基于in silico技术探究益母草在化妆品中的应用前景

doi:10.3969/j.issn.2097-2806.2023.06.011

摘要/Abstract

摘要：

益母草具有行血养血，活血化瘀的作用，临床应用广泛，常用来主治妇科疾病，近年来益母草的美容应用逐渐受到关注。本研究利用in silico技术平台，通过文献计量学对益母草的研究现状和未来的发展态势进行了预测，同时结合网络药理学对益母草皮肤美容的功效及物质基础进行预测，结果表明益母草的活性成分萜类化合物及益母草碱可通过NADPH、PDPK1、MAOB、VEGF2、SIRT2等靶点有效促进血液流动，改善皮肤微循环，调节激素代谢，降低炎症反应，抵御氧化应激，具有延缓皮肤老化，滋养皮肤的功效。本研究为益母草作为化妆品植物功效原料的物质基础及功效机理提供了理论基础，同时证明了益母草作为化妆品功效原料的独特性，具备良好的发展前景。

关键词: 益母草, 化妆品, 皮肤美容, in silico技术, 文献计量, 网络药理学

Abstract:

Motherwort （Leonurus japonicas Houtt.） is a good gynecological medicine, which has the function of promoting circulation of blood, nourishing blood and activating circulation to remove blood stasis. It is widely used in clinical practice and commonly used to treat gynecological diseases, while the beauty application of motherwort has gradually attracted attention in recent year. This article built an in silico technology platform to present a systematic review of the literature concerning motherwort over the past two decades through bibliometrics to explore current research hotspots and predict the future development trends, and combine with network pharmacology to predict the efficacy and material basis of motherwort for skin beauty. The results show that terpenoids and alkali, the main active ingredient of motherwort, can effectively open blood vessles and expand blood passages to improve the facial skin blood micro-circulation and strengthen the skin's metabolism through NADPH, PDPK1, MAOB, VEGF2, SIRT2. In addition, they can regulate hormone metabolism to maintain the skin barrier, regulate the secretion of inflammatory factors to ease skin inflammation and involve in the regulation of cell-cycle to prevents oxidative stress-mediated skin aging by ER-α,ER-β, AKRAC3, CA2, HSP90AA1, MAPK14, CDK2 and other targets. Our research suggests that motherwort has the effect of delaying skin aging and nourishing skin. This study provides the theoretical basis for the material basis and efficacy mechanism of motherwort as a cosmetic plant efficacy raw material, and proves the uniqueness of motherwort as a cosmetic efficacy raw material, and has good development prospects.

Key words: Leonurus japonicus, cosmetics, skin health, in silico, bibliometrics, network pharmacology

中图分类号:

TQ658

刘丽, 尹雅婷, 程康, 李惠, 吕智, 易帆. 基于in silico技术探究益母草在化妆品中的应用前景[J]. 日用化学工业（中英文）, 2023, 53(6): 686-697.

Liu Li, Yin Yating, Cheng Kang, Li Hui, Lv Zhi, Yi Fan. Research on the application prospect of motherwort in cosmetics based on in silico approach[J]. China Surfactant Detergent & Cosmetics, 2023, 53(6): 686-697.

图/表 9

图1

图2

图3

表1

图4

图5

表2

图6

表3

益母草化合物靶点对接信息表"

序号	ID	化合物	Uniprot	Protein	蛋白	分类
1	MOL001445	Leonurine	P15559	NAD（P）H dehydrogenase [QUINONE] 1	脱氢酶[醌]1（NAD（P）H）	人体循环-凝血
2	MOL001445	Leonurine	Q08499	cAMP-specific 3', 5'-cyclic phosphodiesterase 4D	特异性3', 5'-环状磷酸二酯酶4D（cAMP）	其他
3	MOL001445	Leonurine	Q92731	Estrogen receptor beta	雌激素受体β（ER2）	代谢-激素
4	MOL001445	Leonurine	O14757	serine/threonine-protein kinase chk1	丝氨酸/苏氨酸-蛋白激酶 CHK1	细胞-代谢周期
5	MOL001445	Leonurine	O15530	Phosphoinositide-dependent protein kinase 1	磷酸肌醇依赖性蛋白激酶1（PDPK1）	免疫-炎症
6	MOL001445	Leonurine	O15530	Phosphoinositide-dependent protein kinase 1	磷酸肌醇依赖性蛋白激酶1（PDPK1）	人体循环-血管
7	MOL001445	Leonurine	P27338	amine oxidase （flavin-containing b	胺氧化酶（含黄素B）（MAOB）	人体循环-血管
8	MOL001445	Leonurine	P07900	heat shock protein hsp 90-α	热休克蛋HSP 90-α（HSP90AA1）	免疫-炎症
9	MOL001445	Leonurine	P25440	Bromodomain-containing protein 2	含溴结构域蛋白2	其他
10	MOL001445	Leonurine	P11309	Proto-oncogene serine/threonine-protein kinase Pim-1	原癌基因丝氨酸/苏氨酸蛋白激酶Pim-1（PIM1）	细胞-代谢周期
11	MOL001445	Leonurine	P35968	Vascular endothelial growth factor receptor 2	血管内皮生长因子受体2（VEGF2）	人体循环-血管
12	MOL001445	Leonurine	Q16539	Mitogen-activated protein kinase 14	丝裂原活化蛋白激酶14（MAPK14）	免疫-炎症
13	MOL001445	Leonurine	Q04771	Activin receptor type-1	激活素受体1型	其他
14	MOL001445	Leonurine	Q9BZP6	Acidic mammalian chitinase	酸性哺乳动物几丁质酶（CHIA）	免疫-炎症
15	MOL001445	Leonurine	P24941	Cyclin-dependent kinase 2	细胞周期蛋白依赖性激酶2（CDK2）	细胞-衰老
16	MOL001445	Leonurine	P56817	BETA-SECRETASE 1	β-分泌酶1（BACE1）	其他
17	MOL001445	Leonurine	P28482	Mitogen-activated protein kinase 1	丝裂原活化蛋白激1（MAPK1）	细胞-代谢周期
18	MOL001445	Leonurine	P29597	Non-receptor tyrosine-protein kinase TYK2	非受体酪氨酸蛋白激酶（TYK2）	免疫-炎症
19	MOL001445	Leonurine	O60885	Bromodomain-containing protein 4	含溴结构域蛋白4（BRD4）	细胞-代谢周期
20	MOL001445	Leonurine	Q9NYY3	Serine/threonine-protein kinase PLK2	丝氨酸/苏氨酸蛋白激酶（PLK2）	细胞-代谢周期
21	MOL001445	Leonurine	P03372	Estrogen receptor	雌激素受体（ER-α）	代谢-激素
22	MOL001445	Leonurine	P03372	Estrogen receptor	雌激素受体（ER-α）	免疫-炎症
23	MOL001445	Leonurine	Q07343	cAMP-specific 3', 5'-cyclic phosphodiesterase 4B	cAMP特异性3', 5'-环状磷酸二酯酶4B（PDE4B）	其他
24	MOL001445	Leonurine	Q8IXJ6	NAD-dependent protein deacetylase sirtuin-2	NAD依赖性蛋白脱乙酰酶sirtuin-2（SIRT2）	人体循环-血管
25	MOL001445	Leonurine	Q8IXJ6	NAD-dependent protein deacetylase sirtuin-2	NAD依赖性蛋白脱乙酰酶sirtuin-2（SIRT2）	免疫-炎症
26	MOL001427	Leojaponin	P24941	Cyclin-dependent kinase 2	细胞周期蛋白依赖性激酶2（CDK2）	细胞-衰老
27	MOL001426	Hispanolone	P05091	Aldehyde dehydrogenase	醛脱氢酶	其他
28	MOL001426	Hispanolone	P42330	Aldo-keto reductase family 1 member C3	醛酮还原酶家族1成员C3（AKRAC3）	代谢-激素
29	MOL001422	iso-preleoheterin	Q16696	Cytochrome P450 2A13	细胞色素P450 2A13	其他
30	MOL001421	preleoheterin	P00918	Carbonic anhydrase 2	碳酸酐酶2（CA2）	代谢-内分泌

表3

参考文献 43

[1]	Li Jiangfang. Progress in the pharmacy research of motherwort[J]. Physician, 2013, 8 (5) : 533-536.
[2]	Ni Jiekong. Beauty secret recipe of Wu zetian[J]. Literature & History Expo., 2016 (8) : 57-58.
[3]	Wang Hui. The content of rutin in motherwort was determined by RP-HPLC[J]. Jiangsu Traditional Chinese Medicine, 2009, 41 (11) : 54-55.
[4]	Zhao Siqi, Meng Hong, Yi Fan. Recommendations for computer-aided drug design for screening of cosmetic plant-derived efficacy raw materials[J]. China Surfactant Detergent & Cosmetics, 2019, 49 (4) : 253-258, 274.
[5]	Yi F, Li L, Xu L J, et al. In silico approach in reveal traditional medicine plants pharmacological material basis[J]. Chin. Med., 2018, 13: 33.
[6]	Kazmi S R, Jun R, Yu M S, et al. In silico approaches and tools for the prediction of drug metabolism and fate: A review[J]. Comput. Biol. Med., 2019, 106: 54-64. doi: S0010-4825(19)30008-3 pmid: 30682640
[7]	Chen C. Science mapping: a systematic review of the literature[J]. Journal of Data and Information Science, 2017, 2 (2) : 1-40.
[8]	Hao Da C, Xiao P G. Network pharmacology: a Rosetta Stone for traditional Chinese medicine[J]. Drug Dev. Res., 2014, 75 (5) : 299-312. doi: 10.1002/ddr.2014.75.issue-5
[9]	Ren Haiwei, Sun Yifan, Ren Yuwei, et al. Research progress on silage additives based on biblientation[J]. Biotech. Notification, 2022, 38 (8) : 261-274.
[10]	Bu Lan, Liu Fei, Xiong Liang, et al. Progress of chemical composition and pharmacological effects of terpenes[J]. World of Traditional Chinese Medicine, 2020, 15 (9) : 1237-1246.
[11]	Zhou Yaoxiang, Lai Yanhua. Treatment of traditional Chinese medicine and acne removal in 80 cases of acne vulgaris[J]. New Traditional Chinese Medicine, 2007 (1) : 71-72, 78.
[12]	Zhao Lei. Knowledge atlas of online public opinion research in China: based on visual analysis of CiteSpace software[J]. Secretary, 2020 (4) : 40-56.
[13]	Chen Yuzhen. Effect of motherwort injection-assisted anterior and posterior uterine wall-penetrating suture operation on uterine recovery and coagulation function in high-risk and refractory postpartum hemorrhage in women[J]. The Electronic Journal of Modern Medicine and Health Research, 2021, 5 (22) : 71-74.
[14]	Feng Qinxi, Zhang Huichang, Li Guang. Study on traditional Chinese medicine acne beauty cream[J]. Journal of Mudanjiang Medical College, 2001 (1) : 51-52.
[15]	Xu Wenhong. Motherwort facial mask external application to treat acne in 78 cases[J]. Journal of Zhejiang College of Traditional Chinese Medicine, 2004 (5) : 38-39.
[16]	Cheng Jing, Bing Feihong, Dan Hanxiong. Experimental study on anti-skin aging of motherwort juice[J]. Chinese Pharmacist, 2007 (12) : 1181-1183.
[17]	Wang Liming. Experimental study on the inhibitory effect of the motherwort fresh juice on skin melanin[J]. Hubei Journal of Traditional Chinese Medicine, 2008 (3) : 60-61.
[18]	Li Li, Wang Tao. Application of Chinese wort in cosmetics[J]. Daily Chemicals Science, 2013, 36 (12) : 36-38.
[19]	Gu Y, Sheng R, Wu J, et al. Reduced nicotinamide adenine dinucleotide phosphate inhibits rat platelet aggregation and p38 phosphorylation[J]. Thromb. Res., 2018, 171: 121-129. doi: S0049-3848(18)30554-1 pmid: 30292134
[20]	Huang S W, Lien J C, Kuo S C, et al. Antiangiogenic mechanisms of PJ-8, a novel inhibitor of vascular endothelial growth factor receptor signaling[J]. Carcinogenesis, 2012, 33 (5) : 1022-1030. doi: 10.1093/carcin/bgs127
[21]	Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angitogenesis[J]. Circulation Research, 2002, 90 (12) : 1243-1250. doi: 10.1161/01.res.0000022200.71892.9f pmid: 12089061
[22]	Wu B, You S, Qian H, et al. The role of SIRT2 in vascular-related and heart-related diseases: A review[J]. J. Cell Mol. Med., 2021, 25 (14) : 6470-6478.
[23]	Hashimoto-Komatsu A, Hirase T, Asaka M, et al. Angiotensin Ⅱ induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells[J]. Hypertens Res., 2011, 34 (8) : 949-956. doi: 10.1038/hr.2011.64 pmid: 21677656
[24]	Grimsby J, Chen K, Wang L J, et al. Human monoamine oxidase A and B genes exhibit identical exon-intron organization[J]. Proceedings of the National Academy of Sciences of the United States of America, 1991, 88 (9) : 3637-3641. pmid: 2023912
[25]	Ye Wangyun. Blood Rheology and microcirculation[J]. Journal of Microcirculation, 2000 (4) : 19-22.
[26]	Penning T M, Burczynski M E, Jez J M, et al. Human 3 alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones[J]. Biochemical Journal, 2000, 351: 67-77. doi: 10.1042/0264-6021:3510067 pmid: 10998348
[27]	Murphy E. Estrogen signaling and cardiovascular disease[J]. Circ. Res., 2011, 109 (6) : 687-696. doi: 10.1161/CIRCRESAHA.110.236687 pmid: 21885836
[28]	Kumar S, Rulhania S, Jaswal S, et al. Recent advances in the medicinal chemistry of carbonic anhydrase inhibitors[J]. European Journal of Medicinal Chemistry, 2021, 209: 112923. doi: 10.1016/j.ejmech.2020.112923
[29]	Verdler-Sevrain S. Effect of estrogens on skin aging and the potential role of selective estrogen receptor modulators[J]. Climacteric, 2007, 10 (4) : 289-297. doi: 10.1080/13697130701467157
[30]	Sator P G, Schmidt J B, Rabe T, et al. Skin aging and sex hormones in women-clinical perspectives for intervention by hormone replacement therapy[J]. Experimental Dermatology, 2004, 13: 36-40. doi: 10.1111/exd.2004.13.issue-s4
[31]	Jia Shengnan, Shi Jiaxin, Li Xiaomin. Progress in the mechanism of phosphatidylinositol-3-kinase signaling pathway regulating the expression of inflammatory mediators[J]. Chongqing Medicine, 2016, 45 (18) : 2567-2570.
[32]	Wei Y, Chen J, Cai G E, et al. Rosmarinic acid regulates microglial M1/M2 polarization via the PDPK1/Akt/HIF pathway under conditions of neuroinflammation[J]. Inflammation, 2021, 44 (1) : 129-147. doi: 10.1007/s10753-020-01314-w
[33]	Pan W, Wei N, Xu W, et al. MicroRNA-124 alleviates the lung injury in mice with septic shock through inhibiting the activation of the MAPK signaling pathway by downregulating MAPK14[J]. International Immunopharmacology, 2019, 76: 105835. doi: 10.1016/j.intimp.2019.105835
[34]	Mazur M, Zielinska A, Grzybowski M M, et al. Chitinases and Chitinase-Like proteins as therapeutic targets in inflammatory diseases, with a special focus on inflammatory bowel diseases[J]. International Journal of Molecular Sciences, 2021, 22 (13) : 6966. doi: 10.3390/ijms22136966
[35]	Segovia-Mendoza M, Morales-Montor J. Immune tumor microenvironment in breast cancer and the participation of estrogens and its receptors into cancer physiopathology[J]. Frontiers In Immunology, 2019, 10: 348. doi: 10.3389/fimmu.2019.00348 pmid: 30881360
[36]	Lee A S, Jung Y J, Kim D, et al. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages[J]. Biochemical and Biophysical Research communications, 2014, 450 (4) : 1363-1369. doi: 10.1016/j.bbrc.2014.06.135 pmid: 25003320
[37]	Yin Q, Wu L C, Zheng L, et al. Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis[J]. Archives of Dermatological Research, 2018, 310 (9) : 711-728. doi: 10.1007/s00403-018-1858-0 pmid: 30171347
[38]	Zhou Yan. Study on chemical composition and anti-inflammatory activity prediction of motherwort, whitewort and Changshan[D]. Kunming: Yunnan University, 2020.
[39]	Zheng Nan, Xu Yang. Function of cyclin-dependent kinase 2 and its inhibitors[J]. The Chinese Journal of Cell Biology, 2021, 43 (4) : 815-827.
[40]	Upadhya D, Ogata M, Reneker L W. MAPK1 is required for establishing the pattern of cell proliferation and for cell survival during lens development[J]. Development, 2013, 140 (7) : 1573-1582. doi: 10.1242/dev.081042 pmid: 23482492
[41]	Matsuyama M, Goto H, Kasahara K, et al. Nuclear Chk1 prevents premature mitotic entry[J]. Journal of Cell Science, 2011, 124 (13) : 2113-2119. doi: 10.1242/jcs.086488
[42]	Han N, Anwar D, Hama N, et al. Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells[J]. Inflammation and Regeneration, 2020, 40 (1) : 25. doi: 10.1186/s41232-020-00129-4
[43]	Villegas E, Kabotyanski E B, Shore A N, et al. Plk2 regulates mitotic spindle orientation and mammary gland development[J]. Development, 2014, 141 (7) : 1562-1571. doi: 10.1242/dev.108258 pmid: 24598160

出现频次前十的关键词类别（WOS）				出现频次前十的关键词类别（CNKI）
序号	类别	频次	关键词	序号	类别	频次	关键词
1	氧化应激	43	oxidative stress, antioxidant activity, antioxidant, antioxidant activity	1	益母草	1 383	益母草，益母草膏，中药，中草药
2	炎症	37	antiinflammatory activity, NF-κβ, inflammation	2	产科疾病	1 022	产后出血，缩宫素，药物流产，剖宫产
3	苷类	29	glycoside, polysaccharide	3	成分研究	326	益母草碱，含量测定，化学成分，水苏碱
4	凋亡	24	apoptosis, induced apoptosis	4	妇科疾病	170	阴道出血，痛经，崩漏，月经不调
5	挥发油	22	essential oil, essential oil composition	5	临床	169	临床观察，临床应用，临床研究，临床疗效
6	萜类	22	labdane diterpene, monoterpene, diterpenoid, triterpenoid, labdane type diterpenoid, diterpene	6	名医经验	157	名医经验，医案，专家经验，用药规律
7	抗菌	21	antibacterial activity, antimicrobial activity, antibacterial	7	安全性	141	质量标准，不良反应，安全性，质量控制
8	酸	17	acid	8	肾脏疾病	65	慢性肾炎，肾毒性，肾病，慢性肾衰
9	生物碱类	9	alkaloid, stachydrine	9	不孕症	52	不孕症，不孕，不孕证，不孕患者
10	酚类	7	polyphenol, phenolic compound	10	活血	38	活血，活血祛瘀，活血化瘀，活血调经

Mol ID	化合物	AlogP
MOL001445	益母草碱（Leonurine）	1.23
MOL001421	前益母草乙素（preleoheterin）	1.87
MOL001422	iso-preleoheterin	2
MOL001426	益母草素（Hispanolone）	3.7
MOL001427	Leojaponin	4.05