中国药学杂志

序号	化合物名称	分子式	相对分子质量
Terpene lactones
1	Bilobalide	C₁₅H₁₈O₈	326
2	Ginkgolide A	C₂₀H₂₄O₉	408
3	Ginkgolide B	C₂₀H₂₄O₁₀	424
4	Ginkgolide C	C₂₀H₂₄O₁₁	440
5	Ginkgolide J	C₂₀H₂₄O₁₀	424
6	Ginkgolide K	C₂₀H₂₂O₉	406
7	Ginkgolide L	C₂₀H₂₂O₈	390
Flavonol glycosides and their aglycones
8	Quercetin 3-(6-cglc)-glc-(1-2)-rhamnoside	C₄₂H₄₆O₂₃	919
9	7-Glc-quercetin 3-(6-cglc)-(1-2)-rhamnoside	C₄₂H₄₆O₂₃	919
10	Quercetin 3-(2,6-dirha)-glucoside	C₃₃H₄₀O₂₀	757
11	Quercetin 3-(6-cglc)-(1-2)-rhamnoside	C₃₆H₃₆O₁₈	757
12	Quercetin 3-rha-(1-6)-glucoside (rutin)	C₂₇H₃₀O₁₆	611
13	Quercetin 3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₆	611
14	Quercetin 3-glucoside	C₂₁H₂₀O₁₂	464
15	Quercetin 3-rhamnoside	C₂₁H₂₀O₁₁	448
16	Quercetin	C₁₅H₁₀O₇	302
17	Kaempferol 3-(6-cglc)-glc-(1-2)-rhamnoside	C₄₂H₄₆O₂₂	903
18	7-Glc-kaempferol 3-(6-cglc)-(1-2)-rhamnoside	C₄₂H₄₆O₂₂	903
19	Kaempferol 3-(2,6-dirha)-glucoside	C₃₃H₄₀O₁₉	741
20	Kaempferol 3-(6-cglc)-(1-2)-rhamnoside	C₃₆H₃₆O₁₇	741
21	Kaempferol 3-rha-(1-6)-glucoside	C₂₇H₃₀O₁₅	595
22	Kaempferol 3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₅	595
23	Kaempferol 3-glucoside	C₂₁H₂₀O₁₁	448
24	Kaempferol 7-glucoside	C₂₁H₂₀O₁₁	448
25	Kaempferol 3-rhamnoside	C₂₁H₂₀O₁₀	432
26	Kaempferol	C₁₅H₁₀O₆	286
27	Isorhamnetin 3-(2,6-dirha)-glucoside	C₃₄H₄₂O₂₀	771
28	Isorhamnetin 3-(6-cglc)-(1-2)-rhamnoside	C₃₄H₄₂O₂₀	771
29	Isorhamnetin 3-rha-(1-6)-glucoside	C₂₈H₃₂O₁₆	625
30	Isorhamnetin 3-glc-(1-2)-rhamnoside	C₂₈H₃₂O₁₆	625
31	Isorhamnetin 3-glucoside	C₂₂H₂₂O₁₂	478
32	Isorhamnetin	C₁₆H₁₂O₇	316
33	Myricetin 3-rha-(1-6)-glucoside	C₂₇H₃₀O₁₇	627
34	Myricetin-3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₇	627
35	Myricetin 3-glucoside	C₂₁H₂₀O₁₃	480
36	Myricetin 3-rhamnoside	C₂₁H₂₀O₁₂	464
37	Myricetin	C₁₅H₁₀O₈	318
38	Laricitrin 3-rha-(1-6)-glucoside	C₂₈H₃₂O₁₇	641
39	Laricitrin 3-glucoside	C₂₂H₂₂O₁₃	494
40	Laricitrin	C₁₆H₁₂O₈	332
41	Syringetin 3-rha-(1-6)-glucoside	C₂₉H₃₄O₁₇	655
42	Syringetin 3-glc-(1-2)-rhamnoside	C₂₉H₃₄O₁₇	655
43	Syringetin	C₁₇H₁₄O₈	346
44	Tamarixetin	C₁₆H₁₂O₇	316
Flavone glycosides and their aglycones
45	Apigenin 7-glucoside	C₂₁H₂₀O₁₀	432
46	Apigenin	C₁₅H₁₀O₅	270
47	Luteolin 3'-glucoside	C₂₁H₂₀O₁₁	448
48	Luteolin	C₁₅H₁₀O₆	286
49	Acacetin	C₁₆H₁₂O₅	284
Isoflavone
50	Genistein	C₁₅H₁₀O₅	270
Biflavones
51	Amentoflavone	C₃₀H₁₈O₁₀	538
52	Bilobetin	C₃₁H₂₀O₁₀	552
53	Isoginkgetin	C₃₂H₂₂O₁₀	567
54	Ginkgetin	C₃₂H₂₂O₁₀	567
55	Sciadopitysin	C₃₃H₂₄O₁₀	581
56	Ginkgetin 7″-glucoside	C₃₈H₃₂O₁₅	729
57	Isoginkgetin 7-glucoside	C₃₈H₃₂O₁₅	729
58	Sequoiaflavone	C₃₁H₂₀O₁₀	551
Flavanols
59	(-)-Catechin	C₁₅H₁₄O₆	290
60	(-)-Epicatechin	C₁₅H₁₄O₆	290
61	(-)-Gallocatechin	C₁₅H₁₄O₇	306
62	(-)-Epigallocatechin	C₁₅H₁₄O₇	306
Organic acids
63	Vanillic acid	C₈H₈O₄	168
64	(+)-Glucaric acid	C₆H₁₀O₈	210
65	p-Hydroxybenzoic acid	C₇H₆O₃	138
66	Quinic acid	C₇H₁₂O₆	192
67	Shikimic acid	C₇H₁₀O₅	174
68	6-Hydroxykynurenic acid	C₁₀H₇NO₄	205
69	Protocatechuic acid	C₇H₆O₄	154
70	Caffeic acid	C₉H₈O₄	180
71	p-Coumaric acid	C₉H₈O₃	164
72	Ferulic acid	C₁₀H₁₀O₄	194
73	Chlorogenic acid	C₁₆H₁₈O₉	354

序号	化合物名称	分子式	相对分子质量
Terpene lactones
1	Bilobalide	C₁₅H₁₈O₈	326
2	Ginkgolide A	C₂₀H₂₄O₉	408
3	Ginkgolide B	C₂₀H₂₄O₁₀	424
4	Ginkgolide C	C₂₀H₂₄O₁₁	440
5	Ginkgolide J	C₂₀H₂₄O₁₀	424
6	Ginkgolide K	C₂₀H₂₂O₉	406
7	Ginkgolide L	C₂₀H₂₂O₈	390
Flavonol glycosides and their aglycones
8	Quercetin 3-(6-cglc)-glc-(1-2)-rhamnoside	C₄₂H₄₆O₂₃	919
9	7-Glc-quercetin 3-(6-cglc)-(1-2)-rhamnoside	C₄₂H₄₆O₂₃	919
10	Quercetin 3-(2,6-dirha)-glucoside	C₃₃H₄₀O₂₀	757
11	Quercetin 3-(6-cglc)-(1-2)-rhamnoside	C₃₆H₃₆O₁₈	757
12	Quercetin 3-rha-(1-6)-glucoside (rutin)	C₂₇H₃₀O₁₆	611
13	Quercetin 3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₆	611
14	Quercetin 3-glucoside	C₂₁H₂₀O₁₂	464
15	Quercetin 3-rhamnoside	C₂₁H₂₀O₁₁	448
16	Quercetin	C₁₅H₁₀O₇	302
17	Kaempferol 3-(6-cglc)-glc-(1-2)-rhamnoside	C₄₂H₄₆O₂₂	903
18	7-Glc-kaempferol 3-(6-cglc)-(1-2)-rhamnoside	C₄₂H₄₆O₂₂	903
19	Kaempferol 3-(2,6-dirha)-glucoside	C₃₃H₄₀O₁₉	741
20	Kaempferol 3-(6-cglc)-(1-2)-rhamnoside	C₃₆H₃₆O₁₇	741
21	Kaempferol 3-rha-(1-6)-glucoside	C₂₇H₃₀O₁₅	595
22	Kaempferol 3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₅	595
23	Kaempferol 3-glucoside	C₂₁H₂₀O₁₁	448
24	Kaempferol 7-glucoside	C₂₁H₂₀O₁₁	448
25	Kaempferol 3-rhamnoside	C₂₁H₂₀O₁₀	432
26	Kaempferol	C₁₅H₁₀O₆	286
27	Isorhamnetin 3-(2,6-dirha)-glucoside	C₃₄H₄₂O₂₀	771
28	Isorhamnetin 3-(6-cglc)-(1-2)-rhamnoside	C₃₄H₄₂O₂₀	771
29	Isorhamnetin 3-rha-(1-6)-glucoside	C₂₈H₃₂O₁₆	625
30	Isorhamnetin 3-glc-(1-2)-rhamnoside	C₂₈H₃₂O₁₆	625
31	Isorhamnetin 3-glucoside	C₂₂H₂₂O₁₂	478
32	Isorhamnetin	C₁₆H₁₂O₇	316
33	Myricetin 3-rha-(1-6)-glucoside	C₂₇H₃₀O₁₇	627
34	Myricetin-3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₇	627
35	Myricetin 3-glucoside	C₂₁H₂₀O₁₃	480
36	Myricetin 3-rhamnoside	C₂₁H₂₀O₁₂	464
37	Myricetin	C₁₅H₁₀O₈	318
38	Laricitrin 3-rha-(1-6)-glucoside	C₂₈H₃₂O₁₇	641
39	Laricitrin 3-glucoside	C₂₂H₂₂O₁₃	494
40	Laricitrin	C₁₆H₁₂O₈	332
41	Syringetin 3-rha-(1-6)-glucoside	C₂₉H₃₄O₁₇	655
42	Syringetin 3-glc-(1-2)-rhamnoside	C₂₉H₃₄O₁₇	655
43	Syringetin	C₁₇H₁₄O₈	346
44	Tamarixetin	C₁₆H₁₂O₇	316
Flavone glycosides and their aglycones
45	Apigenin 7-glucoside	C₂₁H₂₀O₁₀	432
46	Apigenin	C₁₅H₁₀O₅	270
47	Luteolin 3'-glucoside	C₂₁H₂₀O₁₁	448
48	Luteolin	C₁₅H₁₀O₆	286
49	Acacetin	C₁₆H₁₂O₅	284
Isoflavone
50	Genistein	C₁₅H₁₀O₅	270
Biflavones
51	Amentoflavone	C₃₀H₁₈O₁₀	538
52	Bilobetin	C₃₁H₂₀O₁₀	552
53	Isoginkgetin	C₃₂H₂₂O₁₀	567
54	Ginkgetin	C₃₂H₂₂O₁₀	567
55	Sciadopitysin	C₃₃H₂₄O₁₀	581
56	Ginkgetin 7″-glucoside	C₃₈H₃₂O₁₅	729
57	Isoginkgetin 7-glucoside	C₃₈H₃₂O₁₅	729
58	Sequoiaflavone	C₃₁H₂₀O₁₀	551
Flavanols
59	(-)-Catechin	C₁₅H₁₄O₆	290
60	(-)-Epicatechin	C₁₅H₁₄O₆	290
61	(-)-Gallocatechin	C₁₅H₁₄O₇	306
62	(-)-Epigallocatechin	C₁₅H₁₄O₇	306
Organic acids
63	Vanillic acid	C₈H₈O₄	168
64	(+)-Glucaric acid	C₆H₁₀O₈	210
65	p-Hydroxybenzoic acid	C₇H₆O₃	138
66	Quinic acid	C₇H₁₂O₆	192
67	Shikimic acid	C₇H₁₀O₅	174
68	6-Hydroxykynurenic acid	C₁₀H₇NO₄	205
69	Protocatechuic acid	C₇H₆O₄	154
70	Caffeic acid	C₉H₈O₄	180
71	p-Coumaric acid	C₉H₈O₃	164
72	Ferulic acid	C₁₀H₁₀O₄	194
73	Chlorogenic acid	C₁₆H₁₈O₉	354

银杏酮酯治疗血管相关性疾病的物质基础及作用机制研究进展

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李星源 ¹^,² , 刘爱军 ¹^,²^,^*

中国药学杂志 | 综述 2024,59(12): 1074-1081

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中国药学杂志 | 综述 2024, 59(12): 1074-1081

银杏酮酯治疗血管相关性疾病的物质基础及作用机制研究进展

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李星源¹^,², 刘爱军¹^,²^,^*

作者信息

¹ 山东中医药大学药学院, 济南 250355

² 上海中医药大学附属岳阳中西医结合医院药学研究室, 上海 200437

李星源,男,硕士研究生研究方向:心脑血管药理学

通讯作者:

*刘爱军,男,博士,研究员研究方向:心脑血管药理学 Tel:(021)65161782-3123

Chemical Constitution and Pharmacological Mechanism of Ginkgo biloba Extract 50 in the Treatment of Vascular Related Diseases

Xingyuan LI¹^,², Aijun LIU¹^,²^,^*

Affiliations

¹ School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China

² Department of Pharmacy Research, Yueyang Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China

出版时间: 2024-06-22 doi: 10.11669/cpj.2024.12.002

文章导航

摘要

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银杏用于治疗瘀血阻络、胸痹心痛、中风偏瘫等病症。银杏酮酯是我国使用“双重吸附、双重去除”等技术自主研发出的新型银杏叶提取物,其提高了有效成分银杏总黄酮和银杏内酯的稳定性,降低了毒性成分银杏酸的含量。银杏酮酯含有银杏总黄酮和萜内酯等化学成分,具有抗炎、抗氧化应激、抗血小板聚集等药理作用,在冠心病心绞痛、脑卒中、血管性痴呆等血管相关性疾病治疗上具有重要价值。笔者对银杏酮酯的物质基础、临床应用及作用机制三方面研究进行综述,重点讨论其在作用机制方面的研究进展,以期为银杏酮酯在血管相关性疾病研究提供参考。

关键词

银杏酮酯 / 银杏总黄酮 / 萜内酯 / 血管相关性疾病 / 药理作用机制

Abstract

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Ginkgo biloba has been widely used to treat diseases such as blood stasis blocking collaterals, chest pain, stroke, and hemiplegia. Ginkgo biloba extract 50 (GBE50) is the fifth generation of Ginkgo biloba extract (GBE). The chemical components of GBE50 include total flavonoids and terpene lactones. GBE50 shows multiple pharmacological effects such as anti-inflammatory, antioxidant stress, and antiplatelet aggregation. In clinic, it has been widely used in vascular-related diseases such as coronary heart disease, angina pectoris, stroke, and vascular dementia. The authors review the studies on the material basis, clinical application, and mechanism of GBE50, and mainly focus on the research progress in pharmacological mechanism. These might provide a fresh perspective and idea for research on GBE50 in the treatment of vascular-related diseases.

Key words

Ginkgo biloba extract 50 / Ginkgo total flavone / terpene lactone / vascular related diseases / pharmacological mechanism

引用本文

李星源, 刘爱军. 银杏酮酯治疗血管相关性疾病的物质基础及作用机制研究进展. 中国药学杂志, 2024 , 59 (12) : 1074 -1081 . DOI: 10.11669/cpj.2024.12.002

Xingyuan LI, Aijun LIU. Chemical Constitution and Pharmacological Mechanism of Ginkgo biloba Extract 50 in the Treatment of Vascular Related Diseases[J]. Chinese Pharmaceutical Journal, 2024 , 59 (12) : 1074 -1081 . DOI: 10.11669/cpj.2024.12.002

正文

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银杏(Ginkgo biloba L.)归属于银杏科、银杏属,为中生代孑遗的稀有物种,目前为我国特产,有“活化石”之称。作为中药,常以其叶和种子入药。2020年版《中国药典》描述,银杏叶味甘、苦、涩、平,归心、肺经。有活血化瘀、通络止痛、敛肺平喘、化浊降脂之功效,临床主用于对瘀血阻络、胸痹心痛、中风偏瘫和肺虚咳喘等疾病的治疗^[1]。在血管相关性疾病治疗方面,取得了较好的临床疗效。

银杏酮酯(Ginkgo biloba extract 50, GBE50)是将银杏叶经过“双重吸附、双重去除”等工艺提取是我国自主开发研制的第五代新型银杏叶提取物,是银杏叶提取物的标准化产品。药物质量标准:①总黄酮醇苷含量为24.0%~35.0%;同时建立紫外-可见分光光度(UV)法测定银杏总黄酮,规定其含量为44.0%~55.0%;②规定其萜类内酯(银杏内酯A、B、C和白果内酯)含量在6.0%~12.0%之间;③毒性成分银杏酸含量≤5 mg·kg^-1;④建立指纹图谱检测指标,规定其相似度不得低于90.0%^[2]。严格的标准,使得GBE50质量进一步稳定可靠。同时,随着天然药物化学、药理学等学科的发展,该提取物展现出较好的科研及药用开发价值,在血管性疾病中具有重要的临床应用价值。笔者对相关的文献进行综合分析,同时对GBE50的化学成分和药理作用进行归纳总结。

1 物质基础

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采用UPLC-Q-TOF/MS等技术对GBE50进行鉴定,将文献与对照品相比,共得出73 个化学成分,约占GBE50的75.6%,共可分为四类:银杏总黄酮(黄酮醇苷及其苷元、黄酮苷及其苷元、异黄酮和双黄酮)、萜内酯(银杏内酯A、B、C和白果内酯)、黄烷醇和有机酸^[3-4](表1)。这些化学成分相互协同作用,是GBE50的药理药效作用基础。

1.1 银杏总黄酮

银杏总黄酮化合物具有广泛的药理活性,其中最为显著的是其抗氧化性。其主要包括的槲皮素、杨梅素、山柰酚和异鼠黄素等成分,是多酚中的主要抗氧化剂。黄酮类成分的主要抗氧化特性表现为清除细胞内活性氧(ROS),增加抗氧化蛋白如超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平。同时,由于其酚类结构,也可作为重金属螯合剂,螯合促氧化过渡金属离子,同样产生抗氧化性^[5-7]。槲皮素和杨梅素是两种类黄酮结构,能有效抑制叔丁基过氧化氢氧化^[8]。抗炎是银杏总黄酮另一主要药理活性,通过下调白介素-1β(IL-1β)、白介素-6(IL-6)和肿瘤坏死因子(TNF)-α等炎症因子的表达^[9],从而发挥抗炎作用。

1.2 萜内酯

GBE50主要包含有银杏内酯A、B、C和白果内酯。萜内酯已被研究证实可作为竞争性血小板活化因子(PAF)的天然拮抗剂,使PAF无法参与加速血小板聚集、血栓形成等病理过程^[10],达到改善血液流变学,缓解动脉粥样硬化,抑制血栓的形成。同时萜内酯还具有抗炎^[11]、抗氧化^[12]和抗凋亡^[13]等药理活性,对于改善脑缺血、扩张冠状动脉、保护神经元^[14-15]起到安全、有效的预防及治疗作用。

1.3 黄烷醇

黄烷醇是常见的天然植物多酚类化合物,具有较好的抗氧化活性^[16]。在GBE50中含有的儿茶素、表儿茶素、没食子儿茶素和表没食子儿茶素黄烷醇类化合物,其通过清除ROS、螯合金属离子,同时激活氧化酶、抑制亲氧化酶,产生Ⅱ期解毒酶和抗氧化酶,从而干预氧化应激进程^[17]。如,Aron等^[18]发现二价过渡金属被黄烷-3-醇结合,减少阳离子的含量,从而起到抗氧化作用。Bernatonien等^[19]发现儿茶素的酚羟基可与ROS以及活性氮发生终止反应,干预新自由基的产生,同样产生了抗氧化作用。

1.4 有机酸

有机酸是广泛存在的一种含有羧基的酸性有机化合物。GBE50中含有的阿魏酸、咖啡酸、香草酸和莽草酸等多种有机酸类成分也具有抗氧化活性。Guan等^[20]发现,阿魏酸和咖啡酸对DPPH·和ABTS.⁺自由基具有良好的清除作用,同时多种有机酸类成分的协同作用使抗氧化活性增强。

2 临床应用

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血管相关性疾病主要包括有心血管和脑血管等疾病,该类疾病严重危害患者的身体健康,发病率与致死率高居不下,是人类死亡的主要原因^[21]。心血管疾病是一种与心脏或血管密切相关的疾病,也称为循环系统疾病,主要包括高冠心病心绞痛、心律失常等^[22]。而脑血管疾病^[23]则是由凝血机制、血液黏度等血液流变学异常导致的脑血管闭塞、破裂,血管壁损伤或通透性改变而引发的脑功能障碍性疾病,主要包括缺血性脑白质病变、脑卒中和血管性痴呆等。

GBE50可制备成多种剂型,包括银杏酮酯片、颗粒、胶囊、滴丸和分散片等,以满足临床需求。其通过抗血小板聚集、抗炎和抗氧化应激等作用机制,起到活血化瘀、保护脑功能、改善心肌循环、预防血栓形成和促进溶栓等药理作用,被广泛用于血管相关性疾病预防和治疗,疗效很好。

2.1 防治心血管疾病

2.1.1 冠心病心绞痛

冠状动脉粥样硬化性心脏病,简称冠心病。是由冠状动脉粥样硬化引起的管腔狭窄或闭塞,导致心肌缺血、缺氧或坏死而引发的缺血性心脏病^[24]。心绞痛通常是由冠状动脉供血不足所致,是冠心病最常见、最重要的临床病症,可分为稳定型心绞痛和不稳定型心绞痛。

稳定型心绞痛:稳定型心绞痛(stable angina pectoris, SAP)发生在冠状动脉固定粥样硬化性狭窄的情况下,在达到运动负荷后常出现此临床症状,严重干扰患者日常生活的质量^[25-26]。目前对SAP的防治主要以硝酸酯类、阿司匹林等药物为主要治疗手段,但因副作用、耐药性等问题使药物的疗效大打折扣^[27]。双盲、双模拟实验研究发现,患者在除接受基础治疗外,口服银杏酮酯滴丸加阳性药灯盏花素片模拟剂(一天3次,每次40 mg)治疗8 周后,临床指标发生明显改变。其中医证候积分、硝酸甘油片使用量和试验组单项症状如胸闷、胸痛和心悸不宁等积分显著降低,西雅图心绞痛量表评分显著增加,并且临床疗效优于阳性药灯盏花素片加银杏酮酯滴丸模拟剂的对照组,差异具有统计学意义^[28]。同时,银杏酮酯滴丸联合中药滋阴益气补肾汤^[29-30],或是西药替格瑞洛片以及曲美他嗪等^[31-33],均对稳定型心绞痛具有较好的疗效。综上得知,银杏酮酯滴丸单用或者联合用药均发挥出稳定有效的治疗作用,缓解了患者心绞痛的症状和严重程度。

不稳定型心绞痛:不稳定型心绞痛(unstable angina,UA)是介于急性心肌梗死和稳定型心绞痛之间的临床综合征,具有发展为心肌梗死的“潜力”,并随时会诱导猝死,属于急性心脏事件。研究发现,患者在服用阿司匹林、酒石酸美托洛尔等西药的基础上,同时口服银杏酮酯滴丸(一天3 次,每次8 粒)治疗后,心绞痛的发作持续时间、次数以及发作时硝酸甘油用量都显著降低,与西药单用组差异显著。同时高密度脂蛋白(HDL)水平显著升高,甘油三酯(TG)、低密度脂蛋白(LDL)以及血清超敏C反应蛋白(hs-CRP)水平显著降低^[34]。经过治疗,患者的临床症状和体内血脂水平均得到改善。

2.1.2 心律失常

心律失常可分为室早、室速和室颤等快速性心律失常,以及窦停、房室传导阻滞和束支传导阻滞等缓慢性心律失常。其会诱导循环系统产生障碍,如心输出量下降、动脉血压降低,甚至心源性猝死^[35]。有研究使用乌头碱和硅巴因2种药物诱导大鼠心律失常,随后静脉注射不同剂量的GBE50(8、16、32 mg·kg^-1)进行治疗,同时使用盐酸地尔硫

和奎尼丁作为对照阳性药。结果显示GBE50在一定的剂量范围内,能够显著性提高乌头碱和硅巴因致使大鼠早搏(VP)、室速(VT)、室颤(VF)和心跳停搏(CA)的造模剂量,产生抗心律失常作用^[36]。在细胞水平上,研究发现乌头碱能使心肌细胞的钠通道开放周期延长,促进Na⁺向细胞内渗透^[37],同时增加了I_Ca,L离子流^[38]。导致细胞内钙超载,从而引起延迟后除极(DAD),同时Na⁺增加导致细胞持续的去极化,诱发触发活动(TA)的产生,致使心律失常的产生^[36]。使用膜片钳技术记录大鼠心肌细胞膜通道电流的变化,发现GBE50(25 mg·L^-1)可减弱乌头碱模型组I_Na和I_Ca,L的向内电流,抑制钙超载现象,减少了DAD和TA的发生率^[39],综上得知,GBE50可能通过抑制一系列异常的电活动从而发挥抗心律失常作用。

2.2 防治脑血管疾病

2.2.1 缺血性脑白质病变(WMLs)

WMLs是由大脑低灌注及慢性缺血而诱发的脑小血管疾病,常见于神经系统疾病患者及部分老年患者中^[40]。WMLs恶化后最终转化为卒中和痴呆^[41]。缺血是WMLs的主要病因之一,中医学认为“血瘀”是其关键病因^[42]。研究中,患者在使用阿司匹林、胞磷胆碱钠胶囊等西药治疗的基础上,口服银杏酮酯滴丸(1 d 3次,每次40 mg),治疗3 个月后,患者的临床评分如中医证候评分、美国国立卫生研究院卒中量表(NIHSS)评分显著降低,蒙特利尔认知量表(MoCA)、简易智力状况检查量表(MMSE)评分显著升高,提示患者的症状得到改善。血清神经损伤标志物如S100β蛋白(S100β)、β淀粉样蛋白1-40(Aβ_1-40)水平显著降低,脑源性神经生长因子(BDNF)、髓鞘碱性蛋白(MBP)、β淀粉样蛋白1-42(Aβ_1-42)水平显著升高。血清炎症因子hs-CRP、TNF-α和IL-6水平显著降低。氧化应激指标血清丙二醛(MDA)水平显著降低,抗氧化应激指标SOD水平显著升高^[43]。银杏酮酯滴丸与西药联用对缺血性WMLs产生抗炎、抗氧化应激等药理作用,可用于早期干预治疗。患者的脑功能得到了改善,卒中和痴呆的发生率也有所降低,总体治疗有效率显著提高。

2.2.2 高同型半胱氨酸血症(HHcy)

HHcy的患者体内产生大量同型半胱氨酸(Hcy),而Hcy是近国内外研究中发现除高血压、糖尿病和高脂血症等另一诱导脑血管疾病发生的危险因子^[44],同时也提升了脑卒中的患病率^[45-46]。在临床试验中,患者服用治疗药物叶酸和维生素B的基础上,口服银杏酮酯滴丸(一天3次,每次5粒)治疗30 d后。机体中慢性炎症因子hs-CRP、白细胞计数(WBC)、细胞间黏附分子-1(ICAM-1)及血管细胞间黏附分子-1(VCAM-1)的水平都显著降低,同时抗氧化应激指标SOD水平显著升高。综合分析,银杏酮酯滴丸联合用药治疗降低了Hcy浓度,同时抑制了机体炎症和氧化应激反应,整体疗效优于常规治疗^[47]。

2.2.3 脑卒中

脑卒中是一种发病率和致死率极高的脑血管疾病。其中缺血性脑卒中约占全部卒中的70%^[48]。由大脑内血液流变学异常引起,致使脑组织出现大面积缺血缺氧性坏死,进而引发神经功能受损,对患者的生活造成严重影响^[49-50]。研究发现,患者在接受常规治疗如抗血小板和抗凝等的基础上,口服银杏酮酯分散片(1 d 3次,每次0.15 g)治疗14 d后。患者神经功能缺损评分NIHSS显著降低、日常生活活动能力(BI)评分显著升高。血清IL-6、白介素-8(IL-8)、TNF-α等炎症因子水平显著降低。血脂中TG、总胆固醇(TC)和LDL水平显著降低,HDL水平显著升高,与常规治疗组产生统计学差异^[51-53]。整体来看,银杏酮酯分散片联合治疗,减少了患者的炎症损伤,改善机体血液流变学性能,降低脑卒中的发病率及对患者神经功能的损害,改善患者日常生活能力及认知水平。

2.2.4 血管性痴呆(vascular dementia,VD)

VD是一种学习、记忆和认知能力逐渐下降的脑血管和神经认知性障碍疾病。是由脑循环功能障碍导致脑部发生低灌注损伤而产生,是最常见的痴呆形式之一^[54-55]。VD的发生多与脑血流灌注、神经功能受损而引起的氧化应激反应等机制有关,同时对脑部神经元功能造成了损害^[56]。经临床研究发现,患者除使用西药多奈哌齐外,口服银杏酮酯滴丸(一天3次,每次40 mg)治疗3 个月。机体中氧化应激指标MDA、MBP等水平显著降低,抗氧化应激指标SOD、BDNF等水平显著升高。通过对大脑动脉(MCA)、大脑后动脉(PCA)和基底动脉(BA)等血流数据分析,口服银杏酮酯滴丸后患者脑部平均血流速度加快,同时神经功能NIHSS评分降低,MMSE、日常生活活动(ADL)评分升高,上述指标与西药单用产生统计学差异^[57-58]。由此得知,银杏酮酯滴丸与西药联用减轻了VD患者氧化应激反应程度,增加了脑血流灌注,改善了患者认知功能障碍、降低了神经损伤,对VD治疗效果优于单用西药。

2.3 防治高血压

高血压是指以体循环动脉压升高为主要病理特征,同时常伴随有心、脑和肾功能损害。目前西药为治疗高血压的主要手段,但不良反应较多,对肾功能损害较大。经研究发现,患者使用如厄贝沙坦、苯磺酸左旋氨氯地平等常规降压药物的基础上,同时口服银杏酮酯滴丸(每次40 mg,1 d 3次)治疗6个月,患者的舒张压、收缩压均有明显且平稳地降低。同时血液TG、TC和LDL水平降低,HDL水平升高。经肾功能检测,患者体内尿微量蛋白和血清胱抑素水平降低,肾小球滤过率升高,以上数据与西药单用组具有显著差异^[59-61]。相较于单用西药来说,联用银杏酮酯滴丸发挥出更长期、有效、平稳的降压效果,改善了机体血脂水平及肾功能,降低了不良反应如头晕、头痛和水肿的发生率。

3 作用机制

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3.1 抗炎

正常机体中,促炎反应和抗炎反应之间处于一种动态平衡,这种平衡对于维持体内系统的稳定是必要的。当平衡状态被打破,炎性因子随之释放,继而诱发多种疾病^[62]。研究发现,星形胶质细胞与小胶质细胞是神经炎症的主要效应器^[63-64]。当小胶质细胞受到刺激活化,激活核转录因子-κB(NF-κB)、p38丝裂原活化蛋白激酶(p38MAPK)等信号通路,诱导NOD样受体蛋白3(NLRP3)炎症小体的热蛋白结构域(PYD)与凋亡相关微粒蛋白(ASC)结合,产生活化的胱天蛋白酶-1(caspase-1),促进炎性细胞因子IL-1β、IL-6和TNF-α释放,最终导致神经递质的改变以及一系列炎症疾病的发生^[65-66]。通过脂多糖(LPS)诱导小胶质细胞系(BV-2)小胶质细胞活化,给予银杏总黄酮(40、80、120和160 mg·mL^-1)进行24 h的干预。结果显示,银杏总黄酮可调控NF-κB蛋白表达^[9],抑制海马小胶质细胞的激活从而减弱NLRP3的活性,抑制ASC蛋白表达,使成熟的caspase-1及IL-1β、IL-6、TNF-α等促炎因子的表达减少^[67-68],在此通路中发挥出显著的抗炎作用。

3.2 抗氧化应激

氧化应激是细胞内活性氧与抗氧化之间的失衡所造成的一种过激反应,当平衡被打破时引起代谢异常,最终导致DNA损伤和细胞凋亡。GBE50的主要抗氧化特性即清除细胞内ROS,降低MDA水平,增加抗氧化蛋白SOD和谷胱甘肽过氧化物酶(GSH-Px)水平^[57]。β-淀粉样蛋白(Aβ)聚集物是诱导氧化应激状态的关键物质之一,Aβ_25-35诱导细胞线粒体功能障碍,导致ROS释放量增加,进入氧化应激状态,使细胞损伤^[69]。研究使用GBE50(5、10、25、50、100和200 μg·mL^-1)对原代大鼠海马神经元细胞干预24 h,使用Aβ_25-35进行氧化应激造模。结果显示,GBE50抑制细胞色素C(Cyt C)的释放,而Cyt C是启动细胞凋亡级联反应的关键蛋白。GBE50通过抑制Cyt C的释放,从而抑制caspase-3的活化,改善细胞活力,保护线粒体功能的完整性,并降低ROS的生成。解除细胞内氧化应激状态,逆转Aβ诱导产生细胞内ROS的作用。

3.3 抗血小板聚集

血小板聚集往往会导致血液黏滞性、浓稠性、凝固性和聚集性增加,诱导血液流变学异常。而血液黏稠度增高,血流速度减慢将会加速血栓的形成^[71],进而引发冠心病心绞痛、急性脑卒中等一系列心脑血管疾病。研究发现,银杏内酯A、B、K作为PAF的天然拮抗剂,通过竞争性结合PAF受体,激活环磷酸腺苷(cAMP)信号通路,抑制细胞内Ca²⁺的释放,从而抑制PAF诱导家兔血小板聚集现象,发挥出抗血小板聚集作用^[72]。同时银杏内酯B也可以通过抑制凝血酶激活血小板ATP释放,并降低血小板因子4(PF4)和CD40配体(CD40L)的表达,从而降低血小板聚集率^[73]。改善血液流变学,缓解动脉粥样硬化,抑制血栓的形成。并且通过增加脑部的血流量,降低外周血管阻力,改善脑内微循环,降低血液高黏滞性及纤维蛋白水平^[74],对改善血液流变学产生重要作用。

3.4 抗细胞凋亡

细胞凋亡会导致各种神经退行性疾病的发生。Caspase是细胞凋亡信号转导的常见途径,通过Caspase酶系可以对细胞凋亡进行调控,其中caspase-3被称为凋亡的执行者。Bcl-2相关X蛋白(Bax)是细胞线粒体凋亡通路中的促凋亡成员,抑制其表达可增强细胞的抗凋亡作用。在研究中,使用大鼠心肌缺血再灌注模型模拟细胞凋亡,同时在造模前30 min腹腔注射GBE50(100 mg·kg^-1)。结果显示,经GBE50预处理,大鼠心肌细胞凋亡率明显降低,同时Bax和caspase-3蛋白表达量明显降低^[75]。Aβ是导致细胞凋亡的另一因素,Aβ_1-40和Aβ_25-35会加强caspase-3等凋亡微粒活性,同时Aβ_25-35诱导了促凋亡蛋白Bax的表达,抑制了抗凋亡蛋白B细胞淋巴瘤基因-2(Bcl-2)的表达,破坏了机体细胞核和线粒体DNA的完整性,致使脑内皮细胞的严重凋亡^[76]。GBE50在Aβ致海马神经元细胞凋亡实验中,使海马神经元细胞内抗凋亡蛋白Bcl-2的表达增强,促凋亡蛋白Bax的表达减弱,且使两者表达产生差异。同时,抑制线粒体释放caspase-3,减弱Aβ_25-35对细胞活力的影响^[77-78]。由此抑制细胞凋亡,并改善细胞活力,保护神经元。

4 结语与展望

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银杏资源丰富,分布广泛,为我国特有,其显著的药理活性可用于治疗血管相关性疾病。从银杏叶中提取得到的GBE50是我国自主研发药品,经临床实践,证明其单用或联合用药对多种血管相关性疾病具有较好的临床疗效。

目前,相继有73个化合物从GBE50中被检测出,包括银杏总黄酮(黄酮醇苷及其苷元、黄酮苷及其苷元、异黄酮和双黄酮)、萜内酯(银杏内酯A、B、C和白果内酯)和少量的黄烷醇、有机酸类化合物。银杏总黄酮和萜内酯是其主要成分。随着化学成分及其结构的进一步明确,可充分利用现有的网络药理学、现代分子生物学等技术手段,深入开展并明确GBE50多靶点、多系统、多环节的作用机制,为GBE50在血管相关性疾病治疗中的安全合理应用提供科学依据。

基金

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国家自然科学基金项目资助(82273984)
国家重点研发计划项目资助(YS2019YFC170045)
中医学-中成药临床评价平台项目资助(A1-U21-205-902)
上海中医药大学附属岳阳中西医结合医院基金项目资助(2021yygm01)

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2024年第59卷第12期

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doi: 10.11669/cpj.2024.12.002

接收时间：2023-04-28
首发时间：2025-11-25
出版时间：2024-06-22

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收稿日期：2023-04-28

基金

国家自然科学基金项目资助(82273984)

国家重点研发计划项目资助(YS2019YFC170045)

中医学-中成药临床评价平台项目资助(A1-U21-205-902)

上海中医药大学附属岳阳中西医结合医院基金项目资助(2021yygm01)

作者信息

¹ 山东中医药大学药学院, 济南 250355

² 上海中医药大学附属岳阳中西医结合医院药学研究室, 上海 200437

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*刘爱军,男,博士,研究员研究方向:心脑血管药理学 Tel:(021)65161782-3123

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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序号	化合物名称	分子式	相对分子质量
Terpene lactones
1	Bilobalide	C₁₅H₁₈O₈	326
2	Ginkgolide A	C₂₀H₂₄O₉	408
3	Ginkgolide B	C₂₀H₂₄O₁₀	424
4	Ginkgolide C	C₂₀H₂₄O₁₁	440
5	Ginkgolide J	C₂₀H₂₄O₁₀	424
6	Ginkgolide K	C₂₀H₂₂O₉	406
7	Ginkgolide L	C₂₀H₂₂O₈	390
Flavonol glycosides and their aglycones
8	Quercetin 3-(6-cglc)-glc-(1-2)-rhamnoside	C₄₂H₄₆O₂₃	919
9	7-Glc-quercetin 3-(6-cglc)-(1-2)-rhamnoside	C₄₂H₄₆O₂₃	919
10	Quercetin 3-(2,6-dirha)-glucoside	C₃₃H₄₀O₂₀	757
11	Quercetin 3-(6-cglc)-(1-2)-rhamnoside	C₃₆H₃₆O₁₈	757
12	Quercetin 3-rha-(1-6)-glucoside (rutin)	C₂₇H₃₀O₁₆	611
13	Quercetin 3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₆	611
14	Quercetin 3-glucoside	C₂₁H₂₀O₁₂	464
15	Quercetin 3-rhamnoside	C₂₁H₂₀O₁₁	448
16	Quercetin	C₁₅H₁₀O₇	302
17	Kaempferol 3-(6-cglc)-glc-(1-2)-rhamnoside	C₄₂H₄₆O₂₂	903
18	7-Glc-kaempferol 3-(6-cglc)-(1-2)-rhamnoside	C₄₂H₄₆O₂₂	903
19	Kaempferol 3-(2,6-dirha)-glucoside	C₃₃H₄₀O₁₉	741
20	Kaempferol 3-(6-cglc)-(1-2)-rhamnoside	C₃₆H₃₆O₁₇	741
21	Kaempferol 3-rha-(1-6)-glucoside	C₂₇H₃₀O₁₅	595
22	Kaempferol 3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₅	595
23	Kaempferol 3-glucoside	C₂₁H₂₀O₁₁	448
24	Kaempferol 7-glucoside	C₂₁H₂₀O₁₁	448
25	Kaempferol 3-rhamnoside	C₂₁H₂₀O₁₀	432
26	Kaempferol	C₁₅H₁₀O₆	286
27	Isorhamnetin 3-(2,6-dirha)-glucoside	C₃₄H₄₂O₂₀	771
28	Isorhamnetin 3-(6-cglc)-(1-2)-rhamnoside	C₃₄H₄₂O₂₀	771
29	Isorhamnetin 3-rha-(1-6)-glucoside	C₂₈H₃₂O₁₆	625
30	Isorhamnetin 3-glc-(1-2)-rhamnoside	C₂₈H₃₂O₁₆	625
31	Isorhamnetin 3-glucoside	C₂₂H₂₂O₁₂	478
32	Isorhamnetin	C₁₆H₁₂O₇	316
33	Myricetin 3-rha-(1-6)-glucoside	C₂₇H₃₀O₁₇	627
34	Myricetin-3-glc-(1-2)-rhamnoside	C₂₇H₃₀O₁₇	627
35	Myricetin 3-glucoside	C₂₁H₂₀O₁₃	480
36	Myricetin 3-rhamnoside	C₂₁H₂₀O₁₂	464
37	Myricetin	C₁₅H₁₀O₈	318
38	Laricitrin 3-rha-(1-6)-glucoside	C₂₈H₃₂O₁₇	641
39	Laricitrin 3-glucoside	C₂₂H₂₂O₁₃	494
40	Laricitrin	C₁₆H₁₂O₈	332
41	Syringetin 3-rha-(1-6)-glucoside	C₂₉H₃₄O₁₇	655
42	Syringetin 3-glc-(1-2)-rhamnoside	C₂₉H₃₄O₁₇	655
43	Syringetin	C₁₇H₁₄O₈	346
44	Tamarixetin	C₁₆H₁₂O₇	316
Flavone glycosides and their aglycones
45	Apigenin 7-glucoside	C₂₁H₂₀O₁₀	432
46	Apigenin	C₁₅H₁₀O₅	270
47	Luteolin 3'-glucoside	C₂₁H₂₀O₁₁	448
48	Luteolin	C₁₅H₁₀O₆	286
49	Acacetin	C₁₆H₁₂O₅	284
Isoflavone
50	Genistein	C₁₅H₁₀O₅	270
Biflavones
51	Amentoflavone	C₃₀H₁₈O₁₀	538
52	Bilobetin	C₃₁H₂₀O₁₀	552
53	Isoginkgetin	C₃₂H₂₂O₁₀	567
54	Ginkgetin	C₃₂H₂₂O₁₀	567
55	Sciadopitysin	C₃₃H₂₄O₁₀	581
56	Ginkgetin 7″-glucoside	C₃₈H₃₂O₁₅	729
57	Isoginkgetin 7-glucoside	C₃₈H₃₂O₁₅	729
58	Sequoiaflavone	C₃₁H₂₀O₁₀	551
Flavanols
59	(-)-Catechin	C₁₅H₁₄O₆	290
60	(-)-Epicatechin	C₁₅H₁₄O₆	290
61	(-)-Gallocatechin	C₁₅H₁₄O₇	306
62	(-)-Epigallocatechin	C₁₅H₁₄O₇	306
Organic acids
63	Vanillic acid	C₈H₈O₄	168
64	(+)-Glucaric acid	C₆H₁₀O₈	210
65	p-Hydroxybenzoic acid	C₇H₆O₃	138
66	Quinic acid	C₇H₁₂O₆	192
67	Shikimic acid	C₇H₁₀O₅	174
68	6-Hydroxykynurenic acid	C₁₀H₇NO₄	205
69	Protocatechuic acid	C₇H₆O₄	154
70	Caffeic acid	C₉H₈O₄	180
71	p-Coumaric acid	C₉H₈O₃	164
72	Ferulic acid	C₁₀H₁₀O₄	194
73	Chlorogenic acid	C₁₆H₁₈O₉	354

序号

化合物名称

分子式

相对分子质量

Terpene lactones

Bilobalide

C₁₅H₁₈O₈

326

Ginkgolide A

C₂₀H₂₄O₉

408

Ginkgolide B

C₂₀H₂₄O₁₀

424

Ginkgolide C

C₂₀H₂₄O₁₁

440

Ginkgolide J

C₂₀H₂₄O₁₀

424

Ginkgolide K

C₂₀H₂₂O₉

406

Ginkgolide L

C₂₀H₂₂O₈

390

Flavonol glycosides and their aglycones

Quercetin 3-(6-cglc)-glc-(1-2)-rhamnoside

C₄₂H₄₆O₂₃

919

7-Glc-quercetin 3-(6-cglc)-(1-2)-rhamnoside

C₄₂H₄₆O₂₃

919

Quercetin 3-(2,6-dirha)-glucoside

C₃₃H₄₀O₂₀

757

Quercetin 3-(6-cglc)-(1-2)-rhamnoside

C₃₆H₃₆O₁₈

757

Quercetin 3-rha-(1-6)-glucoside (rutin)

C₂₇H₃₀O₁₆

611

Quercetin 3-glc-(1-2)-rhamnoside

C₂₇H₃₀O₁₆

611

Quercetin 3-glucoside

C₂₁H₂₀O₁₂

464

Quercetin 3-rhamnoside

C₂₁H₂₀O₁₁

448

Quercetin

C₁₅H₁₀O₇

302

Kaempferol 3-(6-cglc)-glc-(1-2)-rhamnoside

C₄₂H₄₆O₂₂

903

7-Glc-kaempferol 3-(6-cglc)-(1-2)-rhamnoside

C₄₂H₄₆O₂₂

903

Kaempferol 3-(2,6-dirha)-glucoside

C₃₃H₄₀O₁₉

741

Kaempferol 3-(6-cglc)-(1-2)-rhamnoside

C₃₆H₃₆O₁₇

741

Kaempferol 3-rha-(1-6)-glucoside

C₂₇H₃₀O₁₅

595

Kaempferol 3-glc-(1-2)-rhamnoside

C₂₇H₃₀O₁₅

595

Kaempferol 3-glucoside

C₂₁H₂₀O₁₁

448

Kaempferol 7-glucoside

C₂₁H₂₀O₁₁

448

Kaempferol 3-rhamnoside

C₂₁H₂₀O₁₀

432

Kaempferol

C₁₅H₁₀O₆

286

Isorhamnetin 3-(2,6-dirha)-glucoside

C₃₄H₄₂O₂₀

771

Isorhamnetin 3-(6-cglc)-(1-2)-rhamnoside

C₃₄H₄₂O₂₀

771

Isorhamnetin 3-rha-(1-6)-glucoside

C₂₈H₃₂O₁₆

625

Isorhamnetin 3-glc-(1-2)-rhamnoside

C₂₈H₃₂O₁₆

625

Isorhamnetin 3-glucoside

C₂₂H₂₂O₁₂

478

Isorhamnetin

C₁₆H₁₂O₇

316

Myricetin 3-rha-(1-6)-glucoside

C₂₇H₃₀O₁₇

627

Myricetin-3-glc-(1-2)-rhamnoside

C₂₇H₃₀O₁₇

627

Myricetin 3-glucoside

C₂₁H₂₀O₁₃

480

Myricetin 3-rhamnoside

C₂₁H₂₀O₁₂

464

Myricetin

C₁₅H₁₀O₈

318

Laricitrin 3-rha-(1-6)-glucoside

C₂₈H₃₂O₁₇

641

Laricitrin 3-glucoside

C₂₂H₂₂O₁₃

494

Laricitrin

C₁₆H₁₂O₈

332

Syringetin 3-rha-(1-6)-glucoside

C₂₉H₃₄O₁₇

655

Syringetin 3-glc-(1-2)-rhamnoside

C₂₉H₃₄O₁₇

655

Syringetin

C₁₇H₁₄O₈

346

Tamarixetin

C₁₆H₁₂O₇

316

Flavone glycosides and their aglycones

Apigenin 7-glucoside

C₂₁H₂₀O₁₀

432

Apigenin

C₁₅H₁₀O₅

270

Luteolin 3'-glucoside

C₂₁H₂₀O₁₁

448

Luteolin

C₁₅H₁₀O₆

286

Acacetin

C₁₆H₁₂O₅

284

Isoflavone

Genistein

C₁₅H₁₀O₅

270

Biflavones

Amentoflavone

C₃₀H₁₈O₁₀

538

Bilobetin

C₃₁H₂₀O₁₀

552

Isoginkgetin

C₃₂H₂₂O₁₀

567

Ginkgetin

C₃₂H₂₂O₁₀

567

Sciadopitysin

C₃₃H₂₄O₁₀

581

Ginkgetin 7″-glucoside

C₃₈H₃₂O₁₅

729

Isoginkgetin 7-glucoside

C₃₈H₃₂O₁₅

729

Sequoiaflavone

C₃₁H₂₀O₁₀

551

Flavanols

(-)-Catechin

C₁₅H₁₄O₆

290

(-)-Epicatechin

C₁₅H₁₄O₆

290

(-)-Gallocatechin

C₁₅H₁₄O₇

306

(-)-Epigallocatechin

C₁₅H₁₄O₇

306

Organic acids

Vanillic acid

C₈H₈O₄

168

(+)-Glucaric acid

C₆H₁₀O₈

210

p-Hydroxybenzoic acid

C₇H₆O₃

138

Quinic acid

C₇H₁₂O₆

192

Shikimic acid

C₇H₁₀O₅

174

6-Hydroxykynurenic acid

C₁₀H₇NO₄

205

Protocatechuic acid

C₇H₆O₄

154

Caffeic acid

C₉H₈O₄

180

p-Coumaric acid

C₉H₈O₃

164

Ferulic acid

C₁₀H₁₀O₄

194

Chlorogenic acid

C₁₆H₁₈O₉

354