药学学报

Pharmacological activity	Structure of probes	Experiment system	Target	Molecular mechanism	Reference
Anti-inflammatory		RAW 264.7	IRGM1	Berberine shows anti-inflammatory activity through inhibiting the PI3K/AKT/mTOR pathway by targeting IRGM1.	[17]
		HEK-293	MAP2K7	Berberine shows anti-inflammatory activity via directly targeting MAP2K7 to inhibit p-JNK rather than JNK activity.	[28]
		PMA-THP-1	NEK7	Berberine directly targets the NEK7 protein to block the NEK7-NLRP3 interaction and exert anti-inflammatory activity.	[29]
		PMA-THP-1	EIF2AK2	Berberine directly inhibits the dimerization of EIF2AK2 to exert synergistic anti-inflammatory effects.	[30]
Glucolipid metabolism regulation		HepG2	AKR1B10	Berberine alleviates NAFLD via mediating PPAR signaling pathways through targeting AKR1B10.	[31]
		HepG2	TIGAR	Berberine shows hypoglycemic effects via attenuating the conversion of fructose-2, 6-bisphosphate to fructose-6-phosphate by targeting TIGAR.	[32]
Anti-microbial		P. anaerobius ATCC27337	FtfL	Berberine can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active left.	[33]
Anti-cancer	—	RPMI-8266 and MM.1S	UHRF1	Berberine shows therapeutic activity against multiple myeloma through targeting UHRF1 and inducing UHRF1 degradation via the ubiquitin-dependent proteasome system.	[34]

Pharmacological activity	Structure of probes	Experiment system	Target	Molecular mechanism	Reference
Anti-inflammatory		RAW 264.7	IRGM1	Berberine shows anti-inflammatory activity through inhibiting the PI3K/AKT/mTOR pathway by targeting IRGM1.	[17]
		HEK-293	MAP2K7	Berberine shows anti-inflammatory activity via directly targeting MAP2K7 to inhibit p-JNK rather than JNK activity.	[28]
		PMA-THP-1	NEK7	Berberine directly targets the NEK7 protein to block the NEK7-NLRP3 interaction and exert anti-inflammatory activity.	[29]
		PMA-THP-1	EIF2AK2	Berberine directly inhibits the dimerization of EIF2AK2 to exert synergistic anti-inflammatory effects.	[30]
Glucolipid metabolism regulation		HepG2	AKR1B10	Berberine alleviates NAFLD via mediating PPAR signaling pathways through targeting AKR1B10.	[31]
		HepG2	TIGAR	Berberine shows hypoglycemic effects via attenuating the conversion of fructose-2, 6-bisphosphate to fructose-6-phosphate by targeting TIGAR.	[32]
Anti-microbial		P. anaerobius ATCC27337	FtfL	Berberine can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active left.	[33]
Anti-cancer	—	RPMI-8266 and MM.1S	UHRF1	Berberine shows therapeutic activity against multiple myeloma through targeting UHRF1 and inducing UHRF1 degradation via the ubiquitin-dependent proteasome system.	[34]

Pharmacological activity	Therapeutical component	Structure of probes	Experiment system	Target	Molecular mechanism	Reference
Anti-inflammatory	Baicalein		RAW 264.7	HSP90	Baicalein shows antipyretic and analgesic activities via targeting HSP90 and inducing the degradation of COX-2.	[43]
Hypolipidemic activity	Baicalin		HeLa	CPT1A	Baicalin shows anti-steatosis activity via directly activating hepatic CPT1 to accelerate the lipid influx into mitochondria for oxidation.	[44]
Anti-cancer	Baicalin		MDA-MB-231	β2-AR	Baicalin could directly bind to β2-AR, subsequently inhibit cAMP-PKA-FAK pathway, and thus impede epithelial-mesenchymal transition.	[45]
Anti-microbial	Baicalein	—	Candida albicans SC5314	Cpd2p	Baicalein could increase intracellular oxidative damage by upregulating the expression of Cpd2p to inhibit the growth of C. albicans.	[46]

Pharmacological activity	Therapeutical component	Structure of probes	Experiment system	Target	Molecular mechanism	Reference
Anti-inflammatory	Baicalein		RAW 264.7	HSP90	Baicalein shows antipyretic and analgesic activities via targeting HSP90 and inducing the degradation of COX-2.	[43]
Hypolipidemic activity	Baicalin		HeLa	CPT1A	Baicalin shows anti-steatosis activity via directly activating hepatic CPT1 to accelerate the lipid influx into mitochondria for oxidation.	[44]
Anti-cancer	Baicalin		MDA-MB-231	β2-AR	Baicalin could directly bind to β2-AR, subsequently inhibit cAMP-PKA-FAK pathway, and thus impede epithelial-mesenchymal transition.	[45]
Anti-microbial	Baicalein	—	Candida albicans SC5314	Cpd2p	Baicalein could increase intracellular oxidative damage by upregulating the expression of Cpd2p to inhibit the growth of C. albicans.	[46]

基于中药药味的化学生物学研究——以苦味中药为例

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冯心池 ¹ , 张强 ² , 姚园园 ¹ , 康宁 ² , 李根 ¹ , 丁丽琴 ³ , 孙成鹏 ¹ , 邱峰 ¹^,³^,^*

药学学报 | 专题报道: 中药化学生物学研究进展与展望 2026,61(1): 21-28

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药学学报 |专题报道: 中药化学生物学研究进展与展望 2026 , 61 (1) : 21 -28

基于中药药味的化学生物学研究——以苦味中药为例

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冯心池¹, 张强², 姚园园¹, 康宁², 李根¹, 丁丽琴³, 孙成鹏¹, 邱峰¹^,³^,^*

作者信息

¹天津中医药大学中药学院, 天津 301617

²天津中医药大学医学技术学院, 天津 301617

³天津市中药功效物质重点实验室, 天津 301617

通讯作者:

邱峰, Tel: 86-22-59791871, E-mail: fengqiu20070118@163.com

作者简介:

共同第一作者.

作者贡献:

冯心池负责论文的撰写和图片的绘制; 张强负责论文的撰写和图片的绘制; 姚园园负责文献的收集与分析; 康宁负责文献的收集与分析; 李根负责图片的绘制; 丁丽琴负责图片的绘制; 孙成鹏负责稿件的修改; 邱峰指导文章的撰写, 并负责稿件的修改与校对。

Chemical biology study of Chinese material medica based on theory of flavors-take bitter-propertied Chinese material medica as examples

Xin-chi FENG¹, Qiang ZHANG², Yuan-yuan YAO¹, Ning KANG², Gen LI¹, Li-qin DING³, Cheng-peng SUN¹, Feng QIU¹^,³^,^*

Affiliations

¹School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

²School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

³Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin 301617, China

出版时间: 2026-01-12 doi: 10.16438/j.0513-4870.2025-0427

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摘要

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中药功效“物质说不清、机制道不明”是制约中医药现代化、国际化的瓶颈问题。作为诠释中药功效的核心理论要素, 五味“药性理论”为中医临床用药提供了重要依据。基于靶标垂钓技术与分子互作分析的中药化学生物学已成为阐释中药作用靶标和分子机制的有力手段。本文以苦味中药的功效物质研究为例, 探讨基于中药药味的化学生物学研究思路, 为药性理论指导下的中药功效物质阐释提供研究范式。

关键词

药性理论 / 化学生物学 / 苦味中药 / 体内过程 / 作用机制

Abstract

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The "unclear substances and mechanisms" underlying the efficacy of Chinese material medica is a bottleneck limiting its modernization and internationalization. As the fundamental attribute that reflects the efficacy of Chinese material medica, the concept of "Five flavors" serves as the theoretical basis guiding its clinical application. Chemical biology, utilizing target fishing technology and molecular interaction analysis, has become a comprehensive approach to elucidate the targets and underlying molecular mechanisms of Chinese material medica. This review focuses on studies of the effective substances found in bitter-propertied Chinese material medica as an example to explore chemical biology strategies based on the flavors of Chinese material medica, providing a research perspective for interpreting effective substances through the lenses of the "Five flavors" theory.

Key words

theory of traditional Chinese medicine property / chemical biology / bitter-propertied Chinese material medica / in vivo process / mechanism of action

引用本文

冯心池, 张强, 姚园园, 康宁, 李根, 丁丽琴, 孙成鹏, 邱峰. 基于中药药味的化学生物学研究——以苦味中药为例. 药学学报, 2026 , 61 (1) : 21 -28 . DOI: 10.16438/j.0513-4870.2025-0427

Xin-chi FENG, Qiang ZHANG, Yuan-yuan YAO, Ning KANG, Gen LI, Li-qin DING, Cheng-peng SUN, Feng QIU. Chemical biology study of Chinese material medica based on theory of flavors-take bitter-propertied Chinese material medica as examples[J]. Acta Pharmaceutica Sinica, 2026 , 61 (1) : 21 -28 . DOI: 10.16438/j.0513-4870.2025-0427

正文

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中药功效物质基础研究作为中医药现代化战略的重中之重, 是阐释中药整体功效及其作用本质的核心环节, 也是中药安全性、有效性和质量控制的重要基础。“中药化学生物学”是在中医药理论指导下, 以中药有效成分为工具, 研究中药的作用靶标、分子机制及其对生命过程的调控作用^[1]。这门学科实现了中药化学与生物学的深度融合, 为揭示中药功效物质的作用机制提供了新的视角。

在以往研究中, 对中药成分的活性评价与其传统功效之间的关联性不强, 且对功效物质的机制研究不够深入。此外, 针对中药体内化学成分, 特别是代谢产物的活性研究重视程度不足, 导致中药体内直接功效物质不明确。因此, 如何基于中药的传统功效和体内代谢信息, 解析其功效物质基础与作用机制, 是中药现代化、国际化进程中亟待解决的关键科学问题。

“五味”最早记载于《神农本草经》, 不仅反映了药物的味道, 更概括了其核心功效—具有相似药味的药物往往具有相近的治疗效果, 这一理论体系为中药功效的阐释与临床应用规律的总结提供了重要依据^[2]。《黄帝内经·素问·脏气法时论篇》首次系统归纳了五味的基本作用, 即辛散、酸收、甘缓、苦坚、咸软。在过去近30年的时间里, 研究人员对中药五味进行了系列研究, 逐渐形成以药性理论为指导, 融合化学生物学技术, 解析五味中药功效物质和机制的创新研究范式。

1　基于中药药味的化学生物学研究思路

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基于中药药味的化学生物学研究主要包括中药功效关联活性物质发现和机制解析两个部分。具体研究思路为: 基于中药的体内外化学信息和生物学信息, 从体内外化学成分获取、功效关联药理活性评价、作用靶标及机制的阐释等多个维度, 深入解析中药的功效物质和分子机制。在各味中药的化学信息表征环节, 纳入中药成分体内信息的解析; 在功效关联药理活性评价环节, 强调中医药理论的指导, 选择与五味功效密切相关的药理活性进行评价。在作用靶标及机制的阐释环节, 充分借助化学生物学的技术手段, 实现作用机制的深度解析。

1.1　中药体内外化学成分的系统分析与获取

中药体内外化学成分的系统分析与获取是基于中药药味的化学生物学研究的基础。相较于中药化学成分的获取, 中药成分体内代谢产物的获取更为复杂。20世纪90年代, 邱峰教授提出了“中药体内直接物质基础研究的新思路”, 并进行了系列探索与实践^[3]。发现中药成分的体内代谢产物在阐明其功效物质的过程中扮演着重要角色, 如穿心莲^[4]、黄连^{[5, 6]}、姜黄^{[7, 8]}等中药成分的代谢产物是其在体内发挥功效的重要形式。基于此, 邱峰教授带领团队创建了代谢产物辨识、分离、鉴定和制备的集成关键技术(图1)^[9-16], 该关键技术为中药成分体内代谢产物的制备提供了技术支撑, 使得代谢产物的活性评价得以实现, 同时也拓宽了中药功效物质发现的新途径。

1.2　多维度的活性评价

在中医药理论的指导下, 构建多维度的功效关联活性评价体系是中药功效物质研究的关键。以苦味中药为例, 苦味中药主要以寒性药物为主, 在临床上主要用于治疗热证。然而, 苦味中药的功效研究与中医临床应用的实际情况脱节, 加之缺乏符合中医证候特点的病证结合模型, 导致体现中医用药特点的苦味中药功效物质难以解析。基于中药药味的功效关联物质研究思路, 聚焦于苦味中药主要临床功效, 选择病证结合模型^{[17, 18]}进行苦味中药功效的生物学本质表征。进一步地, 选择与苦味中药功效密切关联的药理学活性, 对苦味中药进行多维度功效关联活性评价。利用高内涵技术在细胞水平对所建立的化学实体库进行功效关联活性物质筛选, 进一步采用病证结合动物模型评价体内外化学成分功效关联的药理学活性, 从而表征苦味中药的功效关联物质(图2)。

1.3　基于“结构-代谢-活性”设计合成分子探针, 阐明中药功效物质靶标及机制

核心蛋白与疾病的发生、发展密切相关, 药物通过调节核心蛋白的功能引发生物学效应发挥治疗疾病作用。因此, 核心蛋白即药物作用靶标的发现与确证已成为中药功效物质、机制研究以及中药创新药物开发的关键问题, 受到广泛关注。目前, 基于“结构-代谢-活性”设计合成分子探针, 并采用化学生物学技术进行功效成分的靶标发现与机制研究的策略已被研究人员广泛采用。

首先, 结合中药功效物质的化学结构、代谢稳定性和生物活性等特点, 采用炔基标记、叠氮标记和光亲和等技术, 构建活性探针分子, 挖掘中药作用靶标, 为中药科学内涵研究提供方法支持。其次, 靶标蛋白的结构复杂、种类多样且功能各异, 加之现有的“药物分子-靶标蛋白”互作检测技术各有局限, 导致单一技术无法准确识别并确认功效物质的直接作用靶标。因此, 在合成分子探针的基础上, 结合稳定同位素标记技术(stable-isotope labelling by amino acids in cell culture, SILAC)、非定量标记(label free) 等蛋白质组学技术, 从靶器官-靶组织-靶细胞中发掘功效物质的作用靶标, 并结合细胞热迁移技术(cellular thermal shift assay, CETSA)、药物亲和反应靶标稳定技术(drug affinity responsive target stability, DARTS)、生物膜干涉(biolayer interferometry, BLI)、表面等离子体共振(surface plasmon resonance, SPR) 等生物物理学技术, 以及分子对接和分子动力学等计算生物学方法, 验证成分与靶标的直接结合。同时, 运用定点突变、基因敲除与过表达等分子生物学技术进行靶标确证, 为系统全面揭示中药功效物质作用靶标提供有效手段, 助力中药功效科学内涵的阐释。

2　苦味中药的化学生物学研究实例

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苦味中药是临床应用最广泛的药味之一, 在中国药典(2020年版) 中占比高达51.7%。这类药物具有“能泄、能燥、能坚”的特性, 主要功效包括泻火解毒、清热燥湿、泻火存阴等, 并展现出抗炎、抗感染、抗肿瘤及调节糖脂代谢等多种活性^[19]。因此, 苦味中药在治疗感染性疾病、代谢性疾病等重大疾病方面具有重要价值。本文以代表性苦味中药黄连、黄芩为例, 阐述如何基于中药化学生物学研究, 明确苦味中药的功效物质及其作用机制。

2.1　黄连

黄连作为传统的苦味中药, 被《神农本草经》列为上品, 具有清热燥湿、泻火解毒的功效。其临床应用广泛, 常用于治疗泻痢、消渴等症状。现代药理学研究表明, 黄连具有降血糖、抗炎、抗肿瘤、抗菌等多重药理作用^[20]。

黄连含有丰富的化学成分, 已分离出多种化合物, 包括生物碱类、木脂素类、黄酮类、酸性成分及挥发油类等^[20]。研究人员对黄连及其主要生物碱的体内过程进行了系统的分析, 制备了主要成分小檗碱的代谢产物, 并证明了小檗碱及其体内代谢产物是黄连的功效关联物质^[21-26], 也是赋予其苦味及发挥“能泻、能燥”功效的关键物质^[27]。在此基础上, 研究人员采用化学生物学技术, 对苦味中药黄连主要成分小檗碱的作用机制进行系统研究(表1)^{[17, 28-34]}。

炎症常表现为“火毒”、“湿热”、“阴虚内热”等证型, 苦味中药是临床上常用的抗炎药物。因此, 研究人员针对黄连功效成分小檗碱, 设计合成了系列分子探针, 应用化学生物学的方法对小檗碱的抗炎靶标及作用机制进行了研究。Meng等^[17]的研究首先评价了黄连及其主要成分小檗碱对大肠湿热证的治疗作用, 结果表明苦味中药黄连缓解大肠湿热证的功效与其抗炎、调节免疫等药理活性密切相关; 接着采用SILAC技术, 确定了小檗碱通过直接靶向免疫相关鸟苷三磷酸酶M蛋白(immune-related guanosine triphosphatase M protein, IRGM1) 抑制PI3K/AKT/mTOR信号通路, 发挥抗炎作用^[17]。IRGM1主要分布在巨噬细胞和淋巴细胞中, 依赖巨噬细胞自噬途径在炎症性疾病的发生与发展中发挥重要作用^[35]。此外, Zeng等^{[28, 29]}设计合成了多个小檗碱分子探针, 先后在人胚肾细胞293 (HEK-293) 和人单核细胞系-1 (PMA-THP-1) 细胞中发现了小檗碱的直接靶标丝裂原活化蛋白激酶7 (mitogen-activated protein kinase 7, MAP2K7) 与NIMA相关激酶7 (NIMA related kinase 7, NEK7), 证明了小檗碱的抗炎作用与其靶向MAP2K7蛋白密切相关。该团队进一步采用小檗碱二苯酮光亲和探针, 发现并验证真核翻译起始因子2-α激酶2 (eukaryotic translation initiation factor 2-alpha kinase 2, EIF2AK2) 是小檗碱的直接靶标^[30]。小檗碱可以抑制EIF2AK2二聚体形成, 进而调节包括JNK、核因子κB (nuclear factor kappa-B, NF-κB) 和蛋白激酶B (protein kinase B, AKT) 在内的多个信号通路, 协同发挥抗炎作用。

中医理论认为阴虚燥热、痰湿内阻是导致糖脂代谢紊乱疾病的病因、病机。在临床实践中, 具有清热燥湿、泻火解毒功效的苦味中药在治疗糖脂代谢紊乱相关疾病时的使用频率最高^[36]。Yang等^[31]发现小檗碱的靶标是醛酮还原酶1B10 (aldo-keto reductase family 1 member B10, AKR1B10) 蛋白, 通过AKR1B10依赖的机制调节过氧化物酶体增殖物激活受体(peroxisome proliferator activated receptor, PPAR) 信号通路, 改善脂质和葡萄糖的代谢紊乱。Qi等^[32]设计合成了小檗碱光亲和探针, 发现了小檗碱的另一个直接作用靶标——TP53诱导的糖酵解和细胞凋亡调节剂(TP53-induced glycolysis and apoptosis regulator, TIGAR)。小檗碱能够靶向TIGAR, 抑制果糖-2, 6-二磷酸转化为果糖-6-磷酸的过程, 从而发挥降糖作用^[32]。

感染性疾病在中医理论中被归类为温病, 指的是由外感温热邪气引起的疾病。临床上, 针对感染性疾病的治疗一般以清热解毒的苦味中药为主, 这体现了苦味中药苦泄功能的重要药效^[37]。此外, 热毒内蕴是导致肿瘤发生和发展的主要原因, 因此清热解毒是中医治疗肿瘤的重要法则。苦味中药因其清热解毒的功效, 在肿瘤的临床治疗中被广泛应用^[38]。作为传统的苦味中药, 黄连展现出良好的抗肿瘤和抗感染活性^[39]。现有研究表明, 结直肠癌患者的肠道菌群存在显著变化, 黄连主要活性成分小檗碱能够显著抑制与结直肠癌相关的菌群生长, 特别是厌氧消化链球菌^[33], 其直接靶标为甲酰四氢叶酸合成酶(formate-tetrahydrofolate ligase, FtfL)。小檗碱可以与FtfL直接结合, 干扰其构象变化, 同时小檗碱还可以竞争底物与FtfL在活性中心的结合; 此外, 肿瘤细胞中人源FtfL的酶活性也可以被小檗碱抑制^[33]。Gu等^[34]对小檗碱治疗多发性骨髓瘤的作用靶标进行了深入研究, 整合SPR与液质联用技术, 发现小檗碱处理骨髓瘤细胞后, 关键蛋白含植物同源结构域(plant homeodomain, PHD结构域) 和环指结构域的泛素样蛋白1 (ubiquitin-like with PHD and ring finger domains 1, UHRF1) 的泛素化水平增加, 且这种增加可以被蛋白酶抑制剂抵消, 证明了小檗碱通过靶向UHRF1并诱导其发生泛素化降解而发挥抗多发性骨髓瘤的作用。

2.2　黄芩

黄芩味苦, 性寒, 归肺、胆、脾、大肠、小肠经, 具有清热燥湿、泻火解毒、止血、安胎的功效。临床上常用于治疗湿温暑湿、肺热咳嗽、高热烦渴、痈肿疮毒等多种疾病。黄芩含有黄酮类、挥发油和多糖等多种化学成分, 展现出抗炎、抗菌、抗病毒、抗氧化、降脂降糖等多种药理作用^[40]。其中, 黄酮类成分是黄芩的主要功效成分, 代表性化合物包括黄芩苷、黄芩素、汉黄芩苷和汉黄芩素。黄芩的体内过程研究表明, 黄芩苷与黄芩素在体内可以相互转化, 黄芩苷是复原型前体药物, 且生物活性评价研究表明, 黄芩苷及其主要代谢产物是苦味中药黄芩的功效关联物质^{[41, 42]}。在此基础上, 基于化学生物学技术对苦味中药黄芩功效关联物质的作用机制进行了系统的研究, 见表2^[43-46]。

黄芩是中医常用苦味中药之一, 善除上焦之热, 其抗炎解热作用一直受到重视。Zhang等^[43]设计合成了黄芩素分子探针, 通过凝胶电泳、蛋白质谱分析和细胞共定位成像分析, 确定了黄芩素可以靶向热休克蛋白90 (heat shock protein 90, HSP90), 诱导下游蛋白环氧化酶-2 (cyclooxygenase-2, COX-2) 的泛素化降解, 进而降低COX-2下游效应分子前列腺素E2 (prostaglandin E2, PGE2)、白细胞介素-6 (interleukin-6, IL-6) 和肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α) 的表达, 发挥解热抗炎作用^[43]。

在中医理论中, 高脂血症多归属于“脂、膏”范畴, 主要病因为痰湿内盛, 浊脂积聚。黄芩作为清热燥湿的代表性中药, 具有明显的降血脂作用。Dai等^[44]发现肉毒碱棕榈酰基转移酶(carnitine palmitoyltransferase 1A, CPT1A) 是黄芩苷的降脂靶标。线粒体的脂肪酸β-氧化是脂质消耗的主要途径, 其关键步骤是将脂酰辅酶A转移到线粒体内, 并生成乙酰辅酶A, 而CPT1则是这一过程的关键限速酶。黄芩苷能够直接与CPT1A结合, 激活CPT1A的活性, 从而促进脂肪酸的分解代谢。

正气内虚、湿毒蕴结常被认为是导致恶性肿瘤发生的主要原因, 因而在中医治疗肿瘤的过程中, 多选择清热解毒、清热燥湿的药物。经典名方黄芩汤被大量临床实践证明, 具有较好的抗肿瘤作用。在一项关于黄芩苷抑制应激诱导乳腺癌转移机制的研究中, Jia等^[45]通过黄芩苷光亲和探针实验和药物亲和响应靶标稳定性实验, 确定了β2肾上腺素受体(β2 adrenergic receptor, β2-AR) 是黄芩苷的直接靶标。β2-AR是儿茶酚胺类激素的主要应答者, 已被证实与多种癌症的应激诱导转移密切相关。黄芩苷可以通过β2-AR-cAMP-PKA-FAK通路抑制上皮-间质转化, 从而减缓应激诱导的乳腺癌转移。

白色念珠菌是免疫功能低下患者中最常见的真菌病原体之一。黄芩的主要成分黄芩素对白色念珠菌的生长表现出显著的抑制作用。Lv等^[46]采用同位素标记蛋白组学(isobaric tags for relative and absolute quantitation-based proteomics, iTRAQ-based proteomics) 对黄芩素的抗真菌作用机制进行了深入研究。结果表明, 黄芩素抑制白色念珠菌生长的靶标是一种NADH脱氢酶(NADH dehydrogenase, Cpd2p)。黄芩素通过上调Cpd2p的表达, 增加白色念珠菌的胞内氧化应激, 从而抑制其生长, 发挥抗真菌作用。

3　结语与展望

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基于药味的化学生物学研究思路克服了以往功效物质研究中常见的中药成分体内过程重视不足、活性评价与传统功效关联性不强的问题。在中医药理论指导下, 以药味为切入点, 充分考虑中药的传统功效及其临床应用, 结合病证结合动物模型, 采用与中药功效密切相关的多维度活性评价方法进行功效物质的筛选, 并运用化学生物学技术手段解析功效物质的作用靶标, 明确其作用机制。该研究思路已成功应用于系列苦味中药的功效物质解析, 不仅为中药药性理论指导下的功效物质阐释提供研究范式, 也为中药科学监管、合理用药、新药开发和质量控制等提供了科学依据。

未来将人工智能预测、类器官芯片筛选、亚细胞器靶向、空间组学分析等新技术与中药化学生物学深度融合, 可更系统、精准地解析中药“药味-功效”的物质基础与作用机制。未来的研究可从以下方向突破: 人工智能辅助中药功效物质发现与机制预测、基于类器官模型评价中药功效关联活性、设计细胞器定位的分子探针结合超分辨显微技术解析功效物质在亚细胞水平的作用机制、通过质谱成像技术可视化功效物质及其代谢产物在组织或细胞内的空间分布、联合空间单细胞转录组学技术和空间代谢组学等技术明确功效物质与疾病发生发展的精准关联。同时, 在未来的研究中, 应更加关注活性代谢产物的作用机制阐述。总之, 随着多学科的交叉融合, 将进一步阐明中药药味理论的科学内涵, 还将为其他药性理论(如寒热、归经、升降浮沉等) 的现代化研究提供借鉴。

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2026年第61卷第1期

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doi: 10.16438/j.0513-4870.2025-0427

接收时间：2025-04-15
首发时间：2026-09-21
出版时间：2026-01-12

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收稿日期：2025-04-15
修回日期：2025-07-17

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¹天津中医药大学中药学院, 天津 301617

²天津中医药大学医学技术学院, 天津 301617

³天津市中药功效物质重点实验室, 天津 301617

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邱峰, Tel: 86-22-59791871, E-mail: fengqiu20070118@163.com

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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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Pharmacological activity	Structure of probes	Experiment system	Target	Molecular mechanism	Reference
Anti-inflammatory		RAW 264.7	IRGM1	Berberine shows anti-inflammatory activity through inhibiting the PI3K/AKT/mTOR pathway by targeting IRGM1.	[17]
		HEK-293	MAP2K7	Berberine shows anti-inflammatory activity via directly targeting MAP2K7 to inhibit p-JNK rather than JNK activity.	[28]
		PMA-THP-1	NEK7	Berberine directly targets the NEK7 protein to block the NEK7-NLRP3 interaction and exert anti-inflammatory activity.	[29]
		PMA-THP-1	EIF2AK2	Berberine directly inhibits the dimerization of EIF2AK2 to exert synergistic anti-inflammatory effects.	[30]
Glucolipid metabolism regulation		HepG2	AKR1B10	Berberine alleviates NAFLD via mediating PPAR signaling pathways through targeting AKR1B10.	[31]
		HepG2	TIGAR	Berberine shows hypoglycemic effects via attenuating the conversion of fructose-2, 6-bisphosphate to fructose-6-phosphate by targeting TIGAR.	[32]
Anti-microbial		P. anaerobius ATCC27337	FtfL	Berberine can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active left.	[33]
Anti-cancer	—	RPMI-8266 and MM.1S	UHRF1	Berberine shows therapeutic activity against multiple myeloma through targeting UHRF1 and inducing UHRF1 degradation via the ubiquitin-dependent proteasome system.	[34]

Pharmacological activity

Structure of probes

Experiment system

Target

Molecular mechanism

Reference

Anti-inflammatory

RAW 264.7

IRGM1

Berberine shows anti-inflammatory activity through inhibiting the PI3K/AKT/mTOR pathway by targeting IRGM1.

[17]

HEK-293

MAP2K7

Berberine shows anti-inflammatory activity via directly targeting MAP2K7 to inhibit p-JNK rather than JNK activity.

[28]

PMA-THP-1

NEK7

Berberine directly targets the NEK7 protein to block the NEK7-NLRP3 interaction and exert anti-inflammatory activity.

[29]

PMA-THP-1

EIF2AK2

Berberine directly inhibits the dimerization of EIF2AK2 to exert synergistic anti-inflammatory effects.

[30]

Glucolipid metabolism regulation

HepG2

AKR1B10

Berberine alleviates NAFLD via mediating PPAR signaling pathways through targeting AKR1B10.

[31]

HepG2

TIGAR

Berberine shows hypoglycemic effects via attenuating the conversion of fructose-2, 6-bisphosphate to fructose-6-phosphate by targeting TIGAR.

[32]

Anti-microbial

P. anaerobius ATCC27337

FtfL

Berberine can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active left.

[33]

Anti-cancer

—

RPMI-8266 and MM.1S

UHRF1

Berberine shows therapeutic activity against multiple myeloma through targeting UHRF1 and inducing UHRF1 degradation via the ubiquitin-dependent proteasome system.

[34]

Pharmacological activity	Therapeutical component	Structure of probes	Experiment system	Target	Molecular mechanism	Reference
Anti-inflammatory	Baicalein		RAW 264.7	HSP90	Baicalein shows antipyretic and analgesic activities via targeting HSP90 and inducing the degradation of COX-2.	[43]
Hypolipidemic activity	Baicalin		HeLa	CPT1A	Baicalin shows anti-steatosis activity via directly activating hepatic CPT1 to accelerate the lipid influx into mitochondria for oxidation.	[44]
Anti-cancer	Baicalin		MDA-MB-231	β2-AR	Baicalin could directly bind to β2-AR, subsequently inhibit cAMP-PKA-FAK pathway, and thus impede epithelial-mesenchymal transition.	[45]
Anti-microbial	Baicalein	—	Candida albicans SC5314	Cpd2p	Baicalein could increase intracellular oxidative damage by upregulating the expression of Cpd2p to inhibit the growth of C. albicans.	[46]

Pharmacological activity

Therapeutical component

Structure of probes

Experiment system

Target

Molecular mechanism

Reference

Anti-inflammatory

Baicalein

RAW 264.7

HSP90

Baicalein shows antipyretic and analgesic activities via targeting HSP90 and inducing the degradation of COX-2.

[43]

Hypolipidemic activity

Baicalin

HeLa

CPT1A

Baicalin shows anti-steatosis activity via directly activating hepatic CPT1 to accelerate the lipid influx into mitochondria for oxidation.

[44]

Anti-cancer

Baicalin

MDA-MB-231

β2-AR

Baicalin could directly bind to β2-AR, subsequently inhibit cAMP-PKA-FAK pathway, and thus impede epithelial-mesenchymal transition.

[45]

Anti-microbial

Baicalein

—

Candida albicans SC5314

Cpd2p

Baicalein could increase intracellular oxidative damage by upregulating the expression of Cpd2p to inhibit the growth of C. albicans.

[46]