平贝母化学成分、药理作用及临床应用研究进展

刘珈含; 赵维; 王月; 杨炳友

doi:10.14148/j.issn.1672-0482.2024.0315

平贝母化学成分、药理作用及临床应用研究进展

doi: 10.14148/j.issn.1672-0482.2024.0315

黑龙江中医药大学药学院, 黑龙江哈尔滨 150000

基金项目:

国家自然科学基金青年科学基金项目 82205007

黑龙江省重点研发计划项目 GA21D008

详细信息

作者简介:
刘珈含, 女, 博士研究生, E-mail: liujiahan@hljucm.edu.cn

通讯作者:
杨炳友，男, 教授, 主要从事中药药效物质基础研究，E-mail: ybywater@163.com

中图分类号: R282
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- 被引次数: 0
出版历程
- 收稿日期: 2023-11-06
- 网络出版日期: 2024-03-15
- 发布日期: 2024-03-10

Research Progress on Chemical Constituents, Pharmacological Activities and Clinical Application of Fritillaria Ussuriensis

School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150000, China

摘要

摘要: 平贝母是寒地名贵中药, 具有散结解郁, 润肺清心等功效。在临床中广泛应用于气逆咳喘、喉痹、疮痈等病证的治疗, 单味或复方使用皆效果良好, 是具有广阔开发前景的纯天然高效药物。近年来, 随着对平贝母研究不断深入, 已分离得到生物碱类、核苷类、多糖类、挥发油类、有机酸类等成分, 具有平喘、止咳、祛痰、镇静、抗炎、抗菌等药理活性。通过查阅近40年来国内外对平贝母化学成分和药理作用的研究报道并进行系统综述分析, 以期为研究其药效物质基础提供科学的依据, 促进平贝母的开发利用。
- 平贝母 /
- 化学成分 /
- 药理活性
Abstract: Fritillaria ussuriensis is a valuable traditional Chinese medicine in cold regions, which has the functions of dispersing stagnation and relieving depression, moistening lung and clearing heart. It is widely used in the treatment of diseases such as qi adverseness and cough, pharyngitis, sore and carbuncle, etc. Whether it is used alone or in combination, it has good results. It is a pure natural and efficient drug with broad development prospects. In recent years, with the deepening of research on Fritillaria ussuriensis, alkaloids, nucleosides, polysaccharides, volatile oils, organic acids and other components have been isolated.It has pharmacological activities such as relieving asthma, relieving cough, expectorant, calming, anti-inflammatory and antibacterial. By reviewing the reports of chemical constituents and pharmacological effects of Fritillaria ussuriensis in the past 40 years, this paper systematically summarizes and analyzes the research results in order to provide scientific basis for the study of pharmacodynamic substance basis and promote the development and utilization of Fritillaria ussuriensis.
- Fritillaria ussuriensis /
- chemical constituent /
- pharmacological activity

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图 1 平贝母中生物碱类化合物结构

Figure 1. Structures of Alkaloids in Fritillaria ussuriensis

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图 2 平贝母中核苷类化合物结构

Figure 2. Structures of Nucleosides in Fritillaria ussuriensis

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图 3 平贝母中的其他成分结构

Figure 3. Other constituent structures in Fritillaria ussuriensis

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图 4 平贝母各药理作用的主要有效成分及通路

Figure 4. The main active components and pathways of pharmacological actions of Fritillaria ussuriensis

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表 1 平贝母中生物碱类化合物

Table 1. Alkaloids in Fritillaria ussuriensis

序号	名称	分子式	构型	参考文献
1	西贝素(Imperialine)	C₂₇H₄₃NO₃	瑟文型	[10]
2	平贝碱甲(Pingbeimine A)	C₂₇H₄₅NO₅	瑟文型	[10]
3	平贝碱乙(Pingbeimine B)	C₂₇H₄₅NO₆	瑟文型	[10]
4	乌苏里啶(Ussuriedine)	C₂₇H₃₇N0₃	瑟文型	[11]
5	乌苏里啶酮(Ussuriedinone)	C₂₇H₃₅N0₃	瑟文型	[11]
6	乌苏里酮(Ussurienone)	C₂₈H₃₇NO₃	瑟文型	[11]
7	贝母素乙(Verticinone)	C₂₇H₄₃NO₃	瑟文型	[11]
8	平贝酮(Pingbeinone)	C₂₆H₄₁NO₃	瑟文型	[13]
9	黑龙贝母碱(Heilonine)	C₂₇H₃₉N0₂	瑟文型	[12]
10	贝母甲素(Verticine)	C₂₇H₄₅NO₃	瑟文型	[11]
11	去氢鄂贝啶碱(Ebeiedinone)	C₂₇H₄₃NO₂	瑟文型	[13]
12	Benzo[7-8]fluoreno[2, 1-b]quinolizine cevane-3, 6, 16, 20-tetrol	C₂₇H₄₃NO₄	瑟文型	[13]
13	乌苏里宁(Ussurienine)	C₂₈H₃₉NO₃	瑟文型	[14]
14	平贝碱丙(Pingbeimine C)	C₂₇H₄₃NO₆	瑟文型	[15]
15	Puqiedine	C₂₇H₄₅NO₂	瑟文型	[21]
16	Puqiedinone	C₂₇H₄₅NO₂	瑟文型	[21]
17	异贝母素甲(Isoverticine)	C₂₇H₄₅NO₂	瑟文型	[21]
18	鄂贝定碱(Ebeiedine)	C₂₇H₄₅NO₂	瑟文型	[21]
19	西贝素苷(Imperialine-3β-D-glucoside)	C₃₃H₅₃NO₈	瑟文型	[16]
20	平贝碱苷(Pingbeimine glucoside)	C₃₃H₅₅NO₇	瑟文型	[16]
21	茄啶(Solanidine)	C₂₇H₄₃NO	茄碱型	[11]
22	Pingbeinine	C₂₈H₄₇NO₃	裂环茄碱型	[22]
23	Pingbeininoside	C₃₄H₅₇NO₈	裂环茄碱型	[22]
24	平贝定苷(Pingbeidinoside)	C₃₇H₆₃NO₈	裂环茄碱型	[18]
25	平贝母酮A(Pingbeimuone A)	C₂₇H₃₉NO₄	黎芦胺型	[13]
26	贝母辛(Peimisine)	C₂₇H₄₁N0₃	介藜芦型	[10]
27	15β-Hydroxy-23-isopengbeisine B	C₂₇H₄₁NO₅	介黎芦型	[20]

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表 2 平贝母中核苷类化合物

Table 2. Nucleosides in Fritillaria ussuriensis

NO.	名称	分子式	参考文献
28	胸苷(Thymidine)	C₁₀H₁₄N₂O₅	[23]
29	腺苷(Adenosine)	C₁₀H₁₃N₅O₄	[23]

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表 3 平贝母中挥发油类化合物

Table 3. Volatile oil in Fritillaria ussuriensis

NO.	名称	分子式	参考文献
30	Azulene, 1, 2, 3, 5, 6, 7, 8, 8a-octahydro-1, 4-dimethyl-7-(1-methylethenyl)-, [1S-(1α, 7α, 8 aα)]-	C₁₅H₂₄	[26]
31	trans-Caryophyllene	C₁₅H₂₄	[26]
32	γ-Elemene	C₁₅H₂₄	[26]
33	α-Caryphyllene	C₁₅H₂₄	[26]
34	Cyclohexene, 3-(1, 5-dimethyl-4-hexenyl)-6-methylene-	C₁₅H₂₄	[26]
35	1H-Cycloprop[e]azulene, decahydro-1, 1, 7-trimethyl-4-methylene-, [1aR-(1aα, 4aβ, 7α, 7aβ, 7bα)]-	C₁₅H₂₄	[26]
36	β-Caryophyllene	C₁₅H₂₄	[26]
37	Germa-cra-1(10), 4(14), 11-trien-5β-ol	C₁₅H₂₄O	[26]
38	Furano, 5, 9-diene	C₁₅H₂₃O	[26]
39	(+)-α-Cyperone	C₁₅H₂₂O	[26]

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表 4 平贝母中的其他成分

Table 4. Other components in Fritillaria ussuriensis

序号	名称	分子式	参考文献
40	棕榈酸(Palmic acid)	C₁₆H₃₂O₂	[27]
41	β-谷甾醇(β-sitosterol)	C₂₉H₅₀O	[27]
42	曼陀罗酸(Margaric acid)	C₁₇H₃₄O₂	[27]
43	平贝皂苷	C₄₁H₆₆O₁₃	[27]

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表 5 平贝母药效成分及药理作用

Table 5. Pharmacodynamic constituents and pharmacological effects of Fritillaria ussuriensis

NO.	药效成分	药理作用	作用效果和机制	参考文献
1	西贝素 (Imperialine)	镇咳祛痰平喘降血压解痉平滑肌	显著降低氨气所致小鼠的咳嗽频率和增加咳嗽潜伏期显著增强小鼠的气管酚红输出具有良好的祛痰作用通过拮抗M受体松弛气管平滑肌发挥平喘作用具有保护心血管的作用对抗乙酰胆碱、氯化钡及组胺的平滑肌痉挛作用	[32-34] [35] [39-40] [55-56] [57-58]
2	贝母辛 (Peimisine)	平喘抗炎降血压	抑制M受体、兴奋β受体和拮抗钙离子释放, 抑制由乙酰胆碱引起的气管平滑肌收缩通过作用MUC5AC、EGFR和MAPK信号通路降低脂多糖引起的炎症通过抑制血管紧张素转化酶(ACE)和血管紧张素I转化酶活性发挥降压作用	[41] [50] [84]
3	平贝碱甲 (Pingbeimine A)	祛痰降血压	显著增强小鼠气管酚红输出，具有良好的祛痰作用显著降低大鼠和家兔的血压	[38] [55]
4	贝母甲素 (Verticine)	镇咳祛痰平喘抗炎抗肿瘤保护心脑系统	显著降低氨气所致小鼠的咳嗽频率和增加咳嗽潜伏期显著增强小鼠的气管酚红输出，具有良好的祛痰作用通过拮抗M受体松弛气管平滑肌发挥平喘作用增加IL-10的含量，降低TNF-α、IL-1β和IL-6的含量，通过作用于MAPK、AKT/NF-κB、ERK1/2、p38和NF-κB、Kv1.3、Nav1.7等信号通路发挥抗炎作用；通过抑制MUC5AC黏蛋白基因表达，促进气道上皮细胞，治疗炎症性肺炎；通过抑制KV1.3离子通道，抑制T细胞活化抑制人乳腺癌细胞、前列腺癌细胞和直肠癌细胞增殖并促进其凋亡改善脑缺血再灌注损伤、脑动脉栓塞和脑组织坏死的现象，对急性肺损伤也有一定的保护作用	[33-34] [35] [39-40] [52-53] [44-45] [61] [87-89] [63-65]
5	贝母素乙 (Verticinone)	镇咳祛痰平喘抗炎抗肿瘤保护心肌受损	显著降低氨气所致小鼠的咳嗽频率和增加咳嗽潜伏期显著增强小鼠的气管酚红输出，具有良好的祛痰作用通过拮抗M受体松弛气管平滑肌发挥平喘作用通过抑制TGF-β/MAPK/ERK信号转导通路减轻由博莱霉素诱导的大鼠急性肺损伤；减弱AKT和PI3K磷酸化，通过NF-κB信号通路发挥抗炎作用具有逆转肿瘤细胞、多药耐药的特性；能够抑制4T1乳腺癌细胞增殖；通过降低肿瘤组织中P-gp表达, 升高Caspase-3的表达，抑制SGC7901和SGC7901/VCR胃癌细胞生长并增强对化疗药物阿霉素的敏感性可以减轻柯萨奇B病毒性心肌炎的心肌细胞凋亡和炎症	[33-34] [35] [39-40] [48-49] [61] [62-90]
6	西贝素苷 (Imperialine-3β- D-glucoside)	平喘抗炎	通过拮抗M受体松弛气管平滑肌发挥平喘作用通过抑制NF-κB通路中IκB的磷酸化和p65表达, 降低MAPK中p38和ERK的磷酸化发挥抗炎作用	[39-40] [51]
7	平贝碱苷 (Pingbeimine glucoside)	祛痰	显著增强小鼠的气管酚红输出，具有良好的祛痰作用	[35]
8	鄂贝定碱 (Ebeiedine)	抗菌	抑制金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌	[62]
9	腺苷 (Adenosine)	抗血小板聚集	有效阻止血小板活化因子诱导, 并且释放兴奋腺苷环化酶、降低血小板内苷的含量, 抑制血小板聚集	[52]
10	平贝母多糖 (FUP-1)	抗氧化	显著提高肝组织中谷胱甘肽过氧化物酶和SOD活性，并降低脑组织中MAO活力	[59]

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表 6 平贝母的临床应用

Table 6. Clinical application of Fritillaria ussuriensis

名称	主要组成	临床用途	作用机制	参考文献
平贝胶囊	平贝母	清热润肺, 止咳化痰。用于肺热咳嗽, 痰黏胸闷	抑制MUC5AC黏蛋白的基因表达, 促进气道上皮细胞	[66]
金振口服液	羚羊角、平贝母、大黄、黄芩、青礞石、石膏、人工牛黄、甘草	清热解毒, 祛痰止咳。用于小儿急性支气管炎; 小儿热毒袭肺所致的咳嗽、痰黄、发热、苔黄腻等症状	抑制TLR3/TRIF信号传导、调节抗炎-促炎平衡和改善T细胞免疫	[67]
羚竺散	羚羊角粉、水牛容易胆浓缩粉、琥珀、冰片、桔梗、僵蚕、全蝎(去钩)、天竺黄、平贝母、桑白皮、苦杏仁、莱菔子、黄连、前胡、甘草	清热解毒, 通宣理肺, 化痰镇惊。用于热毒壅肺引起的肺炎, 支气管炎等	增强人体免疫力的同时, 有效杀灭病原微生物	[68]
小儿金丹	朱砂、橘红、平贝母、胆南星、前胡、玄参、清半夏、大青叶、关木通、桔梗、荆芥穗、羌活、西河柳、地黄、枳壳、赤芍、钩藤、葛根、牛蒡子、天麻、甘草、防风、冰片、水牛角浓缩粉、羚羊角、薄荷	祛风化痰, 清热镇惊。用于小儿感冒发烧, 鼻塞流涕, 咳嗽气促，咽喉肿痛, 高热惊风	降低炎症因子含量, 改善呼吸系统功能	[69]
宁神丸	地黄(酒蒸)、当归(酒蒸)、白芍(酒炒)、川芎(酒制)、麦冬、酸枣仁(炒)、远志、茯苓(炒)、陈皮、平贝母、甘草	养血安神。用于心神不宁, 烦躁梦多, 神经衰弱, 惊悸失眠	抑制中枢神经系统，调节儿茶酚和5-羟色胺发挥催眠镇静作用	[70]
冬白梅片	天冬、麻黄(蜜制)、乌梅、防风、五味子、黄芩、白果仁、平贝母	敛肺定喘, 止咳化痰。用于气管炎咳痰黄白相兼, 肺寒化热, 寒热错杂	抑制痰液中性粒细胞、嗜酸性细胞表达	[71]
保胎丸	熟地黄、艾叶(炭)、荆芥穗、平贝母、槲寄生、菟丝子(酒制)、黄芪、白术(炒)、枳壳成分(炒)、砂仁、黄芩、厚朴(姜制)、甘草、川芎、白芍、羌活、当归	清热化痰, 止咳平喘。用于肺热咳嗽, 喘息	使凝血纤溶系统失衡, 下调血清中TNF-α、IL-1β和IL-17的表达	[72]
复方贝母片	平贝母、石膏、麻黄、硼砂、苦杏仁、化橘红、百部、甘草、淀粉、糊精、硬脂酸镁	清热化痰, 止咳平喘。用于肺热咳嗽, 喘息	降低循环血液中促炎因子水平及肺部组织中促炎因子的表达	[73]
治咳川贝枇杷露	平贝母、枇杷叶、水半夏、桔梗、薄荷脑	镇咳祛痰。用于感冒引起的咳嗽	促进呼吸道腺体的分泌, 并促进气管纤毛运动, 降低MUC5AC的含量, 促进痰液排出	[74]
蛤蚧治痨丸	蛤蚧、百部、平贝母、白果、白及、乌梅、冬虫夏草	滋肾补肺, 止咳抗痨, 用于肺痨, 潮热, 盗汗, 咳嗽, 咯血	可促进性腺机能, 提高免疫力, 改善泌尿系统、呼吸系统、消化系统的功能	[75]
小儿白贝止咳糖浆	白屈菜、瓜蒌、半夏(矾制)、平贝母	清热解毒, 化痰止咳。用于痰火阻肺, 咳痰黄稠或痰中带血, 胸胁胀痛, 以及火热灼肺, 痰阻气道所致咳嗽	降低血清中IL-2、IL-6、TNF-α、PCT水平; 提高机体溶菌酶及淋巴细胞亚群数量, 增强机体免疫功能	[76]
蛇胆川贝液	蛇胆汁、平贝母	祛风止咳, 除痰散结。用于肺热咳嗽, 痰多, 气喘, 胸闷, 咳痰不爽或久咳不止	降低IL-6含量、CRP水平与ESR、白细胞含量, 改善痰热型咳嗽炎性指标	[77]
治咳川贝枇杷滴丸	枇杷叶、平贝母、桔梗、水半夏、薄荷脑	宣肺降气, 清热化痰。用于痰热郁肺所致咳嗽, 症见咳嗽、咯痰、咽干、咽痛, 发热, 全身不适	抑制TNF-α、IL-6、NF-κB, 进而抑制炎症反应	[78]
百咳宁片	白果(去壳)、青黛、平贝母	清热化痰, 止咳定喘。用于小儿百日咳	辅助治疗NIP, 降低hs-CRP、PCT水平, 抑制炎症反应, 提高免疫功能	[79]
小儿肺热平胶囊	人工牛黄、平贝母、牛胆粉、黄芩、黄连、柴胡、羚羊角、麝香、珍珠(制)、地龙、朱砂、冰片、射干、北寒水石、新疆紫草、拳参、甘草	清热化痰，止咳平喘，镇惊开窍，用于小儿痰热蕴肺引起的喘嗽、壮热烦渴、吐黄稠痰、神昏抽搐	调节机体的免疫功能和抑制病原体的生长繁殖，抗菌消炎，增强白细胞吞噬能力	[80]
小儿清热化痰栓	牛黄、水牛角、忍冬藤、连翘、大黄、黄芩苷、石膏、青礞石(煅)、平贝母、淡竹叶、甘草	清热解毒, 化痰止咳。用于痰热内盛, 肺气下降引起的咳嗽喘息, 痰黄黏稠, 便干溲赤, 高热惊抽等	调控炎症介质, 起到抗炎作用	[81]
复方贝母散	平贝母、麻黄、甘草、炒苦杏仁、炙百部、化橘红、石膏和硼砂	清热化痰, 止咳平喘。用于肺热咳嗽, 喘息	明显改善糖代谢, 止痛效果较好	[82]
九味平凡母散	平贝母、石膏、红花、丁香、远志、北沙参、查干泵嘎、白花龙胆花、葡萄干	润燥化痰，清润宣化并用, 化痰又不伤津。在镇咳、祛痰、降压的同时具有一定的抗菌效果。用于热症咳嗽如风热、燥热、肺火咳嗽。	抑制LSP引起的炎症反应, 降低促炎因子的表达	[83]
七味贝母散	平贝母、石膏、北沙参、查干泵嘎、麝香、黑云香、草乌芽	清热润肺，化痰止咳，增强呼吸道粘膜分泌，稀释痰液以利排出。用于热嗽及痰喘，诸般咳嗽及痰证	降低循环血液中促炎因子水平	[83]

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