成分及生物活性研究进展



全 文 :天然产物研究与开发 Nat Prod Res Dev 2014,26:142-147,141
文章编号:1001-6880(2014)1-0142-07
收稿日期:2013-09-24 接受日期:2013-12-20
基金项目:中国医学科学院 &北京协和医学院药物研究所天然药
物活性成分与功能国家重点实验室项目
* 通讯作者 Tel:86-991-2320227;E-mail:zhaojun21cn@ 163. com
睡莲属植物化学成分及生物活性研究进展
赵 军1,2* ,徐 芳1,吉腾飞2,顾政一1,李晨阳1
1新疆维吾尔自治区药物研究所维吾尔药重点实验室,乌鲁木齐 830004;2 中国医学科学院北京协和医学院药物
研究所 天然药物活性成分与功能国家重点实验室,北京 100050
摘 要:本文综述了睡莲属植物所含的黄酮及酚酸等化学成分,以及其抗氧化、抗菌、抗炎、抗辐射、降血压和降
血糖等多方面的生物活性,以期为睡莲属植物的开发利用提供一定的科学依据。
关键词:睡莲属;化学成分;生物活性;综述
中图分类号:Q946. 91 文献标识码:A
Advances in the Study on Chemical Constituents and
Biological Activities in Nymphaea Genus
ZHAO Jun1,2* ,XU Fang1,JI Teng-fei1,GU Zheng-yi1,LI Chen-yang1
1Xinjiang Key Laboratory for Uighur Medicines,Xinjiang Institute of Materia Medica,Urumqi 830004,China;
2State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,
Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China
Abstract:The study on chemical constituents of Nymphaea was reviewed in this paper,flavonoids and phenolic acids are
rich in Nymphaea genus. The article introduces biological activities of Nymphaea such as anti-baeterical,antioxidant,an-
tiinflammory,antiradiation,hepatoprotective,hyperglycemic and hypotensive effect also.
Key words:Nymphaea genus;chemical compounds;pharmacological activity;review
睡莲属 Nymphaea为睡莲科 Nymphaeaceae 多年
生水生草本植物,广泛分布于温带及热带地区。睡
莲属植物在民间有着悠久的药用历史,其中雪白睡
莲花 Nymphaea candida是我国维吾尔族人民的传统
药材,它的干燥花蕾已被收入《中华人民共和国卫
生部药品标准维吾尔药分册》中,用于感冒发烧、头
痛咳嗽、心悸不安、咽痛等病症的治疗[1]。近年来
研究发现该属植物具有抗氧化、抗菌、抗炎、抗辐射、
降血糖和降血压等多种生物活性,黄酮及酚酸类化
合物是其主要的特征性成分。本文对睡莲属植物的
化学成分及生物活性的研究进展做一综述,以期为
该属植物资源的开发利用提供参考。
1 生物学特性及资源分布
睡莲属植物根茎肥厚,叶二型,浮水叶圆形或卵
形,基部具弯缺,心形或箭形,常无出水叶;沉水叶薄
膜质,质脆。花大形,浮在或高于水面;萼片 4,近离
生;花瓣白色、黄色、粉色或蓝色,12 ~ 32,多成轮;花
柱头成凹入柱头盘;浆果海绵状,不规则开裂,水面
下成熟;种子坚硬,为胶质物包裹,有肉质假种皮,胚
小。该属植物多生长在池沼地,也是睡莲科中分布
最广的一属,除南极之外,世界各地皆可找到睡莲的
踪迹。目前在全世界约有 35 种,我国原产 5 种:白
睡莲、雪白睡莲、延药睡莲、睡莲、柔毛齿叶睡莲,国
内各省区均有栽培,主供观赏[2]。
白睡莲 N. alba,叶全缘或具波状钝齿,两面无
毛;花瓣白色;萼片脱落或花期后腐烂;内轮雄蕊花
丝丝状,柱头扁平;根茎匍匐。主产于我国的河北、
山东、陕西和浙江等地,在印度、欧洲及高加索地区
也有分布。
雪白睡莲 N. candida,内轮花丝披针形;柱头深
凹;萼片矩圆状卵形;根茎直立或斜生;余同白睡莲。
主产于我国新疆的南部地区,在西伯利亚、中亚、欧
洲也有分布。
延药睡莲 N. stellata,叶全缘或具波状钝齿,两
面无毛;花瓣白色带青紫、鲜蓝色或紫红色;萼片宿
存。主产于我国的湖北、广东、海南及云南南部地
区,国外主要分布在印度、越南、缅甸、泰国及非洲中
部等地。
睡莲 N. tetragona,叶全缘或具波状钝齿,两面
无毛;花瓣白色;萼片宿存。大部分原产北非和东南
亚热带地区,少数产于南非、欧洲和亚洲的温带和寒
带地区,日本、朝鲜、印度、前苏联、西伯利亚及欧洲
等地。
柔毛齿叶睡莲 N. lotus,叶边缘有不等三角状锐
齿,下面密生柔毛、微柔毛或近无毛;花瓣白色、红色
或粉色。在我国主要分布云南南部、台湾,常见于南
亚、东南亚等地区,在澳洲东北部、新内几亚也可见。
2 化学成分
睡莲属植物包括黄酮、酚酸、生物碱、木脂素及
多糖等多种类型化合物。
2. 1 黄酮类及酚酸类
从睡莲属植物中共分离的到的黄酮类及酚酸类
化合物 70 余个,分别为黄酮、黄酮醇及异黄酮类,见
表 1。
表 1 睡莲属植物中的黄酮类及酚酸类化合物
Table 1 Flavonoids and phenolic acid compounds in Nymphaea genus
No. Chemical compounds Sourcs Ref
1 apigenin N. alba [3]
2 kaempherol N. alba,N. candida [3,4]
3 kaempferol 3-O-β-D-glucoside N. candida,N. caerulea [4,5]
4 kaempferol 3-O-α-L-rhamnopyranoside
N. candida,N. pulchella,
N. odorataa,N. caerulea [4,12,6,11]
5 kaempferol 3-O-galactoside Nymphaea [7]
6 kaempferol 3-O-β-D-rutinoside N. candida [4]
7 kaempferol 7-O-β-D-glucoside-3-O-β-D-rutinoside N. candida. [4]
8 Kaempferol 3-(2″-acetylrhamnoside) N. caerulea [11]
9 kaempferol 3-O-(3-O-acetyl)-alpha-L-rhamnoside N. Mexicana,N. caerulea [8,5]
10 kaempferol 3-O-(2-O-acetyl-α-l-rhamnopyranoside) N. mexicana [8]
11 kaempferol 3-O-(2″-O-galloyl)rutinoside N. candida [4]
12 kaempferol 7-O-galloylgalactosyl-(1 → 2)-rhamnoside Nymphae [7]
13 kaempferol 7-O-galactosyl-(1 → 2)-rhamnoside Nymphae [7]
14 kaempferol 3-O-methtl ether N. stellata [14]
15 quercetin N. candida,N. x marliacea,N. hybrida ,N. alba [4,9,10,3]
16 quercetin 3-O-β-D-xyloside N. candida,N. ampla,N. marliacea [4,12,8]
17 quercetin 3-O-β-D-xyloside N. x marliacea [9]
18 quercetin 4-O-β-D-xyloside N. alba [3]
19 quercetin 3-O-α-L-rhamnopyranoside
N. odorataa,N. ampla,N. elegans,
N. caerulea,N. elegans
[6,12,12,
5,11,12]
20 quercetin 3-O-β-D-glucopyranoside
N. ampla,N. hybrida,
N. alba,N. caerulea [12,10,3,5]
21 quercetin 3-O-β-D-galactopyranoside N. alba [3]
22 quercetin 3-methyl ether 4-O-β-D-xyloside N. alba [3]
23 quercetin 3-methyl ether 3-O-β-D-xyloside N. alba,N. caerulea,N. x marliacea [3,19,9]
24 quercetin 3-O-β-D-(3-O-acetyl)-α-L-rhamnopyranoside N. mexicana,N. caerulea [8,9,5]
25 quercetin 3-O-β-D-(2″-O-acetyl)-α-L-rhamnopyranoside N. caerulea [11]
341Vol. 26 赵 军等:睡莲属植物化学成分及生物活性研究进展
26 quercetin 3-O-(6″-O-acetyl)-β-D-galactopyranoside N. odorataa [6]
27 quercetin 7-O-galactoside Nymphae [7]
28 quercetin 7-O-galactosyl-(1 → 2)-rhamnopyranoside Nymphae [7]
29 isorhamnetin 7-O-galactoside Nymphae [7]
30 isorhamnetin 7-O-xyloside Nymphae [7]
31 quercetin 3-O-acetylgalactoside Nymphae [7]
32 isokaempferide N. alba,N. x marliacea [3,9]
33 myricetin N. candida,N. hybrida [4,11]
34 myricetin 3-O-β-D-glucoside N. caerulea [5]
35 myricetin 3-O-β-D-xyloside N. candida,N. x marliacea [4,9]
36 myricetin 3-O-α-L-rhamnopyranoside N. caerulea,N. odorataa [9,11,6]
37 myricetin 3-O-α-L-(2″-O-acetyl)-rhamnopyranoside N. caerulea [11]
38 myricetin 3-O-α-rhamnopyranosyl(1 →6)β-galacto pyranoside N. x marliacea [9]
39 myricetin 3-O-β-D-galactopyranoside N. odorataa [6]
40 myricetin 3-O-(3-O-acetyl)-α-L-rhamnoside N. odorataa [6]
41 myricetin 3-O-(6″-O-acetyl)-β-D-galactopyranoside N. odorataa [6]
42 myricetin 3-O-galloylrhamnoside Nymphae [7]
43 myricetin 7-O-rhamnosyl-(1 → 2)-rhamnoside Nymphae [7]
44 annulatin 3-O-β-D-xyloside N. candida [15]
45 7,3,4-trihydroxy-5-O-β-D-(2″-acetyl)-xylopyranosyl-isoflavone N. ampla [12]
46 7,30,4-trihydroxy-5-O-α-L-rhamnopyranosyisoflavone N. pulchella [12]
47 (2R,3R)-3,7-dihydroxyflavanone N. mexicana [8]
48 naringenin N. Mexicana,N. caerulea [8,5]
49 (S)-naringenin 5-O-β-D-glucoside N. caerulea [5]
50 chalcononaringenin 2-O-galactoside Nymphae [7]
51 delphinidin 3-O-(2-O-galloyl-β-galactopyranoside) N. caerulea [13]
52 delphinidin 3-O-(2-O-galloyl-β-galactopyranoside) N. caerulea [13]
53 delphinidin 3-O-(2-O-galloyl-6″-O-acety-β-galactopyranoside N. caerulea [13]
54 delphinidin 3-O-(2-O-galloyl-6″-O-acety-β-galactopyranoside) N. caerulea [13]
55 delphinidin 3-O-rhamnosyl-5-O-galactoside N. caerulea [13]
56 delphinidin 3-O-(2″-O-galloyl-6″-O-oxalyl-rhamnoside) Nymphae [7]
57 delphinidin 3-O-(6″-O-acetyl-β-glucopyranoside) Nymphae [7]
58 cyaniding 3-O-(2″-O-galloyl-galactopyranoside)-5-O-rhamnoside Nymphae [7]
59 gallic acid N. stellata [13]
60 methyl gallate N. caerulea [5]
61 ethyl gallate N. caerulea [5]
62 p-coumaric acid N. caerulea [5]
63 4-methoxybenzoic N. caerulea [5]
64 m,p-methylgalloyl gallic acid N. stellata [14]
65 2S,3S,4S-trihydroxypentanoic acid N. caerulea [5]
66 vanillic acid N. mexicana [8]
441 天然产物研究与开发 Vol. 26
67 ellagic acid N. candida [14]
68 brevifolin N. candida [15]
69 methyl brevifolincarboxylate N. candida [15]
70 4-Methoxy-3,5-dihydroxybenzoic acid N. mexicana [8]
71 corilagin N. stellata [15]
72 isostrictiniin N. candida [15]
73 geraniin N. tetragona [15,16]
74 1,2,3,4,6-penta-O-galloyl-β-D-glucose N. tetragona [15,17]
2. 2 其它
从 N. odorata中分离得到两个木脂素类化合物
nymphaeoside A (75) ,icariside E(76) ,从 N. gracilis
中分离得到两个齐墩果烷型三萜皂苷类化合物
methyl- oleanolate-3-O-β-D-glucopyrnoside (77) ,and
28-O-β-D- glucopyranosyl- oleanolate (78)。此外,
睡莲属植物中还含有多糖类、生物碱(去甲乌药碱,
79) ,以及 Nymphayol (25,26-dinorcholest-5-en-3β-
ol,80)、isosalipurposide (81) ,β-sitosterol (82) ,β-si-
tosterol palmitate (83) ,24-methylenecholesterol palmi-
tate (84) ,4α-methyl-5α-ergosta -7,24 (28)-diene-
3β,4β-diol (85) ,β-谷甾醇(86)和豆甾醇(87)等化
合物[18-21]。
3 药理作用
3. 1 抗菌作用
N. hybrida 中的五倍子鞣酸和鞣花酸具有明显
的抗菌作用[22],进一步研究显示该植物所含的黄酮
醇苷类化合物也具有显著的抗炎、抗菌和止痛作
用[23]。Kurihara等[24]从 N. tetragona 中分离得到了
一种可以抗鱼病原菌的可水解鞣质老鹤草素。N.
odorata中的三个黄酮类化合物 afzelin、quercetin 3-
O-α-L-rhamnopyranoside 和 myricetin 3-O-β-D-galac-
topyranoside具有较为显著的脂肪酸合成酶抑制作
用(IC50分别为 45、50、25 μg /mL)
[25]。Yildirim等通
过生物活性筛选发现白睡莲 N. alba 具有显著的抗
菌和抗肿瘤活性[26]。
3. 2 抗炎作用
柔毛睡莲花 N. pubescens 水提取物可通过抑制
iNOS的表达显著抑制脂多糖刺激巨噬细胞 NO 的
产生(IC50 = 75. 5 μg /mL) ,500 mg /kg 的剂量还能
显著降低角叉菜胶诱导的足肿胀[27]。在四氯化碳
诱导的化学性肝损伤模型中,该药材提取物能明显
降低 ALT、AST 和胆红素的含量,恢复 SOD 和 GSH
的活性[28]。Hsu报道了从黄睡莲 N. mexicana 中分
离纯化得到的 7 个黄酮及酚酸类成分对 LPS诱导小
鼠巨噬细胞 RAW264. 7 产生的 NO、MCP-1 和 TNF-
α具有显著的抑制作用,同时对 iNOS、COX-2 和
phospho-EPK也具有明显的抑制作用[29]。据《印度
草药学》记载[30],睡莲花 N. satellite是治疗肝炎的传
统药物,该植物提取物对四氯化碳引起的肝损伤有
较好的保护作用。雪白睡莲花提取物可明显降低卡
介苗联合脂多糖诱导原代肝细胞引发的 AST、ALT
和 NO的增高,显示了明显的保肝作用[31]。经红睡
莲多糖 NR-PS处理后,鼠骨髓造血细胞的未成熟细
胞中的 CD80 /86 和 MHC class Ⅱ的表达明显增加,
TH1 细胞因子 IL-12 和 TNF-γ显著增加,IL-10 显著
减少,结果说明了 NR-PS是影响未分化细胞成熟和
功能的免疫调节剂[32]。
3. 3 神经保护作用
在古埃及和印第安文明中,睡莲花作为麻醉药
在宗教仪式中使用[33]。清华大学杜力军课题组对
从雪白睡莲中分离得到的 10 种黄酮单体进行了药
理活性研究,结果发现其中新化合物山奈酚 3-O-(
2″-O-没食子酰基)芦丁糖苷同时具有在拟缺血条件
下对神经细胞 PC12 的杀伤和对大鼠皮层原代神经
元的保护作用,且这 10 种黄酮类化合物具有较强的
抗氧化活性[4]。也有学者[34]研究了该属植物的乙
醇提取物,发现该提取物有较好的抗焦虑作用。同
时 Delphaut.和 Balansard[35]对 N. alba根茎提取物用
酒石酸酸化后测得其中含有一种生物碱和一种葡萄
糖苷,动物实验表现出温和的镇静和解痉作用,且无
明显的心脏抑制作用,毒性较小。研究显示,白睡莲
乙醇提取物具有抗焦虑作用[36]。与溶剂对照组相
比较,白睡莲乙醇提取物(100 and 200 mg /kg,p.
o.)能明显增加小鼠在高架十字迷路开臂的次数与
时间(P < 0. 05) ;并可使小鼠在明箱停留时间和穿
箱次数增加,较少了静止不动的持续时间;在旷场试
541Vol. 26 赵 军等:睡莲属植物化学成分及生物活性研究进展
验(OFT)中,白睡莲乙醇提取物可明显增加小鼠后
肢站立次数,水平运动及垂直运动,增强了小鼠的探
究兴趣;在新型食物消耗实验中,该提取物还可明显
改善焦虑相关的攻击行为。
3. 4 降血压和降血糖作用
在印度和尼泊尔,延药睡莲花常用来治疗糖尿
病,其提取物对四氧嘧啶诱导的大鼠糖尿病模型有
降糖作用。进一步研究表明该植物提取物有明显的
肠内葡萄糖苷酶抑制作用,且无急毒或基因毒性,可
以用于治疗糖尿病患者的餐后高血压症[37]。研究
显示延药睡莲花提取物有明显的降血糖作用,以
300 mg /kg的剂量服用 4 h后,能显著降低血糖水平
(45%)[38]。进一步从该部位分离纯化得到的化合
物 Nymphayol(25,26-dinorcholest-5-en-3β-ol)具有明
显的降血糖作用,同时也能有效增加糖尿病大鼠总
胰岛素水平[39]。在四氧嘧啶诱导的大鼠糖尿病模
型中,延药睡莲花提取物能明显降低 FBG、TL、TC、
TG、FFA 和 LDL 的水平,同时也能显著增加 HDL、
血清胰岛素的水平[40,41]。延药睡莲叶乙醇提取物
也能显著降低四氧嘧啶引起的血糖升高,同时也影
响血清胆固醇和甘油三酯水平[42]。延药睡莲花提
取物降血糖作用可能的机制是刺激 β-细胞、增加胰
岛素的分泌和激活胰岛素受体[43]。Khan N 等[44,45]
研究了睡莲花 N. alba提取物对 Fe-NTA诱导的肾氧
化压,高渗透压和肾癌小鼠的预防作用,发现该提取
物是潜在的产生这些作用的化学阻滞剂。Odintsova
等[46]研究发现 N. alba的全草提取物对诱发动物脑
垂体分泌失调性高血压有明显的调节作用,可有效
阻止血压大幅上升,并且毒性较低。
3. 5 抗辐射作用
γ-射线照射可引发 DNA 损伤和处于增殖期干
细胞和外周免疫细胞的凋亡,继而破坏肠腺和淋巴
系统。从 N. tetragona 中分离得到的老鹤草素能通
过提高增殖、减轻 DNA 损伤、减少凋亡基因 P53 和
Bax的表达以及增加抗凋亡基因 Bcl-2 抑制放射敏
感性脾细胞的凋亡;老鹤草素能明显减少 γ-射线照
射下小鼠脾细胞和肠腺细胞的凋亡[16]。老鹤草素
还能显著减少 γ-射线所引起中国仓鼠肺成纤维细
胞中活性氧水平,并能使减少的 SOD 得到恢复,保
护 γ-射线导致的细胞成分及细胞膜的损坏[47]。而
Huang等[48]研究发现睡莲属植物中的 1,2,3,4,6-
penta-O-galloyl-β-D-glucose (PGG)对正常损害剂量
的免疫细胞有保护作用,能显著提高脾细胞的增殖、
减少凋亡基因 P53 的表达以及增加抗凋亡基因 Bcl-
2 抑制放射敏感性脾细胞的凋亡。这些化合物有望
成为抗辐射的药物。
3. 6 其它作用
Saleem等[49]研究了巴基斯坦产睡莲花的抗氧
化活性,结果显示该药材的总酚类成分有着较好的
抗氧化能力,并且明显优于 α-生育酚。睡莲花 N.
rubra乙醇提取物具有显著的驱虫活性[50]。
4 结语
近年来的药理作用研究多集中于该属植物的粗
提物和少数化合物上,对其传统的治疗应用也有所
验证,但对多种药理作用及临床应用的物质基础并
没有得到系统阐明。如雪白睡莲花在在祖卡木颗
粒、炎消迪娜尔糖浆等抗炎抗病毒维吾尔药复方制
剂中广泛使用,并且是这些制剂发挥抗炎抗病毒的
主要药物,但发挥作用的成分仍不清楚。因此,有必
要将化学成分与生物活性研究紧密结合起来,以系
统阐明该属植物的药效物质基础,为其资源的综合
开发应用提供基础数据。
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741Vol. 26 赵 军等:睡莲属植物化学成分及生物活性研究进展
程度高,实验误差小,具有实际应用价值,为白藜芦醇
和白藜芦醇苷的提取开发利用提供了技术支撑。
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141Vol. 26 曹静亚等:快速溶剂萃取提取白藜芦醇和白藜芦醇苷工艺的响应面优化