Kurkumin

Kurkumin

• Kurkumin 3x denně 700mg (tj. 2,1g/d, 95% extrakt) po snídani, obědě a večeři
• Intenzivní měsíční protokol 3x denně po 1400 mg (tj. 4,2 g/d)
• Běžný kurkumin s piperinem
• Jsou formy, které mohou mít lepší biodostupnost
• 1 gram BCM-95 může být ekvivalentem i pro zhruba 4 gramy běžného kurkuminu s piperinem.
• Dávky kurkuminu do 4 gramů budou zřejmě nedostatečné
• Ke zvážení 10-15 gramy kurkuminu + piperin + silymarin + quercetinem
• Klinické studie zatím max. 10 g bez synergentů

Piperin

• 10 gramů kurkuminu podaného bez piperinu je ale srovnatelných s 1 gramem kurkuminu s piperinem
• 5mg piperinu na každých cca. 700mg kurkuminu
• Zvýší 20x biodostupnost

Quercetin

• 200mg quercetinu (quercetin dihydrate) malé množství lze pokaždé přidat do kurkuminové kapsle zvýší se
• Biodostupnost (Moorthi, 2013; Lund, 2014)
• Protinádorová účinnost (Giardiello, 2006; Zhang, 2015)
• Spolu s kurkuminem, vždy po jídle

Silimarin

• 150mg silymarin/silybinin (80% extrakt silymarinu) zvyšuje
• Biodostupnost kurkuminu 3,5x (Grill, 2014; Grill, 2012)
• Protinádorovou aktivitu (Nasiri, 2013)
• 3x denně 150mg kapsli ve stejný čas jako kurkumin - po jídle (liposolubilní)
• Soupeření o GLUT4 (silymarin); část jich bude přenášet silymarin = méně převozníků pro glukózu

Honokiol (látka v magnólii)

• Aktivátorem PTEN;
• Protinádorová aktivita kurkuminu je lepší když je PTEN aktivní
• Horší když je neaktivní (Srivastava, 2007).
• U pacientů s mutací PTEN
• Možnost synergie honokiolu a kurkuminu

Resveratrol

• Aktivace PTEN (Dhar, 2015)

Zázvor

• Zázvorový čaj / v kapsli
• Zesiluje protinádorový účinek
• 250mg min. 5% standard. gingerolů během polední dávky kurkuminu
• Nalačno může způsobovat bolest břicha a podbřišku - přesuňte po jídle.

EGCG

• Působí s kurkuminem synergicky
• 3xd po jídle
• Zlepší biodostupnost - před užitím sníst grapefruit

Omezení

• žlučové kameny
• Léků proti srážlivosti krve (Warfarin, heparin, clopidogrel, aspirin aj.)
• žaludečními vředy, kteří berou antacida (cimetidine, famotidine, ranitidine, esomeprazole, omeprazole a lansoprazole)
• doxorubicin ? (Orlowski, 2002; byť autoři zkoumali pouze po dobu 3 dnů).
• Po dobu 2 týdnů před začátkem chemoterapie doxorubicinem.
• S časovým odstupem 48 hodin od cyclophosphamidu
• kurkumin může zesílit účinek antidiabetický účinek - riziko hypoglykémie
• Neužívat v těhotenství
• Vysoké dávky kurkuminu po delší dobu mohou způsobit nedostatek železa

Patrik Schoupal, 10.6.2018, Alternativní cesta

Curcumin

• Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation
• Induces G1/S arrest
• Suppresses proliferation, and induces apoptosis in mantle cell lymphoma

• Biochem. Pharmacol. 70 (2005) 700–713. doi:10.1016/j.bcp.2005.04.043. Tesi di dottorato in Bioingegneria e Bioscienze, indirizzo Scienze e Tecnologie degli Alimenti e della Nutrizione Umana, di Diana Lelli, discussa presso l’Universita Campus Bio-Medico di Roma in data 28/05/2019.

• Suppression of transcription factor Egr-1 by curcumin

• Thromb. Res. 97 (2000) 179–189.

• Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells
• By up-regulating cyclindependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53

• Int. J. Oncol. 21 (2002) 379–383. M.-J. Park, E.-H. Kim, I.-C. Park, H.-C. Lee, S.-H. Woo, J.-Y. Lee, Y.-J. Hong, C.H. Rhee, S.- H. Choi, B.-S. Shim, S.-H. Lee, S.-I. Hong,

• Curcumin-glutathione interactions and the role of human glutathione Stransferase P1-1

• Chem. Biol. Interact. 128 (2000) 19–38.

• Curcumin-induced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin,

• Biochim. Biophys. Acta. 1773 (2007) 383–390. doi:10.1016/j.bbamcr.2006.11.004.

• Interaction of isoxazolcurcumin with calf thymus DNA

• Int. J. Biol. Macromol. 42 (2008) 14–21. doi:10.1016/j.ijbiomac.2007.08.010.

• Curcumin binding to DNA and RNA, DNA

• Cell Biol. 28 (2009) 201–208. doi:10.1089/dna.2008.0840.

• PH dependent binding of curcumin in the minor groove of natural and synthetic nucleic acids

• Org. Biomol.Chem. 2 (2004) 2902–2910. doi:10.1039/B409724F.

• Curcumin is a modulator of bilayer material properties

• Biochemistry (Mosc.). 46 (2007) 10384–10391. doi:10.1021/bi701013n.

• Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models,

• J. Alzheimers Dis. JAD. 6 (2004) 367-377-449.

• Complementary inhibition of synoviocyte, smooth muscle cell or mouse lymphoma cell proliferation by a vanadyl curcumin complex compared to curcumin alone

• J. Inorg. Biochem. 98 (2004) 2063–2070. doi:10.1016/j.jinorgbio.2004.09.011.

• Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways,

• Anticancer Res. 30 (2010) 3249–3255.

• Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice,

• Fitoterapia. 87 (2013) 57–64. doi:10.1016/j.fitote.2013.02.014.

• Curcumin inhibition of Dermatophagoides farineainduced interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GMCSF) production by lymphocytes from bronchial asthmatics

• Biochem. Pharmacol. 54 (1997) 819–824.

• Curcumin attenuates ovalbumin-induced airway inflammation by regulating nitric oxide,

• Biochem. Biophys. Res. Commun. 375 (2008) 275–279. doi:10.1016/j.bbrc.2008.08.025.

• Anti-inflammatory effects of curcumin in a murine model of chronic asthma,

• Allergol. Immunopathol. (Madr.). 40 (2012) 210–214. doi:10.1016/j.aller.2011.04.006.

• Curcumin inhibits the proliferation of airway smooth muscle cells in vitro and in vivo,

• Int. J. Mol. Med. 32 (2013) 629–636. doi:10.3892/ijmm.2013.1425.

• Oral curcumin supplementation in patients with atopic asthma,

• Allergy Rhinol. 2 (2011) e51–e53. doi:10.2500/ar.2011.2.0016.

• Efficacy of Curcumin as an Add-on therapy in Patients of Bronchial Asthma,

• J. Clin. Diagn. Res. JCDR. 8 (2014) HC19-HC24. doi:10.7860/JCDR/2014/9273.4705.

• Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats,

• Br. J. Pharmacol. 131 (2000) 169–172. doi:10.1038/sj.bjp.0703578.

• Modulatory effects of curcumin and green tea extract against experimentally induced pulmonary fibrosis: a comparison with Nacetyl cysteine

• J. Biochem. Mol. Toxicol. 26 (2012) 461–468. doi:10.1002/jbt.21447.

• Curcumin attenuates radiation-induced inflammation and fibrosis in rat lungs

• Korean J. Physiol. Pharmacol. Off. J. Korean Physiol. Soc. Korean Soc. Pharmacol. 17 (2013) 267–274. doi:10.4196/kjpp.2013.17.4.267.

• Protective effect of curcumin, ellagic acid and bixin on radiation induced toxicity

• Indian J. Exp. Biol. 34 (1996) 845–847.

• Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice,

• Radiat. Res. 173 (2010) 590–601. doi:10.1667/RR1522.1.

• Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome,

• PloS One. 8 (2013) e57285. doi:10.1371/journal.pone.0057285.

• Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects,

• Science. 304 (2004) 600–602. doi:10.1126/science.1093941.

• Curcumin does not stimulate cAMPmediated chloride transport in cystic fibrosis airway epithelial cells,

• Biochem. Biophys. Res. Commun. 322 (2004) 447–451. doi:10.1016/j.bbrc.2004.07.146.

• Curcumin Stimulates Cystic Fibrosis Transmembrane Conductance Regulator Cl– Channel Activity,

• J. Biol. Chem. 280 (2005) 5221–5226. doi:10.1074/jbc.M412972200.

• Curcumin Opens Cystic Fibrosis Transmembrane Conductance Regulator Channels by a Novel Mechanism That Requires neither ATP Binding nor Dimerization of the Nucleotide-binding Domains,

• J. Biol. Chem. 282 (2007) 4533–4544. doi:10.1074/jbc.M609942200.

• Curcumin and genistein additively potentiate G551D-CFTR,

• J. Cyst. Fibros. 10 (2011) 243–252. doi:10.1016/j.jcf.2011.03.001.

• Curcumin Cross-links Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Polypeptides and Potentiates CFTR Channel Activity by Distinct Mechanisms,

• J. Biol. Chem. 284 (2009) 30754–30765. doi:10.1074/jbc.M109.056010.

• Rescue of ?F508-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) by Curcumin: Involvement of the Keratin 18

• Network, J. Pharmacol. Exp. Ther. 317 (2006) 500–505. doi:10.1124/jpet.105.097667.

• Interplay between Inhibitory Ferric and Stimulatory Curcumin Regulates Phosphorylation-Dependent Human Cystic Fibrosis Transmembrane Conductance Regulator and F508 Activity

• Biochemistry (Mosc.). 54 (2015) 1558–1566. doi:10.1021/bi501318h.

• Molecular Basis for Fe(III)-Independent Curcumin Potentiation of Cystic Fibrosis Transmembrane Conductance Regulator Activity,

• Biochemistry (Mosc.). 54 (2015) 2828–2840. doi:10.1021/acs.biochem.5b00219.

• Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice,

• J. Med. Microbiol. 59 (2010) 429–437. doi:10.1099/jmm.0.016873-0.

• Effect of curcumin (Curcuma longa extract) on LPS-induced acute lung injury is mediated by the activation of AMPK,

• J. Anesth. 30 (2016) 100–108. doi:10.1007/s00540-015-2073-1.

• Intranasal Curcumin Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice, Inflammation.

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• The effect of curcumin on sepsis-induced acute lung injury in a rat model through the inhibition of the TGF-b1/SMAD3 pathway,

• Int. Immunopharmacol. 16 (2013) 1–6. doi:10.1016/j.intimp.2013.03.014.

• Effect of curcumin on lung injuries in a rat model induced by aspirating gastrointestinal decontamination agents,

• J. Pediatr. Surg. 47 (2012) 1669–1676. doi:10.1016/j.jpedsurg.2012.01.076.

• Preventive effects of curcumin on different aspiration material-induced lung injury in rats,

• Pediatr. Surg. Int. 25 (2009) 83–92. doi:10.1007/s00383-008-2282-x.

• Curcumin protects against sepsis-induced acute lung injury in rats,

• J. Surg. Res. 176 (2012) e31-39. doi:10.1016/j.jss.2011.11.1032.

• Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway,

• Oncol. Rep. 24 (2010) 1217–1223

• Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway,

• Oncol. Rep. 34 (2015) 2782–2789. doi:10.3892/or.2015.4258.

• Curcumin promotes apoptosis by activating the p53-miR-192-5p/215-XIAP pathway in non-small cell lung cancer,

• Cancer Lett.357 (2015) 196–205. doi:10.1016/j.canlet.2014.11.028.

• Comparative cytotoxicity and ROS generation by curcumin and tetrahydrocurcumin following visible-light irradiation or treatment with horseradish peroxidase,

• Anticancer Res. 27 (2007) 363–371.

• Dual effect of curcumin targets reactive oxygen species, adenosine triphosphate contents and intermediate steps of mitochondria-mediated apoptosis in lung cancer cell lines,

• Eur. J. Pharmacol. 769 (2015) 203–210. doi:10.1016/j.ejphar.2015.11.019.

• Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway,

• PloS One. 7 (2012) e37960. doi:10.1371/journal.pone.0037960.

• Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer,

• Eur. J. Cancer Prev. Off. J. Eur. Cancer Prev. Organ. ECP. 21 (2012) 407–412. doi:10.1097/CEJ.0b013e32834ef194.

• Curcumin suppresses stem-like traits of lung cancer cells via inhibiting the JAK2/STAT3 signaling pathway,

• Oncol. Rep. 34 (2015) 3311–3317. doi:10.3892/or.2015.4279.

• Curcumin inhibits lung cancer progression and metastasis through induction of FOXO1,

• Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med. 35 (2014) 111–116. doi:10.1007/s13277-013-1013-7.

• Curcumin Reactivates Silenced Tumor Suppressor Gene RARb by Reducing DNA Methylation,

• Phytother. Res. PTR. 29 (2015) 1237–1245. doi:10.1002/ptr.5373.

• Curcumin inhibits proliferation-migration of NSCLC by steering crosstalk between a Wnt signaling pathway and an adherens junction via EGR-1,

• Mol. Biosyst. 11 (2015) 859–868. doi:10.1039/c4mb00336e.

• Curcumin inhibits lung cancer cell migration and invasion through Rac1-dependent signaling pathway,

• J. Nutr. Biochem. 25 (2014) 177–185. doi:10.1016/j.jnutbio.2013.10.004.

• Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF?b/MMPs Signaling Pathway,

• PLoS ONE. 10 (2015) e0144462. doi:10.1371/journal.pone.0144462.

• Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway,

• Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med. 36 (2015) 3591–3599. doi:10.1007/s13277-014-2996-4.

• Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1? and caspase-3 mechanisms,

• Phytomedicine Int. J. Phytother. Phytopharm. 19 (2012) 779–787. doi:10.1016/j.phymed.2012.03.005.

• Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines,

• Oncol. Rep. (2015). doi:10.3892/or.2015.4371.

• Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor,

• Oncol. Res. 21 (2013) 137–144. doi:10.3727/096504013X13832473330032.

• Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer,

• Acta Biochim. Biophys. Sin. 44 (2012) 147–153. doi:10.1093/abbs/gmr106.

• Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy,

• PloS One. 6 (2011) e23756. doi:10.1371/journal.pone.0023756.

• Curcumin Triggers DNA Damage and Inhibits Expression of DNA Repair Proteins in Human Lung Cancer Cells,

• Anticancer Res. 35 (2015) 3867–3873.

• Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and antiproliferative responses through a ROS-independent mechanism,

• Carcinogenesis. 28 (2007) 1765–1773. doi:10.1093/carcin/bgm123.