Article(id=1210518232755204992, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1210518228766421884, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2022-1091, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1664812800000, receivedDateStr=2022-10-04, revisedDate=1667404800000, revisedDateStr=2022-11-03, acceptedDate=null, acceptedDateStr=null, onlineDate=1766539637030, onlineDateStr=2025-12-24, pubDate=1670774400000, pubDateStr=2022-12-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766539637030, onlineIssueDateStr=2025-12-24, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766539637030, creator=13701087609, updateTime=1766539637030, updator=13701087609, issue=Issue{id=1210518228766421884, tenantId=1146029695717560320, journalId=1189982191388893191, year='2022', volume='57', issue='12', pageStart='0', pageEnd='3698', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1766539636078, creator=13701087609, updateTime=1766539730802, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1210518626109624560, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1210518228766421884, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1210518626109624561, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1210518228766421884, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=3465, endPage=3479, ext={EN=ArticleExt(id=1210518233220772741, articleId=1210518232755204992, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Research progress on the interactions between gut bacterial β-glucuronidases and Chinese herbal medicines, columnId=1210518233132692356, journalTitle=Acta Pharmaceutica Sinica, columnName=Special Reports: Therapeutic Modulation of Gut Immune and Microbiota Homeostasis by Chinese Medicine, runingTitle=null, highlight=null, articleAbstract=

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.

, correspAuthors=Ru YAN, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2022 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Zhi-qiang CHEN, Shuai TANG, Chang-xuan ZHANG, Ting LI, Hong-qi CHEN, Ru YAN), CN=ArticleExt(id=1210518244255985796, articleId=1210518232755204992, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=肠道菌群β-葡萄糖醛酸苷酶与中草药的互作关系研究进展, columnId=1210518233338213258, journalTitle=药学学报, columnName=专题报道：肠道黏膜免疫及菌群稳态与中医药调控, runingTitle=null, highlight=null, articleAbstract=

口服中药在吸收入血前与肠道菌群的互作是中药发挥整体作用的重要机制, 也使得对中药的研究有别于以系统暴露(入血水平) 为起点和核心的西药的研发。肠道菌群与宿主代谢互补, 共同参与众多内源性生物活性分子的代谢平衡及外源成分的体内处置。其中, 肠道菌群中广泛分布的β-葡萄糖醛酸苷酶(gut bacterial β-glucuronidases, BGUSs) 与宿主尿苷二磷酸葡萄糖醛酸转移酶(UDP-glucuronosyltransferases, UGTs) 协调互作, 调节内外源化合物肝肠循环, 通过影响葡萄糖醛酸化稳态, 改变其肠道局部和/或系统暴露, 对疾病的发生及干预发挥作用。一方面, 许多中草药(Chinese herbal medicines, CHMs) 成分发生肝肠循环; 另一方面, CHMs可直接作用于BGUSs或通过对肠道菌群结构的广泛影响间接改变其分布和功能。BGUSs和CHMs之间的多重互作可能在CHMs的整体治疗益处中发挥重要作用。本综述首先概括了BGUSs的最新研究进展; 进而根据BGUSs的底物谱从营养利用、代谢稳态、治疗响应等多层面解读BGUSs介导内外源化合物代谢的生理、病理及药理意义; 最后, 整合文献, 总结BGUSs与CHMs的多重互作关系。

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Chin J Clin Pharmacol Ther (中国临床药理学与治疗学), 2021, 26: 964-974., articleTitle=Applications of BGUSs inhibition in tumor prevention and chemotherapy, refAbstract=null)], funds=[Fund(id=1210518252741063212, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, awardId=0091/2021/A2, language=CN, fundingSource=澳门科技发展基金资助项目(0091/2021/A2), fundOrder=null, country=null), Fund(id=1210518252858503734, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, awardId=0098/2019/A2, language=CN, fundingSource=澳门科技发展基金资助项目(0098/2019/A2), fundOrder=null, country=null), Fund(id=1210518252959167040, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, awardId=043/2011/A2, language=CN, fundingSource=澳门科技发展基金资助项目(043/2011/A2), fundOrder=null, country=null), Fund(id=1210518253244379719, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, awardId=SGDX20210823103805038, language=CN, fundingSource=深港澳科技创新项目(SGDX20210823103805038), fundOrder=null, country=null), Fund(id=1210518253349237328, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, awardId=81473281, language=CN, fundingSource=国家自然科学基金资助项目(81473281), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1210518244566364308, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, xref=null, ext=[AuthorCompanyExt(id=1210518244574752917, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, companyId=1210518244566364308, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China), AuthorCompanyExt(id=1210518244578947222, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, companyId=1210518244566364308, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=澳门大学中华医药研究院暨中药质量研究国家重点实验室, 澳门 999078)])], figs=[ArticleFig(id=1210518252451656208, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=

Chemical type	Chinese medicine compound	Structure	Substrate	Inhibition potency (IC50/μmol·L-1)		Ref.
				EcoGUS	Other GUSs
Flavonoid	Luteolin		PNPG	8.68 ± 2.02	-	[100]
				5.70	SpasGUS, 5.50; SagaGUS, 12.5	[98]
	Scutellarein		PNPG	5.76 ± 1.53	-	[100]
	Baicalin		PNPG	45.24	SpasGUS, 48.80; SagaGUS, 44.05	[98]
	Baicalein		PNPG	54.44	SpasGUS, 39.12; SagaGUS, 52.70	[98]
				5.76 ± 1.53	-	[100]
	Kuwanone G		PNPG	7.4 ± 1.6	SpasGUS, 0.98 ± 0.25	[99]
			PNPG	2.37 ± 0.11	-	[92]
	Kuwanone C		PNPG	4.27 ± 0.32	-	[92]
	Morusin		PNPG	5.59 ± 0.67	-	[92]
	Kuwanone H		PNPG	6.97 ± 0.97	-	[92]
	Kuwanone A		PNPG	7.92 ± 0.24	-	[92]
	Kuwanone E		PNPG	10.63 ± 0.32		[92]
	Sanggenol A		PNPG	3.27 ± 0.17	-	[92]
	Kushenol X		PNPG	2.07 ± 0.26	-	[96]
	(2S)-Farrerol		PNPG	8.95 ± 0.74	-	[96]
	5, 7, 2′-Trihydroxy-8, 6′-dimethoxy flavone		PNPG	4.97 ± 0.61	-	[96]
	Apigenin		PNPG	156.42	SpasGUS, 48.03; SagaGUS, 30.14	[98]
	Fisetin		PNPG	2.02	SpasGUS, 10.83; SagaGUS, 76.58	[98]
	Icaritin		PNPG	29.43	SpasGUS, 76.57; SagaGUS, 7.59	[98]
	Morin		PNPG	11.89	SpasGUS, 8.36; SagaGUS, 76.81	[98]
			PNPG	1.12 ± 0.09	-	[92]
	Quercetin		PNPG	4.91	SpasGUS, 4.06; SagaGUS, 110.25	[92]
	Myricetin		PNPG	1.58	SpasGUS, 9.25; SagaGUS, 86.94	[92]
	Amentoflavone		PNPG	3.43	SpasGUS, 2.88; CpGUS, 2.36	[93]
					SagaGUS, 2.88 ± 0.38	[92]
			SN-38G	0.49	-	[97]
			DDAOG	0.62	-	[97]
	Bilobetin		PNPG	> 100	CpGUS, 1.32 ± 0.17; SagaGUS, 9.83 ± 2.62	[92]
	Sanggenon C		PNPG	12.5 ± 5.0	SpasGUS, 0.33 ± 0.05	[99]
			PNPG	2.07 ± 0.06	-	[92]
Catechin	(-)-Catechin gallate		SN-38G	1.48	-	[95]
			DDAOG	1.64	-	[95]
	(-)-Epicatechin gallate		SN-38G	6.94	-	[95]
			DDAOG	6.52	-	[95]
	(-)-Gallocatechin gallate		SN-38G	6.84	-	[95]
			DDAOG	4.02	-	[95]
	(-)-Epigallocatechin gallate		SN-38G	14.86	-	[95]
			DDAOG	16.52	-	[95]
Anthracene ketone	Demethylbellidifolin		PNPG	0.91 ± 0.11	-	[96]
	Gentisin		PNPG	0.68 ± 0.10	-	[96]
Theaflavin	Theaflavin-3-monogallate		SN-38G	1.92	-	[95]
			DDAOG	2.35	-	[95]
	Theaflavin-3′-monogallate		SN-38G	1.03	-	[95]
			DDAOG	0.77	-	[95]
	Theaflavin-3, 3′-digallate		SN-38G	1.41	-	[95]
			DDAOG	0.48	-	[95]
Alkaloid	Berberine		4-MUG	54.04 ± 5.104	-	[102]
Tannic acid	3, 4, 8, 9, 10-Pentahydroxy urolithin		PNPG	2.70 ± 0.19	-	[92]
Diterpene	Euphominoid C		PNPG	12.5 ± 5.0	-	[101]
Fatty acid	Linoleic acid		PNPG	*68.27% ± 0.96%	-	[94]

), ArticleFig(id=1210518252581679646, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210518232755204992, language=CN, label=Table 1, caption=

In vitro inhibitory effects of Chinese herbal medicines and their components on gut bacterial β-glucuronidases (BGUSs). IC₅₀: Half-maximal inhibitory concentration; GUSs: β-Glucuronidases; PNPG: p-Nitrophenyl-β-D-glucuronide; DDAOG: 6, 8-Dichloro-7-hydroxy-9, 9-dimethylacridin-2-one-β-D-glucuronide; SN-38G: SN-38 glucuronide; 4-MUG: 4-Methylumbelliferyl-β-D-glucuronide; EcoGUS: Escherichia coli GUS; CpGUS: Clostridium perfringens GUS; SagaGUS: Streptococcus agalactiae GUS; SpasGUS: Staphylococcus pasteuri GUS; -: Not detected; ^*: Inhibition rate

, figureFileSmall=null, figureFileBig=null, tableContent=

Chemical type	Chinese medicine compound	Structure	Substrate	Inhibition potency (IC50/μmol·L-1)		Ref.
				EcoGUS	Other GUSs
Flavonoid	Luteolin		PNPG	8.68 ± 2.02	-	[100]
				5.70	SpasGUS, 5.50; SagaGUS, 12.5	[98]
	Scutellarein		PNPG	5.76 ± 1.53	-	[100]
	Baicalin		PNPG	45.24	SpasGUS, 48.80; SagaGUS, 44.05	[98]
	Baicalein		PNPG	54.44	SpasGUS, 39.12; SagaGUS, 52.70	[98]
				5.76 ± 1.53	-	[100]
	Kuwanone G		PNPG	7.4 ± 1.6	SpasGUS, 0.98 ± 0.25	[99]
			PNPG	2.37 ± 0.11	-	[92]
	Kuwanone C		PNPG	4.27 ± 0.32	-	[92]
	Morusin		PNPG	5.59 ± 0.67	-	[92]
	Kuwanone H		PNPG	6.97 ± 0.97	-	[92]
	Kuwanone A		PNPG	7.92 ± 0.24	-	[92]
	Kuwanone E		PNPG	10.63 ± 0.32		[92]
	Sanggenol A		PNPG	3.27 ± 0.17	-	[92]
	Kushenol X		PNPG	2.07 ± 0.26	-	[96]
	(2S)-Farrerol		PNPG	8.95 ± 0.74	-	[96]
	5, 7, 2′-Trihydroxy-8, 6′-dimethoxy flavone		PNPG	4.97 ± 0.61	-	[96]
	Apigenin		PNPG	156.42	SpasGUS, 48.03; SagaGUS, 30.14	[98]
	Fisetin		PNPG	2.02	SpasGUS, 10.83; SagaGUS, 76.58	[98]
	Icaritin		PNPG	29.43	SpasGUS, 76.57; SagaGUS, 7.59	[98]
	Morin		PNPG	11.89	SpasGUS, 8.36; SagaGUS, 76.81	[98]
			PNPG	1.12 ± 0.09	-	[92]
	Quercetin		PNPG	4.91	SpasGUS, 4.06; SagaGUS, 110.25	[92]
	Myricetin		PNPG	1.58	SpasGUS, 9.25; SagaGUS, 86.94	[92]
	Amentoflavone		PNPG	3.43	SpasGUS, 2.88; CpGUS, 2.36	[93]
					SagaGUS, 2.88 ± 0.38	[92]
			SN-38G	0.49	-	[97]
			DDAOG	0.62	-	[97]
	Bilobetin		PNPG	> 100	CpGUS, 1.32 ± 0.17; SagaGUS, 9.83 ± 2.62	[92]
	Sanggenon C		PNPG	12.5 ± 5.0	SpasGUS, 0.33 ± 0.05	[99]
			PNPG	2.07 ± 0.06	-	[92]
Catechin	(-)-Catechin gallate		SN-38G	1.48	-	[95]
			DDAOG	1.64	-	[95]
	(-)-Epicatechin gallate		SN-38G	6.94	-	[95]
			DDAOG	6.52	-	[95]
	(-)-Gallocatechin gallate		SN-38G	6.84	-	[95]
			DDAOG	4.02	-	[95]
	(-)-Epigallocatechin gallate		SN-38G	14.86	-	[95]
			DDAOG	16.52	-	[95]
Anthracene ketone	Demethylbellidifolin		PNPG	0.91 ± 0.11	-	[96]
	Gentisin		PNPG	0.68 ± 0.10	-	[96]
Theaflavin	Theaflavin-3-monogallate		SN-38G	1.92	-	[95]
			DDAOG	2.35	-	[95]
	Theaflavin-3′-monogallate		SN-38G	1.03	-	[95]
			DDAOG	0.77	-	[95]
	Theaflavin-3, 3′-digallate		SN-38G	1.41	-	[95]
			DDAOG	0.48	-	[95]
Alkaloid	Berberine		4-MUG	54.04 ± 5.104	-	[102]
Tannic acid	3, 4, 8, 9, 10-Pentahydroxy urolithin		PNPG	2.70 ± 0.19	-	[92]
Diterpene	Euphominoid C		PNPG	12.5 ± 5.0	-	[101]
Fatty acid	Linoleic acid		PNPG	*68.27% ± 0.96%	-	[94]

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