贻贝活性肽类研究与展望

蒋鑫怡; 杨大鹏; 韦源青; 王欣之; 林彬燕; 刘睿; 吴皓

doi:10.14148/j.issn.1672-0482.2022.0870

贻贝活性肽类研究与展望

doi: 10.14148/j.issn.1672-0482.2022.0870

蒋鑫怡^1,,
杨大鹏¹,
韦源青¹,
王欣之¹,
林彬燕¹,
刘睿^{1, 2, ,},
吴皓^{1, 2, ,}

1.
南京中医药大学/江苏省海洋药用生物资源研究与开发重点实验室, 江苏南京 210023
2.
南京中医药大学/江苏省中药资源产业化过程协同创新中心/中药资源产业化与方剂创新药物国家地方联合工程研究中心, 江苏南京 210023

基金项目:

江苏省自然科学基金青年项目 BK20210695

江苏省高校“青蓝工程”中青年学术带头人

江苏省农业科技自主创新项目 CX(22)3173

江苏省高等学校自然科学研究重大项目 21KJA360007

南京中医药大学中药学一流学科开放课题 2020YLXK009

详细信息

作者简介:
蒋鑫怡，女, 硕士研究生, E-mail: 20210624@njucm.edu.cn

吴皓，二级教授，博士生导师，获江苏省、南京市有突出贡献的中青年专家、江苏省海洋科技标兵、江苏省优秀科技工作者、江苏省海洋中青年科技标兵、江苏省教育科技系统五一巾帼标兵等荣誉称号。现任国家中医药管理局“中药炮制重点学科”带头人，江苏省海洋药用生物资源综合利用重点实验室主任、江苏省海洋药物研究开发中心主任; 江苏省中药炮制重点实验室副主任、国家级中药炮制技术传承基地副主任。为江苏省“青蓝工程跨世纪学术带头人”，国家教育部优秀骨干教师、全国中医药博士生优秀论文指导教师。主持国家自然科学基金重点项目及国家自然科学基金面上项目6项，主持国家攻关、支撑计划，国家863计划、国家公益性行业专项等国家级重点项目9项。获中国海洋学会科学技术特等奖、国家海洋科技进步二等奖、江苏省科技进步奖二等奖、中华中医药学会科技进步二等奖及江苏省中医药科学技术奖一等奖，江苏省教育教学成果二等奖等多项教学、科研奖励

通讯作者:
刘睿, 男，教授, 主要从事动物药资源化学及海洋药用生物资源开发利用研究, E-mail: liurui@njucm.edu.cn

吴皓, 女，教授, 博士生导师, 主要从事海洋药物研究与开发, E-mail: whao5795@njucm.edu.cn

中图分类号: R282.74
计量
- 文章访问数: 63
- HTML全文浏览量: 12
- PDF下载量: 20
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-15
- 网络出版日期: 2022-10-25
- 发布日期: 2022-10-10

Research and Prospect of Mussel Active Peptides

JIANG Xin-yi^1
,,
YANG Da-peng¹,
WEI Yuan-qing¹,
WANG Xin-zhi¹,
LIN Bin-yan¹,
LIU Rui^{1, 2
, ,},
WU Hao^{1, 2
, ,}

1.
Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing 210023, China
2.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

摘要

摘要: 贻贝是我国重要经济贝类, 也是一味海洋中药, 具补肝益肾, 滋阴息风, 养血调经, 益精填髓, 软坚散结, 止血止泻之功效。以贻贝富含的蛋白质、肽类成分的分离纯化、效应机制、新技术新方法应用等研究为切入点, 梳理了近年来发现的贻贝活性肽类成分, 基于现代药理研究与传统功效关联来发现贻贝活性肽类物质。从贻贝资源调查与品质评价, 基于传统中医药理论指导及资源循环利用理念开发贻贝资源、突破贻贝资源综合利用的关键技术、产学研用合作促进贻贝资源综合利用产业化等方面对贻贝资源开发应用提出展望, 为贻贝资源综合利用与产品开发提供思路与参考, 促进贻贝资源的高质量发展。
- 海洋中药 /
- 贻贝 /
- 活性肽 /
- 传统功效 /
- 功效物质 /
- 资源综合利用
Abstract: Marine traditional Chinese medicine refers to the drugs derived from the ocean for the prevention, treatment and diagnosis of diseases under the guidance of traditional Chinese medicine theory, and is an essential part of traditional Chinese medicine. Mussels are an important economic shellfish in our country, and they are also a kind of marine traditional Chinese medicine, with the effect of nourishing the liver and kidney, nourishing Yin and wind, nourishing blood and regulating menstruation, benefiting essence and filling marrow, softening hardness and dispersing knots, stopping bleeding and diarrhea. In this paper, based on the research on the separation and purification of protein and peptide components rich in mussels, the effect mechanism, the application of new technologies and methods, etc., the active peptide components of mussels discovered in recent years are sorted out, and it is proposed to combine modern pharmacological research with traditional efficacy correlation to discover mussel active peptides. The research will provide an outlook on the development and application of mussel resources in terms of mussel resource investigation and quality evaluation, development of mussel resources based on traditional Chinese medicine theory and resource recycling concept, breakthrough in key technologies for comprehensive utilization of mussel resources, and cooperation between industry, academia, research and application to promote the industrialization of comprehensive utilization of mussel resources, providing ideas and references for comprehensive utilization of mussel resources and product development, and promoting high-quality, green and sustainable development of mussel resources.
- marine traditional Chinese medicine /
- mussels /
- active peptides /
- traditional efficacy /
- functional substances /
- comprehensive utilization of resources

HTML全文

图 1 2010—2020年中国贻贝养殖产量的变化情况

Figure 1. Changes in mussel production in China from 2010 to 2020

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表 1 贻贝的传统功效

Table 1. The traditional efficacy of mussels

本草著作	作者及年代	功能主治
《本草拾遗》^[5]	唐代陈藏器，撰于公元739年	主虚羸劳损, 因产瘦瘠, 血气结积, 腹冷, 肠鸣, 下痢腰疼, 带下。
《日华子本草》^[11]	五代韩保昇，撰于公元908—923年	煮熟食之, 能补五脏, 益阳事, 理腰脚气, 消宿食, 除腹中冷气, 痃癖等。
《嘉祐本草》^[7]	北宋掌禹锡、林亿、苏颂等编修, 撰于公元1057—1060年	治虚劳伤惫, 精血少者, 及吐血, 妇人带下、漏下，丈夫久痢, 并煮食之。
《本草图经》^[12]	宋代苏颂，成书于1061年	补五脏, 益阳事, 消宿食。
《证类本草》^[13]	宋代唐慎微，撰于公元1097—1108年	温。补五脏, 理腰脚气, 益阳事, 能消食, 除腹中冷气, 消痃癖气。亦可烧令汁沸出食之。多食令头闷目暗, 可微利即止。北人多不识, 虽形状不典, 而甚益人。又云: 温, 无毒。补虚劳损, 产后血结, 腹内冷痛, 治癥瘕, 腰痛, 润毛发, 崩中带下。烧一顿令饱, 大效。又名壳菜, 常时频烧食即苦, 不宜人。
《本草纲目》^[6]	明代李时珍，成书于公元1578年	虚劳伤惫, 精血衰少, 吐血久痢, 肠鸣腰痛。
《本草汇言》^[14]	明代倪朱谟撰, 初刊于公元1624年	淡菜, 补虚养肾之药也。蔡心吾曰, 此物本属介类, 原其气味甘美而淡, 性本清凉, 故藏器云, 善治肾虚有热, 及热郁吐血, 痢血便血, 及血郁成瘿, 留结筋脉诸疾。
《本经逢原》^[15]	清代张璐, 成书于公元1695年	甘温无毒。淡菜生咸水而味不沾咸, 为消瘿之善药, 兼补阴虚劳伤, 精血衰少, 及妇人带下, 理腰脚气。不宜多食、久食, 令人阳痿不起及脱人发。一切海中苔菜皆然, 不独淡菜也。
《本草从新》^[16]	清代吴仪洛, 成书于公元1757年	补阴, 甘咸温, 补五脏, 益阳事, 理腰脚气, 治虚劳伤惫, 精血衰少, 及吐血久痢, 肠鸣腰痛, 妇人带下, 产后瘦瘠, 又能消瘿气。
《得配本草》^[17]	清代严西亭，成书于公元1761年	淡菜, 甘, 温。补五脏, 益阳事, 除腹冷, 治带下。产后瘠瘦, 食之而肥。煮汁煎药亦可。
《本草便读》^[18]	清代张秉成，成书于公元1887年	味咸，温, 补阴益阳, 治虚劳, 填精养血。……故能入肾益阴, 治精血衰少。

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表 2 贻贝中的活性肽类成分

Table 2. The active peptide constituents of mussels

来源	多肽氨基酸结构序列	药理活性	效应/机制	参考文献
蓝贻贝	YPPAK	抗氧化	DPPH自由基清除率(EC₅₀=2.62 mg·mL^-1)、羟基自由基清除率(EC₅₀=0.228 mg·mL^-1)和超氧化物自由基(EC₅₀=0.072 mg·mL^-1)	[22]
	PIISVYWK FSVVPSPK	促成骨、预防骨质疏松	100 μmol·L^-1孵育14 d后, 小鼠骨髓间充质干细胞(MBMMSCs)的ALP活性显著增加(324±6)% 100 μmol·L^-1孵育14 d后, MBMMSCs的ALP活性显著增加(315±11)%	[23]
	ELEDSLDSER	抗凝	和凝血酶上的氨基酸Gln38和Thr74位点结合	[24]
	VQQELEDAEERADSAEGSLQK RMEADIAAMQSDLDDALNGQR AAFLLGVNSNDLLK	抗凝	— — —	[25]
	EPTF FTVN	抗氧化	抑制H₂O₂诱导的HUVEC细胞内ROS的产生, 激活HO-1/Nrf2通路, 减少Cyt C释放、Bax表达, Caspase-3活化, 增加Bcl-2表达, 保护细胞免受氧化应激	[26]
	Edman降解测定N-端序列EVMAGNLYPG	ACE抑制	ACE抑制活性: IC₅₀=19.34 μg·mL^-1	[27]
	PIIVYWK TTANIEDRR FSVVPSPK	抗氧化	DPPH自由基清除活性IC₅₀=(0.71±0.01) mmol·L^-1 DPPH自由基清除活性IC₅₀=(2.33±0.56) mmol·L^-1 DPPH自由基清除活性IC₅₀=(1.09±0.03) mmol·L^-1	[28]
紫贻贝	YPRKDETGAERT	促成骨	调节BMP-2信号通路促进成骨细胞的分化; 促进MC3T3-E1成骨细胞增殖	[29-30]
	IK YEGDP WF SWISS	ACE抑制	IC₅₀=(0.77±0.020) mg·mL^-1 IC₅₀=(0.19±0.010) mg·mL^-1 IC₅₀=(0.40±0.015) mg·mL^-1 IC₅₀=(0.32±0.017) mg·mL^-1	[31]
	LGKDQVRT	促成骨、预防骨质疏松	Ca²⁺与LGKDQVRT肽的金属受体螯合, 促进了成骨细胞的增殖、分化和Caco-2细胞对钙的转运、吸收	[32]
	IEELEEELEAER(PIE)	促成骨	PIE可以1∶1的比例螯合钙并促进钙离子的吸收利用。PIE-CPC(骨用磷酸钙接合剂)材料促进MC3T3-E1成骨细胞的生长、增殖, 并对大肠杆菌有抑制作用	[33]
	EADIDGDGQVYEEFVAMMTSK	抗凝	与凝血因子FIX、FX和FII相互作用, 并抑制固有FXase对FX的蛋白水解激活和凝血酶原酶复合物形成FIIa	[34]
	IEELEEELEAER IQLLEEDLER	抗氧化	提高抗氧化应激能力, 降低了内源性ROS水平、老化色素的积累以及细胞凋亡, 通过调节daf-2和daf-16的mRNA表达来促进寿命延长	[35]
	Edman降解测定N-部分序列DCCRKPFRKHCWDCTAGTPYYG YSTRNIFGCTC… 分子量7 533.4 Da	抗菌	对粗糙链球菌和枯枝链球菌的生长有抑制作用	[36]
	SCASRCKGHCRARRCGYYVSVLY-RGRCYCKCLRC(Mytilins B) SCASRCKSRCRARRCRYYVSVRYGGFCYCRC(Mytilins C) GCASRCKAKCAGRRCKGWASASFRRRCYCKCFRC(Mytilins D)	抗菌	对革兰氏阳性和革兰氏阴性细菌有显著活性
	VVTCGSLCKAHCTFRKCGYFMSVLYHGRCYCRCLLC(Mytilins G1)	抗菌	仅对革兰氏阳性菌有活性	[37]
	SCASRCKGHCRARRCGYYVSVLYRGRCYCKCLRC	抗菌	抑制华丽弧菌LGP32 (MIC 125 mmol·L^-1)、鳗弧菌(MIC 2 mmol·L^-1)、溶血微球菌和大肠杆菌(MIC 1 mmol·L^-1)的体外生长	[38]
厚壳贻贝	Edman降解测定N-端部分序列GVSLLQQFFL	抗炎	可抑制脂多糖刺激的RAW264.7细胞中NO的产生	[39]
	SLPIGLMIAM	抗氧化	羟基、DPPH、超氧化物和过氧自由基清除活性的IC₅₀分别为0.118、0.154、0.316和0.243 mg·mL^-1	[40]
	AFNIHNRNLL	抗肿瘤	诱导前列腺、乳腺癌和肺癌细胞的细胞死亡	[21]
	DLY	抗肿瘤	对人前列腺癌DU-145和PC-3细胞有生长抑制作用	[41]
	Edman降解测定N-端部分序列TVKCGMNGKMPCKHGAFYTDAC-DKNVFYR… 分子量6 297.55 Da	抗菌	参与了宿主对细菌感染的免疫反应, 对真菌和革兰氏阳性菌表现出主要的抗菌活性	[42]
	Edman降解测定N-端部分序列SDHQMAQSACMGLAQDAAYASAI 分子量11 182 Da	抗菌	对革兰氏阳性菌和革兰氏阴性菌均有抑菌活性	[43]
	LVGDEQAVPAVCVP	抗氧化	通过抗脂质过氧化作用清除自由基, 对多不饱和脂肪酸表现出更高的保护活性	[44]
	TVKCGMNGKMPCKHGAFYTDTCDKNVFYRCVWGRPVKKACGRGLVWNPRGFCDY	抗菌	对2种革兰氏阳性菌, 金黄色葡萄球菌ATCC 25923和枯草芽孢杆菌151-1都有抗菌作用	[45]
翡翠贻贝	EGLLGDVF	抗炎	减少促炎细胞因子、NO和COX-2活化的产生, 并下调LPS刺激的RAW264.7细胞中iNOS和COX-2蛋白的表达	[46]
翡翠贻贝	MLKLILVACLVLTLSGSEAAPQRRATCDLFSIFGVGDSACAAHCLVLGHRGGYCNSQSVCICRD	抗菌	准确地上调血细胞中Pv-Def mRNA的表达	[47]

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