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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Mini-Review Article

Germacrone: A Multi-targeting Sesquiterpene with Promising Anti-cancer and Chronic Disease Applications

In Press, (this is not the final "Version of Record"). Available online 07 August, 2024
Author(s): Navin Kumar Tailor, Ajmer Singh Grewal*, Geeta Deswal and Ashwani Kumar Dhingra
Published on: 07 August, 2024

DOI: 10.2174/0118715206312324240805075050

Price: $95

Abstract

Background: Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease.

Objective: This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction. Methods: A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities.

Results: Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics.

Conclusion: The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.

[1]
Gupta, S.C.; Patchva, S.; Koh, W.; Aggarwal, B.B. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin. Exp. Pharmacol. Physiol., 2012, 39(3), 283-299.
[http://dx.doi.org/10.1111/j.1440-1681.2011.05648.x] [PMID: 22118895]
[2]
Bordoloi, D.; Roy, N.K.; Monisha, J.; Padmavathi, G.; Kunnumakkara, A.B. Multi-targeted agents in cancer cell chemosensitization: what we learnt from curcumin thus far. Recent Patents Anticancer Drug Discov., 2016, 11(1), 67-97.
[http://dx.doi.org/10.2174/1574892810666151020101706] [PMID: 26537958]
[3]
Gupta, S.C.; Prasad, S.; Kim, J.H.; Patchva, S.; Webb, L.J.; Priyadarsini, I.K.; Aggarwal, B.B. Multitargeting by curcumin as revealed by molecular interaction studies. Nat. Prod. Rep., 2011, 28(12), 1937-1955.
[http://dx.doi.org/10.1039/c1np00051a] [PMID: 21979811]
[4]
Kunnumakkara, A.B.; Anand, P.; Aggarwal, B.B. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett., 2008, 269(2), 199-225.
[http://dx.doi.org/10.1016/j.canlet.2008.03.009] [PMID: 18479807]
[5]
Makhoba, X.H.; Viegas, C., Jr; Mosa, R.A.; Viegas, F.P.D.; Pooe, O.J. Potential impact of the multi-target drug approach in the treatment of some complex diseases. Drug Des. Devel. Ther., 2020, 14, 3235-3249.
[http://dx.doi.org/10.2147/DDDT.S257494] [PMID: 32884235]
[6]
Stoletov, K.; Beatty, P.H.; Lewis, J.D. Novel therapeutic targets for cancer metastasis. Expert Rev. Anticancer Ther., 2020, 20(2), 97-109.
[http://dx.doi.org/10.1080/14737140.2020.1718496] [PMID: 31997674]
[7]
Šorm, F. Advances in terpene chemistry. Pure Appl. Chem., 1970, 21(2), 263-284.
[http://dx.doi.org/10.1351/pac197021020263]
[8]
Takeda, K.; Horibe, I.; Minato, H. Cope rearrangement of some germacrane-type furan sesquiterpenes. Part IV. Preparation of some cyclodeca-cis,trans-diene derivatives and their Cope rearrangements. J. Chem. Soc., Perkin Trans. 1, 1973, I, 2212-2220.
[http://dx.doi.org/10.1039/p19730002212]
[9]
Endo, J.; Nagasawa, M. Studies on the essential oil of Asarum caulescens. Yakugaku Zasshi, 1974, 94(12), 1574-1579.
[http://dx.doi.org/10.1248/yakushi1947.94.12_1574] [PMID: 4477187]
[10]
Hikino, H.; Konno, C.; Nagashima, T.; Kohama, T.; Takemoto, T. Stereoselective epoxidation of germacrone by Cunninghamella blakesleeana. Tetrahedron Lett., 1971, 12(4), 337-340.
[http://dx.doi.org/10.1016/S0040-4039(01)96435-4]
[11]
Takeda, K.; Horibe, I.; Minato, H. Preparation of some cis-1,trans-5-germacratriene derivatives. J. Chem. Soc. D, 1971, 2(2), 87-88.
[http://dx.doi.org/10.1039/c29710000087]
[12]
Scheffer, J.R.; Boire, B.A. Solution photochemistry. II. The photolysis of isogermacrone. Tetrahedron Lett., 1969, 10(45), 4005-4008.
[http://dx.doi.org/10.1016/S0040-4039(01)88599-3]
[13]
Takahashi, T.; Kitamura, K.; Nemoto, H.; Tsuji, J.; Miura, I. A first total synthesis of Germacrone by intramolecular alkylation of protected cyanohydrin. Tetrahedron Lett., 1983, 24(33), 3489-3492.
[http://dx.doi.org/10.1016/S0040-4039(00)86020-7]
[14]
Sakui, N.; Kuroyanagi, M.; Ishitobi, Y.; Sato, M.; Ueno, A. Biotransformation of sesquiterpenes by cultured cells of Curcuma zedoaria. Phytochemistry, 1992, 31(1), 143-147.
[http://dx.doi.org/10.1016/0031-9422(91)83023-E]
[15]
Asakawa, Y.; Takahashi, H.; Toyota, M. Biotransformation of germacrane-type sesquiterpenoids by Aspergillus niger. Phytochemistry, 1991, 30(12), 3993-3997.
[http://dx.doi.org/10.1016/0031-9422(91)83451-P]
[16]
Sakamoto, S.; Tsuchiya, N.; Kuroyanagi, M.; Ueno, A. Biotransformation of germacrone by suspension cultured cells. Phytochemistry, 1994, 35(5), 1215-1219.
[http://dx.doi.org/10.1016/S0031-9422(00)94823-4]
[17]
Lou, G.; Huang, Y.; Wang, Y.; Chen, S.; Liu, C.; Li, Y.; Feng, J. Germacrone, a novel and safe anticancer agent from genus Curcuma: A review of its mechanism. Anticancer. Agents Med. Chem., 2023, 23(13), 1490-1498.
[http://dx.doi.org/10.2174/1871520623666230420094628] [PMID: 37139672]
[18]
Hashem, S.; Nisar, S.; Sageena, G.; Macha, M.A.; Yadav, S.K.; Krishnankutty, R.; Uddin, S.; Haris, M.; Bhat, A.A. Therapeutic effects of curcumol in several diseases; an overview. Nutr. Cancer, 2021, 73(2), 181-195.
[http://dx.doi.org/10.1080/01635581.2020.1749676] [PMID: 32285707]
[19]
Oh, S.; Han, A.R.; Park, H.R.; Jang, E.J.; Kim, H.K.; Jeong, M.G.; Song, H.; Park, G.H.; Seo, E.K.; Hwang, E.S. Suppression of Inflammatory cytokine production by ar-Turmerone isolated from Curcuma phaeocaulis. Chem. Biodivers., 2014, 11(7), 1034-1041.
[http://dx.doi.org/10.1002/cbdv.201300397] [PMID: 25044589]
[20]
Feng, J.; Bai, X.; Cui, T.; Zhou, H.; Chen, Y.; Xie, J.; Shi, Q.; Wang, H.; Zhang, G. in vitro antiviral activity of germacrone against porcine reproductive and respiratory syndrome virus. Curr. Microbiol., 2016, 73(3), 317-323.
[http://dx.doi.org/10.1007/s00284-016-1042-8] [PMID: 27178541]
[21]
He, W.; Zhai, X.; Su, J.; Ye, R.; Zheng, Y.; Su, S. Antiviral activity of germacrone against pseudorabies virus in vitro. Pathogens, 2019, 8(4), 258.
[http://dx.doi.org/10.3390/pathogens8040258] [PMID: 31766701]
[22]
Burapan, S.; Kim, M.; Paisooksantivatana, Y.; Eser, B.E.; Han, J. Thai Curcuma species: Antioxidant and bioactive compounds. Foods, 2020, 9(9), 1219.
[http://dx.doi.org/10.3390/foods9091219] [PMID: 32887356]
[23]
Suphrom, N.; Pumthong, G.; Khorana, N.; Waranuch, N.; Limpeanchob, N.; Ingkaninan, K. Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma aeruginosa Roxb. Fitoterapia, 2012, 83(5), 864-871.
[http://dx.doi.org/10.1016/j.fitote.2012.03.017] [PMID: 22465508]
[24]
Chen, Y.; Dong, Y.; Jiao, Y.; Hou, L.; Shi, Y.; Gu, T.; Zhou, P.; Shi, Z.; Xu, L.; Wang, C. In vitro antiviral activity of germacrone against porcine parvovirus. Arch. Virol., 2015, 160(6), 1415-1420.
[http://dx.doi.org/10.1007/s00705-015-2393-3] [PMID: 25813663]
[25]
Wu, T.; Yin, F.; Kong, H.; Peng, J. Germacrone attenuates cerebral ischemia/reperfusion injury in rats via antioxidative and antiapoptotic mechanisms. J. Cell. Biochem., 2019, 120(11), 18901-18909.
[http://dx.doi.org/10.1002/jcb.29210] [PMID: 31318092]
[26]
Zhang, R.; Tian, A.; Shi, X.; Yu, H.; Chen, L. Downregulation of IL-17 and IFN-γ in the optic nerve by β-elemene in experimental autoimmune encephalomyelitis. Int. Immunopharmacol., 2010, 10(7), 738-743.
[http://dx.doi.org/10.1016/j.intimp.2010.04.003] [PMID: 20399285]
[27]
Kubrak, M.N.; Nguyen, T.N.T.; Nguyen, M.P. Study of the composition of essential oil of two species of Dracocephalum, Labiatae. Biologicheskie i Khimicheskie Nauki, 1978 1978, 24-28.;
b) Zhang, G.; Ling, J.; Cui, Z. Supercritical CO2 extraction of essential oil from Dracocephalum tanguticum Maxim and analysis by GC-MS. J. Liq. Chromatogr. Relat. Technol., 2007, 30(2), 287-292.
[http://dx.doi.org/ 10.1080/10826070601064607];
c) Ahmadi, L.; Mirza, M. . Volatile constituents of Dracocephalum aucheri Boiss. J. Essent. Oil Res., , 2001, 13(4), 202-203.;
d) Barrero,, A.F.; Herrador, M.M.; Arteaga, P. Germacrone: Occurrence, synthesis, chemical transformations and biological properties. Nat. Prod. Commun., , 2007, 30(2), 287-292.
[http://dx.doi.org/10.1080/10826070601064607]
[28]
a) Kuroyanagi, M.; Ueno, A.; Ujiie, K.; Sato, S. Structures of sesquiterpenes from Curcuma aromatica Salisb. Chem. Pharm. Bull. , 1987, 35(1), 53-59.
[http://dx.doi.org/10.1248/cpb.35.53];
b) Choudhury, S.N.; Ghosh, A.C.; Saikia, M.; Choudhury, M.; Leclercq, P.A. Volatile constituents of the aerial and underground parts of Curcuma aromatica Salisb. from India. J. Essent. Oil Res., 1996, 8(6), 633-638.
[http://dx.doi.org/10.1080/10412905.1996.9701031]
[29]
a) Doss, R.P.; Hatheway, W.H.; Hrutfiord, B.F. Composition of essential oils of some lipidote Rhododendrons. Phytochemistry, 1986, 25(7), 1637-1640.
[http://dx.doi.org/10.1016/S0031-9422(00)81225-X];
b) Doss, R.P.; Luthi, R.; Hrutfiord, B.F. Germacrone, a sesquiterpene repellent to obscure root weevil from Rhododendron edgeworthii. Phytochemistry, 1980, 19(11), 2379-2380.
[http://dx.doi.org/10.1016/S0031-9422(00)91031-8];
c) Lu, Y.; Wang, Y.; Bai, Y. Study on the chemical composition of the essential oil of Rhododendron anthopogonoides Maxim. Huaxue Xuebao, 1980, 38, 140-148.
[30]
a) Bordoloi, A.K.; Sperkova, J.; Leclercq, P.A. Essential oils of Zingiber cassumunar Roxb. from northeast India. J. Essent. Oil Res., 1999, 11, 441-445.;
b) Srivastava, A.K.; Srivastava, S.K.; Shah, N.C. Essential oil of Zingiber zarumbet (L.) Sm. from India. J. Essent. Oil Res., 2000, 12, 595-597.
[http://dx.doi.org/10.1016/S0031-9422(00)91031-8]
[31]
Hossain, C.F.; Al-Amin, M.; Sayem, A.S.M.; Siragee, I.H.; Tunan, A.M.; Hassan, F.; Kabir, M.M.; Sultana, G.N.N. Antinociceptive principle from Curcuma aeruginosa. BMC Complement. Altern. Med., 2015, 15(1), 191.
[http://dx.doi.org/10.1186/s12906-015-0720-6] [PMID: 26092132]
[32]
Cardoso, F.; Harbeck, N.; Fallowfield, L.; Kyriakides, S.; Senkus, E. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2012, 23(Suppl. 7), vii11-vii19.
[http://dx.doi.org/10.1093/annonc/mds232] [PMID: 22997442]
[33]
Wilkinson, L.; Gathani, T. Understanding breast cancer as a global health concern. Br. J. Radiol., 2022, 95(1130), 20211033.
[http://dx.doi.org/10.1259/bjr.20211033] [PMID: 34905391]
[34]
Song, A.; Yin, Y. A brief summary of recent research and application of Ezhu essential oil in tumor therapy. J. Shandong University TCM., 2008, 32, 172-174.
[35]
Xie, X.H.; Zhao, H.; Hu, Y.Y.; Gu, X.D. Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells. Exp. Ther. Med., 2014, 8(5), 1611-1615.
[http://dx.doi.org/10.3892/etm.2014.1932] [PMID: 25289068]
[36]
Zhong, Z.; Chen, X.; Tan, W.; Xu, Z.; Zhou, K.; Wu, T.; Cui, L.; Wang, Y. Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis. Eur. J. Pharmacol., 2011, 667(1-3), 50-55.
[http://dx.doi.org/10.1016/j.ejphar.2011.03.041] [PMID: 21497161]
[37]
Khan, M.Z.I.; Uzair, M.; Nazli, A.; Chen, J.Z. An overview on Estrogen receptors signaling and its ligands in breast cancer. Eur. J. Med. Chem., 2022, 241, 114658.
[http://dx.doi.org/10.1016/j.ejmech.2022.114658] [PMID: 35964426]
[38]
Shastry, M.; Hamilton, E. Novel estrogen receptor-targeted agents for breast cancer. Curr. Treat. Options Oncol., 2023, 24(7), 821-844.
[http://dx.doi.org/10.1007/s11864-023-01079-y] [PMID: 37129836]
[39]
Das, A.; Lavanya, K.J. Nandini; Kaur, K.; Jaitak, V. Effectiveness of selective estrogen receptor modulators in breast cancer therapy: An update. Curr. Med. Chem., 2023, 30(29), 3287-3314.
[http://dx.doi.org/10.2174/0929867329666221006110528] [PMID: 36201273]
[40]
Lim, M.S.; Choung, S.Y.; Jeong, K.W. Germacrone inhibits estrogen receptor α‐mediated transcription in MCF‐7 breast cancer cells. Phytother. Res., 2016, 30(12), 2036-2043.
[http://dx.doi.org/10.1002/ptr.5711] [PMID: 27573551]
[41]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[42]
Abu Rous, F.; Singhi, E.K.; Sridhar, A.; Faisal, M.S.; Desai, A. Lung cancer treatment advances in 2022. Cancer Invest., 2023, 41(1), 12-24.
[http://dx.doi.org/10.1080/07357907.2022.2119479] [PMID: 36036470]
[43]
Allemani, C.; Matsuda, T.; Di Carlo, V.; Harewood, R.; Matz, M.; Nikšić, M.; Bonaventure, A.; Valkov, M.; Johnson, C.J.; Estève, J.; Ogunbiyi, O.J.; Azevedo e Silva, G.; Chen, W.Q.; Eser, S.; Engholm, G.; Stiller, C.A.; Monnereau, A.; Woods, R.R.; Visser, O.; Lim, G.H.; Aitken, J.; Weir, H.K.; Coleman, M.P.; Bouzbid, S.; Hamdi-Chérif, M.; Zaidi, Z.; Meguenni, K.; Regagba, D.; Bayo, S.; Cheick Bougadari, T.; Manraj, S.S.; Bendahhou, K.; Fabowale, A.; Bradshaw, D.; Somdyala, N.I.M.; Kumcher, I.; Moreno, F.; Calabrano, G.H.; Espinola, S.B.; Carballo Quintero, B.; Fita, R.; Diumenjo, M.C.; Laspada, W.D.; Ibañez, S.G.; Lima, C.A.; De Souza, P.C.F.; Del Pino, K.; Laporte, C.; Curado, M.P.; de Oliveira, J.C.; Veneziano, C.L.A.; Veneziano, D.B.; Latorre, M.R.D.O.; Tanaka, L.F.; Rebelo, M.S.; Santos, M.O.; Galaz, J.C.; Aparicio Aravena, M.; Sanhueza Monsalve, J.; Herrmann, D.A.; Vargas, S.; Herrera, V.M.; Uribe, C.J.; Bravo, L.E.; Garcia, L.S.; Arias-Ortiz, N.E.; Morantes, D.; Jurado, D.M.; Yépez Chamorro, M.C.; Delgado, S.; Ramirez, M.; Galán Alvarez, Y.H.; Torres, P.; Martínez-Reyes, F.; Jaramillo, L.; Quinto, R.; Castillo, J.; Mendoza, M.; Cueva, P.; Yépez, J.G.; Bhakkan, B.; Deloumeaux, J.; Joachim, C.; Macni, J.; Carrillo, R.; Shalkow Klincovstein, J.; Rivera Gomez, R.; Poquioma, E.; Tortolero-Luna, G.; Zavala, D.; Alonso, R.; Barrios, E.; Eckstrand, A.; Nikiforuk, C.; Noonan, G.; Turner, D.; Kumar, E.; Zhang, B.; McCrate, F.R.; Ryan, S.; MacIntyre, M.; Saint-Jacques, N.; Nishri, D.E.; McClure, C.A.; Vriends, K.A.; Kozie, S.; Stuart-Panko, H.; Freeman, T.; George, J.T.; Brockhouse, J.T.; O’Brien, D.K.; Holt, A.; Almon, L.; Kwong, S.; Morris, C.; Rycroft, R.; Mueller, L.; Phillips, C.E.; Brown, H.; Cromartie, B.; Schwartz, A.G.; Vigneau, F.; Levin, G.M.; Wohler, B.; Bayakly, R.; Ward, K.C.; Gomez, S.L.; McKinley, M.; Cress, R.; Green, M.D.; Miyagi, K.; Ruppert, L.P.; Lynch, C.F.; Huang, B.; Tucker, T.C.; Deapen, D.; Liu, L.; Hsieh, M.C.; Wu, X.C.; Schwenn, M.; Gershman, S.T.; Knowlton, R.C.; Alverson, G.; Copeland, G.E.; Bushhouse, S.; Rogers, D.B.; Jackson-Thompson, J.; Lemons, D.; Zimmerman, H.J.; Hood, M.; Roberts-Johnson, J.; Rees, J.R.; Riddle, B.; Pawlish, K.S.; Stroup, A.; Key, C.; Wiggins, C.; Kahn, A.R.; Schymura, M.J.; Radhakrishnan, S.; Rao, C.; Giljahn, L.K.; Slocumb, R.M.; Espinoza, R.E.; Khan, F.; Aird, K.G.; Beran, T.; Rubertone, J.J.; Slack, S.J.; Garcia, L.; Rousseau, D.L.; Janes, T.A.; Schwartz, S.M.; Bolick, S.W.; Hurley, D.M.; Whiteside, M.A.; Miller-Gianturco, P.; Williams, M.A.; Herget, K.; Sweeney, C.; Johnson, A.T.; Keitheri Cheteri, M.B.; Migliore Santiago, P.; Blankenship, S.E.; Farley, S.; Borchers, R.; Malicki, R.; Espinoza, J.R.; Grandpre, J.; Wilson, R.; Edwards, B.K.; Mariotto, A.; Lei, Y.; Wang, N.; Chen, J.S.; Zhou, Y.; He, Y.T.; Song, G.H.; Gu, X.P.; Mei, D.; Mu, H.J.; Ge, H.M.; Wu, T.H.; Li, Y.Y.; Zhao, D.L.; Jin, F.; Zhang, J.H.; Zhu, F.D.; Junhua, Q.; Yang, Y.L.; Jiang, C.X.; Biao, W.; Wang, J.; Li, Q.L.; Yi, H.; Zhou, X.; Dong, J.; Li, W.; Fu, F.X.; Liu, S.Z.; Chen, J.G.; Zhu, J.; Li, Y.H.; Lu, Y.Q.; Fan, M.; Huang, S.Q.; Guo, G.P.; Zhaolai, H.; Wei, K.; Zeng, H.; Demetriou, A.V.; Mang, W.K.; Ngan, K.C.; Kataki, A.C.; Krishnatreya, M.; Jayalekshmi, P.A.; Sebastian, P.; Nandakumar, A.; Malekzadeh, R.; Roshandel, G.; Keinan-Boker, L.; Silverman, B.G.; Ito, H.; Nakagawa, H.; Sato, M.; Tobori, F.; Nakata, I.; Teramoto, N.; Hattori, M.; Kaizaki, Y.; Moki, F.; Sugiyama, H.; Utada, M.; Nishimura, M.; Yoshida, K.; Kurosawa, K.; Nemoto, Y.; Narimatsu, H.; Sakaguchi, M.; Kanemura, S.; Naito, M.; Narisawa, R.; Miyashiro, I.; Nakata, K.; Sato, S.; Yoshii, M.; Oki, I.; Fukushima, N.; Shibata, A.; Iwasa, K.; Ono, C.; Nimri, O.; Jung, K.W.; Won, Y.J.; Alawadhi, E.; Elbasmi, A.; Ab Manan, A.; Adam, F.; Sanjaajmats, E.; Tudev, U.; Ochir, C.; Al Khater, A.M.; El Mistiri, M.M.; Teo, Y.Y.; Chiang, C.J.; Lee, W.C.; Buasom, R.; Sangrajrang, S.; Kamsa-ard, S.; Wiangnon, S.; Daoprasert, K.; Pongnikorn, D.; Leklob, A.; Sangkitipaiboon, S.; Geater, S.L.; Sriplung, H.; Ceylan, O.; Kög, I.; Dirican, O.; Köse, T.; Gurbuz, T.; Karaşahin, F.E.; Turhan, D.; Aktaş, U.; Halat, Y.; Yakut, C.I.; Altinisik, M.; Cavusoglu, Y.; Türkköylü, A.; Üçüncü, N.; Hackl, M.; Zborovskaya, A.A.; Aleinikova, O.V.; Henau, K.; Van Eycken, L.; Valerianova, Z.; Yordanova, M.R.; Šekerija, M.; Dušek, L.; Zvolský, M.; Storm, H.; Innos, K.; Mägi, M.; Malila, N.; Seppä, K.; Jégu, J.; Velten, M.; Cornet, E.; Troussard, X.; Bouvier, A.M.; Guizard, A.V.; Bouvier, V.; Launoy, G.; Arveux, P.; Maynadié, M.; Mounier, M.; Woronoff, A.S.; Daoulas, M.; Robaszkiewicz, M.; Clavel, J.; Goujon, S.; Lacour, B.; Baldi, I.; Pouchieu, C.; Amadeo, B.; Coureau, G.; Orazio, S.; Preux, P.M.; Rharbaoui, F.; Marrer, E.; Trétarre, B.; Colonna, M.; Delafosse, P.; Ligier, K.; Plouvier, S.; Cowppli-Bony, A.; Molinié, F.; Bara, S.; Ganry, O.; Lapôtre-Ledoux, B.; Grosclaude, P.; Bossard, N.; Uhry, Z.; Bray, F.; Piñeros, M.; Stabenow, R.; Wilsdorf-Köhler, H.; Eberle, A.; Luttmann, S.; Löhden, I.; Nennecke, A.L.; Kieschke, J.; Sirri, E.; Emrich, K.; Zeissig, S.R.; Holleczek, B.; Eisemann, N.; Katalinic, A.; Asquez, R.A.; Kumar, V.; Petridou, E.; Ólafsdóttir, E.J.; Tryggvadóttir, L.; Clough-Gorr, K.; Walsh, P.M.; Sundseth, H.; Mazzoleni, G.; Vittadello, F.; Coviello, E.; Cuccaro, F.; Galasso, R.; Sampietro, G.; Giacomin, A.; Magoni, M.; Ardizzone, A.; D’Argenzio, A.; Castaing, M.; Grosso, G.; Lavecchia, A.M.; Sutera Sardo, A.; Gola, G.; Gatti, L.; Ricci, P.; Ferretti, S.; Serraino, D.; Zucchetto, A.; Celesia, M.V.; Filiberti, R.A.; Pannozzo, F.; Melcarne, A.; Quarta, F.; Russo, A.G.; Carrozzi, G.; Cirilli, C.; Cavalieri d’Oro, L.; Rognoni, M.; Fusco, M.; Vitale, M.F.; Usala, M.; Cusimano, R.; Mazzucco, W.; Michiara, M.; Sgargi, P.; Boschetti, L.; Borciani, E.; Seghini, P.; Maule, M.M.; Merletti, F.; Tumino, R.; Mancuso, P.; Vicentini, M.; Cassetti, T.; Sassatelli, R.; Falcini, F.; Giorgetti, S.; Caiazzo, A.L.; Cavallo, R.; Cesaraccio, R.; Pirino, D.R.; Contrino, M.L.; Tisano, F.; Fanetti, A.C.; Maspero, S.; Carone, S.; Mincuzzi, A.; Candela, G.; Scuderi, T.; Gentilini, M.A.; Piffer, S.; Rosso, S.; Barchielli, A.; Caldarella, A.; Bianconi, F.; Stracci, F.; Contiero, P.; Tagliabue, G.; Rugge, M.; Zorzi, M.; Beggiato, S.; Brustolin, A.; Berrino, F.; Gatta, G.; Sant, M.; Buzzoni, C.; Mangone, L.; Capocaccia, R.; De Angelis, R.; Zanetti, R.; Maurina, A.; Pildava, S.; Lipunova, N.; Vincerževskiené, I.; Agius, D.; Calleja, N.; Siesling, S.; Larønningen, S.; Møller, B.; Dyzmann-Sroka, A.; Trojanowski, M.; Góźdź, S.; Mężyk, R.; Mierzwa, T.; Molong, L.; Rachtan, J.; Szewczyk, S.; Błaszczyk, J.; Kępska, K.; Kościańska, B.; Tarocińska, K.; Zwierko, M.; Drosik, K.; Maksimowicz, K.M.; Purwin-Porowska, E.; Reca, E.; Wójcik-Tomaszewska, J.; Tukiendorf, A.; Grądalska-Lampart, M.; Radziszewska, A.U.; Gos, A.; Talerczyk, M.; Wyborska, M.; Didkowska, J.A.; Wojciechowska, U.; Bielska-Lasota, M.; Forjaz de Lacerda, G.; Rego, R.A.; Bastos, J.; Silva, M.A.; Antunes, L.; Laranja Pontes, J.; Mayer-da-Silva, A.; Miranda, A.; Blaga, L.M.; Coza, D.; Gusenkova, L.; Lazarevich, O.; Prudnikova, O.; Vjushkov, D.M.; Egorova, A.G.; Orlov, A.E.; Kudyakov, L.A.; Pikalova, L.V.; Adamcik, J.; Safaei Diba, C.; Primic-Žakelj, M.; Zadnik, V.; Larrañaga, N.; Lopez de Munain, A.; Herrera, A.A.; Redondas, R.; Marcos-Gragera, R.; Vilardell Gil, M.L.; Molina, E.; Sánchez Perez, M.J.; Franch Sureda, P.; Ramos Montserrat, M.; Chirlaque, M.D.; Navarro, C.; Ardanaz, E.E.; Guevara, M.M.; Fernández-Delgado, R.; Peris-Bonet, R.; Carulla, M.; Galceran, J.; Alberich, C.; Vicente-Raneda, M.; Khan, S.; Pettersson, D.; Dickman, P.; Avelina, I.; Staehelin, K.; Camey, B.; Bouchardy, C.; Schaffar, R.; Frick, H.; Herrmann, C.; Bulliard, J.L.; Maspoli-Conconi, M.; Kuehni, C.E.; Redmond, S.M.; Bordoni, A.; Ortelli, L.; Chiolero, A.; Konzelmann, I.; Matthes, K.L.; Rohrmann, S.; Broggio, J.; Rashbass, J.; Fitzpatrick, D.; Gavin, A.; Clark, D.I.; Deas, A.J.; Huws, D.W.; White, C.; Montel, L.; Rachet, B.; Turculet, A.D.; Stephens, R.; Chalker, E.; Phung, H.; Walton, R.; You, H.; Guthridge, S.; Johnson, F.; Gordon, P.; D’Onise, K.; Priest, K.; Stokes, B.C.; Venn, A.; Farrugia, H.; Thursfield, V.; Dowling, J.; Currow, D.; Hendrix, J.; Lewis, C. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125), 1023-1075.
[http://dx.doi.org/10.1016/S0140-6736(17)33326-3] [PMID: 29395269]
[44]
Nan, Y.; Su, H.; Zhou, B.; Liu, S. The function of natural compounds in important anticancer mechanisms. Front. Oncol., , 2023, 12, 1049888, 12, 1049888..
[http://dx.doi.org/10.3389/fonc.2022.1049888 ] [PMID: 36686745]
[45]
Collins, L.G.; Haines, C.; Perkel, R.; Enck, R.E. Lung cancer: diagnosis and management. Am. Fam. Physician, 2007, 75(1), 56-63.
[46]
Zhao, Y.; Cai, J.; Shi, K.; Li, H.; Du, J.; Hu, D.; Liu, Z.; Wang, W. Germacrone induces lung cancer cell apoptosis and cell cycle arrest via the Akt/MDM2/p53 signaling pathway. Mol. Med. Rep., 2021, 23(6), 452.
[http://dx.doi.org/10.3892/mmr.2021.12091] [PMID: 33880579]
[47]
Anwanwan, D.; Singh, S.K.; Singh, S.; Saikam, V.; Singh, R. Challenges in liver cancer and possible treatment approaches. Biochim. Biophys. Acta Rev. Cancer, 2020, 1873(1), 188314.
[http://dx.doi.org/10.1016/j.bbcan.2019.188314] [PMID: 31682895]
[48]
Rumgay, H.; Ferlay, J.; de Martel, C.; Georges, D.; Ibrahim, A.S.; Zheng, R.; Wei, W.; Lemmens, V.E.P.P.; Soerjomataram, I. Global, regional and national burden of primary liver cancer by subtype. Eur. J. Cancer, 2022, 161, 108-118.
[http://dx.doi.org/10.1016/j.ejca.2021.11.023] [PMID: 34942552]
[49]
Liu, Y.; Wang, W.; Fang, B.; Ma, F.; Zheng, Q.; Deng, P.; Zhao, S.; Chen, M.; Yang, G.; He, G. Anti-tumor effect of germacrone on human hepatoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis. Eur. J. Pharmacol., 2013, 698(1-3), 95-102.
[http://dx.doi.org/10.1016/j.ejphar.2012.10.013] [PMID: 23117090]
[50]
Li, Z.; Wang, Z.; Dong, F.; Shi, W.; Dai, W.; Zhao, J.; Li, Q.; Fang, Z.; Ren, L.; Liu, T.; Wei, Z.; Mou, W.; Lin, L.; Yang, Y.; Xiao, X.; Ma, L.; Bai, Z. Germacrone attenuates hepatic stellate cells activation and liver fibrosis via regulating multiple signaling pathways. Front. Pharmacol., 2021, 12, 745561.
[http://dx.doi.org/10.3389/fphar.2021.745561] [PMID: 34675811]
[51]
Sun, X.; Zhong, X.; Ma, W.; Feng, W.; Huang, Q.; Ma, M.; Lv, M.; Hu, R.; Han, Z.; Li, J.; Zhou, X. Germacrone induces caspase 3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis. Exp. Ther. Med., 2022, 24(1), 456.
[http://dx.doi.org/10.3892/etm.2022.11383] [PMID: 35747157]
[52]
Tuli, H.S.; Kaur, J.; Vashishth, K.; Sak, K.; Sharma, U.; Choudhary, R.; Behl, T.; Singh, T.; Sharma, S.; Saini, A.K.; Dhama, K.; Varol, M.; Sethi, G. Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis. Arch. Toxicol., 2023, 97(1), 103-120.
[http://dx.doi.org/10.1007/s00204-022-03421-z] [PMID: 36443493]
[53]
Wu, J.; Feng, Y.; Han, C.; Huang, W.; Shen, Z.; Yang, M.; Chen, W.; Ye, L. Germacrone derivatives: synthesis, biological activity, molecular docking studies and molecular dynamics simulations. Oncotarget, 2017, 8(9), 15149-15158.
[http://dx.doi.org/10.18632/oncotarget.14832] [PMID: 28148897]
[54]
Ye, L.; Wu, J.; Chen, W.; Feng, Y.; Shen, Z. Novel anti-cancer agents based on germacrone: Design, synthesis, biological activity, docking studies and MD simulations. RSC Advances, 2017, 7(7), 3760-3767.
[http://dx.doi.org/10.1039/C6RA26944C]
[55]
Chen, C.; Xie, L.; Ren, T.; Huang, Y.; Xu, J.; Guo, W. Immunotherapy for osteosarcoma: Fundamental mechanism, rationale, and recent breakthroughs. Cancer Lett., 2021, 500, 1-10.
[http://dx.doi.org/10.1016/j.canlet.2020.12.024] [PMID: 33359211]
[56]
Cersosimo, F.; Lonardi, S.; Bernardini, G.; Telfer, B.; Mandelli, G.E.; Santucci, A.; Vermi, W.; Giurisato, E. Tumor-associated macrophages in osteosarcoma: From mechanisms to therapy. Int. J. Mol. Sci., 2020, 21(15), 5207.
[http://dx.doi.org/10.3390/ijms21155207] [PMID: 32717819]
[57]
Li, E.; Gao, Y.; Mou, L.; Zhang, Z. Anticancer activity of Germacrone terpenoid in human osteosarcoma cells is mediated via autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions and cell migration inhibition. Acta Biochim. Pol., 2022, 69(2), 305-308.
[http://dx.doi.org/10.18388/abp.2020_5712] [PMID: 35468267]
[58]
Harada, K.; Rogers, J.E.; Iwatsuki, M.; Yamashita, K.; Baba, H.; Ajani, J.A. Recent advances in treating oesophageal cancer. F1000 Res., 2020, 1, 9.
[59]
Bolger, J.C.; Donohoe, C.L.; Lowery, M.; Reynolds, J.V. Advances in the curative management of oesophageal cancer. Br. J. Cancer, 2022, 126(5), 706-717.
[http://dx.doi.org/10.1038/s41416-021-01485-9] [PMID: 34675397]
[60]
Huang, H. Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances. Sensors (Basel), 2018, 18(10), 3249.
[http://dx.doi.org/10.3390/s18103249] [PMID: 30262739]
[61]
Zhang, R.; Hao, J.; Guo, K.; Liu, W.; Yao, F.; Wu, Q.; Liu, C.; Wang, Q.; Yang, X. Germacrone inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma cells. BioMed Res. Int., 2020, 2020, 1-13.
[http://dx.doi.org/10.1155/2020/7643248] [PMID: 32071920]
[62]
Nagai, H.; Kim, Y.H. Cancer prevention from the perspective of global cancer burden patterns. J. Thorac. Dis., 2017, 9(3), 448-451.
[http://dx.doi.org/10.21037/jtd.2017.02.75] [PMID: 28449441]
[63]
Smyth, E.C.; Nilsson, M.; Grabsch, H.I.; van Grieken, N.C.T.; Lordick, F. Gastric cancer. Lancet, 2020, 396(10251), 635-648.
[http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]
[64]
McIlwain, D.R.; Berger, T.; Mak, T.W. Caspase functions in cell death and disease. Cold Spring Harb. Perspect. Biol., 2013, 5(4), a008656.
[http://dx.doi.org/10.1101/cshperspect.a008656] [PMID: 23545416]
[65]
Wu, L.; Wang, L.; Tian, X.; Zhang, J.; Feng, H. Germacrone exerts anti-cancer effects on gastric cancer through induction of cell cycle arrest and promotion of apoptosis. BMC Complementary Medicine and Therapies, 2020, 20(1), 21.
[http://dx.doi.org/10.1186/s12906-019-2810-3] [PMID: 32020876]
[66]
Fang, X.; Tan, T.; Gao, B.; Zhao, Y.; Liu, T.; Xia, Q. Germacrone regulates hbxip-mediated cell cycle, apoptosis and promotes the formation of autophagosomes to inhibit the proliferation of gastric cancer cells. Front. Oncol., 2020, 10, 537322.
[67]
Schatten, H. Brief overview of prostate cancer statistics, grading, Diagnosis and treatment strategies. Adv. Exp. Med. Biol., 2018, 1095, 1-14.
[http://dx.doi.org/10.1007/978-3-319-95693-0_1] [PMID: 30229546]
[68]
Porta, C.; Paglino, C.; Mosca, A. Targeting PI3K/Akt/mTOR signaling in cancer. Front. Oncol., 2014, 4, 64.
[http://dx.doi.org/10.3389/fonc.2014.00064] [PMID: 24782981]
[69]
LoRusso, P.M. Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J. Clin. Oncol., 2016, 34(31), 3803-3815.
[http://dx.doi.org/10.1200/JCO.2014.59.0018] [PMID: 27621407]
[70]
Yang, J.; Nie, J.; Ma, X.; Wei, Y.; Peng, Y.; Wei, X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol. Cancer, 2019, 18(1), 26.
[http://dx.doi.org/10.1186/s12943-019-0954-x] [PMID: 30782187]
[71]
Wadosky, K.M.; Koochekpour, S. Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer. Oncotarget, 2016, 7(39), 64447-64470.
[http://dx.doi.org/10.18632/oncotarget.10901] [PMID: 27487144]
[72]
Yu, Z.; Xu, J.; Shao, M.; Zou, J. Germacrone induces apoptosis as well as protective autophagy in human prostate cancer cells. Cancer Manag. Res., 2020, 12, 4009-4016.
[http://dx.doi.org/10.2147/CMAR.S250522] [PMID: 32547235]
[73]
Borrescio-Higa, F.; Valdés, N. The psychosocial burden of families with childhood blood cancer. Int. J. Environ. Res. Public Health, 2022, 19(1), 599.
[http://dx.doi.org/10.3390/ijerph19010599] [PMID: 35010854]
[74]
Li, W.; Wang, F.; Guo, R.; Bian, Z.; Song, Y. Targeting macrophages in hematological malignancies: Recent advances and future directions. J. Hematol. Oncol., 2022, 15(1), 110.
[http://dx.doi.org/10.1186/s13045-022-01328-x] [PMID: 35978372]
[75]
Braconi, L.; Teodori, E.; Riganti, C.; Coronnello, M.; Nocentini, A.; Bartolucci, G.; Pallecchi, M.; Contino, M.; Manetti, D.; Romanelli, M.N.; Supuran, C.T.; Dei, S. New dual P-glycoprotein (P-gp) and human carbonic anhydrase XII (hCA XII) inhibitors as multidrug resistance (MDR) reversers in cancer cells. J. Med. Chem., 2022, 65(21), 14655-14672.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01175] [PMID: 36269278]
[76]
Azzariti, A.; Porcelli, L.; Elisa Quatrale, A.; Silvestris, N.; Paradiso, A. The coordinated role of CYP450 enzymes and P-gp in determining cancer resistance to chemotherapy. Curr. Drug Metab., 2011, 12(8), 713-721.
[http://dx.doi.org/10.2174/138920011798357042] [PMID: 21434858]
[77]
Pan, J.; Miao, D.; Chen, L. Germacrone reverses adriamycin resistance in human chronic myelogenous leukemia K562/ADM cells by suppressing MDR1 gene/P-glycoprotein expression. Chem. Biol. Interact., 2018, 288, 32-37.
[http://dx.doi.org/10.1016/j.cbi.2018.04.012] [PMID: 29655913]
[78]
Gisina, A.; Kholodenko, I.; Kim, Y.; Abakumov, M.; Lupatov, A.; Yarygin, K. Glioma stem cells: Novel data obtained by single-cell sequencing. Int. J. Mol. Sci., 2022, 23(22), 14224.
[http://dx.doi.org/10.3390/ijms232214224] [PMID: 36430704]
[79]
Liu, B.O.; Gao, Y.U.E.Q.I.U.; Wang, X.M.; Wang, Y.C.; Fu, L.I.Q.I. Germacrone inhibits the proliferation of glioma cells by promoting apoptosis and inducing cell cycle arrest. Mol. Med. Rep., 2014, 10(2), 1046-1050.
[http://dx.doi.org/10.3892/mmr.2014.2290] [PMID: 24889088]
[80]
Kamat, P.K.; Rai, S.; Nath, C. Okadaic acid induced neurotoxicity: An emerging tool to study Alzheimer’s disease pathology. Neurotoxicology, 2013, 37, 163-172.
[http://dx.doi.org/10.1016/j.neuro.2013.05.002] [PMID: 23688530]
[81]
Çakır, M.; Yüksel, F.; Mustafa Özkut, M.; Durhan, M.; Kaymak, E.; Tekin, S.; Çiğremiş, Y. Neuroprotective effect of transient receptor potential Vanilloid 1 agonist capsaicin in Alzheimer’s disease model induced with okadaic acid. Int. Immunopharmacol., 2023, 118, 109925.
[http://dx.doi.org/10.1016/j.intimp.2023.109925] [PMID: 37011502]
[82]
Lin, M.; Li, P.; Liu, W.; Niu, T.; Huang, L. Germacrone alleviates okadaic acid-induced neurotoxicity in PC12 cells via M1 muscarinic receptor-mediated Galphaq (Gq)/phospholipase C beta (PLCβ)/protein kinase C (PKC) signaling. Bioengineered, 2022, 13(3), 4898-4910.
[http://dx.doi.org/10.1080/21655979.2022.2036918] [PMID: 35156515]
[83]
Saha, S.; Buttari, B.; Panieri, E.; Profumo, E.; Saso, L. An overview of Nrf2 signaling pathway and its role in inflammation. Molecules, 2020, 25(22), 5474.
[http://dx.doi.org/10.3390/molecules25225474] [PMID: 33238435]
[84]
El-Shitany, N.A.; Eid, B.G. Icariin modulates carrageenan-induced acute inflammation through HO-1/Nrf2 and NF-kB signaling pathways. Biomed. Pharmacother., 2019, 120, 109567.
[http://dx.doi.org/10.1016/j.biopha.2019.109567] [PMID: 31670031]
[85]
Zhuang, S.; Liu, B.; Guo, S.; Xue, Y.; Wu, L.; Liu, S.; Zhang, C.; Ni, X. Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress. BMC Comple. Med. Therap., 2021, 21(1), 6.
[http://dx.doi.org/10.1186/s12906-020-03175-0] [PMID: 33402180]
[86]
Malik Peiris, J.S.; Poon, L.L.M.; Guan, Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J. Clin. Virol., 2009, 45(3), 169-173.
[http://dx.doi.org/10.1016/j.jcv.2009.06.006] [PMID: 19540800]
[87]
Molinari, N.A.M.; Ortega-Sanchez, I.R.; Messonnier, M.L.; Thompson, W.W.; Wortley, P.M.; Weintraub, E.; Bridges, C.B. The annual impact of seasonal influenza in the US: Measuring disease burden and costs. Vaccine, 2007, 25(27), 5086-5096.
[http://dx.doi.org/10.1016/j.vaccine.2007.03.046] [PMID: 17544181]
[88]
Rothberg, M.B.; Haessler, S.D.; Brown, R.B. Complications of viral influenza. Am. J. Med., 2008, 121(4), 258-264.
[http://dx.doi.org/10.1016/j.amjmed.2007.10.040] [PMID: 18374680]
[89]
Liao, Q.; Qian, Z.; Liu, R.; An, L.; Chen, X. Germacrone inhibits early stages of influenza virus infection. Antiviral Res., 2013, 100(3), 578-588.
[http://dx.doi.org/10.1016/j.antiviral.2013.09.021] [PMID: 24095670]
[90]
Berger, A. Science commentary: Th1 and Th2 responses: What are they? BMJ, 2000, 321(7258), 424.
[http://dx.doi.org/10.1136/bmj.321.7258.424] [PMID: 10938051]
[91]
Liu, T.; Zhang, L.; Joo, D.; Sun, S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther., 2017, 2(1), 17023.
[http://dx.doi.org/10.1038/sigtrans.2017.23] [PMID: 29158945]
[92]
Shi, S.; Chen, Y.; Luo, Z.; Nie, G.; Dai, Y. Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy. Cell Commun. Signal., 2023, 21(1), 61.
[http://dx.doi.org/10.1186/s12964-023-01077-5] [PMID: 36918950]
[93]
Chen, Y.; Fang, Z.M.; Yi, X.; Wei, X.; Jiang, D.S. The interaction between ferroptosis and inflammatory signaling pathways. Cell Death Dis., 2023, 14(3), 205.
[http://dx.doi.org/10.1038/s41419-023-05716-0] [PMID: 36944609]
[94]
Wang, Z.; Zhuo, F.; Chu, P.; Yang, X.; Zhao, G. Germacrone alleviates collagen-induced arthritis via regulating Th1/Th2 balance and NF-κB activation. Biochem. Biophys. Res. Commun., 2019, 518(3), 560-564.
[http://dx.doi.org/10.1016/j.bbrc.2019.08.084] [PMID: 31451221]
[95]
Chellappan, D.K.; Yap, W.S.; Bt Ahmad Suhaimi, N.A.; Gupta, G.; Dua, K. Current therapies and targets for type 2 diabetes mellitus. Panminerva Med., 2018, 60(3), 117-131.
[http://dx.doi.org/10.23736/S0031-0808.18.03455-9] [PMID: 29696964]
[96]
Carling, D. AMPK signalling in health and disease. Curr. Opin. Cell Biol., 2017, 45, 31-37.
[http://dx.doi.org/10.1016/j.ceb.2017.01.005] [PMID: 28232179]
[97]
Sun, Y.; Li, L.; Wu, J.; Gong, B.; Liu, H. Germacrone cooperates with dexmedetomidine to alleviate high fat diet induced type 2 diabetes mellitus via upregulating AMPKα1 expression. Exp. Ther. Med., 2019, 18(5), 3514-3524.
[http://dx.doi.org/10.3892/etm.2019.7990] [PMID: 31602228]
[98]
Guo, Y.R.; Choung, S.Y. Germacrone attenuates hyperlipidemia and improves lipid metabolism in high-fat diet-induced obese C57BL/6J Mice. J. Med. Food, 2017, 20(1), 46-55.
[http://dx.doi.org/10.1089/jmf.2016.3811] [PMID: 28098516]
[99]
Ji, D.; Wang, Q.; Zhao, Q.; Tong, H.; Yu, M.; Wang, M.; Lu, T.; Jiang, C. Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy. J. Nanobiotechnology, 2020, 18(1), 86.
[http://dx.doi.org/10.1186/s12951-020-00645-y] [PMID: 32513194]
[100]
Fang, Z.; Yushanjiang, F.; Wang, G.; Zheng, X.; Jiang, X. Germacrone mitigates cardiac remodeling by regulating PI3K/AKTmediated oxidative stress, inflammation, and apoptosis. 2023, 124-110876.
[101]
Zhang, Y.; Alexander, P.B.; Wang, X.F. TGF-β family signaling in the control of cell proliferation and survival. Cold Spring Harb. Perspect. Biol., 2017, 9(4), a022145.
[http://dx.doi.org/10.1101/cshperspect.a022145] [PMID: 27920038]
[102]
Hu, H.H.; Chen, D.Q.; Wang, Y.N.; Feng, Y.L.; Cao, G.; Vaziri, N.D.; Zhao, Y.Y. New insights into TGF-β/Smad signaling in tissue fibrosis. Chem. Biol. Interact., 2018, 292, 76-83.
[http://dx.doi.org/10.1016/j.cbi.2018.07.008] [PMID: 30017632]
[103]
Vander Ark, A.; Cao, J.; Li, X. TGF-β receptors: In and beyond TGF-β signaling. Cell. Signal., 2018, 52, 112-120.
[http://dx.doi.org/10.1016/j.cellsig.2018.09.002] [PMID: 30184463]
[104]
Clark, D.A.; Coker, R. Molecules in focus transforming growth factor-beta (TGF-β). Int. J. Biochem. Cell Biol., 1998, 30(3), 293-298.
[http://dx.doi.org/10.1016/S1357-2725(97)00128-3] [PMID: 9611771]
[105]
Galisteo Pretel, A.; Pérez Del Pulgar, H.; Guerrero de León, E.; López-Pérez, J.L.; Olmeda, A.S.; Gonzalez-Coloma, A.; F Barrero, A.; Quílez Del Moral, J.F. Germacrone derivatives as new insecticidal and acaricidal compounds: A structure-activity relationship. Molecules, 2019, 24(16), 2898.
[http://dx.doi.org/10.3390/molecules24162898] [PMID: 31404973]
[106]
Li, X.; Chen, L.; Wang, H.; Li, Y.; Wu, H.; Guo, F. Germacrone, isolated from Curcuma wenyujin, inhibits melanin synthesis through the regulation of the MAPK signaling pathway. J. Nat. Med., 2024, 2024 Advance online publication
[http://dx.doi.org/10.1007/s11418-024-01818-x] [PMID: 38809333]
[107]
Yuan, Y.; Shao, L. Germacrone protects against NF-κB-mediated inflammatory signaling, apoptosis, and retinal ganglion cell survival in a rat glaucoma model. TJEM, 2024. Epub ahead of Print;
[http://dx.doi.org/10.1620/tjem.2024.J028]
[108]
Lin, Z.; Yang, Y.; Liu, T.; Wu, Z.; Zhang, X.; Yang, J. Germacrone alleviates breast cancer‐associated osteolysis by inhibiting osteoclastogenesis via inhibition of MAPK/NF‐κB signaling pathways. Phytother. Res., 2024, 38(6), 2860-2874.
[http://dx.doi.org/10.1002/ptr.8195] [PMID: 38558446]
[109]
Wang, Y.; He, X.; Xue, M.; Yu, H.; He, Q.; Jin, J. Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice. Acta Biochim. Biophys. Sin. , 2024, 56(3), 414-426.
[http://dx.doi.org/10.3724/abbs.2024021] [PMID: 38429975]
[110]
Wang, Y.; He, X.; Xue, M.; Sun, W.; He, Q.; Jin, J. Germacrone protects renal tubular cells against ferroptotic death and ROS release by re-activating mitophagy in diabetic nephropathy. Free radic. res., 2023, 57, 413-429.
[http://dx.doi.org/10.1080/10715762.2023.2277143]

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