药学学报

Chinese name	Latin name	Alias	Medicinal part	Distribution
Duan ye jinjier	C. brevifolia	Mu zhu ci	Roots	Gansu, Qinghai, Sichuan, Xizang
Chang du jinjier	C. changduensis Liou f.	Zuomo Xing	Stems, roots	Xizang
Yun nan jinjier	C. franchetiana	-	Flowers	Xizang, Yunnan, Sichuan
Shu jinjier	C. arborescens	-	Entire plant	Shanxi, Shaanxi, Hebei, Shandong, Liaoning, Jilin, Heilongjiang, Inner Mongolia, Xinjiang, Gansu
Zhong jian jinjier	C. intermedia	Shalhazhagna	Entire plant, flowers, seeds, roots	Shanxi, Shaanxi, Ningxia, Inner Mongolia
Gui jian jinjier	C. jubata	Gui jian chou	Entire plant	Liaoning, Hebei, Shaanxi, Shanxi, Inner Mongolia, Qinghai, Gansu, Sichuan, Xinjiang, Ningxia, Xizang
Bai pi jinjier	C. leucophloea	-	Roots	Gansu, Inner Mongolia, Xinjiang
Xiao ye jinjier	C. microphylla	Ullezh Harigana	Roots, seeds	Shanxi, Shaanxi, Inner Mongolia, Xinjiang, Gansu, Ningxia, Shandong, Hebei, Sichuan, Jilin, Liaoning, Heilongjiang, Anhui, Xizang
Kun lun jinjier	C. polourensis	-	Flowers	Xinjiang
Ai jinjier	C. pygmaea	-	Roots	Inner Mongolia, Shanxi
A le tai jinjier	C. altaica	-	Roots	Xinjiang
Er se jinjier	C. bicolor	-	Roots	Xizang, Sichuan, Yunnan
Hong hua jinjier	C. rosea	Jinquehua	Roots	Northeast, Hebei, Inner Mongolia, Shanxi, Shaanxi, Henan, Gansu, Jiangsu, Zhejiang, Anhui, Sichuan
Ci ye jinjier	C. acanthophylla	-	Roots	Xinjiang
Gan qing jinjier	C. tangutica	-	Heartwood	Gansu, Sichuan, Qinghai, Xizang, Inner Mongolia
Jinjier	C. sinica/ C. chamlagu	Jinquegen	Flowers, roots	Hebei, Shandong, Henan, Shanxi, Inner Mongolia, Xinjiang, Shaanxi, Gansu, Hubei, Hunan, Sichuan, Jilin, Liaoning, Heilongjiang
Mao ci jinjier	C. tibetica	Zang jinjier Tebudu Harigana Zuomo Xing	Roots, flowers, heartwood	Gansu, Qinghai, Xinjiang, Ningxia, Inner Mongolia, Sichuan, Xizang
Xia ye jinjier	C. stenophylla	Nariin Harigana	Roots	Hebei, Shanxi, Inner Mongolia, Gansu, Shaanxi, Ningxia
Fen ci jinjier	C. pruinosa	-	Roots	Xinjiang

Chinese name	Latin name	Alias	Medicinal part	Distribution
Duan ye jinjier	C. brevifolia	Mu zhu ci	Roots	Gansu, Qinghai, Sichuan, Xizang
Chang du jinjier	C. changduensis Liou f.	Zuomo Xing	Stems, roots	Xizang
Yun nan jinjier	C. franchetiana	-	Flowers	Xizang, Yunnan, Sichuan
Shu jinjier	C. arborescens	-	Entire plant	Shanxi, Shaanxi, Hebei, Shandong, Liaoning, Jilin, Heilongjiang, Inner Mongolia, Xinjiang, Gansu
Zhong jian jinjier	C. intermedia	Shalhazhagna	Entire plant, flowers, seeds, roots	Shanxi, Shaanxi, Ningxia, Inner Mongolia
Gui jian jinjier	C. jubata	Gui jian chou	Entire plant	Liaoning, Hebei, Shaanxi, Shanxi, Inner Mongolia, Qinghai, Gansu, Sichuan, Xinjiang, Ningxia, Xizang
Bai pi jinjier	C. leucophloea	-	Roots	Gansu, Inner Mongolia, Xinjiang
Xiao ye jinjier	C. microphylla	Ullezh Harigana	Roots, seeds	Shanxi, Shaanxi, Inner Mongolia, Xinjiang, Gansu, Ningxia, Shandong, Hebei, Sichuan, Jilin, Liaoning, Heilongjiang, Anhui, Xizang
Kun lun jinjier	C. polourensis	-	Flowers	Xinjiang
Ai jinjier	C. pygmaea	-	Roots	Inner Mongolia, Shanxi
A le tai jinjier	C. altaica	-	Roots	Xinjiang
Er se jinjier	C. bicolor	-	Roots	Xizang, Sichuan, Yunnan
Hong hua jinjier	C. rosea	Jinquehua	Roots	Northeast, Hebei, Inner Mongolia, Shanxi, Shaanxi, Henan, Gansu, Jiangsu, Zhejiang, Anhui, Sichuan
Ci ye jinjier	C. acanthophylla	-	Roots	Xinjiang
Gan qing jinjier	C. tangutica	-	Heartwood	Gansu, Sichuan, Qinghai, Xizang, Inner Mongolia
Jinjier	C. sinica/ C. chamlagu	Jinquegen	Flowers, roots	Hebei, Shandong, Henan, Shanxi, Inner Mongolia, Xinjiang, Shaanxi, Gansu, Hubei, Hunan, Sichuan, Jilin, Liaoning, Heilongjiang
Mao ci jinjier	C. tibetica	Zang jinjier Tebudu Harigana Zuomo Xing	Roots, flowers, heartwood	Gansu, Qinghai, Xinjiang, Ningxia, Inner Mongolia, Sichuan, Xizang
Xia ye jinjier	C. stenophylla	Nariin Harigana	Roots	Hebei, Shanxi, Inner Mongolia, Gansu, Shaanxi, Ningxia
Fen ci jinjier	C. pruinosa	-	Roots	Xinjiang

Compound	Compound type	Name	Plant source	Medicinal part	Ref.
1	Flavonoids	Butein	C. stenophylla	Roots	[12]
2	3-Methoxylquercetin
3	Luteolin
4	Daidzein	C. microphylla	Roots	[13]
5	3′, 7, 8-Trihydroxy-4′-methoxyisoflavone	C. turfanensis	Roots	[14]
6	Conferin	C. conferta	Roots	[15]
7	Pruinosanone F	C. pruiniosa	Roots	[16]
8	Pruinosanone D
9	Pruinosanone A	[17]
10	Pruinosanones C
11	Stilbenes	(-)-ε-Viniferin	C. stenophylla	Roots	[18]
12	Miyabenol C
13	Carasinol A
14	Carasinol C
15	Piceatannol
16	Kompasinol A
17	Cararosinol D
18	α-Viniferin	C. chamlagu	Roots	[19]
19	Kobophenol A	C. sinica	Roots	[20]
20	Triterpenoids	Caraganin A	C. microphylla	Seeds	[21]
21	Caraganin B
22	Caraganin C
23	Caraganin D
24	Caragana C
25	Caragana D
26	Spiro-cyclohexadienyl naphthalene	Acanthophyllas C	C. acanthophylla	Roots	[22]
27		(+)-Acanthophyllas C
28		(-)-Acanthophyllas C
29		Acanthophyllas D
30		(+)-Acanthophyllas D
31		(-)-Acanthophyllas D
32		1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
33		(6R)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
34		(6S)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
35	Lignin	(+)-Medioresinol-4, 4′-O-β-D-diglucopyranoside	C. microphylla	Roots	[13]
36	Coumarin	Caraganolide A	C. turfanensis	Roots	[14]

Compound	Compound type	Name	Plant source	Medicinal part	Ref.
1	Flavonoids	Butein	C. stenophylla	Roots	[12]
2	3-Methoxylquercetin
3	Luteolin
4	Daidzein	C. microphylla	Roots	[13]
5	3′, 7, 8-Trihydroxy-4′-methoxyisoflavone	C. turfanensis	Roots	[14]
6	Conferin	C. conferta	Roots	[15]
7	Pruinosanone F	C. pruiniosa	Roots	[16]
8	Pruinosanone D
9	Pruinosanone A	[17]
10	Pruinosanones C
11	Stilbenes	(-)-ε-Viniferin	C. stenophylla	Roots	[18]
12	Miyabenol C
13	Carasinol A
14	Carasinol C
15	Piceatannol
16	Kompasinol A
17	Cararosinol D
18	α-Viniferin	C. chamlagu	Roots	[19]
19	Kobophenol A	C. sinica	Roots	[20]
20	Triterpenoids	Caraganin A	C. microphylla	Seeds	[21]
21	Caraganin B
22	Caraganin C
23	Caraganin D
24	Caragana C
25	Caragana D
26	Spiro-cyclohexadienyl naphthalene	Acanthophyllas C	C. acanthophylla	Roots	[22]
27		(+)-Acanthophyllas C
28		(-)-Acanthophyllas C
29		Acanthophyllas D
30		(+)-Acanthophyllas D
31		(-)-Acanthophyllas D
32		1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
33		(6R)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
34		(6S)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
35	Lignin	(+)-Medioresinol-4, 4′-O-β-D-diglucopyranoside	C. microphylla	Roots	[13]
36	Coumarin	Caraganolide A	C. turfanensis	Roots	[14]

Plant	Medicinal part	Induction factor	Cellular model	Action mechanism	Active ingredient	Constitutive relationship	Ref.
C. pruinosa	Roots	LPS	RAW264.7	-	Compounds 7, 8	-	[16]
-	Compounds 9, 10	2-Isopropenyl-2, 3-dihydrofuran molecules play an important role in pharmacological effects	[17]
C. stenophylla	Roots	LPS	RAW264.7	-	Compounds 1-3	-	[12]
C. stenophylla	Roots	LPS	RAW264.7	-	Compounds 11-17	-	[18]
C. sinica	Roots	IFN-γ	RAW264.7	Reduces protein levels of iNOS, attenuates mRNA levels of iNOS, IP-10, MIG, inhibits iNOS gene promoter activity	Compound 18	-	[19, 23]
LPS	J774A.1	Inhibites the expression of NO, IL-1β, IL-6, IKKα/β phosphorylation and NF-κB translocation to the nucleus	Compound 19	-	[20]
C. microphylla	Seed	LPS	RAW264.7	-	Compounds 20-25	-	[21]
C. rosea	Root	LPS	RAW264.7	Anti-inflammatory activity through inhibition of the TLR4/ NF-κB/IRF3 signalling pathway	Identification of eight flavonoids by LC-MS/MS	-	[24]

Plant	Medicinal part	Induction factor	Cellular model	Action mechanism	Active ingredient	Constitutive relationship	Ref.
C. pruinosa	Roots	LPS	RAW264.7	-	Compounds 7, 8	-	[16]
-	Compounds 9, 10	2-Isopropenyl-2, 3-dihydrofuran molecules play an important role in pharmacological effects	[17]
C. stenophylla	Roots	LPS	RAW264.7	-	Compounds 1-3	-	[12]
C. stenophylla	Roots	LPS	RAW264.7	-	Compounds 11-17	-	[18]
C. sinica	Roots	IFN-γ	RAW264.7	Reduces protein levels of iNOS, attenuates mRNA levels of iNOS, IP-10, MIG, inhibits iNOS gene promoter activity	Compound 18	-	[19, 23]
LPS	J774A.1	Inhibites the expression of NO, IL-1β, IL-6, IKKα/β phosphorylation and NF-κB translocation to the nucleus	Compound 19	-	[20]
C. microphylla	Seed	LPS	RAW264.7	-	Compounds 20-25	-	[21]
C. rosea	Root	LPS	RAW264.7	Anti-inflammatory activity through inhibition of the TLR4/ NF-κB/IRF3 signalling pathway	Identification of eight flavonoids by LC-MS/MS	-	[24]

Ingredient type	Plant	Medicinal part	Induction factor	Cellular model	Pharmacological effect	Action mechanism	Ref.
Isoflavones, lignans	C. microphylla	Roots	LPS	BV-2	NO inhibition	—	[13]
Coumarins, isoflavonoids	C. turfanensis	Roots	LPS	BV-2	NO inhibition	—	[14]
Spirocyclohexadienyl naphthalenes	C. acanthophylla	Roots	LPS	BV-2	NO inhibition	—	[22]

Ingredient type	Plant	Medicinal part	Induction factor	Cellular model	Pharmacological effect	Action mechanism	Ref.
Isoflavones, lignans	C. microphylla	Roots	LPS	BV-2	NO inhibition	—	[13]
Coumarins, isoflavonoids	C. turfanensis	Roots	LPS	BV-2	NO inhibition	—	[14]
Spirocyclohexadienyl naphthalenes	C. acanthophylla	Roots	LPS	BV-2	NO inhibition	—	[22]

Plant	Extracts /components	Medicinal part	Induction factors	Animal/cell models/clinical patients	Action mechanism	Ref.
C. microphylla	Ethanol extract	Roots/seeds	Type Ⅱ collagen	SD rats	-	[41]
C. sinica	Ethyl acetate extract	Roots	Fuchs'complete adjuvant	SD rats	Inhibition of NF-κB pathway	[42]
Concrete	Roots	Fuchs' complete adjuvant	SD rats	-	[43]
C. sinica	Aqueous extract	Roots	IL-1β	Rat cartilage cell	Inhibition of MAPKs and NF-κB pathways	[44]
Monosodium iodoacetate	SD rats	-	[44]
Ethyl acetate extract	Roots	Fuchs' complete adjuvant	SD rats	Good ligand-receptor binding activity of core components towards NF-κB	[45]
Ethyl acetate extract	Roots	LPS	RAW264.7	Reduce translocation of NF-κB P65 to the nucleus for negative regulation of NF-κB	[45]
C. tangutica	Ethyl acetate extract	Woody heartwood	Carrageenan	SD rats	-	[46]
C. acanthophylla	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	-	[47]
Above-ground parts	Type Ⅱ collagen	SD rats	-	[48]
Type Ⅱ collagen and Fuchs' complete adjuvant	SD rats	-	[49]
C. pruinosa	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	-	[50]
Wistar rats	-	[51]
C. stenophylla	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	Regulation of tyrosine, glycerophospholipid and galactose metabolism	[52]
Regulation of the NF-κB signalling pathway	[18]
C. arborescens or C. microphylla	Water decoction	Roots		Patients with rheumatoid arthritis	-	[53]
C. conferta	Conferin		Carrageenan	Wistar rats	-	[15]

Plant	Extracts /components	Medicinal part	Induction factors	Animal/cell models/clinical patients	Action mechanism	Ref.
C. microphylla	Ethanol extract	Roots/seeds	Type Ⅱ collagen	SD rats	-	[41]
C. sinica	Ethyl acetate extract	Roots	Fuchs'complete adjuvant	SD rats	Inhibition of NF-κB pathway	[42]
Concrete	Roots	Fuchs' complete adjuvant	SD rats	-	[43]
C. sinica	Aqueous extract	Roots	IL-1β	Rat cartilage cell	Inhibition of MAPKs and NF-κB pathways	[44]
Monosodium iodoacetate	SD rats	-	[44]
Ethyl acetate extract	Roots	Fuchs' complete adjuvant	SD rats	Good ligand-receptor binding activity of core components towards NF-κB	[45]
Ethyl acetate extract	Roots	LPS	RAW264.7	Reduce translocation of NF-κB P65 to the nucleus for negative regulation of NF-κB	[45]
C. tangutica	Ethyl acetate extract	Woody heartwood	Carrageenan	SD rats	-	[46]
C. acanthophylla	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	-	[47]
Above-ground parts	Type Ⅱ collagen	SD rats	-	[48]
Type Ⅱ collagen and Fuchs' complete adjuvant	SD rats	-	[49]
C. pruinosa	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	-	[50]
Wistar rats	-	[51]
C. stenophylla	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	Regulation of tyrosine, glycerophospholipid and galactose metabolism	[52]
Regulation of the NF-κB signalling pathway	[18]
C. arborescens or C. microphylla	Water decoction	Roots		Patients with rheumatoid arthritis	-	[53]
C. conferta	Conferin		Carrageenan	Wistar rats	-	[15]

锦鸡儿属植物抗炎活性成分与抗炎作用和机制研究进展

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马玉梅 ¹^,²^,³ , 罗菊元 ¹ , 陈涛 ¹ , 李洪梅 ¹^,³ , 申诚 ¹ , 王硕 ¹ , 宋志博 ¹^,³ , 李玉林 ¹^,^*

药学学报 | 综述 2025,60(1): 58-71

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药学学报 | 综述 2025, 60(1): 58-71

锦鸡儿属植物抗炎活性成分与抗炎作用和机制研究进展

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马玉梅¹^,²^,³, 罗菊元¹, 陈涛¹, 李洪梅¹^,³, 申诚¹, 王硕¹, 宋志博¹^,³, 李玉林¹^,^*

作者信息

1.中国科学院西北高原生物研究所, 青海西宁 810008

2.青海卫生职业技术学院, 青海西宁 810000

3.中国科学院大学, 北京 100049

通讯作者:

^*李玉林, E-mail: liyulin@nwipb.cas.cn

Progress in the study of anti-inflammatory active components with anti-inflammatory effects and mechanisms in Caragana Fabr.

Yu-mei MA¹^,²^,³, Ju-yuan LUO¹, Tao CHEN¹, Hong-mei LI¹^,³, Cheng SHEN¹, Shuo WANG¹, Zhi-bo SONG¹^,³, Yu-lin LI¹^,^*

Affiliations

1. Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China

2. Qinghai Institute of Health Sciences, Xining 810000, China

3. University of Chinese Academy of Sciences, Beijing 100049, China

出版时间: 2025-01-12 doi: 10.16438/j.0513-4870.2024-0587

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摘要

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锦鸡儿属(Caragana Fabr.) 是豆科荒漠植物, 在传统民族医药中应用广泛, 具有滋阴养血、祛风除湿、清热解毒之功效。锦鸡儿属植物的抗炎作用备受关注, 相关机制研究取得一定进展, 但是目前没有任何文献对该属植物的抗炎成分及抗炎作用进行综述。本文通过对锦鸡儿属活性成分的抗炎作用进行总结, 发现其对体外不同炎症细胞模型有很好的抗炎活性, 且对类风湿性关节炎、结肠炎、复合型肾炎和急性肺损伤等疾病模型均具有较好的改善作用。该属植物活性成分抗炎作用主要包括降低多种促炎因子水平, 涉及到的信号通路主要包括TLR4/NF-κB、TLR4/MAPK、TLR4/NF-κB/IRF3、JAK/STAT-1、ERK/STAT-1等。因此, 该文主要对锦鸡儿属植物及其活性成分的抗炎作用与机制研究进展按疾病种类进行综述, 以期为其抗炎活性的深入研究及相关功能新产品的开发提供参考。

关键词

锦鸡儿属 / 活性成分 / 抗炎作用与机制

Abstract

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The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

Key words

Caragana Fabr. / active component / anti-inflammatory effect and mechanism

引用本文

马玉梅, 罗菊元, 陈涛, 李洪梅, 申诚, 王硕, 宋志博, 李玉林. 锦鸡儿属植物抗炎活性成分与抗炎作用和机制研究进展. 药学学报, 2025 , 60 (1) : 58 -71 . DOI: 10.16438/j.0513-4870.2024-0587

Yu-mei MA, Ju-yuan LUO, Tao CHEN, Hong-mei LI, Cheng SHEN, Shuo WANG, Zhi-bo SONG, Yu-lin LI. Progress in the study of anti-inflammatory active components with anti-inflammatory effects and mechanisms in Caragana Fabr.[J]. Acta Pharmaceutica Sinica, 2025 , 60 (1) : 58 -71 . DOI: 10.16438/j.0513-4870.2024-0587

正文

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锦鸡儿属(Caragana Fabr.) 隶属于豆科(Leguminesae) 蝶形花亚科(Papilionoideae), 能作为蜜源、绿肥、饲料和药用植物, 是一种开发价值极高的生态经济型灌木^{[1, 2]}。关于锦鸡儿属植物的分类学研究最早由Royen于1745年提出, 随后于1763年由Philip Caragana Fabricicus正式建立了Caragana属。目前全世界记录了100多种锦鸡儿属植物, 其中我国产62种、9变种^[3]。

锦鸡儿属植物在中药、蒙药、藏药和维吾尔药等各大传统医药学科中都有应用。《新华本草纲要》^[4]中收录了14种药用锦鸡儿属植物。《中华本草》^[5]记载锦鸡儿属有滋阴养血、祛风除湿、清热解毒之功效。蒙药中使用的小叶锦鸡儿(蒙药名: 乌和日-哈日嘎纳) 用于治疗跌打损伤、挫伤、风湿、关节炎、血管性高血压、气喘症状、白带和其他一些妇科疾病^[6]。藏医中鬼箭锦鸡儿、昌都锦鸡儿和甘青锦鸡儿(藏药名: 佐木相、佐木兴) 等可活血散瘀、排内脏淤血、破血、降压, 用于多血症、高血压病及月经不调; 外用可消毒散肿, 治疖疮痈疽^[7]。维吾尔药中的狭叶锦鸡儿和刺叶锦鸡儿(维药名: 卡拉甘) 等用于治疗关节炎、跌打损伤、咳嗽等疾病^{[8, 9]}。国内药用锦鸡儿属植物见表 1^[10]。

炎症参与机体各种急慢性疾病的发展, 持续的炎症反应是关节炎、炎症性肠病、神经退行性疾病、心血管疾病、代谢综合征、癌症等多种疾病的关键驱动因素, 因此寻找抗炎药物对于防治各类疾病至关重要。锦鸡儿属植物在中药及传统民族药中主要用于治疗炎症相关性疾病, 随着该属植物研究的不断推进, 其抗炎作用备受关注, 抗炎药理活性及机制研究取得了一定进展。但是目前未见文献对该属植物的抗炎成分及抗炎作用与机制进行综述, 此项研究尚属空白。

本文通过归纳总结国内外学者相关的研究报道, 按照体内外抗炎实验以及不同炎症性疾病种类, 对该属不同植物的粗提物和单体成分的抗炎作用与机制研究进行系统归纳分析, 以期为该属植物中的抗炎新成分及新机制的发现提供理论基础, 并为其临床合理应用及相关功能新药开发提供参考。

1 主要活性成分

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锦鸡儿属植物的化学成分较为丰富。研究者们已从锦鸡儿属中鉴定出黄酮类110余种、二苯乙烯类40种、三萜类28种、倍半萜类14种、苯丙素15种、生物碱5种、植物甾醇及其苷类11种; 除此还含有少量其他类化合物, 如挥发油类、糖类、高级长链烷类、脂肪酸类、长链醇等, 该属植物中发现的最主要的化合物类型是黄酮类^{[10, 11]}。目前相关药理活性研究证实, 黄酮类、二苯乙烯类、三萜类、螺环己二烯基萘类、香豆素类、木脂素类化合物被认为是该属植物中的抗炎活性成分。本文通过查阅国内外文献, 汇总了锦鸡儿属植物中的抗炎活性成分, 见表 2^[12-22], 其化学结构见图 1~5。

综上所述, 锦鸡儿属植物中化学成分研究最深入的是锦鸡儿。此外, 中间锦鸡儿、红花锦鸡儿、狭叶锦鸡儿和鬼箭锦鸡儿的化学成分在过去十年中得到了一定阐明。然而, 民族医药中经常使用的其他物种如云南锦鸡儿、短叶锦鸡儿和二色锦鸡儿等药用品种^[10]的化学成分研究远远不够。

锦鸡儿属中具有明确抗炎活性的单体成分有36个, 这些成分均进行了体内或体外抗炎活性研究, 它们分别来自狭叶锦鸡儿、小叶锦鸡儿、粉刺锦鸡儿、吐鲁番锦鸡儿、锦鸡儿和刺叶锦鸡儿。这些化学成分中黄酮类最多, 包括黄酮醇、异黄酮、查尔酮、紫檀素和螺色酮类化合物, 且都是游离黄酮, 并未与糖结合成苷。其次是二苯乙烯类、齐墩果烷型五环三萜苷类和螺环己二烯基萘类化合物, 除此还有少量香豆素和木脂素类。

2 体外抗炎作用与机制

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2.1 抑制脂多糖诱导的巨噬细胞炎症

研究证实锦鸡儿属植物具有抑制脂多糖(lipopolysaccharide, LPS) 诱导的巨噬细胞炎症作用。本文对国内外学者开展的研究进行了汇总, 见表 3^{[12, 16-21, 23, 24]}。除红花锦鸡儿使用甲醇提取物以外, 研究者们分别从粉刺锦鸡儿^{[16, 17]}、狭叶锦鸡儿^{[12, 18]}、锦鸡儿^{[19, 20]}和小叶锦鸡儿^[21]中分离出54个单体化合物, 化合物类型包括28个黄酮、17个二苯乙烯类、6个三萜、1个木脂素、1个香豆素、1个生物碱, 所有化合物均进行了抗炎活性筛选。结果显示, 包括9个二苯乙烯类、7个黄酮、6个三萜在内的22个化合物显示出较强的抗炎活性。以上22个化合物的详细信息见表 2, 化学结构见图 1~5。

如上所述, 狭叶锦鸡儿中的化合物1、2和3的IC₅₀分别为23.88、12.70和11.45 μmol·L^-1, 化合物14和15的IC₅₀分别为22.93和34.69 μmol·L^-1, 均比阳性药左旋硝基精氨酸甲酯(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) 显示出更强的抗炎活性^{[12, 18]}。粉刺锦鸡儿中的化合物8的IC₅₀为0.62 μmol·L^-1, 显示出比阳性药氨基胍(aminoguanidine, AG) 更强的抗炎活性; 化合物7的活性中等, IC₅₀为45.70 μmol·L^-1[16]。粉刺锦鸡儿中分离得到的化合物9是一种新型螺色酮, 显著抑制诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS) 蛋白表达, 构效关系表明, 融合的2-异丙烯基-2, 3-二氢呋喃分子对药效起着重要作用^[17]。小叶锦鸡儿中的化合物20~25的IC₅₀值分别为23.4~36.9 µmol·L^-1, 相比阳性药AG, 均显示出中等程度的抑制作用^[21]; 这6个三萜皂苷活性相近, 可能是其结构差异不大, 因其均有相同的齐墩果烷型五环三萜母核, 仅C-23的取代基和糖链上的取代基稍有差异。但是以上锦鸡儿物种都未做进一步机制探究。

作用机制研究较为深入的是锦鸡儿和红花锦鸡儿, 研究者分别从锦鸡儿中分离得到化合物18和19。化合物18的抗炎作用是通过抑制干扰素(interferon, IFN)-γ刺激的巨噬细胞中细胞外信号调节激酶(extracellular regulated protein kinases, ERK) 介导的信号转导与转录激活因子1 (signal transducerand activator of transcription 1, STAT-1) 激活来下调STAT-1诱导的炎症基因^[23]。化合物19的抗炎作用与抑制核因子-κB (nuclear factor kappa-B, NF-κB) 通路有关, 包括抑制κB抑制因子激酶α/β (inhibitor of kappa B kinase α/β, IKKα/β) 磷酸化和NF-κB转位至细胞核, 化合物18和19可能是未来治疗炎症性疾病的潜在候选药物^[20]。

红花锦鸡儿^[24]是唯一用粗提物(Cr-ME) 进行抗炎活性的研究, Cr-ME阻断MyD88和TBK1诱导的NF-κB和干扰素调节因子3 (interferon regulatory factor 3, IRF3) 启动子活性, 降低核因子-κB抑制蛋白(inhibitor of NF-κB, IκBα)、IKKα/β和IRF3的磷酸化水平, 调节上游NF-κB蛋白Syk和Src以及IRF3蛋白TBK1。过量表达Src和TBK1后, Cr-ME可减轻NF-κB亚基p50和p65的磷酸化及IRF3信号传导, 证实其抗炎作用是通过抑制TLR4/NF-κB/IRF3信号通路实现的。研究者用LC-MS/MS鉴定其成分, 鉴定出(2R, 3R)-3, 5, 7, 2′, 6′-五羟基二氢黄烷酮、1, 5-二羟基-2, 3, 4, 7-四甲氧基呫吨酮、花色素苷、鸭跖黄酮甙、山柰酚-4′-甲氧基-3-葡萄糖苷、5, 7, 8, 3′, 4′-五甲氧基黄酮、芫花素、桑黄酮C共8种化合物, 表明黄酮及其苷类成分可能是Cr-ME的主要活性成分。

现有研究中大部分研究者采用LPS刺激巨噬细胞构建炎症模型, 通过测定一氧化氮(NO) 抑制率探讨锦鸡儿属植物抗巨噬细胞炎症反应和机制。LPS刺激的巨噬细胞模型通常用于评价候选药物对促炎细胞因子和炎症介质的抑制作用; LPS可以激活膜上的Toll样受体4 (Toll-like receptor 4, TLR4), 进而影响下游信号通路的炎症蛋白基因NF-κB、丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK) 和IRF3的转录和翻译, 导致炎症介质、细胞因子和趋化因子的分泌增加^{[25, 26]}。NO是重要的炎症介质^{[[27, 28]}, 抑制NO的产生一定程度上能够反映化合物具有抗炎活性。然而, 鉴于炎症这一复杂生理病理过程涉及了众多炎症介质的释放和细胞因子的相互作用, 仅仅局限于对NO抑制活性的测定, 显然无法全面揭示药物在炎症治疗中的实际效果与潜在机制。今后研究应涉及多种炎症介质、细胞因子及其上下游信号通路的炎症基因和蛋白表达的探究。且需构建多种炎症细胞模型, 巨噬细胞RAW264.7是最常用的单核/巨噬细胞炎症模型, 除此还有骨髓来源巨噬细胞BMDM、单核巨噬细胞J774A.1、肺泡巨噬细胞NR8383、急性单核细胞白血病细胞THP-1等多种单核/巨噬细胞炎症模型, 以及多形核中性粒细胞(polymophnuclear leulocyte, PMN)、小鼠淋巴瘤细胞P388D1等其他细胞模型均可用于炎症研究^[29]。

此外, 仅有锦鸡儿和红花锦鸡儿对作用机制进行了探究, 粉刺锦鸡儿研究了抗炎构效关系, 该属其他植物体外抗炎作用机制及构效关系等方面仍然有待探索。今后研究可利用多组学技术探讨可能的抗炎通路, 为该属植物体外抗炎活性研究奠定更为扎实的基础。在细胞水平上的炎症调节活性研究是相对有限的, 还应开展相关体内抗炎活性的研究。

2.2 抑制脂多糖诱导的小胶质细胞炎症

神经炎症是神经退行性疾病发病机制的一个显著标志^[30]。活化的小胶质细胞(BV-2细胞) 释放IL-6、TNF-α等炎症因子, 介导神经炎症反应^{[31, 32]}。因此, 抑制BV-2细胞的过度活化对于神经炎症相关的神经退行性疾病的治疗具有重要意义。已有研究基于BV-2细胞模型探讨锦鸡儿属植物中分离得到的单体成分的抗神经炎作用, 见表 4^{[13, 14, 22]}。

小叶锦鸡儿、吐鲁番锦鸡儿和刺叶锦鸡儿中分离出的9种化合物均可抑制LPS诱导的BV-2细胞过度活化介导的神经炎症。小叶锦鸡儿^[13]中的化合物4 (IC₅₀ 14.04 μmol·L^-1) 和化合物36 (IC₅₀ 10.20 μmol·L^-1)、吐鲁番锦鸡儿^[14]中的化合物5 (IC₅₀ 6.87 μmol·L^-1) 和化合物35 (IC₅₀ 1.01 μmol·L^-1) 均表现出更强的NO抑制作用(阳性药米诺环素), 均有望成为潜在的抗神经炎药物^{[13, 14]}。刺叶锦鸡儿中的螺环已二烯基萘类的抗炎活性与阳性药米诺环素相当, 是首次研究了这些化合物的抗炎作用, 结果表明, 化合物26、29、32~34在开发抗炎药物方面具有应用潜力, IC₅₀值为8.8~13.4 μmol·L^-1; 其中化合物33和34是一对对映异构体, S构型的抗炎活性优于R构型^[22]。但遗憾的是只有以上3种锦鸡儿属植物通过体外实验评价抗神经炎症活性, 且仅测定了NO抑制率, 未对其他炎症因子进行检测, 缺乏对机制的深入探索, 且均未进行进一步体内实验验证。此外, 上述单体化合物均源自三种植物的根部, 鉴于锦鸡儿属植物在生态环境中扮演着防风固沙的重要角色, 其根部作为药用部位的过度采集可能引发生态平衡的破坏。因此, 为了促进资源的可持续利用并探索替代性药用资源, 建议采用HPLC-MS/MS技术, 对锦鸡儿属植物的地上部分(如茎、叶、花、种子) 与地下部分(根) 进行化学成分对比分析, 揭示该属植物地上部分是否同样蕴含具有抗神经炎症活性的化合物, 为拓宽药用资源的利用途径提供科学依据。

2.3 抑制角质细胞炎症

异常或不完全的伤口愈合可能会破坏表皮屏障的功能和机体的平衡^[33]。因此, 研究人员试图开发能更有效地促进伤口修复和恢复表皮屏障功能的材料。Kim等^[34]研究发现锦鸡儿花提取物(CSFAb) 在人角质形成细胞(human immortalized epidermal cells, HaCaT) 中, 能增加细胞的增殖和迁移, 并提高炎症相关通路的ERK1/2、JNK、p38 MAPK和AKT的磷酸化水平, 还可增加Ⅰ型和Ⅳ型胶原蛋白合成, 降低MMP-2和MMP-9活性, 这些结果表明CSFAb可促进伤口愈合, 用于皮肤修复, 可作为潜在的促进伤口愈合的药物或化妆品。未来研究中, 有必要进一步确定CSFAb中的关键生物活性成分, 并研究其在体内或其他皮肤细胞中的活性。

2.4 抑制细菌性炎症

Kakorin等^[35]利用鬼箭锦鸡儿地上部分水提取物研究抗皮肤炎症作用, 结果证实当浓度为4 mg·mL^-1时, 冻干的水提取物对革兰阳性金黄色葡萄球菌209-P、革兰阴性大肠杆菌ATCC25922、粗胞杆菌ATCC6896和绿脓杆菌ATCC9027具有抑菌活性。研究结果证实了黄酮类化合物可作为潜在微生物抑制剂的文献数据。鬼箭锦鸡儿或可制成软膏剂型, 外用治疗皮肤和黏膜的炎症性疾病。

综上所述, 锦鸡儿属植物有多种体外抗炎活性。从5种锦鸡儿属植物中分离出的22个单体化合物和红花锦鸡儿粗提物均能抑制LPS诱导的巨噬细胞炎症, 部分化合物显示出比阳性药更强的抗炎活性, 抗炎机制涉及TLR4/NF-κB/IRF3信号通路。从3种锦鸡儿属植物中分离的9个单体化合物可明显抑制LPS诱导的小胶质细胞炎症, 部分化合物有望成为潜在的抗神经炎药物, 但是均未做机制研究。此外, 锦鸡儿花可抑制角质细胞炎症, 鬼箭锦鸡儿地上部分可抑制细菌性炎症。锦鸡儿属植物作为一类具有显著药用潜力的植物资源, 其体外抗炎活性的研究已展现出确凿的科学依据。这些发现不仅拓宽了天然抗炎资源的研究视野, 而且为炎症相关疾病的治疗提供了新的天然候选物。为了进一步提升其应用潜力并推动药物研发进程, 扩大筛选范围并深入探究其抗炎作用的分子机制显得尤为重要。鉴于当前研究多聚焦于有限种类的锦鸡儿植物及其初步的生物活性评估, 若能进一步拓宽该属植物的筛选范围, 将有望发现更多具有潜在抗炎活性的化学成分, 从而增强药物开发的多样性与可能性。深入研究锦鸡儿属植物抗炎活性的具体机制至关重要。这要求采用多学科交叉的方法, 如分子生物学、细胞生物学及药理学技术等, 解析其作用靶点、信号转导途径及基因表达调控等关键环节, 对于揭示其抗炎作用的本质至关重要, 也为设计高效、低毒的新型抗炎药物提供理论依据。

3 体内抗炎作用与机制

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3.1 抗类风湿性关节炎作用与机制

类风湿性关节炎(rheumatoid arthritis, RA) 作为典型的炎症性自身免疫性疾病, 其病理特征为关节滑膜炎性增生和功能不全的微血管生成, 导致类肿瘤样的病理产物血管翳的产生^[36]。RA的发病率在全球居高不下, 而且治疗效果并不明显。目前, 临床治疗方法主要有手术治疗、化学药物和生物制剂治疗^[37], 然而这些治疗方法都有一些严重的不良反应^[38]。大量证据表明天然药物具有潜在的抗关节炎作用, 是发现RA治疗候选药物的可行途径^{[39, 40]}。

锦鸡儿属中很多物种如锦鸡儿、刺叶锦鸡儿和狭叶锦鸡儿等在民间医学中一直被用于治疗RA。本文整理了锦鸡儿属植物抗RA作用的现代药理学研究结果, 见表 5^{[15, 18, 41-53]}。结果显示该属植物对RA有治疗作用, 可作为治疗RA的潜在候选药物。

由上述结果可知, 锦鸡儿属植物能够缓解RA大鼠关节和滑膜组织炎症。胶原诱导的关节炎(collagen induced arthritis, CIA) 和佐剂诱导的关节炎(adjuvant induced arthritis, AIA) 是RA最常用的两种实验动物模型, 以滑膜炎症和关节破坏为特征, 与人类关节炎的免疫学和病理学特征非常相似^{[54, 55]}。爪肿胀和关节炎评分是评价抗RA候选药物疗效的两个重要指标^{[56, 57]}。在锦鸡儿属抗RA作用中, 研究者们成功复制了CIA和AIA大鼠模型, 并进一步评估抗关节炎活性。结果表明, 该属植物能明显减轻CIA或AIA大鼠的爪肿胀^{[43, 49-51]}和关节炎指数^{[43, 47, 49-51]}。此外, 病理切片显示, 锦鸡儿属植物提取物能明显减轻模型大鼠关节和滑膜组织的炎症和组织的破坏^{[42, 43, 45, 48, 50, 52]}。

为了探究药理机制, 研究者们探讨了锦鸡儿属植物对RA大鼠血清中炎症细胞因子和炎症介质的影响。几种促炎细胞因子, 如TNF-α、IL-1β、IL-6、IL-8和IL-17已被证明在免疫应答中发挥重要作用^{[58, 59]}。NF-κB、环氧化酶-2 (cyclooxygenase-2, COX-2) 和iNOS是炎症反应的关键介质^{[60, 61]}, 前列腺素E₂ (prostaglandin E₂, PGE₂) 与RA患者的疼痛和炎症症状密切相关^[62]。同时, 基质金属蛋白酶3 (matrix metallopeptidase 3, MMP-3) 被认为是RA中重要的参考指标^[59], C-反应蛋白(c-reactive protein, CRP) 是反映炎症程度的重要生物标志物^[63]。相反, 白细胞介素10 (IL-10) 通过抑制促炎细胞因子的释放, 已被公认为是一种有效的抗炎细胞因子, 它还能在RA病变过程中保护关节的完整性^[64]。研究表明, 多种锦鸡儿属植物均可降低RA大鼠血清中IL-1β^{[42, 45, 48, 50, 51]}、IL-6^{[42, 45, 48, 50, 51]}、IL-8^[48]、IL-17^[48]、TNF-α^{[42, 45, 48, 50, 51]}、PGE₂^{[44, 45]}、COX-2^[44]、iNOS^[44]、CRP^[50]的表达, 同时增加IL-10^{[48, 50, 51]}的水平。此外, 锦鸡儿^[44]、刺叶锦鸡儿^[48]和狭叶锦鸡儿^[18]均可使MMP-3、MMP-9含量降低。故锦鸡儿属植物能通过降低多种炎症因子和炎症介质的水平而减轻RA炎症。

迄今为止, RA的发病机制尚不清楚。一般认为, JAK/STAT、NF-κB和RANKL/RANK信号通路在RA中发挥重要作用^{[65, 66]}。目前研究证实, 锦鸡儿^{[42, 44, 45]}和狭叶锦鸡儿^[18]均通过调节NF-κB信号通路对RA大鼠有治疗作用, 锦鸡儿^[44]还可抑制MAPKs信号通路发挥治疗作用。另有研究用代谢组学技术发现狭叶锦鸡儿^[52]可调节酪氨酸、甘油磷脂和半乳糖代谢等通路起到防治RA作用。基于上述研究的深入分析, 锦鸡儿属植物展现出通过调控NF-κB信号通路、MAPKs途径或其关联的代谢网络来缓解RA相关炎症的潜力。然而, 鉴于炎症调控网络的复杂性, 该过程涉及错综复杂的信号通路与分子交互, 当前的研究成果虽具启示性, 但仍在一定程度上受限于其广度和深度, 未能全面揭示该属植物在RA炎症缓解中的全部作用机制。

综上所述, 9种锦鸡儿属植物均进行了体内抗RA作用研究, 且植物的药用部位多样, 包括根、地上部分、种籽和木质心材。但是只有一种单体化合物—conferin^[15]进行了体内实验, 其余研究对象均是粗提物, 缺乏药效物质基础研究。如果能从粗提物中追踪活性化合物, 可为开发抗炎先导化合物奠定基础。此外, 研究相对深入的是锦鸡儿, 多位学者对锦鸡儿浸膏^[43]、水提取物^[44]、乙酸乙酯提取物^{[42, 45]}进行了抗RA验证, 且证实其相关抗炎信号通路, 研究基础较为夯实。但是民族药中常用的小叶锦鸡儿^[41]、甘青锦鸡儿^[46]、刺叶锦鸡儿^{[47, 48]}和粉刺锦鸡儿^{[50, 51]}仅进行了抗RA药效试验, 均未对作用机制进行探究。值得庆幸的是, 由树锦鸡儿或小叶锦鸡儿水煎剂制成的类风湿Ⅰ号^[53]在临床上应用于RA患者, 3个月疗程后, 治疗组用药前后关节压痛指数、15米步行时间、双手握力等各项指标显著好转(P < 0.01), 说明类风湿Ⅰ号有可靠的临床疗效。此外, 值得注意的是, 上述提及的体内实验均尚未涉及对药物安全性的深入研究, 而安全性作为药物的核心属性之一, 是药物研发及生产流程中重要的考量因素。展望未来, 研究者们应致力于整合代谢组学、蛋白质组学、转录组学等多维度组学研究策略, 并深度融合生物信息学技术, 以开展对锦鸡儿属植物抗炎机制深入而全面的剖析。此举措旨在精准识别并验证其在RA炎症中的关键抗炎靶点及相应的活性物质基础。此外, 为了确保药物开发的安全性与有效性, 需结合更为广泛且严格的毒理学评估与临床试验, 以系统地评估其潜在风险与疗效。通过科学严谨的验证流程, 为发现并开发安全、高效的抗RA新型药物奠定坚实的理论基础与实践依据。

3.2 抗溃疡性结肠炎作用与机制

溃疡性结肠炎(ulcerative colitis, UC) 是一种慢性复发性炎症疾病, 由于发病机制复杂且难以完全治愈, UC被世界卫生组织列为世界难治疾病之一^[67]。因此, 寻找有效防治UC的药物尤为重要。Li等^[68]发现锦鸡儿花提取物(FEC) 对葡聚糖硫酸钠盐(dextran sulfate sodium salt, DSS) 诱导的UC小鼠有保护作用, 能明显防止体重下降和结肠缩短, 降低疾病活动指数和组织病理学评分。FEC还能明显降低髓过氧化物酶(myeloperoxidase, MPO)、IL-1β、TNF-α和IL-6的水平, 上调超氧化物歧化酶(superoxide dismutase, SOD)、过氧化氢酶(catalase, CAT)、谷胱甘肽(glutathione, GSH) 和IL-10的水平, 此外还证实了FEC可抑制TLR4/NF-κB和TLR4/MAPK通路相关蛋白的表达。然而, 就该属中的其他植物而言, 目前尚未有文献报道其应用于UC治疗的相关研究。这一现状提示, 在该属植物的药用价值探索中, 针对UC治疗领域的研究可能尚属空白, 有待未来科研工作的进一步发掘与验证。

3.3 抗肾炎作用与机制

肾小球肾炎是一种发病率和死亡率很高的肾脏疾病^[69]。狼疮性肾炎(lupus nephritis, LN) 是系统性红斑狼疮(systemic lupus erythematosus, SLE) 的严重并发症, 也是SLE患者死亡的重要原因^[70]。Ren等^[71]研究发现, 锦鸡儿根部水煎剂对大鼠复合型肾小球肾炎具有良好的治疗作用, 可显著降低大鼠血清中IL-6和尿蛋白的含量, 进而改善大鼠肾脏功能。Zhang等^[72]临床观察金雀根汤(锦鸡儿根) 联合醋酸泼尼松片治疗LN的临床疗效。对照组予以标准疗程的激素治疗, 治疗组患者在对照组治疗基础上加服金雀根汤。通过统计IL-6、IL-18、IL-34、CRP、IgG、ESR、24 h UPR水平, 治疗组总有效率和临床疗效优于对照组。此项研究证实LN患者在标准激素治疗中加用金雀根汤有利于提高临床疗效, 可下调炎症因子水平, 且安全性较高。综上所述, 对于抗肾炎作用的研究, 现有文献均聚焦于锦鸡儿, 且特定地使用了其根部作为药用部位, 提示锦鸡儿根部富含具有抗肾炎活性的特定物质。然而, 截至目前, 关于这些活性物质的具体化学成分尚未进行系统深入的研究。因此, 深入探索并阐明锦鸡儿根部抗肾炎的物质基础及其作用机制, 不仅有助于揭示其药效学本质, 而且将为锦鸡儿在抗肾炎领域的临床应用提供坚实的科学依据与有力的理论支撑, 进一步推动其在传统医学与现代药学融合发展中的应用。

3.4 抗急性肺损伤作用与机制

急性肺损伤(acute lung injury, ALI) 是非心源性的各种致病因素导致的急性低氧性呼吸功能不全或呼吸衰竭, 其死亡率高达40%~60%^[73]。Niu等^[46]通过LPS诱导的ALI动物模型研究了甘青锦鸡儿木质心材乙酸乙酯提取物的抗炎作用。结果表明, 该提取物降低PGE₂水平, 降低COX-2在肺部的表达, 减轻ALI小鼠的炎症反应。说明甘青锦鸡儿通过抑制COX-2发挥抗ALI作用。

4 结语与展望

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锦鸡儿属植物作为一类拥有悠久民族医药应用历史的植物资源, 不仅承载着深厚的民族医药文化传承, 还展现出显著的生态价值, 尤其在我国西北地区资源分布广泛, 预示着巨大的开发与应用潜力。近年来, 研究者们对锦鸡儿属植物的研究日益深入, 大量文献聚焦于其化学成分的多样性以及所展现出的广泛药理活性。这些研究已从初期的单一活性成分及其作用靶点的探索, 逐步拓展至多维度的机制解析层面, 旨在全面验证并深化理解其药用价值的多元性和有效性。

抗炎作用作为锦鸡儿属植物活性研究中的核心热点之一, 受到了广泛关注。研究者们通过多角度、多层次的研究方法, 不仅揭示了其抗炎活性成分的具体种类与结构特征, 还深入探讨了这些成分在生物体内的作用机制, 包括但不限于对炎症信号通路的调控以及炎症介质产生的干预等, 从而为锦鸡儿属植物在抗炎药物开发领域的潜在应用提供了坚实的科学依据。这一系列研究成果不仅丰富了天然产物药理学的理论体系, 也为解决临床炎症相关疾病的治疗难题提供了新的思路和方向。

由体外抗巨噬细胞炎症研究结果得知, 5种锦鸡儿属植物对LPS和IFN-γ诱导的巨噬细胞产生抑制NO生成作用, 其中锦鸡儿通过抑制NF-κB的核转位抑制炎症因子释放, 红花锦鸡儿通过NF-κB和IRF3信号通路实现促炎因子的抑制。此外, 该属植物显示出体外抗神经炎症作用, acanthophyllas A~D、caraganolide A、daidzein等单体成分对LPS诱导的BV-2细胞有NO抑制作用, 但是均缺乏相关体内实验研究数据。锦鸡儿花促进皮肤伤口愈合, 鬼箭锦鸡儿可用于细菌感染引发的皮肤炎症, 均对皮肤和黏膜有保护作用。多项体内实验证实, 锦鸡儿属植物的水、醇、乙酸乙酯等提取物对类风湿性关节炎、溃疡性结肠炎、复合型肾炎、急性肺损伤等有较好的防治作用, 其中对类风湿性关节炎的研究相对较多, 锦鸡儿和狭叶锦鸡儿均通过调节NF-κB信号通路, 减轻关节炎的严重程度。综上可知, 锦鸡儿属植物具有较为显著的体外和体内抗炎活性。

本研究绘制了锦鸡儿属植物的抗炎信号通路示意图(图 6), 深入探讨了该属植物提取物及其所含多种化学成分在多种炎性疾病治疗中的潜在机制。这些机制广泛涉及TLR4/NF-κB、TLR4/MAPK、TLR4/NF-κB/IRF3、JAK/STAT-1及ERK/STAT-1等关键信号通路, 凸显了锦鸡儿属植物通过其多组分、多靶点及多通路协同作用, 在调控炎症过程中展现出的显著优势。

进一步, 通过对锦鸡儿属植物提取物及其单体成分作用效果的关联分析, 本研究初步确认异黄酮、二苯乙烯类、三萜类和香豆素类作为该属植物抗炎活性的核心成分群。这些发现不仅丰富了对锦鸡儿属植物药理作用的理解, 也为后续开发具有特定抗炎效应的药物或功能性产品提供科学依据。

此外, 鉴于已有大量文献报道黄酮类^[74]、二苯乙烯类^[75]及三萜类^[76]成分在其他药用植物中的明确抗炎效果, 本研究结果进一步强化了锦鸡儿属植物在抗炎领域的研究价值与应用潜力。这些发现预示着锦鸡儿属植物在未来抗炎药物研发及市场应用中具有广阔的发展前景, 其潜在的经济与社会价值值得高度关注与期待。

当前, 尽管锦鸡儿属植物的抗炎研究已取得初步进展, 但在其活性成分鉴定与药理机制阐释方面, 尚缺乏深入且系统性的探索。具体而言, 在活性成分研究领域, 现有研究聚焦于黄酮类与二苯乙烯类等少数化合物, 而对其他潜在活性化学成分的挖掘与分析则显得相对不足。多数研究仅停留在成分结构的初步鉴定层面, 缺乏对这些化学成分的全面谱系解析, 从而限制了对其整体药效贡献的深入理解。

在药理机制探索方面, 当前研究大多局限于粗提物的药效评估, 未能深入至具体活性成分及其作用机制的精细化研究。这种局限性导致了对锦鸡儿属植物药效物质基础及作用机制的认知较为薄弱。为克服此现状, 未来研究应致力于构建能够反映成分-效应关系的特征图谱, 以明确该属植物发挥抗炎活性的关键物质基础。同时, 结合多组学技术(如基因组学、转录组学、代谢组学等) 与生物信息学分析工具, 深入挖掘并验证发挥药效的具体成分及其作用靶点, 从而全面揭示锦鸡儿属植物的化学组成与药理机制, 为其深入开发与应用奠定坚实的基础。

此外, 目前锦鸡儿属植物的抗炎活性研究主要依赖于动物模型与细胞实验体系, 缺乏对人体内药效过程及作用特点的直接证据。为推动其临床应用进程, 未来研究应拓展至临床试验阶段, 并结合药代动力学研究, 系统阐述在人体内的代谢过程, 以及其在不同生理病理条件下的药效作用特点。这些综合研究将为锦鸡儿属植物抗炎活性的广泛临床应用提供科学依据与参考, 进一步拓展其在医药健康领域的应用前景。

作者贡献: 马玉梅负责文献检索、文章撰写和插图绘制; 罗菊元参与文章审校; 陈涛、李洪梅参与部分文献检索; 申诚、王硕、宋志博协助参与文章修改; 李玉林负责文章整体设计、审查与指导。

利益冲突: 所有作者声明本文不存在任何利益冲突。

基金

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青海省重点研发与转化计划项目(2023-SF-112)
青海省卫生健康系统指导性计划课题(2021-wjzdx-112)

参考文献

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2025年第60卷第1期

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doi: 10.16438/j.0513-4870.2024-0587

接收时间：2024-06-21
首发时间：2025-11-07
出版时间：2025-01-12

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收稿日期：2024-06-21
修回日期：2024-10-22

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青海省重点研发与转化计划项目(2023-SF-112)

青海省卫生健康系统指导性计划课题(2021-wjzdx-112)

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1.中国科学院西北高原生物研究所, 青海西宁 810008

2.青海卫生职业技术学院, 青海西宁 810000

3.中国科学院大学, 北京 100049

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^*李玉林, E-mail: liyulin@nwipb.cas.cn

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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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Chinese name	Latin name	Alias	Medicinal part	Distribution
Duan ye jinjier	C. brevifolia	Mu zhu ci	Roots	Gansu, Qinghai, Sichuan, Xizang
Chang du jinjier	C. changduensis Liou f.	Zuomo Xing	Stems, roots	Xizang
Yun nan jinjier	C. franchetiana	-	Flowers	Xizang, Yunnan, Sichuan
Shu jinjier	C. arborescens	-	Entire plant	Shanxi, Shaanxi, Hebei, Shandong, Liaoning, Jilin, Heilongjiang, Inner Mongolia, Xinjiang, Gansu
Zhong jian jinjier	C. intermedia	Shalhazhagna	Entire plant, flowers, seeds, roots	Shanxi, Shaanxi, Ningxia, Inner Mongolia
Gui jian jinjier	C. jubata	Gui jian chou	Entire plant	Liaoning, Hebei, Shaanxi, Shanxi, Inner Mongolia, Qinghai, Gansu, Sichuan, Xinjiang, Ningxia, Xizang
Bai pi jinjier	C. leucophloea	-	Roots	Gansu, Inner Mongolia, Xinjiang
Xiao ye jinjier	C. microphylla	Ullezh Harigana	Roots, seeds	Shanxi, Shaanxi, Inner Mongolia, Xinjiang, Gansu, Ningxia, Shandong, Hebei, Sichuan, Jilin, Liaoning, Heilongjiang, Anhui, Xizang
Kun lun jinjier	C. polourensis	-	Flowers	Xinjiang
Ai jinjier	C. pygmaea	-	Roots	Inner Mongolia, Shanxi
A le tai jinjier	C. altaica	-	Roots	Xinjiang
Er se jinjier	C. bicolor	-	Roots	Xizang, Sichuan, Yunnan
Hong hua jinjier	C. rosea	Jinquehua	Roots	Northeast, Hebei, Inner Mongolia, Shanxi, Shaanxi, Henan, Gansu, Jiangsu, Zhejiang, Anhui, Sichuan
Ci ye jinjier	C. acanthophylla	-	Roots	Xinjiang
Gan qing jinjier	C. tangutica	-	Heartwood	Gansu, Sichuan, Qinghai, Xizang, Inner Mongolia
Jinjier	C. sinica/ C. chamlagu	Jinquegen	Flowers, roots	Hebei, Shandong, Henan, Shanxi, Inner Mongolia, Xinjiang, Shaanxi, Gansu, Hubei, Hunan, Sichuan, Jilin, Liaoning, Heilongjiang
Mao ci jinjier	C. tibetica	Zang jinjier Tebudu Harigana Zuomo Xing	Roots, flowers, heartwood	Gansu, Qinghai, Xinjiang, Ningxia, Inner Mongolia, Sichuan, Xizang
Xia ye jinjier	C. stenophylla	Nariin Harigana	Roots	Hebei, Shanxi, Inner Mongolia, Gansu, Shaanxi, Ningxia
Fen ci jinjier	C. pruinosa	-	Roots	Xinjiang

Chinese name

Latin name

Alias

Medicinal part

Distribution

Duan ye jinjier

C. brevifolia

Mu zhu ci

Roots

Gansu, Qinghai, Sichuan, Xizang

Chang du jinjier

C. changduensis Liou f.

Zuomo Xing

Stems, roots

Xizang

Yun nan jinjier

C. franchetiana

Flowers

Xizang, Yunnan, Sichuan

Shu jinjier

C. arborescens

Entire plant

Shanxi, Shaanxi, Hebei, Shandong, Liaoning, Jilin, Heilongjiang, Inner Mongolia, Xinjiang, Gansu

Zhong jian jinjier

C. intermedia

Shalhazhagna

Entire plant, flowers, seeds, roots

Shanxi, Shaanxi, Ningxia, Inner Mongolia

Gui jian jinjier

C. jubata

Gui jian chou

Entire plant

Liaoning, Hebei, Shaanxi, Shanxi, Inner Mongolia, Qinghai, Gansu, Sichuan, Xinjiang, Ningxia, Xizang

Bai pi jinjier

C. leucophloea

Roots

Gansu, Inner Mongolia, Xinjiang

Xiao ye jinjier

C. microphylla

Ullezh Harigana

Roots, seeds

Shanxi, Shaanxi, Inner Mongolia, Xinjiang, Gansu, Ningxia, Shandong, Hebei, Sichuan, Jilin, Liaoning, Heilongjiang, Anhui, Xizang

Kun lun jinjier

C. polourensis

Flowers

Xinjiang

Ai jinjier

C. pygmaea

Roots

Inner Mongolia, Shanxi

A le tai jinjier

C. altaica

Roots

Xinjiang

Er se jinjier

C. bicolor

Roots

Xizang, Sichuan, Yunnan

Hong hua jinjier

C. rosea

Jinquehua

Roots

Northeast, Hebei, Inner Mongolia, Shanxi, Shaanxi, Henan, Gansu, Jiangsu, Zhejiang, Anhui, Sichuan

Ci ye jinjier

C. acanthophylla

Roots

Xinjiang

Gan qing jinjier

C. tangutica

Heartwood

Gansu, Sichuan, Qinghai, Xizang, Inner Mongolia

Jinjier

C. sinica/
C. chamlagu

Jinquegen

Flowers, roots

Hebei, Shandong, Henan, Shanxi, Inner Mongolia, Xinjiang, Shaanxi, Gansu, Hubei, Hunan, Sichuan, Jilin, Liaoning, Heilongjiang

Mao ci jinjier

C. tibetica

Zang jinjier
Tebudu Harigana
Zuomo Xing

Roots, flowers, heartwood

Gansu, Qinghai, Xinjiang, Ningxia, Inner Mongolia, Sichuan, Xizang

Xia ye jinjier

C. stenophylla

Nariin Harigana

Roots

Hebei, Shanxi, Inner Mongolia, Gansu, Shaanxi, Ningxia

Fen ci jinjier

C. pruinosa

Roots

Xinjiang

Compound	Compound type	Name	Plant source	Medicinal part	Ref.
1	Flavonoids	Butein	C. stenophylla	Roots	[12]
2	3-Methoxylquercetin
3	Luteolin
4	Daidzein	C. microphylla	Roots	[13]
5	3′, 7, 8-Trihydroxy-4′-methoxyisoflavone	C. turfanensis	Roots	[14]
6	Conferin	C. conferta	Roots	[15]
7	Pruinosanone F	C. pruiniosa	Roots	[16]
8	Pruinosanone D
9	Pruinosanone A	[17]
10	Pruinosanones C
11	Stilbenes	(-)-ε-Viniferin	C. stenophylla	Roots	[18]
12	Miyabenol C
13	Carasinol A
14	Carasinol C
15	Piceatannol
16	Kompasinol A
17	Cararosinol D
18	α-Viniferin	C. chamlagu	Roots	[19]
19	Kobophenol A	C. sinica	Roots	[20]
20	Triterpenoids	Caraganin A	C. microphylla	Seeds	[21]
21	Caraganin B
22	Caraganin C
23	Caraganin D
24	Caragana C
25	Caragana D
26	Spiro-cyclohexadienyl naphthalene	Acanthophyllas C	C. acanthophylla	Roots	[22]
27		(+)-Acanthophyllas C
28		(-)-Acanthophyllas C
29		Acanthophyllas D
30		(+)-Acanthophyllas D
31		(-)-Acanthophyllas D
32		1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
33		(6R)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
34		(6S)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene
35	Lignin	(+)-Medioresinol-4, 4′-O-β-D-diglucopyranoside	C. microphylla	Roots	[13]
36	Coumarin	Caraganolide A	C. turfanensis	Roots	[14]

Compound

Compound type

Name

Plant source

Medicinal part

Ref.

Flavonoids

Butein

C. stenophylla

Roots

[12]

3-Methoxylquercetin

Luteolin

Daidzein

C. microphylla

Roots

[13]

3′, 7, 8-Trihydroxy-4′-methoxyisoflavone

C. turfanensis

Roots

[14]

Conferin

C. conferta

Roots

[15]

Pruinosanone F

C. pruiniosa

Roots

[16]

Pruinosanone D

Pruinosanone A

[17]

Pruinosanones C

Stilbenes

(-)-ε-Viniferin

C. stenophylla

Roots

[18]

Miyabenol C

Carasinol A

Carasinol C

Piceatannol

Kompasinol A

Cararosinol D

α-Viniferin

C. chamlagu

Roots

[19]

Kobophenol A

C. sinica

Roots

[20]

Triterpenoids

Caraganin A

C. microphylla

Seeds

[21]

Caraganin B

Caraganin C

Caraganin D

Caragana C

Caragana D

Spiro-cyclohexadienyl naphthalene

Acanthophyllas C

C. acanthophylla

Roots

[22]

(+)-Acanthophyllas C

(-)-Acanthophyllas C

Acanthophyllas D

(+)-Acanthophyllas D

(-)-Acanthophyllas D

1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene

(6R)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene

(6S)-1-Carbonyl-3-methoxy-2, 4-diene-spiro[5, 7]-12, 15-dihydroxynaphthalene

Lignin

(+)-Medioresinol-4, 4′-O-β-D-diglucopyranoside

C. microphylla

Roots

[13]

Coumarin

Caraganolide A

C. turfanensis

Roots

[14]

Plant	Medicinal part	Induction factor	Cellular model	Action mechanism	Active ingredient	Constitutive relationship	Ref.
C. pruinosa	Roots	LPS	RAW264.7	-	Compounds 7, 8	-	[16]
-	Compounds 9, 10	2-Isopropenyl-2, 3-dihydrofuran molecules play an important role in pharmacological effects	[17]
C. stenophylla	Roots	LPS	RAW264.7	-	Compounds 1-3	-	[12]
C. stenophylla	Roots	LPS	RAW264.7	-	Compounds 11-17	-	[18]
C. sinica	Roots	IFN-γ	RAW264.7	Reduces protein levels of iNOS, attenuates mRNA levels of iNOS, IP-10, MIG, inhibits iNOS gene promoter activity	Compound 18	-	[19, 23]
LPS	J774A.1	Inhibites the expression of NO, IL-1β, IL-6, IKKα/β phosphorylation and NF-κB translocation to the nucleus	Compound 19	-	[20]
C. microphylla	Seed	LPS	RAW264.7	-	Compounds 20-25	-	[21]
C. rosea	Root	LPS	RAW264.7	Anti-inflammatory activity through inhibition of the TLR4/ NF-κB/IRF3 signalling pathway	Identification of eight flavonoids by LC-MS/MS	-	[24]

Plant

Medicinal part

Induction
factor

Cellular model

Action mechanism

Active ingredient

Constitutive relationship

Ref.

C. pruinosa

Roots

LPS

RAW264.7

Compounds 7, 8

[16]

Compounds 9, 10

2-Isopropenyl-2, 3-dihydrofuran molecules play
an important role in pharmacological effects

[17]

C. stenophylla

Roots

LPS

RAW264.7

Compounds 1-3

[12]

C. stenophylla

Roots

LPS

RAW264.7

Compounds 11-17

[18]

C. sinica

Roots

IFN-γ

RAW264.7

Reduces protein levels of iNOS, attenuates mRNA levels of
iNOS, IP-10, MIG, inhibits iNOS gene promoter activity

Compound 18

[19, 23]

LPS

J774A.1

Inhibites the expression of NO, IL-1β, IL-6, IKKα/β
phosphorylation and NF-κB translocation to the nucleus

Compound 19

[20]

C. microphylla

Seed

LPS

RAW264.7

Compounds 20-25

[21]

C. rosea

Root

LPS

RAW264.7

Anti-inflammatory activity through inhibition of the TLR4/
NF-κB/IRF3 signalling pathway

Identification of eight
flavonoids by LC-MS/MS

[24]

Ingredient type	Plant	Medicinal part	Induction factor	Cellular model	Pharmacological effect	Action mechanism	Ref.
Isoflavones, lignans	C. microphylla	Roots	LPS	BV-2	NO inhibition	—	[13]
Coumarins, isoflavonoids	C. turfanensis	Roots	LPS	BV-2	NO inhibition	—	[14]
Spirocyclohexadienyl naphthalenes	C. acanthophylla	Roots	LPS	BV-2	NO inhibition	—	[22]

Ingredient type

Plant

Medicinal part

Induction factor

Cellular
model

Pharmacological effect

Action mechanism

Ref.

Isoflavones, lignans

C. microphylla

Roots

LPS

BV-2

NO inhibition

—

[13]

Coumarins, isoflavonoids

C. turfanensis

Roots

LPS

BV-2

NO inhibition

—

[14]

Spirocyclohexadienyl naphthalenes

C. acanthophylla

Roots

LPS

BV-2

NO inhibition

—

[22]

Plant	Extracts /components	Medicinal part	Induction factors	Animal/cell models/clinical patients	Action mechanism	Ref.
C. microphylla	Ethanol extract	Roots/seeds	Type Ⅱ collagen	SD rats	-	[41]
C. sinica	Ethyl acetate extract	Roots	Fuchs'complete adjuvant	SD rats	Inhibition of NF-κB pathway	[42]
Concrete	Roots	Fuchs' complete adjuvant	SD rats	-	[43]
C. sinica	Aqueous extract	Roots	IL-1β	Rat cartilage cell	Inhibition of MAPKs and NF-κB pathways	[44]
Monosodium iodoacetate	SD rats	-	[44]
Ethyl acetate extract	Roots	Fuchs' complete adjuvant	SD rats	Good ligand-receptor binding activity of core components towards NF-κB	[45]
Ethyl acetate extract	Roots	LPS	RAW264.7	Reduce translocation of NF-κB P65 to the nucleus for negative regulation of NF-κB	[45]
C. tangutica	Ethyl acetate extract	Woody heartwood	Carrageenan	SD rats	-	[46]
C. acanthophylla	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	-	[47]
Above-ground parts	Type Ⅱ collagen	SD rats	-	[48]
Type Ⅱ collagen and Fuchs' complete adjuvant	SD rats	-	[49]
C. pruinosa	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	-	[50]
Wistar rats	-	[51]
C. stenophylla	Ethanol extract	Roots	Type Ⅱ collagen	SD rats	Regulation of tyrosine, glycerophospholipid and galactose metabolism	[52]
Regulation of the NF-κB signalling pathway	[18]
C. arborescens or C. microphylla	Water decoction	Roots		Patients with rheumatoid arthritis	-	[53]
C. conferta	Conferin		Carrageenan	Wistar rats	-	[15]

Plant

Extracts /components

Medicinal part

Induction factors

Animal/cell models/clinical patients

Action mechanism

Ref.

C. microphylla

Ethanol extract

Roots/seeds

Type Ⅱ collagen

SD rats