银杏酸毒副作用及朴树提取物对其减毒效果研究

doi:10.3969/j.issn.0253-2417.2020.06.013

摘要/Abstract

摘要：

为了解银杏酸的毒副作用，探索朴树提取物对其减毒效果，在检测了银杏酸对人肝癌细胞HepG2细胞的增殖抑制作用，以及对小鼠的促炎作用和接触致敏性的基础上，考察了提取和分级分离的朴树叶、枝和皮中的活性成分对银杏酸的减毒效果。研究结果表明：总银杏酸和主要银杏酸单体C₁₃：0、C₁₅：1对HepG2细胞增殖有显著抑制作用，并能导致炎症反应。朴树叶正丁醇组分(BA)、水溶性组分(Water)、朴树枝的2#和朴树皮的14#提取物能够减轻银杏酸对HepG2细胞的增殖抑制作用，最高可将细胞存活率从26.7%提高到63.0%；朴树枝的8#和朴树皮的16#提取物对T细胞介导炎症反应有较好的抑制作用，对伴刀豆球蛋白A (Con A)活化的T细胞增殖抑制率最高可达95.4%。总银杏酸、银杏酸单体C₁₃：0和C₁₅：1有一定毒副作用，如过度使用银杏酸含量超标的制品，存在肝损伤和过敏等安全隐患；朴树叶、枝和皮中均存在能够抑制银杏酸毒性作用的成分，朴树提取物在银杏制品的减毒上有潜在应用价值。

关键词: 银杏酸, 朴树提取物, 抗肝损伤, 抗炎

Abstract:

To study the toxic and side effects of ginkgolic acid and to explore the detoxification effect of Celtis sinensis Pers. extracts on ginkgolic acid, the active components in C. sinensis leaves, branches and bark were extracted and separated. And then the detoxification effect of each components on ginkgolic acid were compared on the basis of exploring the anti-proliferative effect of ginkgolic acid on HepG2 cells and the pro-inflammatory effect and contact sensitization of ginkgolic acid on mice. The results showed that the total ginkgolic acid, main ginkgolic acids C₁₃:0 and C₁₅:1 showed significantly inhibitory effect on the proliferation of HepG2 cells, and could lead to inflammation. The inhibition on the proliferation of HepG2 cells induced by C₁₃:0 and C₁₅:1 could be reduced by the n-butanol extracts(BA) and water-soluble extracts(Water) of C. sinensis leaves, 2# extracts of C. sinensis branches and 14# extracts of C. sinensis bark, and the cell survival rate could be increased from 26.7% to 63.0% at highest; T cell mediated inflammatory response could be significantly inhibited by 8# extracts of C. sinensis branches and 16# extracts of C. sinensis bark, and the highest inhibition rate on the proliferation of Con A-activated T cells was 95.4%.The total ginkgolic acid, main ginkgolic acids C₁₃:0 and C₁₅:1 had certain toxic and side effects, and excessive use of products with excessive ginkgolic acid content might lead to liver injury and allergy. Components that could inhibit the toxic effect of ginkgolic acid existed in the leaves, branches and bark of C. sinensis, and the extract of C. sinensis had potential application value in reducing the toxicity of ginkgolic products.

Key words: ginkgolic acid, extract of Celtis sinensis leaves, anti-liver injury, anti-inflammation

中图分类号:

TQ35

房仙颖, 谢莹莹, 章祎唯, 曹福亮, 赵林果. 银杏酸毒副作用及朴树提取物对其减毒效果研究[J]. 林产化学与工业, 2020, 40(6): 99-106.

Xianying FANG, Yingying XIE, Yiwei ZHANG, Fuliang CAO, Linguo ZHAO. Toxic and Side Effects of Ginkgolic Acid and Effect of Celtis sinensis Extracts on Detoxification of Ginkgolic Acid[J]. Chemistry and Industry of Forest Products, 2020, 40(6): 99-106.

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化合物 compunds	浓度/(μmol·L^-1) concentration	存活率/% survival rate
C₁₃:0	0	100
	1	83.0±2.21
	10	82.0±2.19
	100	28.7±2.45^**
C₁₅:1	0	100
	1	81.9±3.18
	10	76.6±2.11
	100	20.9±0.31^**
C₁₇:1	0	100
	1	80.3±3.13
	10	80.2±1.18
	100	89.8±1.35

组别¹⁾ group	腘窝淋巴结质量/mg weight of lymph node	淋巴细胞数/×10⁵ numbers of lymphocytes	耳肿胀/mm ear sweling	脾质量/g spleen weight
Sham.	6.02±0.3	12±0.4	22.2±5.01	0.09±0.01
S.c.	8.31±0.012^**	45±2.3^**	95.4±9.74^**	0.13±0.011^*

组别 group	质量浓度/(mg·L^-1) mass concentration	存活率survival rate/%
组别 group	质量浓度/(mg·L^-1) mass concentration	C₁₃:0	C₁₅:1
对照control		100	100
银杏酸损伤blank	银杏酸100 μmol/L	23.4±1.23^##	26.7±2.12^##
CH₂Cl₂	1	22.9±2.13	27.7±1.00
CH₂Cl₂	100	1.09±2.00	1.39±1.21
EA	1	22.8±3.81	25.9±4.11
EA	100	6.8±5.05	8.29±2.99
BA	1	24.9±3.26	29.8±1.89
BA	100	28.8±2.38^*	32.5±2.02^*
Water	1	24.0±5.32	29.5±5.31
Water	100	30.2±1.11^*	35.5±1.03^*
2#	1	32.0±2.02^*	58.4±1.98^**
2#	100	63.0±2.63^**	29.7±3.77
6#	1	29.1±3.12^*	22.3±2.59
6#	100	27.4±1.35	28.8±1.13
9#	1	25.8±2.11	27.6±2.05
9#	100	24.0±6.23	0.31±0.99
10#	1	24.3±6.18	35.9±2.12^*
10#	100	26.3±2.34	56.9±3.31^**
14#	1	33.0±1.76^*	29.5±1.77
14#	100	26.3±1.74	34.8±2.01^*

组别 group	质量浓度/(mg·L^-1) mass concentration	存活率/% survival rate
对照 control		8.68±0.69
3#	1	94.3±1.77
	10	91.2±1.69
	100	6.76±2.58^**
4#	1	93.5±2.55
	10	74.4±31.64
	100	6.80±0.38^**
6#	1	80.9±4.22
	10	85.8±3.26
	100	80.8±5.54
	1	68.3±3.77
8#	10	53.5±1.53^**
	100	4.58±0.22^**
	1	74.9±2.78
9#	10	73.0±2.98
	100	66.5±5.53
Con A活化 blank	5	100
	1	75.7±1.46
10#	10	79.2±6.52
	100	79.4±3.11
	1	85.0±2.48
13#	10	83.2±2.59
	100	56.9±1.65^**
	1	74.2±3.31
14#	10	77.9±2.87
	100	73.0±3.13
	1	76.3±3.25
15#	10	79.1±7.21
	100	78.9±5.13
	1	82.7±3.18
16#	10	55.1±3.01^**
	100	5.30±0.64^**

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