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Kako sprijačiti 5-LOX enzim da uništava naše zdravlje?

eggs_and_steak

Možda će vas iznenaditi da je sedam od deset najčešćih uzroka smrti (bolesti srca, karcinom, kronične boesti plauća, Alzhaimerova bolest, upala pluća i gripa) povezano sa enzimom koji nastaje u našem tijelu.1 Riječ je o enzimu  5-lipoksigenazi  ili skraćeno 5-LOX (eng. 5-lipoxygenase) koji kada se stvori  u tijelu u prevelikoj količini pokreće cijelu kaskadu opasnih upalnih reakcija.

Ironično, upravo je ova sistematska  upalna reakcija uzrokovana 5-lipoksigenazom čuvala naše pretke od infektivnih bolesti.  S obzirom da se ove bolesti sve više iskorjenjuju, protupalna reakcija 5-lipoksigenaze ne samo da nije više nužna, nego je čak i smrtonosna.2-5 Znanstvenicima je ovaj enzim već otprije poznat  zbog njegove uloge u nastanku artritisa, pa farmaceutska industrija pokušava razviti siguran lijek koji bi ublažio učinak 5-lipoksigenaze, međutim trenutno  dostupni  „5-LOX inhibitori“ ne pokazuju ništa veću sigurnost nego ostali dostupni protuupalni lijekovi.6-7

Kako višak  5-lipoksigenaze u tijelu uništava zdravlje?

Zbog loše prehane, u našem tijelu stvara se previše arahidonske kiseline. Da bi neutraliziralo arahidonsku kiselinu, naše tijelo pojačano proizvodi  5-lipoksigenazu (5-LOX). Povišene vrijednosti 5-LOX enzima te krajnji produkti razgradnje arahidonske kiseline usko su povezani s bolestima srednje i starije životne dobi.
U dolje prikazanom šematskom prikazu jasno je prikazano kako hrana tipična za zapadnjačku prehranu  uzrokuje stvaranje viška arahidonske kiseline te štetne posljedice povišenih vrijednosti enzima  5-lipoksigenaze.

arahidonska_kiselina

Shema prikazuje kako tijelo metabolizira „zapadnjačku“ prehranu  putem enzima 5-lipoksigenaza

5-lipoksigenaza potiče proizvodnju proupalnih molekula u tijelu koje se zovu leukotrieni.8 Stotine objavljenih zanstvenih studija povezuju leukotriene s pojavom kardiovaskularnih oboljenja9, karcinoma10-16, artritisa17-19,   te bolestima dišnog sustava kao što su astma i kronična opstruktivna plućna bolest (KOPB)8.  Ove molekule povezuju se i s Alzheimerovom bolešču20-25, inflamatornim bolestima debelog crijeva26-28 i osteoporozom.29,30
Prihvaćanjem zdravijih prehrambenih obrazaca smanjuje se razina 5-lipoksigenaze, iako tipična  zapadnjačka  prehrana i optimalna supresija 5-LOX i njenog štetnog djelovanja može biti izazov. Srećom, ekstrakt tamjana pokazao se djelotvoran kod inhibicije ovog enzima.

Klinička potvrda tradicionalnih biljnih lijekova

Tisućljećima su stare kulture priznavale smole tamjana i smirne  kao ugodan miris, ali također i kao lijek u liječenju reumatizma, groznice  i gastrointestinalnih poremećaja.
Moderna istraživanja su prvi put potvrdila medicinsku vrijednost tamjana otkrićem bosvelijskih kiselina koje se nalaze u tamjanu. 3-acetil-11-keto-betabosvelijska kiselina  (AKBA) se pokazala najučinkovitijom u inhibiciji 5-lipoksigenaze i spriječavanju nastanka proupalnih leukotriena.39,40Pokusi na životinjama potvrdili su da ekstrakti tamjana imaju snažan protuupalni učinak posebice kod ublažavanja upale zglobova kod artritisa.41

Početna istraživanja na ljudima pokazala su sličan uvjerljiv rezultat potvrđujući tradicionalnu uporabu tamjana. Ekstrakti tamjana pokazali su se učinkoviti kod pacijenata koji su patili od reumatoidnog artritisa, Crohn-ove bolesti, ulcerativnog kolitisa i astme.39,42 Kroz tisućljeća upotrebe tamjana nisu priemijećene neke značajnije nuspojave. Novija toksikološka i sigurnosna istraživanja potvrdila su da ekstrakti tamjana imaju širok sigurnosni  spektar kako u vanjskoj tako i u  unutarnjoj primjeni.43

Renarthro - sinergijska formulacija ekstrakta tamjana

Hrvatska tvrtka Farmavita razvila je proizvod Renarthro (www.renarthro.com) koji sadrži ekstrakt tamjana, ekstrakt smirne i Osteol. U labororijskim ispitvanjima pronađeno je da ekstrakt smirne spriječava djelovanje enzima (hijaluronidaze, kolagenaze)  koji razgrađuju hrskavicu. Također je potvrđeno je da dodatak ekstrakta smirne pojačava djelovanje ostalih biljaka za 20-tak puta. U drugim laboratorijskim ispitivanjima potvrđeno je da jedan protein iz mlijeka (Osteol) također višestruko poboljašava djelovanje ostalih sastojaka.  Inovacija koju je tvrtka Farmavita patentno zaštitila je činjenica da kombinacija ova tri sastojaka tvori jedinstvenu  sinergiju koja je višestruko efikasnija od pojedinačnih komponenti. 

Zaštita srca i krvnih žila

Uloga upalnih procesa u tijelu kod pojave ateroskleroze (otvrdnuće i zakrčenje krvih žila) poznata je dulje  od 20 godina. Godine 1991. je otkriveno da jedan od čimbenika ateroskleroze je molekula koja je završni produkt porcesa koji započinje s djelovanjem enzima 5-lipoksigenaze.50,51 Tako se više od deset godina pokušavaju izolirati 5-LOX inhibitori koji bi spriječili ili čak preokrenuli pojavu starenja kardiovaskularnog sustava.52 Ekstrakti tamjana pokazali su se kao jedan od najboljih  prirodnih inhibitora 5-LOX enzima, kod pojave ateroskleroze.53
U vaskularnom tkivu, ekstrakti tamjana imaju višestruki učinak koji se nadopunjuju. Imaju snažan učinak na vezanje slobodnih radikala.54 Također, smanjuju ukupni kolesterol do 48% te povisuju „dobar kolesterol“ (kolesterol visoke gustoće- HDL) do 30 %.55 No, kardiolozima je upravo učinak ekstrakta tamjana na inhibiciju 5-lipoksigenaze i ostalih upalnih čimbenika najinteresantniji. U ljudskom kapilarnom endotelu, ekstrakti tamjana značajno utječu na spriječavanje stvaranja oštećenja stijenki povezanih sa aterosklerozom43,56. Pretpostavlja se da tamjan pozitivno modulira 113 gena koji su uključeni u stvaranju upale krvnih žila.56,57

Ekstrakti bogati s AKBA kiselinom, glavnim bioaktivnim agentom u tamjanu, pokazali su 50%-tno smanjenje oštećenja nastalih aterosklerozom.58 Također, značajno se smanjila aktivnost nekoliko različitih faktora koagulacije (zgrušavanja) u krvi. Slično djelovanje pripisuje se i gugulsteronima koji se nalaze u ekstraktu smirne.54

Neurozaštita i zdravlje mozga

Sastojak iz smole tamjanovog drveta pokazao se kao potencijalni stimulator sistema receptora u mozgu koji se zove TRPV3, a koji je odgovoran za regulaciju tjeskobe te djeluje slično kao antidepresivi.59
Jedna od glavnih komponenti jedne vrste tamjana Boswellia carterri, koji se zove acetat incensola, inhibira posrednike upale u moždanom tkivu, što je učinak koji koji pruža značajnu nadu u liječenju oštećenja moždanog tkiva.60 Opasne inflamatorne reakcije mozga mogu prouzročiti oštećenje moždanog tkiva unutar par sati, uzrokujući dugotrajne neurološke deficite.
Acetat incensola posebice inhibira degeneraciju moždanih stanica u hipokampusu, regiji mozga odgovornoj za memoriju.60 Istraživanja na životinjama potvrđuju ovaj učinak. Laboratorijski štakori kojima je davana supstanca za okrnjavanje memorije, zajedno sa ekstraktom tamjana, pokazali su puno bolje rezultate na testovima prostorne orijentacije i učenja nego životinje koje nisu uzimale ekstrakt tamjana.61 Slični rezultati dobiveni su i s životinjama kojima nije davana supstanca za uništavanje memorije. Ekstrakti dobiveni od Boswellia papyrifera, jedne od 5 vrsti tamjanovog drveta koje se koriste u proizvodnji mirisne smole tamjana, u testiranjima na štakorima pokazali su da je životinjama poboljšana prostorna orijentacija i da  brže pronađu put kroz labirint.62

Zaštita od karcinoma

Bosvelijska kiselina, jedna od glavnih komponenti tamjana, djeluje kroz nekoliko mehanizama koji spriječavaju proliferaciju (širenje) stanica karcinoma. AKBA inducira apoptozu ili programiranu smrt stanice tako što utječe na tzv. „receptor smrti“ na površini stanice koji uzrokuje  „samoubojstvo“ stanice karcinoma.63
Bosvelijska kiselina također blokira međustaničnu komunikaciju stanica karcinoma koja je zaslužna za replikaciju stanica.64 I AKBA dodatno koči rast tumora tako da inhibira faktor rasta VEGF (eng. vascular endothelial growth factor) kojeg stanice karcinoma trebaju za razvoj njima potrebnih novih krvnih žila.65
Naposlijetku, AKBA se nedavno pokazala efikasnom kod inhibicije staničnog receptora CXCR4 kojeg stanice karcinoma koriste da bi potaknule metastaze, a koje se smatraju uzrokom smrti kod karcinoma u 90% slučajeva. Do danas, ekstrakti tamjana su pokazali i obećavajuće rezultate kod smanjivanja rasta malignih stanica, replikacije ili metastaza kod karcinoma prostate, mokraćnog mjehura, cerviksa materinice, crijeva kao i kod multiplog mijeloma, raka koštane srži.66-73

Ekstrakti tamjana ublažavaju bol kod artritisa

Ranije studije s ekstraktima tamjana uključivale su i sastojke koji  su poznati po svojim  prouupalnim svojstvima poput biljke ašvagandha (Withania somnifera), kurkume (Curcuma longa) i cinka. U jednoj takvoj studiji, 42 pacijenta primala su kombinaciju ovih nutrijenata ili placebo kroz tri mjeseca.83 Grupa koja je primala ovu kombinaciju, za razliku od placebo grupe, osjetila je značajno olakšanje boli i veći stupnj pokretnosti zglobova.
Slična studija koja je koristila široko primjenjivan WOMAC osteoartritis indeks pokazala je značajnu redukciju ovog parametra kao i smanjenje boli i stupnja nepokretljivosti.84 Ni u jednoj studiji nisu zabilježene značajnije nus pojave.

Novija istraživanja provedena su isključivo s ekstraktima tamjana u dvostruko slijepoj, placebo-kontroliranoj studiji s dozom i do 3 600 mg dnevno. Opet, evidentirano je značajano poboljšanje  u svim parametrima, uključujući bolove u zglobovima,  oticanje zglobova, sposobnost pokretljivosti zglobova i povećanje kilometraže prilikom šetanja.85
Studija iz 2008. g. s ekstraktom tamjana koji sadržavao 30% AKBA kiseline provedena je na 70 pacijenata s osteoartritisom.86 Bolesnici su primali ekstrakt doze od 100 mg/dan, 250 mg/dan, ili placebo u razdoblju od 90 dana. Obje grupe koje su primale ekstrakt, ali ne i placebo grupa, pokazale su klinički i statistički značajno poboljšanje u indeksu boli i fizičkoj funkciji.86 Još neke značajke ove studije vrijedne su spominjanja. Prvo, uzorci zglobne tekućine pokazali su na značajan pad enzima MMP-3 (matriks metaloproteinaza-3), koji je zaslužan za upalne procese i propadanje hrskavice u osteoartritisu. Drugo, olakšanje boli i povećanje pokretljivosti bili su evidentni već nakon 7 dana od 90 dana studije.  Studija provedena je 2010. g. sa ekstraktima tamjana pokazala je sličan učinak.43

Na koji način se još može ublažiti učinak 5-LOX enzima

Tipična zapadnjačka prehrana obiluje omega-6 masnim kiselinama, zasičenim masnim kiselinama, rafiniranim ugljikohidratima i arahidonskom kiselinom. Prevelika konzumacija ove hrane i nedovoljan unos hrane bogate omega-3 masnim kiselinama značajno doprinosi razvoju sistemskih kroničnih upalnih oboljenja.
Ljudi koji se brinu o svom zdravlju koriste nutrijente kao što je riblje ulje ili kurkuma koji smanjuju aktivnost 5-lipoksigenaze u tijelu.109-111  Njihov utjecaj na supresiju 5-LOX enzima djelomično objašnjava i pregršt pogodnosti koji ovi nutrijenti pružaju.
Međutim, kako ljudi stare preveliko stvaranje 5-LOX enzima zahtjeva efikasnije metode za njegovu supresiju. Biljni preparati s ektraktom tamjana su uz prihvaćanje zdravijih prehrambenih navika, učinkovit prirodni način selektivne inhibicije 5-LOX enzima.112,113

Zaključak

Višak 5-lipoksigenaze uzrokuje stvaranje pro-inflamatornih molekula, uključujući leukotrijene. Upalni procesi u organizmu, koje pokreće enzim 5-lipoksigenaza,  povezani su sa sedam od deset vodećih uzoraka smrti u SAD-u, uključujući karcinom i bolesti srca.
Za sada postoji neznatan broj sigurnih lijekova koji inhibiraju 5-LOX, no nedavno je otkriven prirodni 5-LOX inhibitor koji efikasno inhibira aktivnost ovog enzima. Obilje uvjerljivih podataka ukazuju da bioaktivne komponente tamjana blokiraju upalne reakcije nastale enzimom 5-LOX koji ubrzava pojavu brojnih smrtonosnih bolesti uzrokovanih starenjem.


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