Generic placeholder image

Medicinal Chemistry

Author(s): Zahra Sobhani , Sara Nikoofal-Sahlabadi, Mohammad S. Amiri, Mahin Ramezani, Seyed A. Emami* and Amirhossein Sahebkar*

DOI: 10.2174/1573406415666191031143553

DownloadDownload PDF Flyer Cite As
Therapeutic Effects of Ziziphus jujuba Mill. Fruit in Traditional and Modern Medicine: A Review

Page: [1069 - 1088] Pages: 20

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Ziziphus jujuba Mill. belonging to the Rhamnaceae family, has been consumed since ancient times as a medicine and food. In the different traditional medical schools, Z. jujuba has been used to treat various diseases such as respiratory system diseases (asthma, cough, and laryngitis), gastrointestinal problems (constipation, colitis and liver diseases), as well as cardiovascular and genitourinary system diseases. From the perspective of Islamic traditional medicine (ITM), Z. jujuba fruit is an emollient, laxative, and maturative, it can purify blood and improve blood circulation, relieve internal heat and reduce inflammation. Some therapeutic uses of Z. jujuba such as antibacterial, antioxidant, sedative, hepato-protective, anti-hyperglycemic, and anti-hyperlipidemic activities have been shown in modern pharmacological studies. In the current study, traditional and ethno-medicinal uses, botany, phytochemistry and pharmacological activities of Z. jujuba were reviewed.

Keywords: Traditional medicine, Ziziphus jujuba, Rhamnaceae, jujube, food, flavonoids.

Graphical Abstract

[1]
Fabricant, D.S.; Farnsworth, N.R. The value of plants used in traditional medicine for drug discovery. Environ. Health Perspect., 2001, 109(Suppl. 1), 69-75.
[http://dx.doi.org/10.1289/ehp.01109s169]
[2]
Gao, Q.H.; Wu, C.S.; Wang, M. The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. J. Agric. Food Chem., 2013, 61(14), 3351-3363.
[http://dx.doi.org/10.1021/jf4007032]
[3]
Aqili Alawi Khorâsâni Shirâzi, M.H. Makhzan al-Adwyah (Drug Treasure); Sabz Arang publisher: Tehran, 2014, pp. 578-579. (in Persian)
[4]
Ibn Nafis Qarshi, A.A. Ash-Shȃmel fi aṭ-Ṭibbe (The Comprehensive in Medicine); Cultural Foundation Publications: Abu Dhabi, 1999, Vol. 21, pp. 427-428. (in Arabic)
[5]
Ibn Sinâ, H.A. Al-Qânun fi at- aṭ-Ṭibbe (Canon of Medicine); Dâr –al Fikr: Beirut, 2002, Vol. 1, pp. 769-770. (in Arabic)
[6]
Ibn Beytâr, A.A. Al-Jâmee le Mofradât al-Adwyah wa al-Aghḏiah (Comprehensive Book in Simple Drugs and Foods); Dâr al-Kotob al-Ilamiyah: Beirut, 2001, Vol. 2, p. 191. (in Arabic)
[7]
Mahajan, R.T.; Chopda, M. Phyto-pharmacology of Ziziphus jujuba Mill. A plant review. Pharmacogn. Rev., 2009, 3(6), 320-329.
[8]
Liu, M.; Cheng, C. A taxonomic study on the genus Ziziphus. Acta Hortic., 1994, (390), 161-166.
[9]
Mengjun, L. Genetic diversity of Chinese jujube (Ziziphus jujuba Mill.). Acta Hortic., 2002, 623(623), 351-355.
[10]
Arndt, S.; Clifford, S.; Popp, M. Ziziphus—a Multipurpose Fruit Tree for Arid Regions. In: Breckle, S.W. Veste M. Wucherer W. Eds., Sustainable land use in deserts. Springer , 2001; pp. 388-399.
[11]
Huang, J.; Chen, R.; Li, X. Comparative analysis of the complete chloroplast genome of four known Ziziphus species. Genes (Basel), 2017, 8(12)E340
[http://dx.doi.org/10.3390/genes8120340]
[12]
Li, J.W.; Fan, L.P.; Ding, S.D.; Ding, X.L. Nutritional composition of five cultivars of Chinese jujube. Food Chem., 2007, 103(2), 454-460.
[http://dx.doi.org/10.1016/j.foodchem.2006.08.016]
[13]
Baker, W.L.; White, C.M.; Kluger, J.; Denowitz, A.; Konecny, C.P.; Coleman, C.I. Effect of perioperative corticosteroid use on the incidence of postcardiothoracic surgery atrial fibrillation and length of stay. Heart Rhythm, 2007, 4(4), 461-468.
[http://dx.doi.org/10.1016/j.hrthm.2006.11.026]
[14]
Amini, M.H. Hamdam, S.A. Medicinal plants used traditionally in Guldara District of Kabul, Afghanistan. Int. J. Pharmacogn. Chinese Med., 2017, 1(3)e000118
[http://dx.doi.org/ 10.23880/IPCM-16000118]
[15]
Pieroni, A. Traditional uses of wild food plants, medicinal plants, and domestic remedies in Albanian, Aromanian and Macedonian villages in South-Eastern Albania. J. Herb. Med., 2017, 9, 81-90.
[http://dx.doi.org/10.1016/j.hermed.2017.05.001]
[16]
Jiang, S.; Quave, C.L. A comparison of traditional food and health strategies among Taiwanese and Chinese immigrants in Atlanta, Georgia, USA. J. Ethnobiol. Ethnomed., 2013, 9e61
[http://dx.doi.org/10.1186/1746-4269-9-61]
[17]
Hurrell, J.A.; Puentes, J.P. Plant species and products of the Traditional Chinese Phytotherapy in the Ciudade Autónoma de Buenos Aires, Argentina. Ethnobiol. Conserv., 2017, 6 , e1.
[18]
Mahmud, S.; Mahmud, S.; Hasan, M.K.; Rahman, S.; Kar, A.; Shathy, E.J.; Mohiuddin, A. A survey on medicinal plants usage by folk medicinal practitioners in different villages of Jhenaigati Upazila, Sherpur district. Bangladesh. J. Pharmacogn. Phytochem., 2016, 5(4), 167-180.
[19]
Olivier, T.T.; Francis, N.T.; Jackson, A.S.; Justin, K.; Justin, N. Ethnobotanic survey of medicinal plants used for malaria therapy in western Cameroon. J. Med. Plants Stud., 2016, 248(43), 248-258.
[20]
Teng, Y.; Guo, H.; Liang, Z.; Shu, Z.; Li, Z.; Wu, W. Ethnobotanical survey of medicinal plants and their utilization in Shaanxi Province, China. J. Med. Plants Res., 2011, 5(9), 1762-1778.
[21]
Hong, L.; Guo, Z.; Huang, K.; Wei, S.; Liu, B.; Meng, S.; Long, C. Ethnobotanical study on medicinal plants used by Maonan people in China. J. Ethnobiol. Ethnomed., 2015, 11(1)e32
[http://dx.doi.org/10.1186/s13002-015-0019-1]
[22]
Emami, S.; Nadjafi, F.; Amine, G.; Amiri, M.; Khosravi, M.; Naseri, M. Les espèces de plantes médicinales utilisées par les guérisseurs traditionnels dans la province de Khorasan, nord-est de l’Iran. Ethnopharmacologia, 2012, 48(juillet), 48-59.
[23]
Amiri, M.S.; Joharchi, M.R.; Taghavizadehyazdi, M.E. Ethnomedicinal plants used to cure jaundice by traditional healers of Mashhad, Iran. Iran. J. Pharm. Res., 2014, 13(1), 157-163.
[24]
Ahmed, H.M. Ethnopharmacobotanical study on the medicinal plants used by herbalists in Sulaymaniyah Province, Kurdistan, Iraq. J. Ethnobiol. Ethnomed., 2016, 12e8
[http://dx.doi.org/10.1186/s13002-016-0081-3]
[25]
Lev, E.; Amar, Z. Ethnopharmacological survey of traditional drugs sold in the Kingdom of Jordan. J. Ethnopharmacol., 2002, 82(2-3), 131-145.
[http://dx.doi.org/10.1016/S0378-8741 (02)00182-4]
[26]
Kim, H.; Song, M.J. Analysis and recordings of orally transmitted knowledge about medicinal plants in the southern mountainous region of Korea. J. Ethnopharmacol., 2011, 134(3), 676-696.
[http://dx.doi.org/10.1016/j.jep.2011.01.024]
[27]
Song, M.J.; Kim, H. Ethnomedicinal application of plants in the western plain region of North Jeolla Province in Korea. J. Ethnopharmacol., 2011, 137(1), 167-175.
[http://dx.doi.org/10.1016/j.jep.2011.05.001]
[28]
Pieroni, A.; Quave, C.L. Traditional pharmacopoeias and medicines among Albanians and Italians in southern Italy: a comparison. J. Ethnopharmacol., 2005, 101(1-3), 258-270.
[http://dx.doi.org/10.1016/j.jep.2005.04.028]
[29]
El-Youbi, A.H.; Ouahidi, I.; El-Mansouri, L.; Daoudi, A.; Bousta, D. Ethnopharmacological survey of plants used for immunological diseases in four regions of Morocco. European J. Med. Plants, 2016, 13, 1-24.
[http://dx.doi.org/10.9734/EJMP/2016/12946]
[30]
Akhtar, N.; Begum, S. Ethnopharmacological important plants of Jalala, district Mardan, Pakistan. Pak. J. Pl. Sci., 2009, 15(1), 95-100.
[31]
Parada, M.; Carrió, E.; Vallès, J. Ethnobotany of food plants in the Alt Emporda region (Catalonia, Iberian Peninsula). J. Appl. Bot. Food Qual., 2011, 84, 11-25.
[32]
Polat, R.; Satıl, F. An ethnobotanical survey of medicinal plants in Edremit Gulf (Balıkesir–Turkey). J. Ethnopharmacol., 2012, 139(2), 626-641.
[http://dx.doi.org/10.1016/j.jep.2011.12.004]
[33]
Bhandaria, S.K.; Shresthaa, P.; Choudhurya, S.R.; Sharmina, T.; Rashidb, M.A. Ethnomedical investigation on herbal drugs used in Dang district of Nepal. J. Ethnobiol. Ethnomed., 2006, 2e41
[http://dx.doi.org/10.1186/1746-4269-2-41.]
[34]
Hussain, K.; Nisar, M.F.; Majeed, A.; Nawaz, K.; Bhatti, K.H. Ethnomedicinal survey for important plants of Jalalpur Jattan, district Gujrat, Punjab, Pakistan. Ethnobotanical Leaflets, 2010, 14, 807-825.
[35]
Gao, Q.H.; Wu, C.S.; Yu, J.G.; Wang, M.; Ma, Y.J.; Li, C.L. Textural characteristic, antioxidant activity, sugar, organic acid, and phenolic profiles of 10 promising jujube (Ziziphus jujuba Mill.) selections. J. Food Sci., 2012, 77(11), C1218-C1225.
[http://dx.doi.org/10.1111/j.1750-3841.2012.02946.x]
[36]
Wang, B.N.; Cao, W.; Gao, H.; Fan, M.T.; Zheng, J.B. Simultaneous determination of six phenolic compounds in jujube by LC-ECD. Chromatographia, 2010, 71(7-8), 703-707.
[http://dx.doi.org/10.1365/s10337-010-1485-1]
[37]
Choi, S.H.; Ahn, J.B.; Kim, H.J.; Im, N.K.; Kozukue, N.; Levin, C.E.; Friedman, M. Changes in free amino acid, protein, and flavonoid content in jujube (Ziziphus jujuba) fruit during eight stages of growth and antioxidative and cancer cell inhibitory effects by extracts. J. Agric. Food Chem., 2012, 60(41), 10245-10255.
[http://dx.doi.org/10.1021/jf302848u]
[38]
Choi, S.H.; Ahn, J.B.; Kozukue, N.; Levin, C.E.; Friedman, M. Distribution of free amino acids, flavonoids, total phenolics, and antioxidative activities of jujube (Ziziphus jujuba) fruits and seeds harvested from plants grown in Korea. J. Agric. Food Chem., 2011, 59(12), 6594-6604.
[http://dx.doi.org/10.1021/jf200371r]
[39]
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(45), 8915-8920.
[http://dx.doi.org/10.1016/S0040-4020 (00)00842-5]
[40]
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 (Lond.), 2013, 138(22), 6881-6888.
[http://dx.doi.org/10.1039/c3an01478a]
[41]
Wu, Y.; Chen, M.; Du, M.B.; Yue, C.H.; Li, Y.Y.; Zhu, M.; Liu, C.; Wang, D.Y.; Liu, J.G.; Hu, Y.L. Chemical constituents from the fruit of Zizyphus jujuba Mill. var. spinosa. Biochem. Syst. Ecol., 2014, 57, 6-10.
[http://dx.doi.org/10.1016/j.bse.2014.07.009]
[42]
Gao, Q.H.; Wu, C.S.; Wang, M.; Xu, B.N.; Du, L.J. Effect of drying of jujubes (Ziziphus jujuba Mill.) on the contents of sugars, organic acids, α-tocopherol, β-carotene, and phenolic compounds. J. Agric. Food Chem., 2012, 60(38), 9642-9648.
[http://dx.doi.org/10.1021/jf3026524]
[43]
Li, X.S.; Mu, H.X.; Huang, H.T.; Li, Z.; Hu, Q.F. Phenolic compounds from the fruits of Ziziphus jujuba Mill. Asian J. Chem., 2012, 24(1), 73-75.
[44]
Wang, B.N.; Liu, H.F.; Zheng, J.B.; Fan, M.T.; Cao, W. Distribution of phenolic acids in different tissues of jujube and their antioxidant activity. J. Agric. Food Chem., 2011, 59(4), 1288-1292.
[http://dx.doi.org/10.1021/jf103982q]
[45]
Cui, C.B.; Tezuka, Y.; Kikuchi, T.; Nakano, H.; Tamaoki, T.; Park, J.-H. Constituents of a fern, Davallia mariesii Moore. IV. Isolation and structures of a novel norcarotane sesquiterpene glycoside, a chromone glucuronide, and two epicatechin glycosides. Chem. Pharm. Bull. (Tokyo), 1992, 40(8), 2035-2040.
[http://dx.doi.org/10.1248/cpb.40.2035]
[46]
Guo, S.; Duan, J.A.; Tang, Y.; Su, S.; Shang, E.; Ni, S.; Qian, D. High-performance liquid chromatography-Two wavelength detection of triterpenoid acids from the fruits of Ziziphus jujuba containing various cultivars in different regions and classification using chemometric analysis. J. Pharm. Biomed. Anal., 2009, 49(5), 1296-1302.
[http://dx.doi.org/10.1016/j.jpba.2009.03.006]
[47]
Guo, S.; Duan, J.A.; Tang, Y.P.; Yang, N.Y.; Qian, D.W.; Su, S.L.; Shang, E.X. Characterization of triterpenic acids in fruits of Ziziphus species by HPLC-ELSD-MS. J. Agric. Food Chem., 2010, 58(10), 6285-6289.
[http://dx.doi.org/10.1021/jf101022p]
[48]
Guo, S.; Tang, Y.P.; Duan, J.A.; Su, S.L.; Ding, A.W. Two new terpenoids from fruits of Ziziphus jujuba. Chin. Chem. Lett., 2009, 20(2), 197-200.
[http://dx.doi.org/10.1016/j.cclet.2008.10.041]
[49]
Tonekâboni, M.M. Toḥfat al-Moʿmenin (Rarity of the Faithful); Shahar Publishers: Tehran, 2008, p. 606. (in Persian)
[50]
Ghasâni, A.M. Hadiqat al-Azhâr fi Mâhiyyat al-Uʿshb wa al- Uʿqqâr (Flower Garden in the Nature of Herbs and Drugs) Al- Khattâbi, M. A, Ed. Beirut: Dâr al-Gharb al-Islâmi. , 1990. p. 206. (in Arabic).
[51]
Râzi, M.Z. Al-Hâwi fi aṭ-Ṭibbe (Comprehensive Book of Medicine); Dâr Ehia al-Tourath al-Arabi: Beirut, 2002, Vol. 6, p. 273. (in Arabic)
[52]
Anṭâki, D. Taḏkirat Oli al-Albâb (Memorandum Book). Beirut: Dâr-al-Kotob al-ʿIlmiyah 2000. p. 230. (in Arabic).
[53]
Jorjâni, S.E. Ḏakhireh Khârazmshâhi (Treasure of Kharazmshah). Tehran: Amir Kabir Publications; , 2011, p. 733. (in Persian)
[54]
Ghasâni Torkmâni, M.M. al-Mo’tamad fi al-Adwiyah al-Mofradah (Approved Book in Simple Drugs). Beirut: Dâr al-Kotob al- ʿIlamiyah. 2000, 247-248. (in Arabic).
[55]
Ahwâzi Arjâni, A.A. Kâmel al-Sinâh aṭ-Ṭibbiyah (Complete Book of Medicine). Qum. In: Natural Medicine Resuscitation Institution; , 2009; Vol. 1:, p. 530.
[56]
Anṣâri Shirâzi, A.H. Ekhtiyârât Badiʿi (Badiʿi’s Excerpts); Pakhshe Razi Private Joint Stock Co.: Tehran, 1993, p. 308. (in Persian)
[57]
Su, B-N.; Cuendet, M.; Farnsworth, N.R.; Fong, H.H.; Pezzuto, J.M.; Kinghorn, A.D. Activity-guided fractionation of the seeds of Ziziphus jujuba using a cyclooxygenase-2 inhibitory assay. Planta Med., 2002, 68(12), 1125-1128.
[http://dx.doi.org/10.1055/s-2002-36354]
[58]
Al-Reza, S.M.; Yoon, J.I.; Kim, H.J.; Kim, J-S.; Kang, S.C. Antiinflammatory activity of seed essential oil from Zizyphus jujuba. Food Chem. Toxicol., 2010, 48(2), 639-643.
[http://dx.doi.org/10.1016/j.fct.2009.11.045]
[59]
Goyal, R.; Sharma, P.L.; Singh, M. Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat. J. Nat. Med., 2011, 65(3-4), 514-518.
[http://dx.doi.org/10.1007/s11418-011-0531-0]
[60]
Wang, D.; Zhao, Y.; Jiao, Y.; Yu, L.; Yang, S.; Yang, X. Antioxidative and hepatoprotective effects of the polysaccharides from Zizyphus jujuba cv. Shaanbeitanzao. Carbohydr. Polym., 2012, 88(4), 1453-1459.
[http://dx.doi.org/10.1016/j.carbpol.2012.02.046]
[61]
Kumar, S.P.; Asdaq, S.; Kumar, N.P.; Asad, M.; Khajuria, D. Protective effect of Zizyphus jujuba fruit extract against paracetamol and thioacetamide induced hepatic damage in rats. Int. J. Pharmacol., 2009, 7(1)e13667
[62]
Plastina, P.; Bonofiglio, D.; Vizza, D.; Fazio, A.; Rovito, D.; Giordano, C.; Barone, I.; Catalano, S.; Gabriele, B. Identification of bioactive constituents of Ziziphus jujuba fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J. Ethnopharmacol., 2012, 140(2), 325-332.
[http://dx.doi.org/10.1016/j.jep.2012.01.022]
[63]
Vahedi, F.; Najafi, M.F.; Bozari, K. Evaluation of inhibitory effect and apoptosis induction of Zizyphus Jujuba on tumor cell lines, an in vitro preliminary study. Cytotechnology, 2008, 56(2), 105-111.
[http://dx.doi.org/10.1007/s10616-008-9131-6]
[64]
Hung, C-F.; Hsu, B-Y.; Chang, S-C.; Chen, B-H. Antiproliferation of melanoma cells by polysaccharide isolated from Zizyphus jujuba. Nutrition, 2012, 28(1), 98-105.
[http://dx.doi.org/10.1016/j.nut.2011.05.009]
[65]
Lee, S.M.; Park, J.G.; Lee, Y.H.; Lee, C.G.; Min, B.S.; Kim, J.H.; Lee, H.K. Anti-complementary activity of triterpenoides from fruits of Zizyphus jujuba. Biol. Pharm. Bull., 2004, 27(11), 1883-1886.
[http://dx.doi.org/10.1248/bpb.27.1883]
[66]
Zhang, H.; Jiang, L.; Ye, S.; Ye, Y.; Ren, F. Systematic evaluation of antioxidant capacities of the ethanolic extract of different tissues of jujube (Ziziphus jujuba Mill.) from China. Food Chem. Toxicol., 2010, 48(6), 1461-1465.
[http://dx.doi.org/10.1016/j.fct.2010.03.011]
[67]
Gao, Q.H.; Wu, P.T.; Liu, J.R.; Wu, C.S.; Parry, J.W.; Wang, M. Physico-chemical properties and antioxidant capacity of different jujube (Ziziphus jujuba Mill.) cultivars grown in loess plateau of China. Sci. Hortic. (Amsterdam), 2011, 130(1), 67-72.
[http://dx.doi.org/10.1016/j.scienta.2011.06.005]
[68]
Xue, Z.; Feng, W.; Cao, J.; Cao, D.; Jiang, W. Antioxidant activity and total phenolic contents in peel and pulp of Chinese jujube (Ziziphus jujuba Mill) fruits. J. Food Biochem., 2009, 33(6), 613-629.
[http://dx.doi.org/10.1111/j.1745-4514.2009.00241.x]
[69]
Zare-Zardini, H.; Tolueinia, B.; Hashemi, A.; Ebrahimi, L.; Fesahat, F. Antioxidant and cholinesterase inhibitory activity of a new peptide from Ziziphus jujuba fruits. Am. J. Alzheimers Dis. Other Demen., 2013, 28(7), 702-709.
[http://dx.doi.org/10.1177/1533317513500839]
[70]
Shou, C.H.; Wang, J.; Zheng, X.X.; Guo, D.W. Inhibitory effect of jujuboside A on penicillin sodium induced hyperactivity in rat hippocampal CA1 area in vitro. Acta Pharmacol. Sin., 2001, 22(11), 986-990.
[71]
Zhang, M.; Ning, G.; Shou, C.; Lu, Y.; Hong, D.; Zheng, X. Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med., 2003, 69(8), 692-695.
[http://dx.doi.org/10.1055/s-2003-42786]
[72]
Pahuja, M.; Mehla, J.; Reeta, K.; Joshi, S.; Gupta, Y.K. Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Epilepsy Behav., 2011, 21(4), 356-363.
[http://dx.doi.org/10.1016/j.yebeh.2011.05.013]
[73]
Chen, J.; Maiwulanjiang, M.; Lam, K.Y.; Zhang, W.L.; Zhan, J.Y.; Lam, C.T.; Xu, S.L.; Zhu, K.Y.; Yao, P.; Lau, D.T. A standardized extract of the fruit of Ziziphus jujuba (Jujube) induces neuronal differentiation of cultured PC12 cells: a signaling mediated by protein kinase A. J. Agric. Food Chem., 2014, 62(8), 1890-1897.
[http://dx.doi.org/10.1021/jf405093f]
[74]
Lam, C.T.; Gong, A.G.; Lam, K.Y.; Zhang, L.M.; Chen, J-P.; Dong, T.T.; Lin, H-Q.; Tsim, K.W. Jujube-containing herbal decoctions induce neuronal differentiation and the expression of antioxidant enzymes in cultured PC12 cells. J. Ethnopharmacol., 2016, 188, 275-283.
[http://dx.doi.org/10.1016/j.jep.2016.05.015]
[75]
Rabiei, Z.; Rafieian-Kopaei, M.; Heidarian, E.; Saghaei, E.; Mokhtari, S. Effects of Zizyphus jujuba extract on memory and learning impairment induced by bilateral electric lesions of the nucleus Basalis of Meynert in rat. Neurochem. Res., 2014, 39(2), 353-360.
[http://dx.doi.org/10.1007/s11064-013-1232-8]
[76]
Han, D.; Wan, C.; Liu, F.; Xu, X.; Jiang, L.; Xu, J. Jujuboside A protects H9C2 cells from isoproterenol-induced injury via activating PI3K/Akt/mTOR signaling pathway. Evid. Based Complement. Alternat. Med., 2016, 2016e9593716
[77]
Salimi, M.; Sarkhail, P.; Sarkheil, P.; Mostafapour Kandelous, H.; Baeeri, M. Evaluation of anti-melanogenic activity of Ziziphus jujuba fruits obtained by two different extraction methods. Res. J. Pharmacog., 2016, 3(2), 1-7.
[78]
Kumar, A. Renoprotective activity of ziziphus jujuba fruit extract in gentamicin-induced nephrotoxic rats. Int. J. Pharm. Therapeutics, 2015, 6(4), 194-198.
[79]
Yu, L.; Jiang, B.; Luo, D.; Shen, X.; Guo, S.; Duan, J.; Tang, Y. Bioactive components in the fruits of Ziziphus jujuba Mill. against the inflammatory irritant action of Euphorbia plants. Phytomedicine, 2012, 19(3-4), 239-244.
[http://dx.doi.org/10.1016/j.phymed.2011.09.071]
[80]
Mesaik, A.M.; Poh, H.W.; Bin, O.Y.; Elawad, I.; Alsayed, B. In vivo anti-inflammatory, anti-bacterial and anti-diarrhoeal activity of Ziziphus jujuba fruit extract. Open Access Maced. J. Med. Sci., 2018, 6(5), 757-766.
[http://dx.doi.org/10.3889/oamjms.2018.168]
[81]
Lin, T.; Liu, Y.; Lai, C.; Yang, T.; Xie, J.; Zhang, Y. The effect of ultrasound assisted extraction on structural composition, antioxidant activity and immunoregulation of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds. Ind. Crops Prod., 2018, 125, 150-159.
[http://dx.doi.org/10.1016/j.indcrop.2018.08.078]
[82]
Ji, X.; Liu, F.; Ullah, N.; Wang, M. Isolation, purification, and antioxidant activities of polysaccharides from Ziziphus Jujuba cv. Muzao. Int. J. Food Prop., 2018, 21(1), 1-11.
[http://dx.doi.org/10.1080/10942912.2018.1425702]
[83]
Arab, M. Evaluation of antioxidant and cytoprotective effects of aqueous extract of Ziziphus jujuba Mill. fruit against tert-butyl hydroperoxide- induced damages on human fibroblast cells and its cytotoxic effects on Caco-2 colorectal cancer cells; Birjand University of Medical Sciences, 2018.
[84]
Adjdir, S.; Benariba, N.; Laoufi, H.; Djaziri, R. Teneur en polyphénols et activité antioxydante des extraits de fruits de Ziziphus jujuba Mill. Phytotherapie, 2019, 17(2), 74-82.
[http://dx.doi.org/ 10.3166/phyto-2018-0033]
[85]
Klaab, Z.M.; AlMalki, F.A.; Hassan, A.M. Anticancer activities of Ziziphus jujuba extract on breast cancer cells in vitro. Int. J. Pharm. Sci. Rev. Res., 2018, 52(1), 125-132.
[86]
Shyu, M.H.; Kao, T.C.; Yen, G.C. Oleanolic acid and ursolic acid induce apoptosis in HuH7 human hepatocellular carcinoma cells through a mitochondrial-dependent pathway and downregulation of XIAP. J. Agric. Food Chem., 2010, 58(10), 6110-6118.
[http://dx.doi.org/10.1021/jf100574j]
[87]
Kim, D.K.; Baek, J.H.; Kang, C.M.; Yoo, M.A.; Sung, J.W.; Kim, D.K.; Chung, H.Y.; Kim, N.D.; Choi, Y.H.; Lee, S.H.; Kim, K.W. Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of DNA replication. Int. J. Cancer, 2000, 87(5), 629-636.
[http://dx.doi.org/10.1002/1097-0215 (20000901)87:5<629:AIDIJC2> 3.0.CO; 2-P]
[88]
De Angel, R.E.; Smith, S.M.; Glickman, R.D.; Perkins, S.N.; Hursting, S.D. Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutr. Cancer, 2010, 62(8), 1074-1086.
[http://dx.doi.org/10.1080/01635581.2010.492092]
[89]
Li, J.; Guo, W.J.; Yang, Q.Y. Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15. World J. Gastroenterol., 2002, 8(3), 493.
[http://dx.doi.org/10.3748/wjg.v8.i3.493]
[90]
Tahergorabi, Z.; Abedini, M.R.; Mitra, M.; Fard, M.H.; Beydokhti, H. “Ziziphus jujuba”: A red fruit with promising anticancer activities. Pharmacogn. Rev., 2015, 9(18), 99-106.
[http://dx.doi.org/10.4103/0973-7847.162108]
[91]
Pisha, E.; Chai, H.; Lee, I.S.; Chagwedera, T.E.; Farnsworth, N.R.; Cordell, G.A.; Beecher, C.W.; Fong, H.H.; Kinghorn, A.D.; Brown, D.M.; Wani, M.C. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat. Med., 1995, 1(10), 1046-1051.
[http://dx.doi.org/10.1038/nm1095-1046]
[92]
Selzer, E.; Thallinger, C.; Hoeller, C.; Oberkleiner, P.; Wacheck, V.; Pehamberger, H.; Jansen, B. Betulinic acid-induced Mcl-1 expression in human melanoma—mode of action and functional significance. Mol. Med., 2002, 8(12), 877-884.
[http://dx.doi.org/10.1007/BF03402094]
[93]
Thurnher, D.; Turhani, D.; Pelzmann, M.; Wannemacher, B.; Knerer, B.; Formanek, M.; Wacheck, V.; Selzer, E. Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells. Head Neck, 2003, 25(9), 732-740.
[http://dx.doi.org/10.1002/hed.10231]
[94]
Damle, A.A.; Pawar, Y.P.; Narkar, A.A. Anticancer activity of betulinic acid on MCF-7 tumors in nude mice. Indian J. Exp. Biol., 2013, 51(7), 485-491.
[95]
Takada, Y.; Aggarwal, B.B. Betulinic acid suppresses carcinogeninduced NF-κB activation through inhibition of IκBα kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9. J. Immunol., 2003, 171(6), 3278-3286.
[http://dx.doi.org/10.4049/jimmunol.171.6.3278]
[96]
Shin, M.; Lee, B.M.; Kim, O.; Tran, H.N.K.; Lee, S.; Cheol, H.; Min, B.S.; Lee, J-H. Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production. Food Funct., 2018, 9(7), 3895-3905.
[http://dx.doi.org/10.1039/C8FO00526E]
[97]
Dabaghian, F.H.; Hassani, A.; Nayeri, N.; Shojaii, A.; Entezari, M. Anti-proliferative and apoptotic effects of aqueous extract of ziziphus jujuba in human thyroid carcinoma cell lines (C643). Int. J. Cancer Manag., 2018, 11(7)e65820
[http://dx.doi.org/10.5812/ijcm.65820]
[98]
Yahyaei, B.; Nouri, M.; Matmir, H. Healing effects of Ziziphus jujuba hydroalcoholic extract with exercise training on histopathological changes of male wistar rats testicular tissue in response to Boldenone steroid administration. Jorjani Biomed. J., 2018, 6(1), 12-21.
[http://dx.doi.org/10.29252/jorjanibiomedj.6.1.12]
[99]
Etebari, M.; Zolfaghari, B.; Jafarian-Dehkordi, A.; Mirzaei, A. Hydroalcoholic and polyphenolic extracts of Ziziphus Jujuba Mill. fruits prevent methyl methanesulfonate-induced DNA damage in HepG2 cells. Pharmaceut. Biomed. Res., 2015, 1(3), 20-30.
[http://dx.doi.org/10.18869/acadpub.pbr.1.3.20]
[100]
Naftali, T.; Feingelernt, H.; Lesin, Y.; Rauchwarger, A.; Konikoff, F.M. Ziziphus jujuba extract for the treatment of chronic idiopathic constipation: a controlled clinical trial. Digestion, 2008, 78(4), 224-228.
[http://dx.doi.org/10.1159/000190975]
[101]
Tanideh, N.; Jamshidzadeh, A.; Saghesloo, A.G.; Rahmanifar, F.; Mokhtari, M.; Koohi-Hosseinabadi, O.; Omidi, M.; Najibi, A. Effects of hydroalcoholic extract of Ziziphus jujuba on acetic acid induced ulcerative colitis in male rat (Rattus norvegicus). J. Coloproctol. (Rio J.), 2016, 36(4), 189-195.
[http://dx.doi.org/10.1016/j.jcol.2016.04.007]
[102]
Huang, Y.L.; Yen, G.C.; Sheu, F.; Chau, C.F. Effects of water soluble carbohydrate concentrate from Chinese jujube on different intestinal and fecal indices. J. Agric. Food Chem., 2008, 56(5), 1734-1739.
[http://dx.doi.org/10.1021/jf072664z]
[103]
Wang, B. Chemical characterization and ameliorating effect of polysaccharide from Chinese jujube on intestine oxidative injury by ischemia and reperfusion. Int. J. Biol. Macromol., 2011, 48(3), 386-391.
[http://dx.doi.org/10.1016/j.ijbiomac.2010.12.005]
[104]
Li, J.; Shan, L.; Liu, Y.; Fan, L.; Ai, L. Screening of a functional polysaccharide from Zizyphus Jujuba cv. Jinsixiaozao and its property. Int. J. Biol. Macromol., 2011, 49(3), 255-259.
[http://dx.doi.org/10.1016/j.ijbiomac.2011.04.006]
[105]
Sabzghabaee, A.M.; Khayam, I.; Kelishadi, R.; Ghannadi, A.; Soltani, R.; Badri, S.; Shirani, S. Effect of Zizyphus jujuba fruits on dyslipidemia in obese adolescents: a triple-masked randomized controlled clinical trial. Med. Arh., 2013, 67(3), 156.
[http://dx.doi.org/10.5455/medarh.2013.67.156-159]
[106]
Solati, J.; Soleimani, N. Antihyperglycemic and antihyperlipidemic effects of Ziziphus vulgaris L. onreptozocin-induced diabetic adult male Wistar rats. Acta Diabetol., 2010, 47(Suppl. 1), 219-223.
[http://dx.doi.org/10.1007/s00592-009-0166-8]
[107]
Shen, X.; Tang, Y.; Yang, R.; Yu, L.; Fang, T.; Duan, J-A. The protective effect of Zizyphus jujuba fruit on carbon tetrachlorideinduced hepatic injury in mice by anti-oxidative activities. J. Ethnopharmacol., 2009, 122(3), 555-560.
[http://dx.doi.org/10.1016/j.jep.2009.01.027]
[108]
Moossavi, M.; Hoshyar, R.; Hemmati, M.; Farahi, A.; Javdani, H. An in vivo study on the hepato-protective effects of Crocus sativus, Ziziphus jujuba and Berberis vulgaris against acute acetaminophen and rifampicin-induced hepatotoxicity. Clin. Phytosci., 2017, 2e16
[http://dx.doi.org/10.1186/s40816-016-0030-7]
[109]
Shou, C.; Wang, J.; Zheng, X.; Guo, D. Inhibitory effect of jujuboside A on penicillin sodium induced hyperactivity in rat hippocampal CA1 area in vitro. Acta Pharmacol. Sin., 2001, 22(11), 986-990.
[110]
Cao, J.X.; Zhang, Q.Y.; Cui, S.Y.; Cui, X.Y.; Zhang, J.; Zhang, Y H.; Bai, Y-J.; Zhao, Y-Y. Hypnotic effect of jujubosides from Semen Ziziphi spinosae. J. Ethnopharmacol., 2010, 130(1), 163-166.
[http://dx.doi.org/10.1016/j.jep.2010.03.023]
[111]
Peng, W.H.; Hsieh, M.T.; Lee, Y.S.; Lin, Y.C.; Liao, J. Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. J. Ethnopharmacol., 2000, 72(3), 435-441.
[http://dx.doi.org/10.1016/S0378-8741 (00)00255-5]
[112]
Jiang, J.G.; Huang, X.J.; Chen, J. Separation and purification of saponins from semen Ziziphus jujuba and their sedative and hypnotic effects. J. Pharm. Pharmacol., 2007, 59(8), 1175-1180.
[http://dx.doi.org/10.1211/jpp.59.8.0017]
[113]
Jiang, J.G.; Huang, X.J.; Chen, J.; Lin, Q.S. Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from semen Ziziphus jujuba. Nat. Prod. Res., 2007, 21(7), 310-320.
[http://dx.doi.org/10.1080/14786410701192827]