杜仲叶化学成分及其神经保护活性研究

doi:10.3969/j.issn.0253-2417.2023.03.002

Abstract

Abstract:

The ethanolic extracts of Eucommia ulmoides Oliv. leaves were isolated and purified, where thirteen compounds were obtained, including one new compound and twelve known compounds. The structures of the compounds were identified by spectral data as follows: (R, 9Z, 12E, 15Z)-11-hydroxyoctadeca-9, 12, 15-trienoic acid(1), 7-hydroxycoumarin(2), astragaline(3), quercetine(4), quercetin-3-O-glucoside(5), 2-(3, 4-dihydroxyphenyl)-5, 7-dihydroxy-3-[(3-O-α-D-xylopyranosyl-α-D-galactopy-ranosyl)oxy]-4H-1-benzopyran-4-one(6), (2R, 3S)-3-(4-hydroxy-3-methoxyphenyl)-3-methoxypropane-1, 2-diol(7), (2S, 3R)-3-(4-hydroxy-3-methoxyphenyl)-3-methoxypropane-1, 2-diol(8), chlorogenic acid(9), gardendiol(10), 4-benzyloxy benzoic acid(11), vanillic acid(12) and myristic acid(13). Among them, compound 1 was a new fatty acid compound. The anti-neuroinflammatory and neuroprotective activities of 13 compounds were studied. The results showed that compounds 4, 5 and 10 exhibited significant anti-neuroinflammatory activity by inhibiting the release of nitric oxide(NO) production in lipopolysaccharide(LPS)-induced in mouse microglia(BV-2 cells), with half inhibitory concentration(IC₅₀) values of (10.8±0.9), (9.7±1.1) and (10.7±0.3) μmol/L, respectively. Compound 5 exhibited significant neuroprotective activity under oxidative stress. After pretreatment with 20 μmol/L H₂O₂-induced rat adrenal pheochromocytoma cells(PC-12 cells), the cell survival rate was (86.5±0.5)%, which was higher than that of the positive control hesperidin.

Key words: Eucommia ulmoides leaves, chemical constituents, anti-neuroinflammatory, neuroprotection

CLC Number:

TQ35

Fengcheng HU, Rui HAN, Cong GUO, Jiangjiang TANG, Jinming GAO. Chemical Constituents of the Leaves of Eucommia ulmoides and Its Neuroprotective Activity[J]. Chemistry and Industry of Forest Products, 2023, 43(3): 9-15.

Figures/Tables 4

Fig.1

Fig.2

Table 1

Table 2

References 27

1	周政贤, 郭光典. 我国杜仲类型、分布及引种[J]. 林业科学, 1980, (增刊): 84- 91.
	ZHOU Z X , GUO G D . Types, distribution and introduction of Eucommia ulmoides in China[J]. Scientia Silvae Sinicae, 1980, (Suppl.): 84- 91.
2	栾庆祥. 杜仲化学成分和药理作用研究进展[J]. 安徽农业科学, 2016, 44 (9): 153- 156. doi: 10.13989/j.cnki.0517-6611.2016.09.053
	LUAN Q X . Advance in chemical component and pharmacologica action of Eucommia ulmoides Oliv[J]. Journal of Anhui Agricultural Sciences, 2016, 44 (9): 153- 156. doi: 10.13989/j.cnki.0517-6611.2016.09.053
3	孙桂梅. 杜仲叶的有效成分及绿原酸提取工艺研究[D]. 西安: 西北大学, 2007.
	SUN G M. Study on the effective components and Chlorogenic acid extraction process of Eucommia ulmoides leaves[D]. Xi'an: Northwest University, 2007.
4	曾桥, 韦承伯, 吕生华. 杜仲叶主要活性成分研究进展[J]. 安徽农业科学, 2017, 45 (34): 133- 135. doi: 10.13989/j.cnki.0517-6611.2017.34.043
	ZENG Q , WEI C B , LYU S H . Research progress on main active components of Eucommia ulmoides Leaves[J]. Journal of Anhui Agricultural Sciences, 2017, 45 (34): 133- 135. doi: 10.13989/j.cnki.0517-6611.2017.34.043
5	李家实, 阎玉凝. 杜仲皮与叶化学成分初步研究[J]. 中药通报, 1986, 11 (8): 41- 42.
	LI J S , YAN Y N . A preliminary study on the chemical composition of the bark and leaves of Eucommia ulmoides[J]. Traditional Chinese Medicine Journal, 1986, 11 (8): 41- 42.
6	LIN J , FAN Y J , MEHL C , et al. Eucommia ulmoides Oliv.antagonizes H₂O₂-induced rat osteoblastic MC3T3-E1 apoptosis by inhibiting expressions of caspases 3, 6, 7, and 9[J]. Journal of Zhejiang University-Science B, 2011, 12 (1): 47- 54. doi: 10.1631/jzus.B1000057
7	SUN A P , CHOI M S , JUNG U J , et al. Eucommia ulmoides Oliver leaf extract increases endogenous antioxidant activity in type 2 diabetic mice[J]. Journal of Medicinal Food, 2006, 9 (4): 474- 479. doi: 10.1089/jmf.2006.9.474
8	LUO D , OR T C , YANG C L , et al. Anti-inflammatory activity of iridoid and catechol derivatives from Eucommia ulmoides Oliver[J]. ACS Chemical Neuroscience, 2014, 5 (9): 855- 866. doi: 10.1021/cn5001205
9	BAI M M , SHI W , TIAN J M , et al. Soluble epoxide hydrolase inhibitory and anti-inflammatory components from the leaves of Eucommia ulmoides Oliver(Duzhong)[J]. Journal of Agricultural and Food Chemistry, 2015, 63 (8): 2198- 2205. doi: 10.1021/acs.jafc.5b00055
10	HENLEY S M , BATES G P , TABRIZI S J . Biomarkers for neurodegenerative diseases[J]. Current Opinion in Neurology, 2005, 18 (6): 698- 705. doi: 10.1097/01.wco.0000186842.51129.cb
11	CUNNANE S C , TRUSHINA E , MORLAND C , et al. Brain energy rescue: An emerging therapeutic concept for neurodegenerative disorders of ageing[J]. Nature Reviews Drug Discovery, 2020, 19 (9): 609- 633. doi: 10.1038/s41573-020-0072-x
12	CHOU S C , AGGARWAL A , DAWSON V L , et al. Recent advances in preventing neurodegenerative diseases[J]. Revista Cientifica-Facultad de Ciencias, 2021, 10, 81.
13	ELMALEH D R , FARLOW M R , CONTI P S , et al. Developing effective Alzheimer's disease therapies: Clinical experience and future directions[J]. Journal of Alzheimer's Disease, 2019, 71, 715- 732. doi: 10.3233/JAD-190507
14	BUTTERFIELD D A , HALLIWELL B . Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease[J]. Nature Reviews Neuroscience, 2019, 20, 148- 160. doi: 10.1038/s41583-019-0132-6
15	LIAO S, WU J N, LIU R M, et al. A novel compound DBZ ameliorates neuroinflammation in LPS-stimulated microglia and ischemic stroke rats: Role of Akt(Ser473)/GSK3 beta(Ser9)-mediated Nrf2 activation[J/OL]. Redox Biology, 2020, 36: 101644[2022-01-01]. https://doi.org/10.1016/j.redox.2020.101644.
16	SARLUS H , HENEKA M T . Microglia in Alzheimer's disease[J]. Journal of Clinical Investigation, 2017, 127, 3240- 3249. doi: 10.1172/JCI90606
17	白猛猛. 秦巴山区三种药用植物的化学成分及生物活性研究[D]. 杨凌: 西北农林科技大学, 2015.
	BAI M M. Chemical composition and biological activity of three medicinal plants from the Qinba mountainous area[D]. Yangling: Northwest A&F University, 2015.
18	YONG S G , KARUNAKARAN T , MURUGAIYAH V , et al. Accelerated solvent extractions(ASE) of Mitragyna speciosa Korth.(Kratom) leaves: Evaluation of its cytotoxicity and antinociceptive activity[J]. Molecules, 2021, 26 (12): 3704- 3713. doi: 10.3390/molecules26123704
19	TIAN Y , LAAKSONEN O , HAIKONEN H , et al. Compositional diversity among blackcurrant(Ribes nigrum) cultivars originating from european countries[J]. Journal of Agricultural and Food Chemistry, 2019, 67 (19): 5621- 5633. doi: 10.1021/acs.jafc.9b00033
20	LI L , PENG Y , XU L J , et al. Flavonoid glycosides and phenolic acids from Ehretia thyrsiflora[J]. Biochemical Systematics and Ecology, 2008, 36 (12): 915- 918. doi: 10.1016/j.bse.2008.11.008
21	YAN X J , WEN J , XIANG Z , et al. Two new phenolic acids from the fruits of Forsythia suspense[J]. Journal of Asian Natural Products Research, 2017, 19 (3): 254- 259. doi: 10.1080/10286020.2016.1205589
22	KIM K H , HA S K , CHOI S U , et al. Phenolic constituents from the twigs of Euonymus alatus and their cytotoxic and anti-inflammatory activity[J]. Planta Medica, 2013, 79 (5): 361- 364. doi: 10.1055/s-0032-1328286
23	辛颖, 达拉胡, 红艳, 等. 梅花草抗肿瘤活性部位化学成分研究[J]. 中国药学杂志, 2019, 54 (4): 264- 267.
	XIN Y , DA L H , HONG Y , et al. Chemical constituents of antitumor active fractions from Parnassia palustris[J]. Chinese Pharmaceutical Journal, 2019, 54 (4): 264- 267.
24	SHOHKO T , KANEDA M , KAKINUMA K . Activation of guinea pig polymorphonuclear leukocytes with soluble stimulators leads to nonrandom distribution of NADPH oxidase in the plasma membrane[J]. Journal of Biochemistry, 1983, 94 (3): 655- 664. doi: 10.1093/oxfordjournals.jbchem.a134405
25	WEIBEL D B , SHEVY L E , SCHROEDER F C , et al. Synthesis of mayolene-16 and mayolene-18:Larval defensive lipids from the European cabbage butterfly[J]. Journal of Organic Chemistry, 2002, 67 (17): 5896- 5900. doi: 10.1021/jo011102q
26	SMEDLEY S R , SCHROEDER F C , WEIBEL D B , et al. Mayolenes: Labile defensive lipids from the glandular hairs of a caterpillar(Pieris rapae)[J]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99 (10): 6822- 6827. doi: 10.1073/pnas.102165699
27	LONG S , YEN G C . Neuroprotective effects of the citrus flavanones against H₂O₂-induced cytotoxicity in PC12 cells[J]. Journal of Agricultural and Food Chemistry, 2008, 56 (3): 859- 864. doi: 10.1021/jf072826r

序号No.	δ_C	δ_H
1	174.9(COOH)
2	34.2(CH₂)	2.19(m)
3	25.1(CH₂)	1.47(m)
3	25.1(CH₂)	1.22(m)
4	29.0(CH₂)	1.25-1.31(m)
5	29.1(CH₂)	1.25-1.31(m)
6	28.9(CH₂)	1.25-1.31(m)
7	29.6(CH₂)	1.25-1.31(m)
8	27.6(CH₂)	2.11(m); 1.96(m)
9	131.5(CH)	5.33(d, J=5.54)
10	128.8(CH)	5.96(t, J=10.73)
11	71.0(CH)	4.01(m)
12	137.8(CH)	5.64(dd, J=5.52, 14.96)
13	124.5(CH)	6.42(t, J=14.05)
14	35.8(CH₂)	2.17(m)
15	125.8(CH)	5.38(d, J=6.57)
16	132.9(CH)	5.40(d, J=7.84)
17	20.7(CH₂)	1.97(m)
18	14.5(CH₃)	0.90(t, J=7.18)
11-OH		11.96(s)

化合物compound	NO		PC-12细胞存活率/%cell viability of PC-12
化合物compound	IC₅₀/(μmol·L^-1)	抑制率(20 μmol·L^-1)/%inhibitory rate	PC-12细胞存活率/%cell viability of PC-12
1	13.7±0.7	71.7±1.4	79.0±3.0
2	18.4±0.1	67.1±0.6	85.0±9.0
3	15.2±0.5	78.5±0.06	80.5±11.5
4	10.8±0.9	73.0±2.5	52.2±1.2
5	9.7±1.1	78.3±1.7	86.5±0.5
6	18.9±0.4	62.5±1.0	60.6±0.8
7	＞20	7.1±0.65	43.2±1.2
8	＞20	47.1±0.9	54.0±5.7
9	17.4±0.4	66.7±0.9	79.0±0.2
10	10.7±0.3	81.5±0.8	77.0±0.1
11	16.1±0.8	71.1±0.5	83.5±2.5
12	19.5±0.8	57.7±0.5	69.0±1.1
13	17.8±0.6	61.1±1.0	69.0±1.0
橙皮苷hesperidin			77.0±1.2

[1]	CAO Bin, CHI Jun, WANG Pei, XIE Anqi, DAI Liping, WANG Zhimin. Identification of the Chemical Components in the Milky Sap of Euphorbia helioscopia L. by UPLC-Oribtrap-Exploris-120-MS/NMR [J]. Chemistry and Industry of Forest Products, 2023, 43(3): 49-60.
[2]	Liangjie TANG, Wei LUO, Hulan CHEN. Research Progress of Chemical Constituents and Pharmacological Effects of Euscaphis Plants [J]. Chemistry and Industry of Forest Products, 2023, 43(2): 153-170.
[3]	Wenjuan ZHOU, Yuanwang QIU, Jiayan BEI, Yuzhou WANG, Shiqi RUAN, Lin NI. Separation and Identification of Aqueous Extracts of Cinnamomum longe-paniculatum Leaves and Their Anti-hepatocellular-cancer Activity [J]. Chemistry and Industry of Forest Products, 2022, 42(6): 1-10.
[4]	Wenjun LI, Chengzhang WANG, Jiandu LEI, Fengxia TANG, Dong PEI, Xiaobo SONG. Research Progress on Olive Oil Secondary Metabolite of Oleocanthal [J]. Chemistry and Industry of Forest Products, 2022, 42(6): 136-146.
[5]	Meng LIANG, Yafeng WANG, Taojie XIE, Hongjie ZHU, Yonglin HUANG. Chemical Constituents and Tyrosinase Inhibitory Activities from the Pink Flowers of Bauhinia variegata L. [J]. Chemistry and Industry of Forest Products, 2022, 42(4): 68-74.
[6]	Feng YU, Zhihong WANG, Guangyao ZHANG, Zhiyun DU, Mijun PENG. Extraction of Chlorogenic Acid From Eucommia ulmoides Leaves by Natural Deep Eutectic Solvent and Its Antioxidant Activity [J]. Chemistry and Industry of Forest Products, 2022, 42(1): 101-109.
[7]	Hongdan ZHUANG, Fengqiu LI, Ruilong LUO, Liqin WANG. Research Progress of Chemical Constituents and Pharmacological Activity of Elaeagnus Plants [J]. Chemistry and Industry of Forest Products, 2021, 41(4): 135-146.
[8]	Hongxia CHEN, Hao ZHOU, Jianzhong YE, Ran TAO, Wenjun LI, Chengzhang WANG. Matrix Solid-phase Dispersion Combined with GC-MS for Determination of Chemical Constituents of Essential Oil in Agarwood [J]. Chemistry and Industry of Forest Products, 2021, 41(3): 47-54.
[9]	Ziying YANG, Jing LI, Jie SU, Huiling LI, Zhang ZHANG, Feng PENG. Research Progress on Chemical Constituents and Activities of Genus Usnea Lichens [J]. Chemistry and Industry of Forest Products, 2021, 41(3): 112-124.
[10]	Xian CHENG, Liangwu BI, Weixing ZENG, Zhendong ZHAO, Yuxiang CHEN, Zuohui ZHANG. Chemical Constituents of Distillation Residues from Cinnamon Twigs and Leaves by Using UHPLC-QTOF MS [J]. Chemistry and Industry of Forest Products, 2020, 40(6): 50-60.
[11]	Jingxin CHEN,Yuying ZHAN,Yan CHEN,Huiyou XU,Shuangquan ZOU,Lin NI. Chemical Constituents and Anti-inflammatory Activity from the Twigs of Euscaphis konishii Hayata [J]. Chemistry and Industry of Forest Products, 2019, 39(6): 88-94.
[12]	WEI Qiang, JI Xiao-ying, LONG Xian-shun, LI Qian-rong, YIN Hao. Chemical Constituents Extracted from Leaves of Prunus cerasifera Ehrh.cv. Atropurpurea Jacg. and Their Antioxidant Activities in vitro [J]. Chemistry and Industry of Forest Products, 2015, 35(5): 116-122.
[13]	ZHANG Ni, MU Shu-zhen, WANG Jia-sheng, KONG Qi, YU Zheng-wen. Chemical Constituents of n-Butanol-insoluble Portion from Parochetus communis Buch.Extract [J]. Chemistry and Industry of Forest Products, 2015, 35(3): 121-124.
[14]	JIN Xiao-xi, HE Pei, JIANG Yan, LI Hui-jun. Chemical Constituents from the Stems of Viburnum dilatatum Thunb. var. fulvotomentosum (Hsu) Hsu [J]. Chemistry and Industry of Forest Products, 2014, 34(1): 97-100.
[15]	WAN Chun-peng;ZHOU Shou-ran. Chemical Constituents of Acer rubrum L. and Their Antioxidant Activities [J]. , 2013, 33(5): 93-96.

Chemical Constituents of the Leaves of Eucommia ulmoides and Its Neuroprotective Activity

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References 27

Related Articles 15

Recommended Articles

Metrics

Comments