植物源性天然产物在口腔细菌感染性疾病中的研究进展

doi:10.3877/cma.j.issn.1674-1366.2023.03.006

天然产物是来源于自然界中具有药理生物活性的化合物。其中，来源于植物的天然产物具有抗菌作用广、细胞毒性小和生物相容性好等特点而受到关注。植物源性天然产物主要包括多酚类、生物碱类、萜类、醌类和醛类化合物，它们可以通过损伤细菌膜结构、抑制细菌酶活性、诱导氧化应激反应、促进铁离子的螯合和抑制细菌二元信号通路等途径抗菌。研究发现，植物源性天然产物可以抑制变异链球菌、牙龈卟啉单胞菌和粪肠球菌等常见的口腔致病菌。本文就植物源性天然产物的抗菌机制及其在口腔感染性疾病中的相关应用作一综述。

关键词: 植物源性化合物, 天然产物, 抗菌剂

Natural products are compounds derived from nature that are pharmacologically bioactive. Among them, plant-derived natural products have attracted attention for their wide antibacterial effect, low cytotoxicity, and good biocompatibility. Plant-derived natural products mainly include polyphenols, alkaloids, terpenoids, quinones and aldehydes, which can be antibacterial by damaging bacterial membrane structure, inhibiting bacterial enzyme activity, inducing oxidative stress response, promoting iron ion chelation, and inhibiting bacterial binary signaling pathway. In recent years, studies have found that plant-derived natural products can inhibit common oral pathogenic bacteria such as Streptococcus mutans, Porphyromonas-gingivalis, and Enterococcus faecalis. This article reviewed the antibacterial mechanism of plant-derived natural products and their related applications in the treatment of oral infectious diseases.

Key words: Plant-derived compounds, Natural products, Anti-bacterial agent

图1 植物源性天然产物抗菌机制示意图　Gtfs：葡聚糖转移酶；Ftfs：果聚糖转移酶；ROS：活性氧分子；Fe²⁺：二价铁离子；Fe³⁺：三价铁离子；ComD：ComCDE双组分信号转导系统的跨膜激酶；ComC、ComD、ComE：ComCDE双组分信号转导系统基因；CSP：ComCD双组分系统编码的肽信号分子；VicR、VicK、VicX：VicRK信号转导系统基因；F₁F₀-ATP酶：质子ATP合酶。

表1 植物源性天然产物的类型及其抗菌作用

天然产物分类及化合物				抗菌种类	最低抑菌浓度	参考文献
多酚	类黄酮	黄酮醇	槲皮素	变形链球菌	2 mg/mL	[18,20]
				牙龈卟啉单胞菌	4 mg/mL
				粪肠球菌	512 mg/mL
			杨梅素	变形链球菌	512 μg/mL	[22,25]
				粪肠球菌	250 μg/mL
		黄酮	黄芩素	变形链球菌	-	[27]
				白色念珠菌
			芹菜素	白色念珠菌	5 μg/mL	[29]
		黄烷酮	松属素	变形链球菌	（1.4 ± 0.4）μg/mL	[30,31]
				粪肠球菌
		黄烷醇	EGCG	变形链球菌	31.25 μg/mL	[5,13,33]
				粪肠球菌	5 μg/mL
				牙龈卟啉单胞菌	-
		异黄酮	光甘草定	变形链球菌	6.25 ~ 25 μg/mL	[34,35,36]
				粪肠球菌	25 μg/mL
	非类黄酮	单宁类	没食子单宁	变形链球菌	-	[37]
				牙龈卟啉单胞菌	-
			缩合单宁	粪肠球菌	-	[39,41]
		姜黄素		变形链球菌	-	[10,42,43,44,45]
				牙龈卟啉单胞菌	62.5 ~ 125 μg/mL
				粪肠球菌	-
		厚朴酚		变形链球菌	10 μg/mL	[46]
		白藜芦醇		变形链球菌	800 μg/mL	[49,50]
				牙龈卟啉单胞菌	-
		咖啡酸苯乙酯		变形链球菌	0.08 μg/mL	[52]
				白色念珠菌	-
萜类	单萜类	香芹酚		变形链球菌	93.4 μg/mL	[53]
		百里酚		变形链球菌	-	[54]
				白色念珠菌	39 μg/mL
		萜品烯四醇		变形链球菌	-	[55]
				白色念珠菌	2.34 mg/mL
	倍半萜	反式法尼醇		变形链球菌	6.25 mmol/L	[3,57]
				白色念珠菌	150 mmol/L
	二萜	松萝酸		变形链球菌	5 μg/mL	[58]
	三萜	熊果酸		变形链球菌	256 ~ 1 024 μg/mL	[59]
		人参皂苷Rh2		变形链球菌	-	[61]
				远缘链球菌
				血链球菌
	四萜	辣椒素		变形链球菌	50 μg/mL	[63,64]
				粪肠球菌	256 μg/mL
				牙龈卟啉单胞菌	16 μg/mL
生物碱类		血根碱		变形链球菌	4 ~ 8 μg/mL	[65]
		小檗碱		变形链球菌	300 μg/mL	[67,68,69,70]
				粪肠球菌	500 μg/mL
				白色念珠菌	31.25 μg/mL
				牙龈卟啉单胞菌	31.3 μg/mL
醌类		大黄酸		变形链球菌	5.69 μg/mL	[72,73]
				牙龈卟啉单胞菌	15.625 μg/mL
醛类		肉桂醛		变形链球菌	1 000 ~ 2 000 μg/mL	[14,74,75]
				粪肠球菌	250 ~ 500 μg/mL

表1 植物源性天然产物的类型及其抗菌作用

天然产物分类及化合物				抗菌种类	最低抑菌浓度	参考文献
多酚	类黄酮	黄酮醇	槲皮素	变形链球菌	2 mg/mL	[18,20]
				牙龈卟啉单胞菌	4 mg/mL
				粪肠球菌	512 mg/mL
			杨梅素	变形链球菌	512 μg/mL	[22,25]
				粪肠球菌	250 μg/mL
		黄酮	黄芩素	变形链球菌	-	[27]
				白色念珠菌
			芹菜素	白色念珠菌	5 μg/mL	[29]
		黄烷酮	松属素	变形链球菌	（1.4 ± 0.4）μg/mL	[30,31]
				粪肠球菌
		黄烷醇	EGCG	变形链球菌	31.25 μg/mL	[5,13,33]
				粪肠球菌	5 μg/mL
				牙龈卟啉单胞菌	-
		异黄酮	光甘草定	变形链球菌	6.25 ~ 25 μg/mL	[34,35,36]
				粪肠球菌	25 μg/mL
	非类黄酮	单宁类	没食子单宁	变形链球菌	-	[37]
				牙龈卟啉单胞菌	-
			缩合单宁	粪肠球菌	-	[39,41]
		姜黄素		变形链球菌	-	[10,42,43,44,45]
				牙龈卟啉单胞菌	62.5 ~ 125 μg/mL
				粪肠球菌	-
		厚朴酚		变形链球菌	10 μg/mL	[46]
		白藜芦醇		变形链球菌	800 μg/mL	[49,50]
				牙龈卟啉单胞菌	-
		咖啡酸苯乙酯		变形链球菌	0.08 μg/mL	[52]
				白色念珠菌	-
萜类	单萜类	香芹酚		变形链球菌	93.4 μg/mL	[53]
		百里酚		变形链球菌	-	[54]
				白色念珠菌	39 μg/mL
		萜品烯四醇		变形链球菌	-	[55]
				白色念珠菌	2.34 mg/mL
	倍半萜	反式法尼醇		变形链球菌	6.25 mmol/L	[3,57]
				白色念珠菌	150 mmol/L
	二萜	松萝酸		变形链球菌	5 μg/mL	[58]
	三萜	熊果酸		变形链球菌	256 ~ 1 024 μg/mL	[59]
		人参皂苷Rh2		变形链球菌	-	[61]
				远缘链球菌
				血链球菌
	四萜	辣椒素		变形链球菌	50 μg/mL	[63,64]
				粪肠球菌	256 μg/mL
				牙龈卟啉单胞菌	16 μg/mL
生物碱类		血根碱		变形链球菌	4 ~ 8 μg/mL	[65]
		小檗碱		变形链球菌	300 μg/mL	[67,68,69,70]
				粪肠球菌	500 μg/mL
				白色念珠菌	31.25 μg/mL
				牙龈卟啉单胞菌	31.3 μg/mL
醌类		大黄酸		变形链球菌	5.69 μg/mL	[72,73]
				牙龈卟啉单胞菌	15.625 μg/mL
醛类		肉桂醛		变形链球菌	1 000 ~ 2 000 μg/mL	[14,74,75]
				粪肠球菌	250 ~ 500 μg/mL

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Research progress of plant-derived natural products against oral bacterial infectious disease

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Research progress of plant-derived natural products against oral bacterial infectious disease