Alantolactone

==Nom de la substance==
Alantolactone
==Famille moléculaire==
Lactone sesquiterpénique (eudesmanolide) contenant deux cycles benzéniques
==Source végétale==
* Aunée Inula helenium, Inula racemosa Hook.f et autres plantes de la Pharmacopée chinoise Ketai W, Huitao L, Yunkun Z, Xingguo C, Zhide H, Yucheng S, Xiao M. Separation and determination of alantolactone and isoalantolactone in traditional Chinese herbs by capillary electrophoresis. Talanta. 2000 Sep 5;52(6):1001-5. PMID 18968060
==Propriétés==
* Détoxifiant par action sur des enzymes de type 2, quinone réductase (QR) et glutathion-S-transférase (GST) Seo JI, Lim SS, Kim JR, Ji-Sun L, Ha YR, Lee IA, Kim EJ, Park JHY, Jong-Sang K. Nrf2-mediated Induction of Detoxifying Enzymes by Alantolactone Present in Inula helenium. Phytotherapy research. 2008, vol. 22, no11, pp. 1500-1505. PMID 18702092, Seo JY, Park J, Kim HJ, Lee IA, Lim JS, Lim SS, Choi SJ, Park JH, Kang HJ, Kim JS. Isoalantolactone from Inula helenium caused Nrf2-mediated induction of detoxifying enzymes. J Med Food. 2009 Oct;12(5):1038-45. PMID 19857067, Lim SS, Kim JR, Lim HA, Jang CH, Kim YK, Konishi T, Kim EJ, Park JH, Kim JS. Induction of detoxifying enzyme by sesquiterpenes present in Inula helenium. J Med Food. 2007 Sep;10(3):503-10. PMID 17887945
* Antimicrobien Cantrell CL, Abate L, Fronczek FR, Franzblau SG, Quijano L, Fischer NH. Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia subtomentosa. Planta Med. 1999 May;65(4):351-5. PMID 10364842
* Antiviral vis-à-vis de HSV-1 (Herpes simplex virus 1) Rezeng, Caidan & Yuan, Dongping & Long, Jun & Suonan, Dengdeng & Yang, Fang & Li, Wenyuan & Tong, Li & Jiumei, Pengcuo. (2016). Alantolactone exhibited anti-herpes simplex virus 1 (HSV-1) action in vitro. BioScience Trends. 9. 420-422. 10.5582/bst.2015.01171.
* Antitumoral Li Y, Ni ZY, Zhu MC, Dong M, Wang SM, Shi QW, Zhang ML, Wang YF, Huo CH, Kiyota H, Cong B. Antitumour activities of sesquiterpene lactones from Inula helenium and Inula japonica. Z Naturforsch C J Biosci. 2012 Jul-Aug;67(7-8):375-80. PMID 23016276
* Cytotoxique sur cellules cancéreuses Dirsch VM, Stuppner H, Vollmar AM. Cytotoxic sesquiterpene lactones mediate their death-inducing effect in leukemia T cells by triggering apoptosis. Planta Med. 2001 Aug;67(6):557-9. PMID 11509981, Konishi T, Shimada Y, Nagao T, Okabe H, Konoshima T. Antiproliferative sesquiterpene lactones from the roots of Inula helenium. Biol Pharm Bull. 2002 Oct;25(10):1370-2. PMID: 12392098, Dupuis G, Brisson J. Toxic effect of alantolactone and dihydroalantolactone in in vitro cultures of leukocytes. Chem Biol Interact. 1976 Nov;15(3):205-17. PMID 1000726, inducteur d'apoptose pour les cellules cancéreuses Rasul A, Khan M, Ali M, Li J, Li X. Targeting apoptosis pathways in cancer with alantolactone and isoalantolactone. ScientificWorldJournal. 2013 Oct 27;2013:248532. doi: 10.1155/2013/248532. eCollection 2013. PMID 24288468, de cancer gastrique Zhang X, Zhang HM. Alantolactone induces gastric cancer BGC-823 cell apoptosis by regulating reactive oxygen species generation and the AKT signaling pathway. Oncol Lett. 2019 Jun;17(6):4795-4802. doi: 10.3892/ol.2019.10172. PMID 31186685
** L'alantolactone pourrait sensibiliser les cellules cancéreuses pancréatiques humaines aux inhibiteurs d'EGFR (thérapie potentielle pour le cancer du pancréas) Zheng H, Yang L, Kang Y, Chen M, Lin S, Xiang Y, Li C, Dai X, Huang X, Liang G, Zhao C. Alantolactone sensitizes human pancreatic cancer cells to EGFR inhibitors through the inhibition of STAT3 signaling. Mol Carcinog. 2019 Apr;58(4):565-576. doi: 10.1002/mc.22951. PMID 30520143, elle est inducteur d’apoptose sur cellules de cancer du sein Cui L, Bu W, Song J, Feng L, Xu T, Liu D, Ding W, Wang J, Li C, Ma B, Luo Y, Jiang Z, Wang C, Chen J, Hou J, Yan H, Yang L, Jia X. Apoptosis induction by alantolactone in breast cancer MDA-MB-231 cells through reactive oxygen species-mediated mitochondrion-dependent pathway. Arch Pharm Res. 2018 Mar;41(3):299-313. doi: 10.1007/s12272-017-0990-2. PMID 29214600, de glioblastomes Khan M, Yi F, Rasul A, Li T, Wang N, Gao H, Gao R, Ma T. Alantolactone induces apoptosis in glioblastoma cells via GSH depletion, ROS generation, and mitochondrial dysfunction. IUBMB Life. 2012 Sep;64(9):783-94. doi: 10.1002/iub.1068. PMID 22837216, cellules de leucémie myéloïde chronique Yang C, Yang J, Sun M, Yan J, Meng X, Ma T. Alantolactone inhibits growth of K562/adriamycin cells by downregulating Bcr/Abl and P-glycoprotein expression. IUBMB Life. 2013 May;65(5):435-44. doi: 10.1002/iub.1141. PMID 23441067, par inhibition de la voie de signalisation NF-κB et l'épuisement de la protéine Bcr/Abl. Wei W, Huang H, Zhao S, Liu W, Liu CX, Chen L, Li JM, Wu YL, Yan H. Alantolactone induces apoptosis in chronic myelogenous leukemia sensitive or resistant to imatinib through NF-κB inhibition and Bcr/Abl protein deletion. Apoptosis. 2013 Sep;18(9):1060-70. doi: 10.1007/s10495-013-0854-2. PMID 23613107, induit l'apoptose, favorise la glutathionylation STAT3 et améliore la chimiosensibilité des cellules d'adénocarcinome pulmonaire A549 à la doxorubicine Maryam, A., Mehmood, T., Zhang, H. et al. Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress. Sci Rep 7, 6242 (2017). https://doi.org/10.1038/s41598-017-06535-y
* Anti-inflammatoire sur lésions pulmonaires aiguës Ding YH, Song YD, Wu YX, He HQ, Yu TH, Hu YD, Zhang DP, Jiang HC, Yu KK, Li XZ, Sun L, Qian F. Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury. Acta Pharmacol Sin. 2019 Jan;40(1):64-74. doi: 10.1038/s41401-018-0061-3. PMID 30013035, Yuan CB, Tian L, Yang B, Zhou HY. Isoalantolactone protects LPS-induced acute lung injury through Nrf2 activation. Microb Pathog. 2018 Oct;123:213-218. doi: 10.1016/j.micpath.2018.07.010. Epub 2018 Jul 19. PMID 30009971
* L’alantolactone est un candidat prometteur pour le traitement de la résistance à l'insuline et de l'intolérance au glucose associée à l'inflammation, en infléchissant une élévation prolongée de l'IL-6 Kim M, Song K, Kim YS. Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance. Front Pharmacol. 2017 Jun 29;8:405. doi: 10.3389/fphar.2017.00405. eCollection 2017. PMID 28706484, Kim M, Song K, Kim YS. Alantolactone improves palmitate-induced glucose intolerance and inflammation in both lean and obese states in vitro: Adipocyte and adipocyte-macrophage co-culture system. Int Immunopharmacol. 2017 Aug;49:187-194. doi: 10.1016/j.intimp.2017.05.037. PMID 28599253
==Effet thérapeutique==
* Détoxification
* Pneumopathies 
* Prévention des lésions inflammatoires du sepsis (septicémie) He G, Zhang X, Chen Y, Chen J, Li L, Xie Y. Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis. Biomed Pharmacother. 2017 Jun;90:598-607. doi: 10.1016/j.biopha.2017.03.095. PMID 28407580
* Cancers (?)
==Effets indésirables==
* Risques allergiques Jovanović M, Mimica-Dukić N, Poljacki M, Boza P. Erythema multiforme due to contact with weeds: a recurrence after patch testing. Contact Dermatitis. 2003 Jan;48(1):17-25. PMID 12641574, Kanerva L, Estlander T, Alanko K, Jolanki R. Patch test sensitization to Compositae mix, sesquiterpene-lactone mix, Compositae extracts, laurel leaf, Chlorophorin, Mansonone A, and dimethoxydalbergione. Am J Contact Dermat. 2001 Mar;12(1):18-24. PMID 11244135, Kuno Y, Kawabe Y, Sakakibara S. Allergic contact dermatitis associated with photosensitivity, from alantolactone in a chrysanthemum farmer. Contact Dermatitis. 1999 Apr;40(4):224-5. PMID 10208523
* Inhibition du CYP34A, risques d'interaction avec les drogues éliminées par ce cytochrome P450 Qin CZ, Lv QL, Wu NY, Cheng L, Chu YC, Chu TY, Hu L, Cheng Y, Zhang X, Zhou HH. Mechanism-based inhibition of Alantolactone on human cytochrome P450 3A4 in vitro and activity of hepatic cytochrome P450 in mice. J Ethnopharmacol. 2015 Apr 7. pii: S0378-8741(15)00220-2. doi: 10.1016/j.jep.2015.03.061. PMID 25858508
==Bibliographie==
* Xin XL, Ma XC, Liu KX, Han J, Wang BR, Guo DA. Microbial transformation of alantolactone by Mucor polymorphosporus. J Asian Nat Prod Res. 2008 Sep-Oct;10(9-10):933-7. PMID 19003611
Catégorie:principes actifs