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

Abstract

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

CLC Number:

TQ35

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.

Figures/Tables 6

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Fig.2

Table 3

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References 23

1	蒋娅兰.银杏保健茶的质量控制研究[D].广州: 广东药科大学, 2016.
	JIANG Y L.Studies on quality control of Ginkgo dietary supplement tea[D]. Guangzhou: Guangdong Pharmaceutical University, 2016.
2	吴雅琼, 国靖, 周琦, 等. 不同产地银杏黄酮及相关活性物质含量变异分析[J]. 南京林业大学学报(自然科学版), 2019, 43 (3): 183- 188.
	WU Y Q , GUO J , ZHOU Q , et al. Variation analysis of flavonoids and related active substances content in ginkgo leaves from different regions[J]. Journal of Nanjing Forestry University(Natural Sciences Edition), 2019, 43 (3): 183- 188.
3	张昌伟, 马余璐, 陶冉, 等. 银杏叶聚戊烯醇的分离纯化及其亲水衍生物的合成[J]. 林产化学与工业, 2019, 39 (1): 41- 45.
	ZHANG C W , MA Y L , TAO R , et al. Separation, purification and hydrophilic derivative synthesis of Ginkgo biloba leaves polyprenol[J]. Chemistry and Industry of Forest Products, 2019, 39 (1): 41- 45.
4	WANG R , KOBAYASHI Y , LIN Y , et al. HPLC quantification of all five ginkgolic acid derivatives in Ginkgo biloba extracts using 13:0 ginkgolic acid as a single marker compound[J]. Planta Medica, 2015, 81 (1): 71- 78.
5	JIANG L , SI Z H , LI M H , et al. ¹ H NMR-based metabolomics study of liver damage induced by ginkgolic acid(15:1) in mice[J]. Journal of Pharmaceutical and Biomedical Analysis, 2017, 136, 44- 54.
6	YAO Q Q , LI L , XU M C , et al. The metabolism and hepatotoxicity of ginkgolic acid(17:1) in vitro[J]. Chinese Journal of Natural Medicines, 2018, 16 (11): 829- 837.
7	GROLLINO M G , RASCHELL G , CORDELLI E , et al. Cytotoxicity, genotoxicity and gene expression changes elicited by exposure of human hepatic cells to Ginkgo biloba leaf extract[J]. Food and Chemical Toxicology, 2017, 109, 486- 496.
8	KANDIAH N , ONG P A , YUDA T , et al. Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease:Expert consensus on the use of Ginkgo biloba extract, EGb 761^®[J]. CNS Neuroscience & Therapeutics, 2019, 25 (2): 288- 298.
9	张彩虹, 黄立新, 谢普军, 等. 白果直链/支链淀粉的分离及性能研究[J]. 林产化学与工业, 2017, 37 (4): 103- 109.
	ZHANG C H , HUANG L X , XIE P J , et al. Extraction and performance of Ginkgo biloba Linn.amylase and amylopectin[J]. Chemistry and Industry of Forest Products, 2017, 37 (4): 103- 109.
10	谢莹莹, 房仙颖, 萧伟, 等. 朴树化学成分及药理活性研究进展[J]. 中国药学杂志, 2016, 51 (19): 1633- 1637.
	XIE Y Y , FANG X Y , XIAO W , et al. Advances in research on chemical constituents and pharmacological activities of Celtis sinensis[J]. Chinese Pharmaceutical Journal, 2016, 51 (19): 1633- 1637.
11	MA X M , LU R , MIYAKOSHI T . Recent advances in research on lacquer allergy[J]. Allergology International:Official Journal of the Japanese Society of Allergology, 2012, 61 (1): 45- 50.
12	LEPOITTEVIN J P , BENEZRA C , ASAKAWA Y . Allergic contact dermatitis to Ginkgo biloba L.:Relationship with urushiol[J]. Archives of Dermatological Research, 1989, 281 (4): 227- 230.
13	HAUSEN B M . The sensitizing capacity of ginkgolic acids in guinea pigs[J]. American Journal of Contact Dermatitis:Official Journal of the American Contact Dermatitis Society, 1998, 9 (3): 146- 148.
14	齐志鹏.朴树叶抗炎组分的分离及其活性评价[D].南京: 南京林业大学, 2018.
	QI Z P.The Separation and activity evaluation of the anti-inflammatory components of the leaves of Celtis sinensis[D]. Nanjing: Nanjing Forestry University, 2018.
15	王晓杰, 黄立新, 张彩虹, 等. 油橄榄叶提取物的制备及理化性质研究[J]. 林产化学与工业, 2019, 39 (4): 83- 90.
	WANG X J , HUANG L X , ZHANG C H , et al. Preparation and physicochemical properties of olive leaf extract[J]. Chemistry and Industry of Forest Products, 2019, 39 (4): 83- 90.
16	李小阳, 韩冠英, 马涛, 等. 碱蓬草总生物碱提取工艺优化及其对高脂饮食小鼠的体内抗氧化活性[J]. 食品工业科技, 2020, 1- 18.
	LI X Y , HAN G Y , MA T , et al. Extraction of total alkaloids from Suaeda salsa and its antioxidant activity in mice fed with high-fat diet[J]. Technology of Food Industry, 2020, 1- 18.
17	熊双丽, 李安林, 黄妮. 绵麦冬皂苷的提取分离及免疫活性研究[J]. 林产化学与工业, 2015, 35 (1): 121- 125.
	XIONG S L , LI A L , HUANG N . Extraction, separation, and immunoregulatory activity of saponins from Ophiopogon japonicus(L.f.) Ker-Gawl[J]. Chemistry and Industry of Forest Products, 2015, 35 (1): 121- 125.
18	陈乃东, 王成, 陈乃富, 等. 响应面法优化霍山石斛三萜皂苷提取工艺研究[J]. 皖西学院学报, 2019, 35 (2): 11- 15, 48.
	CHEN N D , WANG C , CHEN N F , et al. Optimization of extraction technology of the total triterpenoid saponins from Dendrobium huoshanese by response surface methodology[J]. Journal of West Anhui University, 2019, 35 (2): 11- 15, 48.
19	FANG X Y, DONG Y R, XIE Y Y, et al.Effects of β-glucosidase and α-rhamnosidase on the contents of flavonoids, ginkgolides, and aroma components in ginkgo tea drink[J/OL]. Molecules, 2019, 24(10): 1-16[2020-03-20]. http://ncbi.nlm.nih.gov/pmc/articles/PMC6572456.DOI:10.3390/mdecules24102009.
20	CHOI J M , OH S J , LEE S Y , et al. HepG2 cells as an in vitro model for evaluation of cytochrome P450 induction by xenobiotics[J]. Archives of Pharmacal Research, 2015, 38 (5): 691- 704.
21	明汇, 崔东艳, 孙黎飞, 等. 以淋巴结肿大为首发的HIV感染与梅毒感染患者淋巴结细胞学表现二例[J]. 中华医学杂志, 2016, 96 (24): 1945- 1946.
	MING H , CUI D Y , SUN L F , et al. Two cases of lymph node cytological features in HIV and syphilis patients with lymphadenopathy as first symtom[J]. National Medical Journal of China, 2016, 96 (24): 1945- 1946.
22	何静仁.银杏酸的变应原性及致过敏作用机制研究[D].武汉: 华中农业大学, 2003.
	HE J R.Studies on allergenicity and sensitization mechanism of ginkgolic acids from Ginkgo biloba L.[D]. Wuhan: Huazhong Agricultural University, 2003.
23	ZHOU Y Q , WENG X F , DOU R , et al. Betulin from Hedyotis hedyotidea ameliorates concanavalin A-induced and T cell-mediated autoimmune hepatitis in mice[J]. Acta Pharmacologica Sinica, 2017, 38 (2): 201- 210.

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^**

[1]	SHI Qi-tian. RESEARCH ON PREVENTION AND ELIMINATION OF AGRICULTURAL PESTS BY GINKGO PHENOLS AND PHENOLIC ACIDS [J]. , 2004, 24(2): 83-86.
[2]	WU Xiang-yang;YANG Liu-qing;CHEN Jun;YUAN Xin-hua;XIA Guo-hua. PREPARATION OF GINKGOLIC ACID MONOMERS AND THEIR ANTIFUNGAL ACTIVITY [J]. , 2003, 23(04): 17-21.
[3]	TAN Wei-hong;SHEN Zhao-bang;WANG Cheng-zhang;YU Qing . QUANTITATIVE DETERMINATION OF ALKYLPHENOLS IN GINKGO BILOBA LEAVES,EXTRACTS AND PREPARATIONS [J]. , 2002, 22(3): 6-10.
[4]	TAN Wei-hong;SHEN Zhao-bang;WANG Cheng-zhang;YU Qing. ISOLATION AND IDENTIFICATION OF ALKYLPHENOLS FROM GINKGO BILOBA LEAVES [J]. , 2001, 21(04): 1-6.

Toxic and Side Effects of Ginkgolic Acid and Effect of Celtis sinensis Extracts on Detoxification of Ginkgolic Acid

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