Omenirea si bolile secolului XXI
Datorita schimbarilor in alimentatie si stilului de viata, oamenii sunt mai predispusi la diverse boli si tulburari, cancerul aflandu-se printre cele mai frecvente dintre ele. Cancerul gastric are a doua rata de malignitate fatala in lume [1].
Cercetarile asupra cancerului gastric indus de microorganisme nu au fost intense, de aceea acum cercetatorii se concentreaza in detaliu pe oncogeneza indusa microbiologic. Optzeci la suta din cazurile de cancer gastric diagnosticate sunt considerate a fi induse de microbi. [2]. Dupa descoperirea Helicobacter pylori de catre Marshall si Warren la un pacient cu gastrita, s-au realizat numeroase studii de microbiologie asupra influentei acestei bacterii in diversele patologii ale sistemul digestiv. [3]. Numeroase rapoarte sugereaza ca debutul infectiei cu H. pylori in copilarie apare prin relatii de sange vizand tatal, mama si fratii. [4] Este ingrijorator faptul ca aproximativ jumatate din populatia mondiala este infectata cu acest agent patogen [5]. H. pylori joaca un rol determinant la pacientii cu gastrita cronica, ulcere peptice, adenocarcinoame gastrice si formatiuni limfoide ale mucoasei gastrice [6,7]. H. pylori este cunoscut pentru producerea mai multor factori virali (de exemplu, CagA, VacA, peptidoglican si alti multi factori de aderenta care sunt considerati cei mai importanti factori de virulenta) [8]. OMS a declarat H. pylori carcinogen, deoarece este asociat cu adenocarcinomul gastric [9]. Dupa o infectie importanta , o varietate de factori de virulenta se traduc in celule epiteliale gastrice [8]. Proteina citotoxica CagA este transpusa in celulele epiteliale gastrice prin intermediul sistemului de secretie de tip IV [10], aceasta fiind considerata cauza principala a producerii cancerului gastric.
Numerosi agenti chimioterapeutici sunt disponibili pentru tratamentul cancerului, desi ei au efecte citotoxice si asupra celulelor normale [29].
Totodata insa , mai multe studii raporteaza ca unii compusi naturali si unele suplimentele nutritive manifesta o bioactivitate importanta impotriva cancerului [30].
Aportul de alimente naturale, cum ar fi legumele si fructele, determina o scadere a incidentei cancerului [20]. Cercetatorii se concentreaza acum pe acesti compusi naturali si realizeaza numeroase investigatii clinice privind efectele lor. Rapoartele sugereaza ca aportul de legume in cantitate mai mare de 400 g / zi poate reduce dezvoltarea cancerului cu pana la 20% [20]. Suplimentele alimentare care contin compusi bioactivi sunt acum considerati deosebit de importanti si sunt studiati pe larg pentru actiunea lor anticancerigena.
In urma unui studiu sustinut la Universitatea Yonsei din Coreea de Sud, s-au raportat numeroase efecte benefice ale Piperinei in prevenirea si tratamentul bolilor cronice, in special acele efecte care vizeaza reducerea riscurilor de cancer si actiunea sa importanta impotriva infectiei cu H. pylori.
Ce este Piperina?
Piperul negru (Piper nigrum) este cunoscut drept „regele mirodeniilor”. Piperina este un alcaloid prezent in Piperul negru (Piper nigrum) sau Ardeiul negru, cum se mai numeste acesta in literatura anglo-saxona, unul dintre cele mai utilizate condimente. Mai gasim, de asemenea, Piperina si in Ardeiul lung (Piper longum) si in alte fructe ale unor plante apartinand familiei Piperaceae. Alcaloizii includ o familie de compusi chimici naturali care contin in principal azot. Piperina, o substanta azotata care este deosebit de prezenta in Piperul negru, se crede ca isi exercita functia mai ales la nivel gastrointestinal [22], fiind un compus natural folosit ca potentator alimentar si raportat ca un compus cu efecte anticancerigene [31,32]. Dupa numeroase studii medicale s-a constatat ca rezistenta la medicamente a H. pylori a crescut continuu in timp [33]. Pe baza acestei constatari, cercetatorii au cautat compusul natural care ar putea actiona impotriva H. pylori, Piperina fiind gasita ca prim agent de protectie impotriva ulcerelor gastrice [34], avand un rol antibacterian, antiinflamator, dovedindu-se astfel a fi si un anticancerigen important.
Efectele farmacologice si beneficiile Piperinei asupra sanatatii:
- Protejeaza organismul in cazul racelilor obisnuite, tusei, bolilor din sfera ORL si febrei intermitente;
- Benefic in caz de colici si dizenterie;
- Eficient in lupta impotriva bolilor cronice;
- Reduce rezistenta la insulina;
- Reduce simptomele steatozei hepatice;
- Previne si combate diverse inflamatiile [21];
- Actioneaza impotriva cancerului prin inhibarea celulara in metastazele pulmonare [23] si, in cancerul de prostata, prin inhibarea proliferarii celulelor cauzatoare ale bolii.[24];
- Inhiba cresterea bacteriilor si previne aderenta acestora la celulele epiteliale gastrice. Are un efect sinergic asupra functiei antibacteriene atunci cand se combina cu ciprofloxacina (antibiotic din familia chinolonelor) ;
- Avand in vedere ca Piperina restrictioneaza cresterea si aderenta bacteriana, aceasta are un rol foarte important si in tratarea infectiei cu H. pylori. Piperina actioneaza ca un inhibitor al pompei de reflux bacterian inhiband cresterea bacteriana chiar si in tulpinile multifunctionale rezistente [52-54];
- S-a raportat ca Piperina poate actiona cu succes impotriva declansarii cancerului [23,29,31]. Efectele supresive ale Piperinei asupra nivelului de β-catenina din celulele infectate cu H. pylori au sustinut ideea ca Piperina este unul dintre agentii activi care au suprimat declansarea cancerului gastric.
Concluziile cercetatorilor in privinta cancerului gastric tratat cu Piperina:
Primul aspect in cazul utilizarii Piperinei in infectia cu H. pylori si impotriva proliferarii celulelor adenocarcinomului gastric a fost acela ca administrarea acesteia in timpul infectiei cu H. pylori a scazut clivajul de E-cadherina si nivelul de β-catenina, a scazut secretia de interleucina [46-48] si de IL-8 in celulele infectate cu H. pylori.
Tratamentul cu Piperina suprima intrarea Helicobacter pylori in epiteliul gastric si reduce la minimum oncogeneza mediata de β-catenina si secretia de IL-8 in vitro.
Efectul major al Piperinei consta in capacitatea ei considerabila de inhibare a inflamatiei.
Recomandari
Consumul zilnic de Ardei negru reduce sansele de infectie si cancer gastric cauzate de H. pylori.
Aproximativ 600 mg de Piper negru, luate zilnic, pot preveni infectia cu H. pylori și efectul sau carcinogen la nivel gastric.
Va recomandam suplimentul nostru BIOPIPERINE, pentru o eficienta maxima.
BIOPIPERINE (BIOPIPERINA)
- Foarte bun potentator de absorbtie fitonutritieni.
- Initiator termogeneza (arderea grasimilor inutile).
- Mareste considerabil gradul de bioabsorbtie al suplimentelor nutritive, a vitaminelor si alimentelor.
- Imbunatateste metabolismul.
Referinte:
- Parkin DM, Laara E, Muir CS. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988;41:184–197. [Abstract] [Google Scholar]
- Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–3044. [Abstract] [Google Scholar]
- Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;16:1311–1315. [Abstract] [Google Scholar]
- Weyermann M, Rothenbacher D, Brenner H. Acquisition of Helicobacter pyloriinfection in early childhood: independent contributions of infected mothers, fathers, and siblings. Am J Gastroenterol. 2009;104:182–189. [Abstract] [Google Scholar]
- Parsonnet J. Helicobacter pylori: the size of the problem. Gut. 1998;43:S6–S9. [Europe PMC free article] [Abstract] [Google Scholar]
- Graham DY, Lew GM, Klein PD, Evans DG, Evans DJ Jr, Saeed ZA, Malaty HM. Effect of treatment of Helicobacter pyloriinfection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. 1992;116:705–708. [Abstract] [Google Scholar]
- Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK. Helicobacter pyloriinfection and the risk of gastric carcinoma. N Engl J Med. 1999;325:1127–1131. [Abstract] [Google Scholar]
- Polk DB, Peek RM Jr. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010;10:403–414. [Europe PMC free article] [Abstract] [Google Scholar]
- Peek RM Jr, Blaser MJ. Helicobacter pyloriand gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2:28–37. [Abstract] [Google Scholar]
- Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W, Haas R. Translocation of Helicobacter pyloriCagA into gastric epithelial cells by type IV secretion. Science. 2000;287:1497–1500. [Abstract] [Google Scholar]
- Stein M, Rappuoli R, Covacci A. Tyrosine phosphorylation of the Helicobacter pyloriCagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A. 2000;97:1263–68. [Europe PMC free article] [Abstract] [Google Scholar]
- McClain MS, Schraw W, Ricci V, Boquet P, Cover TL. Acid activation of Helicobacter pylorivacuolating cytotoxin (VacA) results in toxin internalization by eukaryotic cells. Mol Microbiol. 2000;37:433–442. [Abstract] [Google Scholar]
- Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, Aburatani H, Akiyama T, Peek RM Jr, Azuma T, Hatakeyama M. Helicobacter pyloriCagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 2007;26:4617–4626. [Abstract] [Google Scholar]
- Semb H, Christofori G. The Tumor-Suppressor Function of E-Cadherin. Am J Hum Genet. 1998;63:1588–1593. [Europe PMC free article] [Abstract] [Google Scholar]
- O’Connor PM, Lapointe TK, Jackson S, Beck PL, Jones NL, Buret AG. Helicobacter pyloriactivates calpain via toll-like receptor 2 to disrupt adherens junctions in human gastric epithelial cells. Infect Immun. 2011;79:3887–3894. [Europe PMC free article] [Abstract] [Google Scholar]
- Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, Imagawa K, Kikuchi M, Mukaida N, Matsushima K. Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun. 1997;65:3218–3224. [Europe PMC free article] [Abstract] [Google Scholar]
- Brandt S, Kwok T, Hartig R, König W, Backert S. NF-κB activation and potentiation of proinflammatory responses by the Helicobacter pyloriCagA protein. Proc Natl Acad Sci U S A. 2005;102:9300–9305. [Europe PMC free article] [Abstract] [Google Scholar]
- Yamaoka Y, Kwon DH, Graham DY. A Mr 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori . Proc Natl Acad Sci U S A. 2000;97:7533–7538. [Europe PMC free article] [Abstract] [Google Scholar]
- Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, Le Bourhis L, Karrar A, Viala J, Mak J, Hutton ML, Davies JK, Crack PJ, Hertzog PJ, Philpott DJ, Girardin SE, Whitchurch CB, Ferrero RL. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol. 2010;12:372–385. [Abstract] [Google Scholar]
- Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O. Cancer Prevention With Natural Compounds. Semin Oncol. 2010;37:258–281. [Abstract] [Google Scholar]
- Kunnumakkara AB, Koca C, Dey S, Gehlot P, Yodkeeree S, Danda D, Sung B, Aggarwal BB. In: Molecular targets and therapeutic uses of spices modern uses for ancient medicine. 1st edition. Aggarwal BB, Kunnumakkara AB, editors. Singapore: World Scientific Publishing Co. Pte. Ltd; 2009. pp. 1–56. [Google Scholar]
- Srinivasan K. Black pepper and its pungent principle-piperine: A review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47:735–748. [Abstract] [Google Scholar]
- Pradeep CR, Kuttan G. Effect of piperine on the inhibition of lung metastasis induced B16F-10 melanoma cells in mice. Clin Exp Metastasis. 2002;19:703–708. [Abstract] [Google Scholar]
- Ouyang DY, Zeng LH, Pan H, Xu LH, Wang Y, Liu KP. Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy. Food Chem Toxicol. 2013;60:424–430. [Abstract] [Google Scholar]
- Tharmalingam N, Kim SH, Park M, Woo HJ, Kim HW, Yang JY, Rhee KJ, Kim JB. Inhibitory effect of piperine on Helicobacter pylorigrowth and adhesion to gastric adenocarcinoma cells. Infect Agent Cancer. 2014;9:43. [Europe PMC free article] [Abstract] [Google Scholar]
- Kim SH, Park M, Woo H, Tharmalingam N, Lee G, Rhee KJ, Eom YB, Han SI, Seo WD, Kim JB. Inhibitory effects of anthocyanins on secretion of Helicobacter pyloriCagA and VacA toxins. Int J Med Sci. 2012;9:838–842. [Europe PMC free article] [Abstract] [Google Scholar]
- O’Connor PM, Lapointe TK, Jackson S, Beck PL, Jones NL, Buret AG. Helicobacter pyloriactivates calpain via toll-like receptor 2 to disrupt adherens junctions in human gastric epithelial cells. Infect Immun. 2011;79:3887–3894. [Europe PMC free article] [Abstract] [Google Scholar]
- Hoy B, Geppert T, Boehm M, Reisen F, Plattner P, Gadermaier G, Sewald N, Ferreira F, Briza P, Schneider G, Backert S, Wessler S. Distinct roles of secreted HtrA proteases from gramnegativepathogens in cleaving the junctional protein and tumor suppressor E-cadherin. J Biol Chem. 2012;287:10115–10120. [Europe PMC free article] [Abstract] [Google Scholar]
- Wang S, Konorev EA, Kotamraju S, Joseph J, Kalivendi S, Kalyanaraman B. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms intermediacy of H2O2-and p53-dependent pathways. J Biol Chem. 2004;279:25535–25543. [Abstract] [Google Scholar]
- Talalay P, Fahey JW. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr. 2001;131:3027S–3033S. [Abstract] [Google Scholar]
- Greenshields AL, Doucette CD, Sutton KM, Madera L, Annan H, Yaffe PB, Knickle AF, Dong Z, Hoskin DW. Piperine inhibits the growth and motility of triple-negative breast cancer cells. Cancer Lett. 2015;357:129–140. [Abstract] [Google Scholar]
- Makhov P, Golovine K, Canter D, Kutikov A, Simhan J, Corlew MM, Uzzo RG, Kolenko VM. Co-administration of piperine and docetaxel results in improved anti-tumor efficacy via inhibition of CYP3A4 activity. Prostate. 2012;72:661–667. [Europe PMC free article] [Abstract] [Google Scholar]
- Francesco VD, Giorgio F, Hassan C, Manes G, Vannella L, Panella C, Ierardi E, Zullo A. Worldwide H. pyloriantibiotic resistance: A systematic review. J Gastrointestin Liver Dis. 2010;19:409–414. [Abstract] [Google Scholar]
- Fu BY, Hong X. Protective action of piperine against gastric ulcer. Acta Pharmocol Sin. 2000;21:357–359. [Abstract] [Google Scholar]
- Ali SM, Khan AA, Ahmed I, Musaddiq M, Ahmed KS, Polasa H, Rao LV, Habibullah CM, Sechi LA, Ahmed N. Antimicrobial activities of eugenol and cinnamaldehyde against the human gastric pathogen Helicobacter pylori. Ann Clin Microbiol Antimicrob. 2005;4:20. [Europe PMC free article] [Abstract] [Google Scholar]
- Burger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek I. Inhibition of Helicobacter pyloriadhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr. 2002;42:279–284. [Abstract] [Google Scholar]
- Stein M, Rappuoli R, Covacci A. Tyrosine phosphorylation of the Helicobacter pyloriCagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A. 2000;97:1263–1268. [Europe PMC free article] [Abstract] [Google Scholar]
- Selbach M, Moese S, Hauck CR, Meyer TF, Backert S. Src is the kinase of the Helicobacter pyloriCagA protein in vitro and in vivo . J Biol Chem. 2002;277:6775–6778. [Abstract] [Google Scholar]
- Galmiche A, Rassow J. Targeting of Helicobacter pyloriVacA to mitochondria. Gut Microbes. 2010;1:392–395. [Europe PMC free article] [Abstract] [Google Scholar]
- Seto K, Hayashi-Kuwabara Y, Yoneta T, Suda H, Tamaki H. Vacuolation induced by cytotoxin from Helicobacter pyloriis mediated by the EGF receptor in HeLa cells. FEBS Lett. 1998;431:347–350. [Abstract] [Google Scholar]
- Li J, Lv C, Sun W, Li Z, Han X, Li Y, Shen Y. Cytosporone B, an inhibitor of the type III secretion system of Salmonella entericaserovar Typhimurium . Antimicrob Agents Chemother. 2013;57:2191–2198. [Europe PMC free article] [Abstract] [Google Scholar]
- Khokhani D, Zhang C, Li Y, Wang Q, Zeng Q, Yamazaki A, Hutchins W, Zhou SS, Chen X, Yang CH. Discovery of plant phenolic compounds that act as type III secretion system inhibitors or inducers of the fire blight pathogen, Erwinia amylovora. Appl Environ Microbiol. 2013;79:5424–5436. [Europe PMC free article] [Abstract] [Google Scholar]
- Moore SA, Jia Y. Structure of the cytoplasmic domain of the flagellar secretion apparatus component FlhA from Helicobacter pylori. J Biol Chem. 2010;285:21060–21069. [Europe PMC free article] [Abstract] [Google Scholar]
- Hoy B, Geppert T, Boehm M, Reisen F, Plattner P, Gadermaier G, Sewald N, Ferreira F, Briza P, Schneider G, Backert S, Wessler S. Distinct roles of secreted HtrA proteases from gramnegative pathogens in cleaving the junctional protein and tumor suppressor E-cadherin. J Biol Chem. 2012;287:10115–10120. [Europe PMC free article] [Abstract] [Google Scholar]
- Beswick EJ, Das S, Pinchuk IV, Adegboyega P, Suarez G, Yamaoka Y, Reyes VE. Helicobacter pylori-induced IL-8 production by gastric epithelial cells up-regulates CD74 expression. J Immunol. 2005;175:171–176. [Abstract] [Google Scholar]
- Xia Y, Pham NK, Yoon HY, Lian S, Joo YE, Chay KO, Kim KK, Jun YD. Piperine inhibits IL-1binduced IL-6 expression by suppressing p38 MAPK and STAT3 activation gastric cancer cells. Mol Cell Biochem. 2015;398:147–155. [Abstract] [Google Scholar]
- Doucette CD, Greenshields AL, Liwski RS, Hoskin DW. Piperine blocks interleukin-2-driven cell cycle progression in CTLL-2 T lymphocytes by inhibiting multiple signal transduction pathways. Toxicol Lett. 2015;234:1–12. [Abstract] [Google Scholar]
- Bang JS, Oh da H, Choi HM, Sur BJ, Lim SJ, Kim JY, Yang HI, Yoo MC, Hahm DH, Kim KS. Antiinflammatory and antiarthritic effects of piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res Ther. 2009;11:R49. [Europe PMC free article] [Abstract] [Google Scholar]
- Petry A, Djordjevic T, Weitnauer M, Kietzmann T, Hess J, Görlach A. NOX2 and NOX4 mediate proliferative response in endothelial cells. Antioxid Redox Signal. 2006;8:1473–1484. [Abstract] [Google Scholar]
- Srinivasan K. Black pepper and its pungent principle-piperine: A review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47:735–748. [Abstract] [Google Scholar]
- Ouyang DY, Zeng LH, Pan H, Xu LH, Wang Y, Liu KP. Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy. Food Chem Toxicol. 2013;60:424–430. [Abstract] [Google Scholar]
- Khan IA, Mirza ZM, Kumar A, Verma V, Qazi GN. Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus. J Antimicrob Agents Chemother. 2006;50:810–812. [Europe PMC free article] [Abstract] [Google Scholar]
- Kumar A, Khan IA, Koul S, Koul JL, Taneja SC, Ali I, Ali F, Sharma S, Mirza ZM, Kumar M, Sangwan PL, Gupta P, Thota N, Qazi GN. Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J Antimicrob Chemother. 2008;61:1270–1276. [Abstract] [Google Scholar]
- Sharma S, Kumar M, Sharma S, Nargotra A, Koul S, Khan IA. Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. J Antimicrob Chemother. 2010;65:1694–1601. [Abstract] [Google Scholar]
- Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002;302:645–650. [Abstract] [Google Scholar]
- Boonjakuakul JK, Canfield DR, Solnick JV. Comparison of Helicobacter pylorivirulence gene expression in vitro and in the Rhesus Macaque. Infect Immun. 2005;73:4895–4904. [Europe PMC free article] [Abstract] [Google Scholar]
- Nilsen EM, Johansen FE, Jahnsen FL, Lundin KEA, Scholz T, Brandtzaeg P, Haraldsen G. Cytokine profiles of cultured microvascular endothelial cells from the human intestine. Gut. 1998;42:635–642. [Europe PMC free article] [Abstract] [Google Scholar]
- Tharmalingam N1, Park M2, Lee MH2, Woo HJ2, Kim HW2, Yang JY2, Rhee KJ2, Kim JB2
- American Journal of Translational Research, 15 februarie 2016, 8 (2): 885-898
- PMID: 27158376 PMCID: PMC4846933 http://europepmc.org/article/med/27158376
- Derosa G., Maffioli P., Sahebkar A. (2016) Piperine and Its Role in Chronic Diseases. In: Gupta S., Prasad S., Aggarwal B. (eds) Anti-inflammatory Nutraceuticals and Chronic Diseases. Advances in Experimental Medicine and Biology, vol 928, p. 173. Springer, Cham. https://doi.org/10.1007/978-3-319-41334-1_8