Abstract
The chemical compounds in the seeds of Ziziphus jujuba var. spinosa were investigated by biblio- graphical searching through the papers published since 2000. Terpenoids, flavonoids, alkaloids, phe- nolics, and fatty acids were reported as chemical compounds from the seed of Z. jujuba var. spinosa.
Terpenoid-related compounds were terpenoid-saponins, triterpenoids, sesquriterpenoids, and steroids.
Diverse structures of flavonoids were reported, such as flavones, flavanones, chalcone, and isoflavones.
Most phenolic compounds were glycoside-contained forms. Cyclopeptide-, aporphine-, indole-, pyrrole-, and benzylisoquinoline-types of alkaloids were reported. Fatty acids were divided into saturated, un- saturated, and their esterified forms.
Introduction
Sanjoin, the seeds of Ziziphus jujuba var. spinosa (Rhamnaceae), has traditionally been used as hypnotic or sedative drugs for its tranquillizing effect. Recent studies also report that the chemical components from Sanjoin have pharmacological effects on central nervous system: jujuboside A on the increase of type-A -aminobutyric acid receptors (GABAγ A) receptor mRNA expression in rat hippocampal neurons; spinosin on the reduction of memory impairment induced through amyloid-β1-42 oligomer (A O) in Alzheimer’s disease miceβ 1,2). Therefore, in the present study, the chemical compounds in the seeds of Ziziphus jujuba var. spinosa were investigated through bibliographic research and their chemical structures were represented.
Materials and methods
1. Searching strategy and terms
A variety of Korean and foreign electronic bibliographic databases were searched for papers published from 2000 and the present, including the Korea Education and Research Information
Chemical compounds in the seeds of Ziziphus jujuba var. spinosa
Kim Jung-Hoon*
Division of Pharmacology, School of Korean Medicine, Pusan National Univ., Yangsan, Republic of Korea
Keywords:
Ziziphus jujubavar.
spinosa, chemical compounds
Service (KERIS), National Discovery for Science Leaders (NDSL), PubMed, and Google Scholar, 산조인
using search terms such as “酸棗仁”, “ ”, “Zizyphus jujuba var. spinosa”, or “Ziziphus jujuba var. spinosa”.
2. Selection of papers
The papers reporting the chemical compounds in the seed of Z. jujuba var. spinosa were selected, which contained instrumental analysis and single compound isolation. Papers of compounds from different species or used for only biological effect, and literature only were excluded.
Each chemical structure was represented drawn by using the ChemDraw (ver. Ultra 10.0;
Cambridge Soft, USA), a software for drawing the chemical structure.
Results
Triterpenoid-related compounds involved 18 triterpenoid-saponins, 14 tritepenoids, 2 sesqui- terpenoids, and 2 steroids (Table 1).
Table 1. Terpenoid-related compounds in the seeds of
Z. jujubavar.
spinosaStructure Compound Chemical structure Ref
Triterpenoid- saponin
Jujuboside A
OH
O O
O O OH
O O
HOHO O
O O
O HOHO OH
O HO
HO OH
HO
O HO OH HO
3-14
Jujuboside A
1OH
O O
O O OH O
HOHO O
O O O HOHO
OH HO
O O OH
HO OH
O HOHO
OH
6,12
Jujuboside A
2OH
O O
O O OH
O O
HOHO O
O O O HOHO
OH HO
O HO
OH OH OH O
HOHO OH
7,8,15
Jujuboside B
OH
O O
O O OH O
HOHO O
O HO
O HOHO OH
O O HO OH HO
5-14,16
Jujuboside B
1OH
O O
O OH O O
HOHO O
O HO
O HOHO OH
O HO
OH HO
O
6,12,17
Jujuboside C
OH
O O
O OH O
O O
HOHO O
O O O HOHO
OH HO
O OH
OH OH O
HOHO OH HO
6,18
Jujuboside D
OH
O O
O O OH O
HOHO O
O O
O HOHO OH
O HO
HO OH
HO
O O OH
HO OH
9,17
Jujuboside I
OH
O O
O OH O HO
O O OH
OH OH
18
Acetyljujuboside B
OH
O O
O OH O
O O
HOHO O O OH O
OH OH O
HOHO OH
O O
6
Jujuboside Ⅰ
OH
O O
O OH O
O O
HOHO O O HO
OH O
OH OH O
HOHO OH HO
6
Jujuboside Ⅱ
OH
O O
O OH O
O O
HOHO O
O HO
O
HO O
6
Jujuboside Ⅲ
O O
OH O
O O
HOHO O
O HO
O HOHO OH
O HO OH HO
HO
O
6,7
Jujuboside Ⅳ
O O
OH O
O O HOHO O
O O
O HOHO OH
O HO OH HO
HO
O
O HOHO OH
HO
6
Zizyphus saponin II
OH
O O
O OH O
O O
HOHO OH O HO
OH O
OH OH
6
Azukisaponin II
OH
O H
H H
OH O HO
HO O
O
HOHO OH
HO O OH
14
Azukisaponin V
OH
O H
H H
OH O HO
HO O
O HOHO
O HO
O OH
O OH
OH OH
14
Soyasapogenol B -3-O- -D-gl β ucopyranosyl(1 2)- -D-gluc
→ β
opyranosyl(1→
2)- -glucurono β pyranoside
OH
O H
H H
OH O HOHO
O O HOHO
O HO
O OH
O
HOHO OH
OH
14
Jujubasaponin V
O
O H
O HOO
O
O OH
OH OH OH
O
HOHO OH
OH
H
O HO HH
5
Triterpenoids
Betulinic acid
HO
COOH
H
5,11,14,17,
19
Betulin
HO
H
OH
14,18,19
Ceanothic acid
COOHH HOOC HO
5,19
Epiceanothic acid
COOHH HOOC
HO
14,19
Ceanothic acid 2
8-methyl ester
COOCH3H HOOC
HO
19
Ceanothic acid 2
-methyl ester
COOHH H3COOC
HO
19
Epiceanothic acid
COOH HHO HOOC
H H
H
5
Alphitolic acid
COOHH
HO
HO H
H
H
5,19
Zizyphursolic aci
d
H COOHHO H
H
H
5
Pomolic acid
COOHHO
HO
19
Pomonic acid
COOHHO
O
19
Pomolic acid 28-
methyl ester
COOCH3HO
HO
19
Oleanolic acid
H
COOCH3
HO H
H
H
3
Squalene 5
Sesquiterpenoi ds
Dihydrophaseic a cid 3-O- -D-g β
lucopyranoside
O COOHO OH O
HOHO OH
OH
7
Flavonoids involved 22 flavones (2 flavonol contained), 3 flavanones, 1 chalcone, and 4 iso- flavones (Table 2).
Table 2. Flavonoid-related compounds in the seeds of
Z. jujubavar.
spinosaAlismoxide
OH H HO H
14
Steroids
-Sitosterol
β
HH H
H
HO
14
Daucosterol
H
H H
H
O O
HOHO OH
OH
14
Structure Compound Chemical structure Ref
Flavone
Spinosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
OH
3-5,8-10, 12,14,17,2 0-25
6 ′′′ -Feruloylspi nosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
O O
HO O
4,8-10,12, 14,20-25
6 ′′′ -Sinapoylspi nosin
O O
OH
O OH O
HOHO O
OH
O HO
HO OH
O O
HO O
O
8,24
6 - ′′′
p-Coumaro ylspinosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
O O
HO
8,21
6 -Vanilloylspi ′′′
nosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
O O
HO O
21,22
Isospinosin
O OOH
O OH O
HOHO O
OH
O
HOHO OH
OH
8,14,21-2
3,25
6 -feruloylisos ′′′
pinosin
O OOH
O OH O
HOHO O
OH
O
HOHO OH
O O
HO
O
14,25
6 -(4 ′′′ ′′′′ -O- β -D-glucopyrano syl)-vanilloyl sp inosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
O O
O O O
HOHO OH
OH
23
6 -O-(3S-1- ′′′
N- -D-glucopy β ranosyl-2-oxo -3-hydroxy-in dole-3-acetyl)s pinosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
N O
O
HOHO OH
OH
O O
HO
20
6 -O-(3R-1- ′′′
N- -D-glucopy β ranosyl-2-oxo -3-hydroxy-in dole-3-acetyl)s pinosin
O O
OH
O OH O
HOHO O
OH
O
HOHO OH
N O
O
HOHO OH
OH
O O
HO
20
6 -O-(3S-1- ′′′
N- -D-glucopy β ranosyl-2-oxo -3-hydroxy-in dole-3-acetyl)s pinosin
O O
OH
O OH O HO
HO O
O HO
HO OH
N O
O HO
HO OH
OH
O O HO
OH
20
6 -O-(3R-1- ′′′
N- -D-glucopy β ranosyl-2-oxo -3-hydroxy-in dole-3-acetyl)s pinosin
O O
OH
O OH O
HOHO O
O
HOHO OH
N O
O
HOHO OH
OH
O O HO
OH
20
6 -O-(3S-1- ′′
N- -D-glucopy β ranosyl-2-oxo -3-hydroxy-in dole-3-acetyl) -6 -feruloylspi ‴ nosin
O O
OH
O OH O HO
HO O
O HO
HO OH
N O
O HO
HO
OH
OH O
O HO
O
HO O
O
20
6 -O-(3R-1- ′′
N- -D-glucopy β ranosyl-2-oxo -3-hydroxy-in dole-3-acetyl) -6 -feruloylspi ‴ nosin
O O
OH
O OH O
HOHO O
O HO
HO OH
N O
O HO
HO OH
OH O
O HO
O O
HO O
20
Vicenin II
HO OOH
O OH O
HOHO OH
OH
O
HOHO OH
OH
5
Kaempferol 3-O -rutinoside
O HO
OH
O OH
HO O
OH OH
O O
H3C O
OH HO
HO
5,21
Kaempferol 3-O -a-L-rhamnop yranosyl-(1 2) → -O-[O- -L-r α hamnopyranosyl -(1 6)]- -D → β -glucopyranosid e
O HO
OH
O OH
O HO
HO O
O O O HO
OH OH
O HO
OH OH
23
Swertisin
O OOH
O OH O
HOHO OH
OH
12,23,25
Camelliaside B
O HO
OH
O OH
O OH
OH O O
H3C O
OH HO
HO HO O
OH OH O
21
Isovitexin
HO OOH
O OH O
HOHO OH
OH
25
Isovitexin-2 - ′′
O- -glucopyran β oside
O HO
OH
O OH O
HOHO O
OH
O
HOHO OH
OH
9,25
5, 6, 7, 8, 3 , 4 - ′ ′ hexamethoxy fla vone
O H3CO
OCH3
O OCH3
OCH3 OCH3
H3CO
14
Flavanone
6,8-Diglucopyra nosyl-4 ,5,7-tri ′ hydroxyflavanon e
O HO
OH
O OH O
HOHO OH
OH O
HOHO OH
OH
5
Clematine
O OOH
O OH O
HOHO OH
O
OCH3 OH O
OH OH
14
Hesperidin
O OOCH3
O OH O
HOHO OH
O
OH O
OH
OH OH
14
Chalcone
3‘,5‘-Di-C- - β D-Glucosylphlor etin
O OH
OH
OH
HO O
HOHO OH
OH O
HOHO OH
OH
5
Isoflavone
Glycitin
O O
H3CO O O
HO
HO OH
OH
OH
14
Genistin
O O
O O
HOHO OH
OH
OH OH
14
Daidzin
O O
O O
HO
HO OH
OH
OH
14
Puerarin
HO OO
OH O
HO
HO OH
OH
25
Phenolic compounds involved 3 phenolic glycosides and a auronol (Table 3).
Table 3. Phenolic compounds in the seeds of
Z. jujubavar.
spinosaAlkaloids involved 3 cyclopeptide types, 2 aporphine types, 2 indole types, a pyrrole types, and 2 benzylisoquinoline types (Table 4).
Table 4. Alkaloid compounds in the seeds of
Z. jujubavar.
spinosaStructure Compound Chemical structure Ref
Phenolic gly- coside
Pseudolaroside B
OH O
O O O HO
OH OH OH
5
Jujuphenoside
OCH3 O
O
O O
HOHO OH
14
Thymol-glucosi
de
O OHOHO OH
OH
5
Auronol Hovetrichoside C
O
OH
O
HO OH
O O
HOHO OH
OH
21
Structure Compound Chemical structure Ref
Cyclopeptide alkaloid
Amphibine D
O NH O
HN O
N O
NH O
N
12
Frangufoline
O NH O
HN HN O
O
3
Sanjoinine A
O NH O
HN HN O
O N
26
Aporphine al- kaloid
Magnoflorine
N+ H3CO
HO HO
H3CO
CH3 CH3
H
4,8,21
Zizyphusine
N+ HO
HO H3CO
H3CO
CH3
CH3
12,23
Indole alkaloid
3S-1-N- -D- β Glucopyranosyl- 2-oxo-3-hydro xy-indole-3-ac etic acid
N O
HO COOH
O
HOHO OH
OH
20
3R-1-N- -D- β Glucopyranosyl- 2-oxo-3-hydro xy-indole-3-ac etic acid
N O HO COOH
O
HOHO OH
OH
20
Pyrrole alka- loid
6-(2 ,3 - ′ ′ dihydroxyl-4'-h ydroxymethyl-t etrahydro-furan -1'-yl)-cyclop entene[c]pyrrole -1,3-diol
N OH
OH H
H O
HO OH
H HO
23
Benzylisoquino line alkaloid
Sanjoinine K
NH
OH O
HO
H
12
Juzirine
N O
HO
OH
14
Fatty acid involves 9 saturated fatty acids (a fatty alcohol contained), 9 unsaturated fatty acids, and 6 fatty acid esters (Table 5).
Table 5. Fatty acid-related in the seeds of
Z. jujubavar.
spinosaStructure Compound Chemical structure Ref
Fatty acid (Saturated)
Octyl 3-alcohol
OH5
Palmitic acid
HOO
5,13,27 Heptadecanoic ac
id
HOO
5
Stearic acid
HO O
5,13,27 Eicosanoic acid
(Arachidic acid)
HO O5,13,27 Tetracosanoic ac
id (Lignoceric aci d, carnaubic aci d)
HO
O
5
Behenic acid (Do cosanoic acid)
HOO
13,27
Myristic acid (T etradecanoic aci
d)
HOO
5,13
Lauric acid (Dod
ecanoic acid)
HOO
13
Fatty acid (Unsaturated)
Palmitelaidic acid
OOH
5
Palmitoleic acid
HO O
13
Linoleic acid
HO O
5,13,27
Oleic acid
HO O
5,13,27 9-Octadecenoic
acid
HOO
5
Ethyl oleate
O O
5 11-Eicosenoic a
cid
HOO
5 Gadoleic acid (9
-Eicosenoic aci
d)
HOO
27
2-(9,12-Octade cadienyloxy)- et hanol
O
HO
5
Fatty acid es- ter
Linoleic acid met
hyl ester
OO
5
Linoleic acid eth
OConclusions
Diverse chemical components in the seeds of Z. jujuba var. spinosa, such as triterpenoids, fla- vonoids, alkaloids and fatty acids were reported in previous literatures from 2000 to the present date. Those components could be further used to evaluate the quality or investigate the mecha- nism of therapeutic effect of the crude drugs.
References
1. You ZL, Xia Q, Liang FR, Tang YJ, Xu CL, Huang J, Zhao L, Zhang WZ, He JJ. Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neuro ns. J Ethnopharmacol. 2010;128:419 23.–
2. Ko SY, Lee HE, Park SJ, Jeon SJ, Kim B, Gao Q, Jang DS, Ryu JH. Spinosin, a C-glucosylflavon e, from Zizyphus jujuba var. spinosa ameliorates Aβ1-42 oligomer-induced memory impairment in mice. Biomol Ther. 2015;23(2):156-64.
3. Oshima N, Zaima K, Kamakura H, Hamato A, Yamamoto Y, Kang DH, Yokokura T, Goda Y, Hakamatsuka T, Maruyama T. Identification of marker compounds for Japanese Pharmacopoeia non-conforming jujube seeds from Myanmar. J Nat Med. 2015;69(1):68 75.–
4. Kim WI, Zhao BT, Zhang HY, Lee JH, Son JK, Woo MH. Quantitative and pattern recognition analyses of magnoflorine, spinosin, 6’’’-feruloyl spinosin and jujuboside A by HPLC in Zizyphi Semen. Arch Pharm Res. 2014;37:1139 47.–
5. Yang B, Yang H, Chen F, Hua Y, Jiang Y. Phytochemical analyses of Ziziphus jujuba Mill. var.
spinosa seed by ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Analyst. 2013;138:6881 8.−
6. Wang Y, Ding B, Luo D, Chen LY, Hou YL, Dai Y, Yao XS. New triterpene glycosides from Ziziphi Spinosae Semen. Fitoterapia. 2013;90:185 91.–
7. Lee SY, Kim JS, Lee JH, Kim YS, Kang SS. A New Saponin from the Seeds of Zizyphus jujuba var. spinosa. Bull Korean Chem Soc. 2013;34(2):657 60.–
8. Liao L, Won TH, Kang SS. Shin J. Simultaneous analysis of bioactive metabolites from Ziziphus
Oleic acid methyl
ester
OO
5 1-Monopalmitoy
lglycerol
HO OOH O
5
2-Monooctadece noylglycerol
O
OH HO
O
5
2-Monoeicosano ylglycerol
O
OH HO
O
5
jujuba by HPLC DAD ELSD MS/MS. J Pharm Investig. 2012;42:21 31.– – – –
9. Bao KD, Li P, Li HJ, Qi LW. Simultaneous determination of flavonoids and saponins in Semen Ziziphi Spinosae (Suanzaoren) by high performance liquid chromatography with evaporative ligh t scattering detection. Chin J Nat Med. 2009;7(1):47 53.–
10. Zeng W, Bai Y, Zhang Q, Zhao Y. Chromatographic fingerprint analysis of Semen Ziziphi spinos ae by HPLC-DAD method. Analytical Letters. 2009;42:205 15.–
11. Zhang M, Zhang Y, Xie J. Simultaneous determination of jujuboside A, B and betulinic acid in semen Ziziphi spinosae by high performance liquid chromatography-evaporative light scatt ering detection. J Pharm Biomed Anal. 2008;48:1467 70.–
12. Liu J, Chen B, Yao S. Simultaneous analysis and identification of main bioactive constituents in extract of Zizyphus jujuba var. sapinosa (Zizyphi spinosi semen) by high-performance liqui d chromatography photodiode array detection electrospray mass spectrometry. Talanta. 200– – 7;71:668 75.–
13. Zhao J, Li SP, Yang FQ, Li P, Wang YT. Simultaneous determination of saponins and fatty acids in Ziziphus jujuba (Suanzaoren) by high performance liquid chromatography-evaporative light scattering detection and pressurized liquid extraction. J Chromatogra A. 2006;1108:188–
94.
14. Li LM, Liao X, Peng SL, Ding LS. Chemical Constituents from the Seeds of Ziziphus jujuba var. spinosa (Bunge) Hu. J Integ Plant Biol. 2005;47(4):494 8.−
15. Lee SY, Kim JS, Lee JH, Kim YS, Kang SS. A New Saponin from the Seeds of Zizyphus jujuba var. spinosa. Bull Korean Chem Soc. 2013;34(2):1 7.−
16. Xu MY, Lee SY, Kang SS, Kim YS. Antitumor activity of jujuboside B and the underlying mechanism via induction of apoptosis and autophagy. J Nat Prod. 2014;77:370 76.− 17. Zhao X, Xie L, Wu H, Kong W, Yang M. Analysis of six bioactive components in Semen Ziziphi
Spinosae by UPLC-ELSD and UPLC-Q/TOF-MS. Anal Methods. 2014;6:5856 64.− 18. Wu Y, Zhang J, Wang D, Liu JG, Hu Y. Triterpenoid saponins from Ziziphus jujuba var. spinosa.
Chem Nat Compd. 2013;49(4):677 81.−
19. Fujiwara Y, Hayashida A, Tsurushima K, Nagai R, Yoshitomi M, Daiguji N, Sakashita N, Takey a M, Tsukamoto S, Ikeda T. Triterpenoids isolated from Zizyphus jujuba inhibit foam cell form ation in macrophages. J Agric Food Chem. 2011;59:4544 52.–
20. Li M, Wang Y, Tsoi B, Jin XJ, He RR, Yao XJ, Dai Y, Kurihara H, Yao XS. Indoleacetic acid derivatives from the seeds of Ziziphus jujuba var. spinosa. Fitoterapia. 2014;99:48 55.– 21. Lee SY, Lee JY, Kim JS, Lee JH, Kang SS. Flavonoids from the Seeds of Zizyphus jujuba
var. spinosa. Kor J Pharmacogn. 2012;43(2):127 36.–
22. Wu Y, He F, Pan Q, Shi Y, Min Z, Liang J. C-Glucosyl flavones from the seeds of Ziziphus jujuba var. spinosa. Chem Nat Compd. 2011;47(3):369 72.–
23. Xie YY, Xu ZL, Wang H, Kano Y, Yuan D. A novel spinosin derivative from Semen Ziziphi Spinosae. J Asian Nat Prod Res. 2011;13(12):1151 7.–
25. Cheng G, Bai Y, Zhao Y, Tao J, Liu Y, Tu G, Ma L, Liao N, Xu X. Flavonoids from Ziziphus jujuba Mill var. spinosa. Tetrahedron. 2000;56:8915 20.–
26. Ma Y, Han H, Eun JS, Kim HC, Hong JT, Oh KW. Sanjoinine A isolated from Zizyphi Spinosi Semen Augments pentobarbital-induced sleeping behaviors through the modification of GABA -ergic systems. Biol Pharm Bull. 2007;30(9):1748 53.–
27. Li YJ, Bi KS, Liang XM, Xiao HB. Analysis of fatty oil in Semen Ziziphi Spinosae by capillary gas chromatography. J Chromatogr Sci. 2003;41:41 3.−
