Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Cucurbitacins and the Immune System: Update in Research on Anti- inflammatory, Antioxidant, and Immunomodulatory Mechanisms

Author(s): Geovana F. Guedes Silvestre, Renally Pereira de Lucena and Harley da Silva Alves*

Volume 29, Issue 21, 2022

Published on: 10 February, 2022

Page: [3774 - 3789] Pages: 16

DOI: 10.2174/0929867329666220107153253

Price: $65

Abstract

Cucurbitacins are a wide group of natural products found in several plant families, especially in the Cucurbitaceae family. In the last decade, there has been a significant increase in studies aimed at identifying new biological activities of cucurbitacins and describing their mechanisms of action. The most researched pharmacological activities are antineoplastic and anti-inflammatory activity, the first being recently reviewed. The present review explains the anti-inflammatory, antioxidant, and immunomodulatory potential of cucurbitacins, identifying the most studied compounds in this area and exploring their mechanisms of action already studied. A brief report was made about the main structural characteristics of cucurbitacins, in addition to an update on the biological activities attributed to this class in the last 5 years. Cucurbitacin B and cucurbitacin E have been identified as the most investigated when it comes to the immune response, playing roles in both innate and adaptive immunity. The most cited mechanisms were inhibition of COX-2 and NOS, reduction of oxidative stress, suppression of proinflammatory cytokines and modulation of acquired immunity proteins. It was found that cucurbitacins are promising molecules in the search for therapeutic innovation and have wide versatility in the immune response.

Keywords: Cucurbitacins, cytokines, macrophages, COX-2, cucurbitacin B, cucurbitacin E, NF-κB, lymphocytes.

« Previous Next »
[1]
Kaushik, U.; Aeri, V.; Mir, S.R. Cucurbitacins - An insight into medicinal leads from nature. Pharmacogn. Rev., 2015, 9(17), 12-18.
[http://dx.doi.org/10.4103/0973-7847.156314] [PMID: 26009687]
[2]
Ali, M.S.; Mukherjee, S.; Makar, S.; Pal, G. Cucurbitacins a vibrant triterpenoid: A review on its anticancer property. PharmaTuto, 2019, 7, 43.
[http://dx.doi.org/10.29161/PT.v7.i2.2019.43]
[3]
Chen, J.C.; Chiu, M.H.; Nie, R.L.; Cordell, G.A.; Qiu, S.X. Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat. Prod. Rep., 2005, 22(3), 386-399.
[http://dx.doi.org/10.1039/b418841c] [PMID: 16010347]
[4]
Morries, J.D. On the analysis of elaterium, and its active principle. Edinb. Med. Surg. J., 1831, 35(107), 339-342.
[PMID: 30329891]
[5]
Miró, M. Cucurbitacins and their pharmacological effects. Phytother. Res., 1995, 9(3), 159-168.
[http://dx.doi.org/10.1002/ptr.2650090302]
[6]
Machado, V.R.; Lang, L.K.; Durán, F.J.; Cobrera, G.M.; Palermo, J.A.; Schenkel, E.P.; Bernardes, L.S.C. Di-hidrocucurbitacina B: Semi-síntese de novos derivados glicosilados. Quim. Nova, 2015, 38, 37-41.
[7]
Tannin-Spitz, T.; Bergman, M.; Grossman, S. Cucurbitacin glucosides: Antioxidant and free-radical scavenging activities. Biochem. Biophys. Res. Commun., 2007, 364(1), 181-186.
[http://dx.doi.org/10.1016/j.bbrc.2007.09.075] [PMID: 17942079]
[8]
Achenbach, H.; Waibel, R.; Hefter-Bübi, U.; Constenla, M.A. Constituents of Fevillea cordifolia: New norcucurbitacin and cucurbitacin glycosides. J. Nat. Prod., 1993, 388, 1506-1519.
[http://dx.doi.org/10.1021/np50099a009]
[9]
Valente, L.M.M.; Gunatilaka, A.A.L.; Kingston, D.G.I.; Pinto, A.C. Norcucurbitacin gentiobiosides from Fevillea trilobata. J. Nat. Prod., 1994, 57(11), 1560-1563.
[http://dx.doi.org/10.1021/np50113a015] [PMID: 7853005]
[10]
Himeno, E.; Nagao, T.; Honda, J.; Okabe, H.; Irino, N.; Nakasumi, T. Studies on the constituents of the root of Cayaponia tayuya (Vell.) Cogn. III. Structures of cayaponosides, 29-Nor-1,2,3,4,5,10-hexadehydrocucurbit-6-ene Glucosides. Chem. Pharm. Bull. (Tokyo), 1994, 42, 2370-2317.
[http://dx.doi.org/10.1248/cpb.42.2370]
[11]
Bhandari, P.; Kumar, N.; Singh, B.; Kaul, V.K. Cucurbitacins from Bacopa monnieri. Phytochemistry, 2007, 68(9), 1248-1254.
[http://dx.doi.org/10.1016/j.phytochem.2007.03.013] [PMID: 17442350]
[12]
Wang, S.; Tang, L.; Guo, Y.; Yan, F.; Chen, F. Determination of momordicoside A in bitter melon by high-performance liquid chromatography after solid-phase extraction. Chromatographia, 2001, 53, 372-374.
[http://dx.doi.org/10.1007/BF02491069]
[13]
Méndez-Cuesta, C.A.; Campos, A.L.E.; Sánchez, D.S.; González, C.P.; Gutiérrez, S.P. Cytotoxic and antitumoral activities of compounds isolated from Cucurbitaceae plants. In: Pharmacognosy - Medicinal Plants; Intechopen, 2018; pp. 1-18.
[14]
Morales-vela, K.; Pérez-Sánchez, F.C.; Padrón, J.M.; Márquez-Fernándes, O. Antiproliferative activity of Cucurbitaceae species extracts from southeast of Mexico. Preprints, 2019, 2019, 2019080127.
[http://dx.doi.org/10.20944/preprints201908.0127.v1]
[15]
Ríos, J.L.; Escandell, J.M.; Recio, M.C. New insights into the bioactivity of cucurbitacins. Stud. Nat. Prod. Chem., 2005, 32, 429-469.
[http://dx.doi.org/10.1016/S1572-5995(05)80062-6]
[16]
Cárdenas, P.D.; Almeida, A.; Bak, S. Evolution of structural diversity of triterpenoids. Front. Plant Sci., 2019, 10, 1523.
[http://dx.doi.org/10.3389/fpls.2019.01523] [PMID: 31921225]
[17]
Cai, Y.; Fang, X.; He, C.; Li, P.; Xiao, F.; Wang, Y.; Chen, M. Cucurbitacins: A systematic review of the phytochemistry and anticancer activity. Am. J. Chin. Med., 2015, 43(7), 1331-1350.
[http://dx.doi.org/10.1142/S0192415X15500755] [PMID: 26503558]
[18]
Gamlath, C.B.; Gunatilaka, A.A.L.; Alvi, K.A.; -Rahman, Atta-Ur; Balasubramaniam, S. Cucurbitacins of Colocynthis vulgaris*. Phytochemistry, 1988, 27, 3225-3229.
[http://dx.doi.org/10.1016/0031-9422(88)80031-1]
[19]
Hylands, P.J.; Mansour, E.S.S. A revision of the structure of cucurbitacin from Bryonia dioica. Phytochemistry, 1982, 21, 2703-2707.
[http://dx.doi.org/10.1016/0031-9422(82)83102-6]
[20]
Jiang, H.Z.; Hu, S.; Tan, R.X.; Tan, R.; Jiao, R.H. Neocucurbitacin D, a novel lactone-type norcucurbitacin as xanthine oxidase inhibitor from Herpetospermum pedunculosum. Nat. Prod. Res., 2018, 34(12), 1728-1734.
[http://dx.doi.org/10.1080/14786419.2018.1528592] [PMID: 30450968]
[21]
Kawahara, N.; Kurata, A.; Hakamatsuka, T.; Sekita, S.; Satake, M. Two novel cucurbitacins, neocucurbitacins A and B, from the Brazilian folk medicine “Buchinha” (Luffa operculata) and their effect on PEBP2alphaA and OCIF gene expression in a human osteoblast-like Saos-2 cell line. Chem. Pharm. Bull. (Tokyo), 2001, 49(10), 1377-1379.
[http://dx.doi.org/10.1248/cpb.49.1377] [PMID: 11605678]
[22]
Kumar, R.P.; Roopa, L.; Nongthomba, U.; Sudheer Mohammed, M.M.; Kulkarni, N. Docking, molecular dynamics and QM/MM studies to delineate the mode of binding of CucurbitacinE to F-actin. J. Mol. Graph. Model., 2016, 63, 29-37.
[http://dx.doi.org/10.1016/j.jmgm.2015.11.007] [PMID: 26615469]
[23]
Xu, J.; Chen, Y.; Yang, R.; Zhou, T.; Ke, W.; Si, Y.; Yang, S.; Zhang, T.; Liu, X.; Zhang, L. Cucurbitacin B inhibits gastric cancer progression by suppressing STAT3 activity. Arch. Biochem. Biophys., 2020, 684, 108314.
[http://dx.doi.org/10.1016/j.abb.2020.108314]
[24]
Chen, J.C.; Lau, C.B.S.; Chan, J.Y.W.; Fung, K.P.; Leung, P.C.; Liu, J.Q.; Zhou, L.; Xie, M.J.; Qiu, M.H. The antigluconeogenic activity of cucurbitacins from Momordica charantia. Planta Med., 2015, 81(4), 327-332.
[http://dx.doi.org/10.1055/s-0035-1545695] [PMID: 25760384]
[25]
Li, Y.; Zheng, Z.; Zhou, L.; Liu, Y.; Wang, H.; Li, L.; Yao, Q. Five new cucurbitane triterpenoids with cytotoxic activity from Hemsleya jinfushanensis. Phytochem. Lett., 2015, 14, 239-244.
[http://dx.doi.org/10.1016/j.phytol.2015.10.019]
[26]
Chawech, R.; Jarraya, R.; Girardi, C.; Vansteelandt, M.; Marti, G.; Nasri, I.; Racaud-Sultan, C.; Fabre, N. Cucurbitacins from the leaves of Citrullus colocynthis (L.) schrad. Molecules, 2015, 20(10), 18001-18015.
[http://dx.doi.org/10.3390/molecules201018001] [PMID: 26437392]
[27]
Song, F.; Dai, B.; Zhang, H.Y.; Xie, J.W.; Gu, C.Z.; Zhang, J. Two new cucurbitane-type triterpenoid saponins isolated from ethyl acetate extract of Citrullus colocynthis fruit. J. Asian Nat. Prod. Res., 2015, 17(8), 813-818.
[http://dx.doi.org/10.1080/10286020.2015.1015999] [PMID: 25761128]
[28]
Li, Y.D.; Yi, S.R.; Sun, X.B.; Zhou, X.Y.; Zhang, H.Y.; Wang, Y.Q.; Yang, J.S.; Xu, X.D.; Ma, G.X. Bioactive cucurbitane triterpenoids from the tubers of Hemsleya penxianensis. Phytochem. Lett., 2016, 18, 5-9.
[http://dx.doi.org/10.1016/j.phytol.2016.08.011]
[29]
Li, Y.; Wang, W.X.; Zheng, Z.F.; Mu, Y.L.; Liu, Y.J.; Wang, H.Y.; Li, L.; Yao, Q.Q. Eight new cucurbitane triterpenoids from “Xue Dan,” the roots of Hemsleya pengxianensis. J. Asian Nat. Prod. Res., 2018, 20(1), 36-48.
[http://dx.doi.org/10.1080/10286020.2017.1355363] [PMID: 28929786]
[30]
Wang, W.; Yang, H.; Li, Y.; Zheng, Z.; Liu, Y.; Wang, H.; Mu, Y.; Yao, Q. Identification of 16,25-O-diacetyl-cucurbitane F and 25-O-acetyl-23,24-dihydrocucurbitacin F as novel anti-cancer chemicals. R. Soc. Open Sci., 2018, 5(8), 180723.
[http://dx.doi.org/10.1098/rsos.180723] [PMID: 30225067]
[31]
Sun, Z.; Hu, M.; Zhu, N.; Huo, X.; Zhou, X.; Sun, Z.; Yang, J.; Ma, G.; Xu, X. Polyhydroxy cucurbitane triterpenes from Hemsleya penxianensis tubers. Sci. Rep., 2019, 9(1), 11835.
[http://dx.doi.org/10.1038/s41598-019-48365-0] [PMID: 31413307]
[32]
Douhoré, G.Y.T.; Attioua, K.B.; Soro, Y.; Kabran, F.A.; Kablan, L.C.A.; Vedrenne, M.; Mathieu, C.; Vaca-Garcia, C. Nor-cucurbitacins from the leaves of Mareya micrantha (Benth.) Müll. Arg. (Euphorbiaceae). Fitoterapia, 2020, 143, 104538.
[http://dx.doi.org/10.1016/j.fitote.2020.104538]
[33]
Morikawa, T.; Inoue, N.; Nakanishi, Y.; Manse, Y.; Matsuura, H.; Okino, K.; Hamasaki, S.; Yoshikawa, M.; Muraoka, O.; Ninomiya, K. Collagen synthesis-promoting and collagenase inhibitory activities of constituents isolated from the rhizomes of Picrorhiza kurroa Royle ex Benth. Fitoterapia, 2020, 143, 104584.
[http://dx.doi.org/10.1016/j.fitote.2020.104584] [PMID: 32247053]
[34]
Sallam, A.M.; Esmat, A.; Abdel-Naim, A.B. Cucurbitacin-B attenuates CCl4 -induced hepatic fibrosis in mice through inhibition of STAT-3. Chem. Biol. Drug Des., 2018, 91(4), 933-941.
[http://dx.doi.org/10.1111/cbdd.13160] [PMID: 29250925]
[35]
Lin, Y.; Kotakeyama, Y.; Li, J.; Pan, Y.; Matsuura, A.; Ohya, Y.; Yoshida, M.; Xiang, L.; Qi, J. Cucurbitacin B exerts antiaging effects in yeast by regulating autophagy and oxidative stress. Oxid. Med. Cell. Longev., 2019, 2019, 4517091.
[http://dx.doi.org/10.1155/2019/4517091] [PMID: 31281576]
[36]
Xiao, Y.; Yang, Z.; Wu, Q.Q.; Jiang, X.H.; Yuan, Y.; Chang, W.; Bian, Z.Y.; Zhu, J.X.; Tang, Q.Z. Cucurbitacin B protects against pressure overload induced cardiac hypertrophy. J. Cell. Biochem., 2017, 118(11), 3899-3910.
[http://dx.doi.org/10.1002/jcb.26041] [PMID: 28390176]
[37]
Hassan, S.T.S.; Berchová-Bímová, K.; Petráš, J.; Hassan, K.T.S. Cucurbitacin B interacts synergistically with antibiotics against Staphylococcus aureus clinical isolates and exhibits antiviral activity against HSV-1. S. Afr. J. Bot., 2017, 108, 90-94.
[http://dx.doi.org/10.1016/j.sajb.2016.10.001]
[38]
Zhong, Y.; Xu, H.; Zhong, Y.; Zhang, X.; Zeng, T.; Li, L.; Xu, G.; Li, M.; Liu, J.; Yang, T. Identification and characterization of the Cucurbitacins, a novel class of small- molecule inhibitors of Tropomyosin receptor kinase a. BMC Complement. Altern. Med., 2019, 19(1), 295.
[http://dx.doi.org/10.1186/s12906-019-2709-z] [PMID: 31694615]
[39]
Li, J.; Sun, K.; Muroi, M.; Gao, L.; Chang, Y.T.; Osada, H.; Xiang, L.; Qi, J. Cucurbitacin B induces neurogenesis in PC12 cells and protects memory in APP/PS1 mice. J. Cell. Mol. Med., 2019, 23(9), 6283-6294.
[http://dx.doi.org/10.1111/jcmm.14514] [PMID: 31257716]
[40]
Zhong, H.; Huang, Y.; Deng, X.; Liu, M.; Luo, W. Cucurbitacin B supplementation reduces inflammatory responses and alveolar bone loss via regulating MPO, COX-2 and RANK/RANKL/OPG signals in a rodent model of ligature-induced periodontitis. J. King Saud Univ. Sci., 2020, 32, 1889-1895.
[http://dx.doi.org/10.1016/j.jksus.2020.01.028]
[41]
Song, H.; Wang, Y.; Li, L.; Sui, H.; Wang, P.; Wang, F. Cucurbitacin E inhibits proliferation and migration of intestinal epithelial cells via activating cofilin. Front. Physiol., 2018, 9, 1090.
[http://dx.doi.org/10.3389/fphys.2018.01090] [PMID: 30131725]
[42]
Murtaza, M.; Khan, G.; Aftab, M.F.; Afridi, S.K.; Ghaffar, S.; Ahmed, A.; Hafizur, R.M.; Waraich, R.S. Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway. PLoS One, 2017, 12(6), e0178910.
[http://dx.doi.org/10.1371/journal.pone.0178910] [PMID: 28598969]
[43]
Jeong, M.H.; Kim, S.J.; Kang, H.; Park, K.W.; Park, W.J.; Yang, S.Y.; Yang, D.K. Cucurbitacin I attenuates cardiomyocyte hypertrophy via inhibition of connective tissue growth factor (CCN2) and TGF- β/Smads signalings. PLoS One, 2015, 10(8), e0136236.
[http://dx.doi.org/10.1371/journal.pone.0136236] [PMID: 26296085]
[44]
Zhou, S.M.; Guan, S.Y.; Yang, L.; Yang, L.K.; Wang, L.; Nie, H.F.; Li, X.; Zhao, M.G.; Yang, Q.; Wu, H. Cucurbitacin IIa exerts antidepressant-like effects on mice exposed to chronic unpredictable mild stress. Neuroreport, 2017, 28(5), 259-267.
[http://dx.doi.org/10.1097/WNR.0000000000000747] [PMID: 28240721]
[45]
Arjaibi, H.M.; Ahmed, M.S.; Halaweish, F.T. Mechanistic investigation of hepato-protective potential for cucurbitacins. Med. Chem. Res., 2017, 26, 1567-1573.
[http://dx.doi.org/10.1007/s00044-017-1872-3]
[46]
Liang, J.; Dan, C. Advances in research on the anticancer mechanism of the natural compound cucurbitacin from Cucurbitaceae plants: A review. Tradit. Med. Res., 2019, 4, 68-81.
[http://dx.doi.org/10.53388/TMR20190225102]
[47]
Ferrer, M.D.; Busquets-Cortés, C.; Capó, X.; Tejada, S.; Tur, J.A.; Pons, A.; Sureda, A. Cyclooxigenase-2 inhibitors as a therapeutic target in inflammatory diseases. Curr. Med. Chem., 2019, 26(18), 3225-3241.
[http://dx.doi.org/10.2174/0929867325666180514112124] [PMID: 29756563]
[48]
Yesilada, E.; Tanaka, S.; Sezik, E.; Tabata, M. Isolation of an anti-inflammatory principle from the fruit juice of Ecballium elaterium. J. Nat. Prod., 1988, 51(3), 504-508.
[http://dx.doi.org/10.1021/np50057a008] [PMID: 3404148]
[49]
Almeida, F.R.C.; Rao, V.S.N.; Matos, M.E.O. Antiinflammatory, antitumour and antifertility effects in rodents of two nor-cucurbitacin glucosides from Wilbrandia species. Phytother. Res., 1992, 6, 189-193.
[http://dx.doi.org/10.1002/ptr.2650060405]
[50]
Cheng, S.E.; Lee, I.T.; Lin, C.C.; Wu, W.L.; Hsiao, L.D.; Yang, C.M. ATP mediates NADPH oxidase/ROS generation and COX-2/PGE2 expression in A549 cells: role of P2 receptor-dependent STAT3 activation. PLoS One, 2013, 8(1), e54125.
[http://dx.doi.org/10.1371/journal.pone.0054125] [PMID: 23326583]
[51]
Hashemi Goradel, N.; Najafi, M.; Salehi, E.; Farhood, B.; Mortezaee, K. Cyclooxygenase-2 in cancer: A review. J. Cell. Physiol., 2019, 234(5), 5683-5699.
[http://dx.doi.org/10.1002/jcp.27411] [PMID: 30341914]
[52]
Jayaprakasam, B.; Seeram, N.P.; Nair, M.G. Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana. Cancer Lett., 2003, 189(1), 11-16.
[http://dx.doi.org/10.1016/S0304-3835(02)00497-4] [PMID: 12445672]
[53]
Siqueira, J.M., Jr; Peters, R.R.; Gazola, A.C.; Krepsky, P.B.; Farias, M.R.; Rae, G.A.; de Brum-Fernandes, A.J.; Ribeiro-do-Valle, R.M. Anti-inflammatory effects of a triterpenoid isolated from Wilbrandia ebracteata Cogn. Life Sci., 2007, 80(15), 1382-1387.
[http://dx.doi.org/10.1016/j.lfs.2006.12.021] [PMID: 17286991]
[54]
Peters, R.R.; Baier Krepsky, P.; Siqueira-Junior, J.; da Silva Rocha, J.C.; Marques Bezerra, M.; de Albuquerque Ribeiro, R.; de Brum-Fernandes, A.J.; Rocha Farias, M.; Castro da Rocha, F.A.; Ribeiro-do-Valle, R.M. Nitric oxide and cyclooxygenase may participate in the analgesic and anti-inflammatory effect of the cucurbitacins fraction from Wilbrandia ebracteata. Life Sci., 2003, 73(17), 2185-2197.
[http://dx.doi.org/10.1016/S0024-3205(03)00602-7] [PMID: 12927589]
[55]
Abdelwahab, S.I.; Hassan, L.E.A.; Sirat, H.M.; Yagi, S.M.A.; Koko, W.S.; Mohan, S.; Taha, M.M.E.; Ahmad, S.; Chuen, C.S.; Narrima, P.; Rais, M.M.; Hadi, A.H. Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme inhibition. Fitoterapia, 2011, 82(8), 1190-1197.
[http://dx.doi.org/10.1016/j.fitote.2011.08.002] [PMID: 21871542]
[56]
Hussein, M.A.; El-Gizawy, H.A-E.; Gobba, N.A.E.K.; Mosaad, Y.O. Synthesis of cinnamyl and caffeoyl derivatives of cucurbitacin-E glycoside isolated from Citrullus colocynthis fruits and their structures antioxidant and anti-inflammatory activities relationship. Curr. Pharm. Biotechnol., 2017, 18(8), 677-693.
[http://dx.doi.org/10.2174/1389201018666171004144615] [PMID: 28982326]
[57]
Marzouk, B.; Mahjoub, M.A.; Bouraoui, A.; Fenina, N.; Aouni, M.; Marzouk, Z. Anti-inflammatory and analgesic activities of a new cucurbitacin isolated from Citrullus colocynthis seeds. Med. Chem. Res., 2013, 22, 3984-3990.
[http://dx.doi.org/10.1007/s00044-012-0406-2]
[58]
Gülçin, I. Antioxidant and antiradical activities of L-carnitine. Life Sci., 2006, 78(8), 803-811.
[http://dx.doi.org/10.1016/j.lfs.2005.05.103] [PMID: 16253281]
[59]
Attard, E.; Cuschieri, A.; Scicluna-Spiteri, A.; Brincat, M.P. The effects of cucurbitacin E on two lymphocyte models. Pharm. Biol., 2004, 42, 170-175.
[http://dx.doi.org/10.1080/13880200490512124]
[60]
Park, C.S.; Lim, H.; Han, K.J.; Baek, S.H.; Sohn, H.O.; Lee, D.W.; Kim, Y.G.; Yun, H.Y.; Baek, K.J.; Kwon, N.S. Inhibition of nitric oxide generation by 23,24-dihydrocucurbitacin D in mouse peritoneal macrophages. J. Pharmacol. Exp. Ther., 2004, 309(2), 705-710.
[http://dx.doi.org/10.1124/jpet.103.063693] [PMID: 14752064]
[61]
Escandell, J.M.; Recio, M.C.; Máñez, S.; Giner, R.M.; Cerdá-Nicolás, M.; Ríos, J.L. Cucurbitacin R reduces the inflammation and bone damage associated with adjuvant arthritis in lewis rats by suppression of tumor necrosis factor-α in T lymphocytes and macrophages. J. Pharmacol. Exp. Ther., 2007, 320(2), 581-590.
[http://dx.doi.org/10.1124/jpet.106.107003] [PMID: 17065367]
[62]
U-Pratya, Y.; Lueangamornnara, U.; Jiratchariyakul, W.; Kummalue, T. Immunosuppressive effects of cucurbitacin B on human peripheral blood lymphocytes. J. Med. Plants Res., 2010, 4, 2340-2347.
[http://dx.doi.org/10.5897/JMPR10.459]
[63]
Escandell, J.M.; Recio, M.C.; Giner, R.M.; Máñez, S.; Cerdá-Nicolás, M.; Merfort, I.; Ríos, J.L. Inhibition of delayed-type hypersensitivity by Cucurbitacin R through the curbing of lymphocyte proliferation and cytokine expression by means of nuclear factor AT translocation to the nucleus. J. Pharmacol. Exp. Ther., 2010, 332(2), 352-363.
[http://dx.doi.org/10.1124/jpet.109.159327] [PMID: 19846588]
[64]
Escandell, J.M.; Recio, M.C.; Giner, R.M.; Máñez, S.; Ríos, J.L. Bcl-2 is a negative regulator of interleukin-1beta secretion in murine macrophages in pharmacological-induced apoptosis. Br. J. Pharmacol., 2010, 160(7), 1844-1856.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00856.x] [PMID: 20649584]
[65]
Song, Y.; Ding, N.; Kanazawa, T.; Yamashita, U.; Yoshida, Y. Cucurbitacin D is a new inflammasome activator in macrophages. Int. Immunopharmacol., 2013, 17(4), 1044-1050.
[http://dx.doi.org/10.1016/j.intimp.2013.10.003] [PMID: 24140411]
[66]
Wang, Y.; Zhao, G.X.; Xu, L.H.; Liu, K.P.; Pan, H.; He, J.; Cai, J.Y.; Ouyang, D.Y.; He, X.H. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes. PLoS One, 2014, 9(2), e89751.
[http://dx.doi.org/10.1371/journal.pone.0089751] [PMID: 24587010]
[67]
Park, S.Y.; Kim, Y.H.; Park, G. Cucurbitacins attenuate microglial activation and protect from neuroinflammatory injury through Nrf2/ARE activation and STAT/NF-κB inhibition. Neurosci. Lett., 2015, 609, 129-136.
[http://dx.doi.org/10.1016/j.neulet.2015.10.022] [PMID: 26472707]
[68]
Li, Z.J.; Shin, J.M.; Choi, D.K.; Lim, S.K.; Yoon, T.J.; Lee, Y.H.; Sohn, K.C.; Im, M.; Lee, Y.; Seo, Y.J.; Kim, C.D.; Lee, J.H. Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation. Biochem. Biophys. Res. Commun., 2015, 459(4), 673-678.
[http://dx.doi.org/10.1016/j.bbrc.2015.03.001] [PMID: 25767074]
[69]
Kim, M.; Park, S.Y.; Jin, M.L.; Park, G.; Son, H.J. Cucurbitacin B inhibits immunomodulatory function and the inflammatory response in macrophages. Immunopharmacol. Immunotoxicol., 2015, 37(5), 473-480.
[http://dx.doi.org/10.3109/08923973.2015.1085065] [PMID: 26466646]
[70]
Wang, L.; Li, C.; Lin, Q.; Zhang, X.; Pan, H.; Xu, L.; Shi, Z.; Ouyang, D.; He, X. Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling. Acta Biochim. Biophys. Sin. (Shanghai), 2015, 47(6), 459-465.
[http://dx.doi.org/10.1093/abbs/gmv030] [PMID: 25921411]
[71]
Jia, Q.; Cheng, W.; Yue, Y.; Hu, Y.; Zhang, J.; Pan, X.; Xu, Z.; Zhang, P. Cucurbitacin E inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via suppression of PI3K/Akt/NF-κB pathways. Int. Immunopharmacol., 2015, 29(2), 884-890.
[http://dx.doi.org/10.1016/j.intimp.2015.08.026] [PMID: 26453509]
[72]
Jevtić, B.; Djedović, N.; Stanisavljević, S.; Despotović, J.; Miljković, D.; Timotijević, G. Cucurbitacin E potently modulates the activity of encephalitogenic cells. J. Agric. Food Chem., 2016, 64(24), 4900-4907.
[http://dx.doi.org/10.1021/acs.jafc.6b00951] [PMID: 27225664]
[73]
Cui, L.; Bi, J.; Yan, D.; Ye, X.; Zheng, M.; Yu, G.; Wan, X. JSI-124 inhibits IgE production in an IgE B cell line. Biochem. Biophys. Res. Commun., 2017, 483(1), 669-673.
[http://dx.doi.org/10.1016/j.bbrc.2016.12.085] [PMID: 27988336]
[74]
Kim, S.Y.; Park, M.J.; Kwon, J.E.; Jung, K.A.; Jhun, J.Y.; Lee, S.Y.; Seo, H.B.; Ryu, J.Y.; Beak, J.A.; Choi, J.Y.; Cho, M.L. Cucurbitacin E ameliorates acute graft-versus-host disease by modulating Th17 cell subsets and inhibiting STAT3 activation. Immunol. Lett., 2018, 203, 62-69.
[http://dx.doi.org/10.1016/j.imlet.2018.09.012] [PMID: 30240636]
[75]
Shang, J.; Liu, W.; Yin, C.; Chu, H.; Zhang, M. Cucurbitacin E ameliorates lipopolysaccharide-evoked injury, inflammation and MUC5AC expression in bronchial epithelial cells by restraining the HMGB1-TLR4-NF-κB signaling. Mol. Immunol., 2019, 114, 571-577.
[http://dx.doi.org/10.1016/j.molimm.2019.09.008] [PMID: 31525576]
[76]
Du, Z.; Zhang, S.; Lin, Y.; Zhou, L.; Wang, Y.; Yan, G.; Zhang, M.; Wang, M.; Li, J.; Tong, Q.; Duan, Y.; Du, G. Momordicoside G regulates macrophage phenotypes to stimulate efficient repair of lung injury and prevent urethane-induced lung carcinoma lesions. Front. Pharmacol., 2019, 10, 321.
[http://dx.doi.org/10.3389/fphar.2019.00321] [PMID: 30984004]
[77]
Abdulkhaleq, L.A.; Assi, M.A.; Abdullah, R.; Zamri-Saad, M.; Taufiq-Yap, Y.H.; Hezmee, M.N.M. The crucial roles of inflammatory mediators in inflammation: A review. Vet. World, 2018, 11(5), 627-635.
[http://dx.doi.org/10.14202/vetworld.2018.627-635] [PMID: 29915501]
[78]
Gupta, K.K.; Khan, M.A.; Singh, S.K. Constitutive inflammatory cytokine storm: A major threat to human health. J. Interferon Cytokine Res., 2020, 40(1), 19-23.
[http://dx.doi.org/10.1089/jir.2019.0085] [PMID: 31755797]
[79]
Qiao, J.; Xu, L.H.; He, J.; Ouyang, D.Y.; He, X.H. Cucurbitacin E exhibits anti-inflammatory effect in RAW 264.7 cells via suppression of NF-κB nuclear translocation. Inflamm. Res., 2013, 62(5), 461-469.
[http://dx.doi.org/10.1007/s00011-013-0598-z] [PMID: 23360962]
[80]
Hua, S.; Liu, X.; Lv, S.; Wang, Z. Protective effects of cucurbitacin B on acute lung injury induced by sepsis in rats. Med. Sci. Monit., 2017, 23, 1355-1362.
[http://dx.doi.org/10.12659/MSM.900523] [PMID: 28315572]
[81]
Lee, M.; Park, J. Regulation of NFAT activation: A potential therapeutic target for immunosuppression. Mol. Cells, 2006, 22(1), 1-7.
[PMID: 16951543]
[82]
Nefedova, Y.; Nagaraj, S.; Rosenbauer, A.; Muro-Cacho, C.; Sebti, S.M.; Gabrilovich, D.I. Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res., 2005, 65(20), 9525-9535.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0529] [PMID: 16230418]
[83]
Paiva-Oliveira, E. L.; Silva, A. C.; Silva, R. M.; Sevenini, L. A.; Melo, H. A.; Lagrota-Candido, J. M.; Quirico-Santos, T. Inflammasome and its clinical repercussion: literature review. J. Med. Biol. Sci, 2012, 11, 96-102.
[http://dx.doi.org/10.9771/cmbio.v11i1.6245]
[84]
Kanaya, S.; Nemoto, E.; Ogawa, T.; Shimauchi, H. Porphyromonas gingivalis lipopolysaccharides induce maturation of dendritic cells with CD14+CD16+ phenotype. Eur. J. Immunol., 2004, 34(5), 1451-1460.
[http://dx.doi.org/10.1002/eji.200324549] [PMID: 15114679]
[85]
Kambara, K.; Ohashi, W.; Tomita, K.; Takashina, M.; Fujisaka, S.; Hayashi, R.; Mori, H.; Tobe, K.; Hattori, Y. In vivo depletion of CD206+ M2 macrophages exaggerates lung injury in endotoxemic mice. Am. J. Pathol., 2015, 185(1), 162-171.
[http://dx.doi.org/10.1016/j.ajpath.2014.09.005] [PMID: 25447055]
[86]
Sundin, M.; Tesi, B.; Sund Böhme, M.; Bryceson, Y.T.; Pütsep, K.; Chiang, S.C.; Thunberg, S.; Winiarski, J.; Wikström, A.C. Novel STAT3 mutation causing hyper-IgE syndrome: studies of the clinical course and immunopathology. J. Clin. Immunol., 2014, 34(4), 469-477.
[http://dx.doi.org/10.1007/s10875-014-0011-x] [PMID: 24627079]
[87]
Liu, M.; Yan, Q.; Peng, B.; Cai, Y.; Zeng, S.; Xu, Z.; Yan, Y.; Gong, Z. Use of cucurbitacins for lung cancer research and therapy. Cancer Chemother. Pharmacol., 2021, 88(1), 1-14.
[http://dx.doi.org/10.1007/s00280-021-04265-7] [PMID: 33825035]
[88]
Yang, K.; Wen, Y.; Wang, C. Clinical application of anticancer nanoparticles targeting metastasis foci of cervical lymph nodes in patients with oral carcinoma. Hua Xi Kou Qiang Yi Xue Za Zhi, 2003, 21(6), 447-450.
[89]
Lu, P.; Yu, B.; Xu, J. Cucurbitacin B regulates immature myeloid cell differentiation and enhances antitumor immunity in patients with lung cancer. Cancer Biother. Radiopharm., 2012, 27(8), 495-503.
[http://dx.doi.org/10.1089/cbr.2012.1219] [PMID: 22746287]
[90]
Varricchio, A.; Lucia, A. Sinuclean Nebules treatment in children suffering from otitis media with effusion. Int. J. Pediatr. Otorhinolaryngol., 2017, 94, 30-35.

Rights & Permissions Print Cite
Article Metrics
37
1
© 2024 Bentham Science Publishers | Privacy Policy