Update di

gastroenterologia in

relazione all'integrazione

nutraceutica naturale

PROF. BENIAMINO PALMIERI

NETWORK DEL SECONDO

PARERE

MODENA

«SYNOVIOLOGY»

Email: palmieri@unimo.it

Tel. 059 4222483335 332900

Prof. Beniamino PalmieriDipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con Interesse Trapiantologico,

Oncologico e di Medicina Rigenerativa - Università degli Studi di Modena e Reggio Emilia, Modena Network del

Secondo Parere, Modena

I Lignani

I Fitoestrogeni

Sono dei principi attivi allo stato naturale in un certo numero di piante.

Appartengono alla famiglia dei polifenoli

Si trovano soprattutto negli alimenti: frutta legumi, radici, spezie, piante non alimentari.

Le piante che hanno un’attività estrogenica sono:

La soja (semi), la luserna ( foglie), il luppolo ( coni) , il trifoglio rosso( foglie) ,

la liquirizia ( radice), il lino ( semi) , Il finocchio ( frutto) , il kudzu ( foglie e radice)

Altre piante sono considerate Estrogeniche : la salvia officinale, l’angelica cinese, il ginseng, la cimicifuga, loYam.

Appartengono alle classi degli isoflavonoidi, dei cumestani,dei flavonoidi, degli stilibeni dei lignani o enterolignali, e l’insieme di queste sostanze fa parte del vasto assieme dei polifenoli.

Varie categorie di sostanze che hanno un potere estrogenico possono essere assorbite tramite l’alimentazione. Li si classifica nel vocabolo –Estrogeni alimentari- I prodotti naturali (steroidi ovarici, Phytoestrogeni e Micoestrogeni), nonchè i contaminanti di sintesi (Farmaci e xenoestrogeni, DDt,PCB etc…)

I FITOESTROGENI

La loro costituzione chimica è simile a quella degli ormoni steroidei (estradiolo, estrione ed estriolo) secreti dalle ovaie ma in via accessoria anche dalle ghiandole surrenali e dai testicoli.

I Fitoestrogeni

I fito estrogeni producono degli effetti anti-estrogenici come antagonisti dell’estradiolo a livello dei ricettori, senza produrre una risposta estrogenica

completa dopo essersi legati al nucleo.

D’altra parte a seconda dei tessuti o delle cellule considerate, i fitoestrogeni

possono svolgere un’attività indipendentemente dai ricettori ad estrogeni

Questi ricettori sono presenti nel sistema nervoso centrale,gastro-intestinale,urogenitale,nel tessuto osseo,nel fegato e nelle ghiandole mammarie

I fitoestrogeni

4 categorie principali

Gli isoflavoni

I cumestani

Gli stilbeni

I lignani

I fitoestrogeniGli isoflavoni ( daidzeina et genisteina)

La daidzeina ha una struttura molto vicina agli estrogeni

La genisteina viene anch’essa metabolizzata ed il suo derivato ha un effetto inibitore della protein-kinasi

I fitoestrogeni

I cumestani appaiono spesso nelle piante dopo un’aggressione batterica o micotica, si legano ai ricettori degli estrogeni ed hanno un attività uterotropica

I lignani si transformano grazie ai batteri intestinali in enterolignani poi in enterodioli ed enterolattoni che sono dei phytoestrogeni.

Gli stilbeni di cui il più importante è il transresveratrolo (buccia dell’uva e vino) può avere un effetto agonista o antagonista degli estrogeni

Effetti estrogenici e piante

Piante Effetti

Finocchio Agonista

Luppolo Agonista

Kudzu Agonista

Lino Agonista

Luserna ou Alfalfa Agonista

Liquirizia Agonista

Soja Agonista

Trifoglio rosso Agonista

Molecole estrogeniche et loro fonti

IsoflavonoidiGenisteina - dadzeina - biochanina AFormononetine – glyciteine

7 O-glucoside et 7 O-glucoside acile di genisteina -daidzeina - biochanina A formononetina – gliciteina8C-glucoside daidzeina = puerarina

Soja E DerivatiFagioli - Piselli- Ceci - Lenticchie - Arachidi - Orzo - Segale -NociTrifoglio Rosso - Kudzu - Luppolo

Thé - IrisAstragalo

Isoflavonati et isoflavoni Liquirizia

Flavanoni Luppolo

Calconi Liquirizia Luppolo

cumestani AlfalfaGermogli Di SojaTrifoglio

Spinaci

Molecole estrogeniche et loro fonti

LignaniMatairesinolo

Secoisolariciresinolo

Pinoresinolo

Synrigaresinolo

Arctigenina

Sesamina

Semi di Lino, Girasole,segale,Sesamo,Cereali integrali,ZuccaFrutta: Ciliege, Mele,Père,Bacche (Mirtillo palustre, Lamponi) Verdura ( Carote , Finocchio , Cipolla, Aglio, Sedano)Thé e CaffèBetulla,Pino

Estroni Nocciuolo dei datteriSemi del melograno

Stilbeni Rabarbaro Polygonum Sp.

Biodisponibilità dei fitoestrogeni In molti casi, le molecole presenti nella pianta sono legate a dei glucidi sotto forma di glicosidi o sotto

forma di precursori (matairesinolo, secoisolariciresinolo, lariciresinolo per i lignani, Daidzeina per l’equolo). Acquisiscono la loro attività estrogenica in seguito ad una trasformazione metabolica che avviene grazie alla flora batterica intestinale, o grazie agli enzimi enterocitari.

Il metabolismo ottenuto grazie alla flora intestinale può generare metaboliti inattivi e dei metaboliti attivi. L’assorbimento intestinale può avvenire solo se sono passati dalla forma di glucosidi alla loro forma agliconica grazie all’intermediazione di enzimi specifici (betaglucosidasi)

Se i batteri sembra che svolgano un ruolo importante, molti pareri concordano nell’affermare oggi il ruolo preponderante degli enzimi enterocitari (notoriamente la β glucosidasi).

La facoltà delle molecole di passare la barriera intestinale dipende in gran parte dalle attività enzimatiche intestinali, dalla solubilità dei composti (specialmente nei lipidi della membrana delle cellule epiteliali), dalle iterazioni che avvengono con altri componenti del bolo alimentare, e dalla velocità del transito nell’apparato digerente.

La maggior parte di questi parametri sono soggetti ad una certa variabilità.(polimorfismo genetico tipico di ogni individuo, ogni razza o specie, ma anche ad un adattamento a lungo termine ad un certo regime alimentare (I vegetariani sembrerebbe che riescano a metabolizzarli meglio)

Biodisponibilità dei fitoestrogeni

Il fegato può influenzare in modo importante il tasso circolante, grazie all’attività enzimatica che svolge.

L’attività metabolica è, anche qui, influenzata dal polimorfismo genetico delle specie delle razze e degli individui.

Di fatto nella maggior parte dei casi , dei xenobiotici polifenolici sono presi in carico dagli stessi sistemi di detossinazione così come quelli che prendono in carico i fitoestrogeni.

Per concludere, la penetrazione nella cellula è legata alle funzioni ossidative ed ai meccanismi di trasporto delle sostanze extracellulari verso il contenuto intracellulare.

I LIGNANI

Esistono centinaia di lignani nei vegetali. Affinché questi fitoestrogeni si attivino nell’organismo devono dapprima essere metabolizzati dai batteri intestinali.

L’enterolattone e l’enterodiolo dei lignani, derivano da una fermentazione microbica d’origine alimentare del secoisolariciresinolo e del matairesinolo, e vengono escreti per via urinaria.

Si trasformano, grazie ai batteri intestinali, in enterolignani poi in enterodiolo e poi in enterolattone che altro non è che un fitoestrogeno: hanno un’azione agonista degli estrogeni.

Lignani

1) Antiestrogeni per competizione con i ricettori ad estrogeni e di conseguenza inibiscono la crescita e la proliferazione delle cellule ormono-dipendenti

2) Inibizione del legame degli estrogeni alla proteina deputata a trasportarli ( SHBG sex hormone binding globuline)

Lignani

3) La SHBG accompagna i lignani e li orienta verso le cellule –target che possono inibire la produzione di estrogeni

Gli ormoni colpiscono tutte le cellule, ma riescono ad agire solo su alcune : le cellule target dell’ormone che hanno dei ricettori sui quali possono fissarsi.

Lignani

4) Inibiscono l’aromatasi che ha il compito di convertire l’estrone in estradiolo ed il testosterone in estriolo.

Lignani

5) Attività antiossidante (scavenger radicali liberi)

Lignani

6) inibizione della 5 alfa riduttasi

All’interno della cellula bersaglio, il testosterone si trasforma in Diidrotestosterone sotto l’azione della

5-alfa-riduttasi

Il DHT si fissa su dei ricettori specifici a livello della membrana del nocciuolo e innesca delle azioni androgeniche (moltiplicazione cellulare e sintesi di proteine)

Lignani

7) Inibizione della 17-ketoriduttasi , enzima responsabile della conversione del testosterone in androstenedione, essendo quest’ultimo precursore dell’estriolo è

implicato nei tumori alle ovaie.

Lignani

8) Inibizione del legame degli estrogeni con l’alfa-fetoproteina, caratteristica nello sviluppo dei tumori.

L'alfa-fetoproteina ou alfa-1-fetoproteina (AFP) è una proteina normalmente prodotta dal feto durante il periodo della gestazione. Se la si trova negli adulti serve come marker di un tumore. Se troviamo dei tassi elevati di AFP nel liquido amniotico, indica un problema nello sviluppo del feto.

Un marker tumorale è una sostanza che possiamo dosare nel sangue, e che corrisponde alla presenza o allo sviluppo di un tumore maligno. Questi Marker possono essere anche elevati a causa di altre patologie.

Lignani9) Diminuzione dell’angiogenesi

Formazione di nuovi vasi partendo da vasi preesistenti.

10) Diminuzione dell’esposizione

ad estrogeni con allungamento della fase luteale del ciclo mestruale.

Lignani 11) inibizione della proteinkinasi

Enzima che interviene nella regolazione della proliferazione cellulare

Enzima che interviene nel processo di fosforilazione e defosforilazione. L’attività delle proteine dipende spesso dal loro stato di attività (proteina fosforilata) o inattività (proteina de-fosforilata).

L’attivazione della proteinkinasi (PK) può indurre la fosforilazione di una proteina e regolarne la funzione.

Lignani

12) Effetti dei lignani del lino sulle vampate di calore : - 41% Uno studio recente realizzato all’università Laval nel Quebec ha comparato una

supplementazione di 40 gr.di semi di lino/giorno (che rappresenta un apporto di 21 mg di lignani/die) al trattamento ormonale sostitutivo (estrogeni+ progesterone) nelle donne in menopausa.

L’effetto sulla sintomatologia è stato valutato tramite l’indice composto di Kupperman che quantifica le 11 manifestazioni sintomatiche più frequenti della menopausa.

L’indice di Kuppermann è migliorato nei due gruppi, rispettivamente : -32% con il Trattamento ormonale sostitutivo e -24% con i lignani, i risultati dal punto di vista statistico, non sono significativamente differenti.

Effetti dei lignani sulle manifestazioni della menopausa (indice composto di Kupperman): miglioramento paragonabile a quello ottenuto con il trattamento ormonale sostitutivo.

I lignani sembrano quindi essere dei fitoestrogeni efficaci sui problemi vascolari, particolarmente sicuri e presentano una efficacia metabolica molto favorevole nella donna in menopausa.

Plant-derived lignans caused cell loss by apoptosis in colorectal adenoma and carcinoma cells.

Nordihydroguaiaretic acid (NDGA), commonly used for the inhibition of lipoxygenase isoenzymes, showed

the strongest growth inhibition with an IC 50 of 1.9±0.5 lg followed by epiashantin (IC 50 =9.8±4.5 lM)

and arctigenin (IC 50 =16.5±8.5 lM).

The lignans caused a time- and dose-dependent loss of mitochondrial membrane potential

(MMP), down regulation of the anti-apoptotic protein bcl xl and an increase of the apoptotic

index. The time interval until loss of MMP and down modulation of bcl xl became evident

correlated with the efficiency of growth inhibition by NDGA, epiashantin and yangambin. Bcl

2 and caspase 3 were not involved. NDGA also induced a shift of the culture population to

the G 2 /M phase of the cell cycle.

With respect to these results, naturally occurring lignans could be useful in the therapy and chemoprevention

of colorectal tumors.

Semi di lino

Il lino (Linum usitatissimum= lino comune)

Descrizione e famiglia

Il lino, Linum sp., famiglia delle Linaceae, è una pianta erbacea annuale delle regioni temperate, ha una crescita rapida, con fiori blu; un campo di lino in fiore offre uno spettacolo magnifico. Si raccoglie quattro mesi dopo la seminagione.

Etimologia: Il nome del genere deriva dal latino "linon" = "filo" così chiamato per l'antichissimo uso fatto dall'uomo per estrarne fibra (nelle tombe dei faraoni d'Egitto sono state ritrovate alcune mummie fasciate di tela di lino e risalenti a circa 8000 a.c.). Fu ripreso da Linneo per indicarne il genere.

L'epiteto della specie indica che la pianta è di uso molto comune.

Il lino (Linum usitatissimum= lino comune) Origine

Il lino è originario del medio oriente (Egitto, Persia) e si è adattato in numerose regioni. Le comunità neolitiche del levante lo coltivavano già settemilacinquecento anni prima di Cristo, per uso sia tessile sia alimentare.

Plinio il Vecchio ha consacrato un volume della sua Storia Naturale a questa pianta che fornisce dei fili di una « bianchezza e finezza rimarchevole…...". Le vele della flotta di Alessandro Magno sono fatte con questo tessuto.

Agli inizi del 20mo secolo, il lino attraversa l’atlantico e si specializza. In Argentina ed in Canada, diventa « oleaginoso », la selezione si orienta verso la produzione di semi piuttosto che di fili. I fiori blu che colorano la Pampa argentina e le grandi pianure del Canada Ovest produrranno tanti semi che alimenteranno le industrie dei coloranti, degli inchiostri, o del « Lin oleum ». Il fusto si accorcia ed il rendimento dei semi aumenta, il tenore in omega 3 diminuisce.

Il lino (Linum usitatissimum)

Negli anni 70, i produttori di lino canadesi si preoccupano in quanto il lino sembra essere sempre più difettoso:

Contiene acidi grassi « bizzarri », gli Omega 3 che nuocciono all’assimilazione degli A.G. buoni : gli Omega 6.

Contiene delle molecole « strane », dei lignani con proprietà estroginiche verificate.

Contiene fibre « bizzarre », le mucillagini con proprietà lassative ben conosciute.

Contiene dei Glucosidi cianogeni.

L’olio quando viene estratto dal seme si ossida troppo velocemente (va bene per i dipinti ma non in nutrizione).

I ricercatori delle università canadesi si mettono al lavoro per trovare delle spiegazioni ed esplorare le proprietà dei Lignani e includerli nella lista dei fitoestrogeni. Parallelamente il modo d’azione delle mucillagini viene decodificato e viene descritta la composizione dei cianogeni.

Gli Omega 3 sono prima di tutto Canadesi, prima sicuramente che gli studiosi di tutto il mondo inizino a fare ricerche sull’efficacia degli stessi.

Il lino (Linum usitatissimum)

Anni 90: le varietà dette low-linolenic , povere in Omega 3 sembra trovino un mercato nella produzione di margarine.

Alla fine del 20mo secolo, il lino oleaginoso viene principalmente prodotto in Canada ed i semi arrivano fino in Belgio ove vengono triturati.

Il XX secolo ha quindi permesso una selezione delle varietà, tessile con gambo lungo o lino oleaginoso ricco di semi con un tenore di olio elevato sul peso dei semi (dal 25 al 50%), e con una concentrazione elevata di omega 3 che arriva fino al 70% in certe specie (lino tipo oro).

Linum usitatissinum : semiFamiglia: Linacee

Nomi

Lein ( tedesco)

Flax ( inglese)

Caratteristiche

Semi ovoidali piatti, appuntiti ad una estremità, colore bruno o oro a seconda della varietà.

Brillanti e lisci

Debole odore caratteristico che si accentua quando si spaccano

Sapore simile a quello delle noci, leggermente zuccherato

Componenti

Mucillagini+++

pectina,

AGE (ω 3)

Sali minerali Glicosidi cianogenici

Eccezionale contenuto in Lignani nella specie di tipo oro.

Proprietà

Lassativo, emolliente

Rigenera la flora intestinale regolando il processo di putrefazione e fermentazione.

Azione anti-infiammatoria ed emolliente che favorisce la rigenerazione delle mucose digestive danneggiate

Azione calmante l’infiammazione delle vie respiratorie ed urinarie: bronchiti e cistiti, grazie alla sua azione specifica sulle mucose.

Da consigliare anche ai diabetici per il basso tenore in glucidi e l’alto tenore sia in proteine che in Acidi grassi essenziali.

Azione antispastica, sedativa, antinfiammatoria

Piante alimentari Seccoisolariciresinolo µg /100g materia secca

Semi di lino 369900

Semi di girasole 610

Noci 257

Nocciole 163

More 3718

Lamponi 3040

Ciliege 1500

Ribes nigrum 368

Thé verde ( Cina) 2890

Thé nero 2420

Caffé arabica 716

Semi di lino

Fibre alimentari nei lignaniUn cucchiaio di semi di lino Linusan contiene fibre alimentari pari a:

• Mezza tazza di crusca d’avena cotta;

• 1 fetta di pane di farina integrale;• 1/3 di tazza di broccoli sminuzzati e cotti;• 1/3 di tazza d’orzo perlato cotto;

• 1/2 tazza di riso integrale;

Semi di lino

Requisiti indispensabili per il consumo dei semi di lino:

• Controllo sulla presenza di aflatossine (frequenti nei semi di lino);

• Controllo sulla filiera di produzione;

• Conservazione in ambiente sotto gas inerte (l’ossigeno ossida gli Omega 3 qualora il seme sia stato “spaccato”; es. Linusan);

• Conservazione al riparo della luce (l’olio di lino si ossida molto velocemente come Omega 3);

Il seme di lino va consumato non triturato con un frullatore (il caldo

generato rovina l’omega 3) e al limite potrebbe essere messo in

ammollo la sera prima per poi ingurgitare la “pappina” con le sue

mucillagini al mattino: questo ha una scarsa compliance da parte del

paziente.

ES. Il Linusan non necessita di triturazione ne di essere messo in

ammollo in quanto è stato “incrinato” e basta ingerirlo con un

grande bicchiere di acqua o sulle insalate per far si che il tegumento

acido-resistente già incrinato rilasci il contenuto del seme già a livello

gastrico.

Semi di lino

Modalità di consumo dei semi di lino:

As a traditional medicine, flaxseed has been used to treat constipation for centuries, but the controlled

trials are rare. The purpose of the present study was to assess that whether partially defatted

flaxseed meal (PDFM) has the potential role to facilitate fecal output in normal and experimental

constipated mice.

METHODS: After supplemented with 2.5%, 5% and 10% (w/w) PDFM (L-, M- and H-PDFM) for 14

days, the constipation models of mice were induced by atropine-diphenoxylate. The small intestinal

transit rates, start time of defecation, amount of defecation and wet weight of feces were researched

in normal and constipation model mice.

RESULTS: M- and H-PDFM significantly increase small intestinal transit rates in constipation model

mice. All dose of PDFM markedly shortened the start time of defecation and M- and H-PDFM

significantly increase stool frequency and weight in both normal and constipation model mice.

CONCLUSIONS: PDFM may be a useful laxative to facilitate fecal output in normal and

constipation conditions.

The aim of this study was to determine the immune response after preventive administration of flax-seed oil or probiotic strain Lactobacillus plantarum -Biocenol™ LP96 or their combination in the jejunum of ETEC-challenged gnotobiotic pigs. Subsequently, gene expression of selected cytokines, phagocytic activity of leukocytes from peripheral blood and percentage of CD2(+), CD4(+), CD8(+) and CD4(+)CD25(+) lymphocytes in jejunal mucosa were evaluated. Results showed that combined treatment down-regulates IL-1α and IL-8 gene expression, up-regulates IFN-γ and tends to regulate inflammation

induced by ETEC through cytokine IL-10. In general, changes in cytokine gene expression correlated with the proportions of immune cells isolated from the same part of the jejunal mucosa. Results indicate that probiotic L. plantarum in combination with flax-seed oil has anti-inflammatory properties, stimulates Th1-mediated cell immunity and phagocytosis, and tends to regulate the inflammatory response induced by ETEC.

The objective of this study was to explicate the effects of

feeding flax seed oil and flax seed meal on AOM-

induced aberrant crypt foci (ACF) in Fisher 344 male

rats. Following an acclimatization period, rats were

divided into six groups and fed AIN 93G diet Control

(C), C+7 and 14% soybean oil (SBO), C+7 and 14%

flax seed oil (FSO) and C+10 and 20% flax seed meal

(FSM). All rats received 16 mg/kg body weight of AOM

at 7 and 8 weeks of age. The rats were euthanized with

CO2 at 17 weeks of age.

FSM and FSO reduced the incidence of ACF which are

putative precursor lesions in the development of colon

cancer in the distal colon by 88% and 77%, in the

proximal colon by 86% and 87% with a total reduction

of 87.5% and 84%, respectively.

Glutathione-S-transferase (GST) activities were

significantly (P<0.05) higher in rats fed C+7 and 14%

FSO and C+10 and 20% FSM, as compared to rats fed

C+SBO diets.

Results of this study showed that FSO and FSM reduced

the incidence of AOM-induced ACF formation and may

therefore be effective chemopreventive agents.

Rats were fed AIN 93G control (American Institute of Nutrition 93

Growth diet, Reeves et al, 1993), C + 7% soybean oil (SBO), C +

14% SBO (double fat, mimicking a high fat western diet), C +

20% Flax seed meal (FSM), C + 10% FSM, C + 7% Flax seed oil

(FSO) and C + 14% FSO for 13 weeks (Table 1).

Nutr Cancer. 2006;54(2):216-22.Chemopreventive effects of dietary flaxseed on colon tumor development.

Bommareddy A1, Arasada BL, Mathees DP, Dwivedi C.

The objective of this investigation is to study the effects of dietary flaxseed meal, a source of both omega-3 fatty

acid and lignans, on colon tumor development and compare them with the effects of dietary corn meal.

Male Fischer rats, two groups of 24 each, were assigned to the AIN-93M diet supplemented with either 15% corn

meal or 15% flaxseed meal, respectively. Carcinogenesis was initiated with subcutaneous injections of

azoxymethane (15 mg/kg) once a week for 3 consecutive wk. After 35 wk of initiation, rats were anesthetized with

ether. Blood was collected by cardiac puncture, and rats were sacrificed. The gastrointestinal tract was isolated. The

site, size, and number of tumors were recorded. The fatty acid analysis of the collected serum and colon samples was

performed. Expression of cyclooxygenase (COX)-1 and COX-2 was performed by Western blot method. Lignan levels

in serum and colon samples were assayed.

Colon tumor incidence, multiplicity, and size were found to be 82.6% and 29.4%; 1.3 and 0.3; and 44.4 and 5.3

mm(2) in corn and flaxseed meal groups, respectively. Colon and serum samples of the corn meal group showed

higher levels of omega-6 fatty acid levels whereas the flaxseed meal group exhibited higher levels of omega-3

fatty acids. COX-1 and COX-2 expression in the flaxseed group was significantly lower (P < 0.05) as compared

to the corn group.

Dietary flaxseed meal containing high levels of omega-3 fatty acids and lignans is effective in preventing colon

tumor development when compared with dietary corn meal possibly by increasing omega-3 fatty acid levels and

decreasing COX-1 and COX-2 levels.

MATERIALS AND METHODS: The oil and mucilage of Flaxseeds were studied for their laxative, and

antidiarrheal activities in mice. The mechanisms of laxative and antidiarrheal activities were further studied

using the isolated tissue preparations (rabbit jejunum and guinea-pig ileum) immersed in Tyrode׳s solution

maintained at 37°C and aerated with carbogen gas. Isotonic responses were measured on spontaneously

contracting isolated jejunum and guinea-pig ileum preparations.

RESULTS: Oral administration of Flaxseed oil (30 and 70mg/kg, orally) and mucilage (1 and 2.5g/kg,

orally) caused dose-dependent increase in wet feces in mice. The spasmogenic effect of Flaxseed oil was

partially blocked by pyrilamine (p<0.05) and atropine (p<0.01) in isolated rabbit jejunum whereas atropine

completely blocked the effect of Flaxseed mucilage on isolated guinea-pig ileum. When studied for its

antidiarrheal effect, Flaxseed oil reduced the castor oil-induced diarrheal score by 49.35% and 84.41%

and intestinal secretions by 19% and 33.62% at the oral doses of 100 and 300mg/kg respectively. In

isolated rabbit jejunum preparations, Flaxseed oil produced a dose-dependent inhibition of both

spontaneous and low K(+) (25mM) -induced contractions in rabbit jejunum. The inhibitory effect against

low K(+) was most sensitive to tetra-ethylammonium chloride, a non-specific K(+) channel blocker,

followed by glibenclamide, a partial ATP-dependent K(+) channels blocker and 4-Aminopyridine, a

voltage gated K(+)-channel blocker.

CONCLUSIONS: Our results indicate that Flaxseed oil and mucilage exhibit laxative activity, mediated

primarily through cholinergic pathway with weak histaminergic effect component evident in Flaxseed oil,

which also showed antidiarrheal activity, mediated possibly through K(+) channels activation. Thus this study

rationalizes the medicinal use of Flaxseed in both the constipation and diarrhea with sound mechanistic basis.

The objective was to determine the influence of consuming 50 g flaxseed/d for 4 wk on several indexes of

nutrition in young healthy adults.

During flaxseed consumption, alpha-linolenate was increased significantly in adipose tissue, and n-3

polyunsaturates were increased in plasma lipids. Plasma LDL cholesterol was also reduced by up to 8%,

and total urinary lignan excretion was increased more than five fold (P < 0.05).

Muffins containing 25 g flaxseed did not differ significantly from control muffins in their content of

thiobarbituric acid-reactive substances, and alpha-linolenate in the muffins was not significantly reduced

by baking.

Antioxidant vitamins and lipid hydroperoxides in plasma were not significantly affected by flaxseed

consumption. Bowel movements per week increased by 30% while flaxseed was consumed (P < 0.05).

We conclude that traditional flaxseed has modest beneficial effects on several indexes of nutritional status

without compromising antioxidant status

Resina

CHIOS MASTIHA

Chios mastic gum (Mastiha Chia) is a natural resin that is excreted from the trunk and branches of the mastic

tree (Pistacia Lentiscus var. Chia of the Anacardiaceae family), o anche noto come LENTISCO. Mastic gum

has been used in traditional Greek medicine for various gastrointestinal disorders like gastralgia,

dyspepsia, and peptic ulcer for more than 2,500 years. Ancient Greek physicians, such as Hippocrates,

Dioscorides, Theophrastos, and Galenos, mentioned its properties and recommended its use.

Biological activities

oAnti-indigestion

oAnti-ulcer (acting against Helicobacter pylori)

oAntimicrobial and antifungal

oAntioxidant

oHypolipidemic

oAnti-inflammatory

oAnti-Crohn’s disease

oAnti-neoplasmatic.

COMPONENTS: CMG’s main components are an insoluble polymer (25%) and a

triterpenic fraction (67%), which is further sub-classified as acidic (39%) and neutral

(28%) fractions.

The acidic fraction seems to have the greatest anti-microbial activity and its main

components are the masticadienonic acid (30%), isomasticadienonic acid (30%),

oleanonic acid (15%) and moronic acid (10%).

The neutral fraction’s main components include butyspermol, tirucallol, oleanolic

aldehyde, oleanonic aldehyde and betulonal. Neutral compounds like butyspermol

and tirucallol present a typical phytosterolic structure.

Another monoterpenic constituent of CMG, camphene, seems to possess promising

hypolipidemic activity.

Furthermore, anti-oxidant effects of Chios mastic, that may result in reducing LDL

cholesterol oxidation, could be attributed to the resin’s remarkable concentration of

various polyphenols.

Helicobacter pylori – meccanismo d’azione

Il gene cagA trascrive per una delle più importanti proteine dell'H. pylori, la CagA, molto diffusa tra i batteri del

genere Helicobacter. I ceppi batterici che possiedono il gene cagA sono dotati della capacità di generare ulcere

molto gravi e difficili da curare. La proteina CagA è trasportata all'interno delle cellule umane, dove la funzione

normale del citoscheletro verrà annullata, alterando le regolari attività della cellula. La patogenica cag contiene

circa 30 geni, che collaborano per il quarto sistema di secrezione. Dopo la fissazione dell'H. pylori alle cellule

epiteliali gastriche, la proteina cagA è iniettata in esse passando per il quarto sistema di secrezione. La proteina

cagA è fosforilata sui residui di tirosina da una cellula collegata alla membrana cellulare la quale favorisce

l'ingresso della sostanza. Nei ceppi patogenici dell'H. pylori è stata inoltre evidenziata la capacità di attivare

l'EGFR (il recettore del fattore di crescita dell'epidermide), una proteina della membrana dotata di attività

tirosina chinasica. L'attivazione dell'EGFR dall'H. pylori è associata a trasduzioni del segnale ed espressioni

geniche all'interno delle cellule epiteliali che contribuiscono alla patogenesi. È stato inoltre provato che il dominio

C-terminale della proteina cagA (amminoacidi 873–1002) può regolare la trascrizione genica della cellula

ospite indipendentemente dalla fosforilazione delle tirosine.

Helicobacter pylori virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa

protein encoded on the 40kb cag pathogenicity island (PAI).[1]

H. pylori strains can be divided into CagA positive or negative strains. Around 60% of H.

pylori isolates in Western countries are positive, whereas the majority of East Asian isolates

are positive.

The cag PAI also encodes for a type 4 secretion system which is used to "inject" CagA into a

target cell upon H. pylori attachment. After translocation, CagA localises to the inner surface of

the cell membrane and undergoes tyrosine phosphorylation by Src family kinases (e.g. Fyn and

Lyn).

Terapia

farmacologica per

eradicazione H.

pylori

LIMITI della Terapia farmacologica

eradicante?

Antibiotico-resistenza

Comparsa di ceppi mutanti

Ricomparsa dell’infezione

FALLIMENTO DELLA TERAPIA

PERSISTENZA DELL’INFEZIONE E DEL

DANNO ALLA MUCOSA GASTRICA

TASSI DI RESISTENZA ANTIBIOTICA

Claritromicina= 35%

Fluorochinoloni= 26%

TASSI DI RICOMPARSA DELL’INFEZIONE

Paesi sviluppati= 2.67%

Paesi in via di sviluppo= 13%

The Helicobacter pylori (H. pylori) neutrophil activating protein (HPNAP) is one of a

number of virulence factors produced by the bacterium H. pylori. This protein was shown

to induce neutrophil adhesion to endothelial cells in vitro as well as in vivo, to increase

the adhesion of neutrophils to endothelial cells, to induce migration and activation of

human neutrophils and monocytes and to be a potent stimulant of mast cells.

Its binding to neutrophil-glycosphingolipis and mucin, a component of the stomach

mucus layer, has also been reported. HPNAP induces the production of ROS that involves a

cascade of intracellular activation events, including increase of cytosolic calcium ion

concentration and phosphorylation of cytosolic proteins, leading to the production of

NADPH on the neutrophil plasma membrane.

CHIOS MASTHIA GUM

inhibit the neutrophil

attachment to

endothelial cells caused

by the HPNAP and its

C-terminal region

(helicles H3 and H4) by

arabino galactans of

the rhesin.

The extracts and pure major constituents of Chios mastic gum (resin of Pistacia lentiscus var. chia) were

tested for their activities against Helicobacter pylori.

A total mastic extract without polymer (TMEWP) was prepared after removal of the contained insoluble

polymer in order to ameliorate solubility and enhance in vivo activity.

Administration of TMEWP to H. pylori SS1-infected mice over the period of 3 months with an

average dose of 0.75 mg/day led to an approximately 30-fold reduction in the H. pylori

colonization (1.5 log CFU/g of tissue).

However, no attenuation in the H. pylori-associated chronic inflammatory infiltration and the activity of

chronic gastritis was observed.

To further characterize potential active mastic constituents, the TMEWP was separated into an acidic and a

neutral fraction. Both were extensively characterized by nuclear magnetic resonance and mass spectroscopy to

elucidate the structure of the components contained within each fraction. After chromatographic separation,

the acid fraction gave the major triterpenic acids, while the neutral fraction gave several triterpenic

alcohols and aldehydes.

Mastic extracts and isolated pure triterpenic acids were tested for in vitro activity against a panel of 11 H.

pylori clinical strains. The acid fraction was found to be the most active extract (minimum bactericidal

concentration [MBC], 0.139 mg/ml), and the most active pure compound was isomasticadienolic acid (MBC,

0.202 mg/ml [0.443 mM]). These results show that administration of TMEWP may be effective in reducing H.

pylori colonization and that the major triterpenic acids in the acid extract may be responsible for such an

activity.

The crude resin that was used in this study contained a high percentage (30%)

of an insoluble and sticky polymer (poly-"-myrcene) that obviously hinders its

oral administration and reduces the bioavailability of the contained active

compounds.

Il mircene o β-mircene è un terpene che si trova nell'olio essenziale di piante quali la verbena, la citronella,

cannabis indica e la mircia (da cui trae il nome).

Extraction process. Commercial mastic gum was supplied by the Chios Mastic Growers Association, which is the

exclusive worldwide producer of the resin. A quantity of mastic gum (500 g) was diluted in ethyl acetate (500

ml), and then methanol (1,500 ml) was added (Fig. 1). The mixture was let stand, and after a period of 2 days,

a layer of poly-"-myrcene (150 g) was decanted. The clear supernatant solution was obtained by filtration, and

the solvent mixture was evaporated in a rotary evaporator at 45°C with an 80-kPa vacuum (extraction A).

The resulting semisolid residue was dried in a desiccator at 70°C and 1,000-mbar vacuum and gave a white

powder (350 g). The TMEWP was freely soluble in ethanol, which is feasible for the crude resin only under

protracted heating. TMEWP was partitioned between aqueous 5% Na2CO3 (1 liter) and ether (3.5 liter) as

described by Barton (5) (extraction B). The organic phase was reextracted three times with 5% Na2CO3 (1 liter

each time) (extraction C) and afforded the neutral fraction of mastic (135 g) as the organic phase. The aqueous

phase was added to that of extraction B and acidified with 1 N HCl (3 liters). The acidic solution was

reextracted with ether (6 liters) (extraction D), and the organic phase afforded the acid fraction of mastic (190

g).

The aim of this study was to study the effect of pure mastic gum on Helicobacter pylori (H. pylori)

eradication in patients suffering from an H. pylori infection.

52 patients were randomized to receive either 350mg three times a day (tid) of pure mastic gum for 14

days (Group A), or 1,05g tid of pure mastic gum (Group B) for 14 days, or pantoprazole 20mg twice a

day (bd) plus pure mastic gum 350mg tid for 14 days (Group C) or pantoprazole 20mg bd plus

amoxicillin 1g bd plus clarithromycin 500mg bd for 10 days (Group D).

All patients harboured H. pylori before entering the study and that was confirmed by a (13)C urea breath

test (UBT).

H. pylori eradication was tested by a UBT 5 weeks after completion of the eradication regime.

Eradication of H. pylori was confirmed in 4/13 patients in Group A and in 5/13 in Grour B.

No patient in Group C achieved eradication whereas 10/13 patients in Group D had a

negative UBT. There were no statistically significant differences in mean UBT values in

Groups A, B, C although there was a trend in Group A (p=0.08) and in Group B (p=0.064).

The difference was significant in Group D (p=0.01).

All patients tolerated mastic gum well and no serious adverse events were reported. Mastic gum has

bactericidal activity on H. pylori in vivo.

This study evaluated the effects of CMG on cholesterol and fasting plasma glucose (FPG) levels of healthy

volunteers.

Design: A prospective, randomized, placebo-controlled, pilot study.

Methods: 179 volunteers with total cholesterol levels >200 mg/dl were randomized to four groups. Finally,

156 volunteers completed the follow-up period and were anal:ysed (1) control group (C, n= 23), receiving

placebo; (2) total mastic (TM, n= 72) receiving daily a total dose of 1 g of crude CMG (330 mg capsules,

tid); (3) polymer-free mastic (PFM, n= 33), receiving daily a total dose of 1 g of polymer free mastic (330

mg caps, tid); and (4) powder mastic (PM, n= 28), receiving daily a total dose of 2 g of crude CMG.

Results: After 8 weeks, the TM group reduced total cholesterol by 11.5 mg/dl (p<0.05) and FPG

by 4.5 mg/dl (p<0.05) adjusted for age, gender, BMI and baseline characteristics. The effect was

stronger in overweight and obese patients (BMI>25), with an estimated mean reduction of total

cholesterol by 13.5 mg/dl (p<0.05) and FPG by 5.1 mg/dl (p<0.05). Administration of PFM and

PM resulted in no statistically significant alteration. No effect was observed on LDL, HDL,

triglycerides, uric acid and CRP. No gastrointestinal, liver or renal adverse events were

recorded.

Conclusions: CMG has a significant lowering effect on total cholesterol and glucose levels of healthy

volunteers, with excellent tolerance and no detectable side effects, especially in overweight and obese

individuals.

J Med Food. 2012 Nov;15(11):974-83. Chios mastic fractions in experimental colitis: implication of the nuclear factor κB pathway in

cultured HT29 cells.Papalois A1, Gioxari A, Kaliora AC, Lymperopoulou A, Agrogiannis G, Papada E, Andrikopoulos NK.

Oleanolic acid (OA) is a major triterpenic acid in CM with several antioxidant and anti-inflammatory

properties. This study show that CM is beneficial in experimental colitis in the form of powder mixture with

inulin, as supplied commercially. However, the biobased on the hypothesis that terpenoids exhibit functional

activities via distinguishable pathwaysactive fraction or compound of CM is unidentified. Thus,, authors

fractionated CM and applied different fractions or individual OA in experimental colitis.

Furthermore, authors investigated the mechanism underlying this effect in human colon epithelial cells.. CM

powder mixture (100 mg/kg of body weight) or the respective CM powder mixture components (i.e., inulin,

AF, NF, or OA) were individually administered in trinitrobenzene sulfonic acid-treated rats Colonic damage

was assessed microscopically, and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and

intercellular adhesion molecule-1were measured. A model of inflammation in co-cultured human colon

epithelial HT29 cells and monocytes/macrophages was established. Lactate dehydrogenase release and

levels of TNF-α, IL-8, and nuclear factor-κB (NF-κB) p65 were measured.

In vivo, histological amelioration of colitis and significant regulation in inflammation occurred with CM

powder mixture, even at the mRNA level. Although no histological improvement was observed, AF and NF

reduced levels of inflammatory markers. Inulin was ineffective. In vitro, CM treatment down-regulated IL-8

and NF-κB p65. Neither fractions nor OA was the bioactive component solely. Most probably, the entire CM

rather than its individual fractions reduces inflammation via NF-κB regulation.

LACTOBACILLUS REUTERI

Lactobacillus reuteri (L. reuteri) è una specie di batterio appartenente alla famiglia delle Lactobacillaceae che colonizza naturalmente il tratto gastro-intestinale di uomini e animale. Numerosi studi clinici hanno dimostrato come una adeguata somministrazione di L. reuteri possa apportare benefici alla salute dell'uomo. Per tale motivo, il L. reuteri è attualmente considerato un organismo probiotico. Alcuni ceppi di L. reuteri (principalmente ATCC55730 e DSM17938) vengono al momento utilizzati come agenti terapeutici (fermenti lattici in gergo) contro diversi disturbi intestinali, tra cui le coliche del lattante.

Impiego clinico:

•Coliche

•Infezioni da Helicobacter pylori

•Dispsia

Lactobacillus reuteri

Premature newborns

Children 4-18 years

Adults

Adults

OZONO

Ozono (olio ozonizzato)

L’olio ozonizzato ha una riconosciuta azione battericida e antifungina. Come l’ossigeno crea un habitat poco

favorevole alla proliferazione di funghi e batteri, così l’ozono, racchiuso con tecniche speciali ad elevate

concentrazioni di perossidi, è in grado di mantenere la cute ossigenata ed irrorata, penetrando in

profondità.

La forma dell’olio ozonizzato ben si presta per l’applicazione al tessuto orale. L’attività antimicrobica

dell’olio ozonizzato, la sua efficacia antibatterica e di prevenzione delle infezioni secondarie, il suo effetto

sulla dentina, la mancanza di tossicità e controindicazioni con uso appropriato, hanno fatto sì che si siano

moltiplicati gli studi e le applicazioni in questo campo.

Anche l’odontoiatria utilizza ampiamente l’olio ozonizzato, efficace nella guarigione di ascessi gengivali,

tasche paradontali e gengiviti. Se usato regolarmente, inoltre, puó prevenire la formazione della placca

dentaria.

Oltre che per le problematiche gengivali e palatali, l’ozono ha sul dente un effetto sbiancante tutt’altro che

da sottovalutare , oggetto di numerosi studi, ricerche ed applicazioni avanzate.

L’olio ozonizzato è ingrediente efficace di numerose preparazioni per la cura naturale di ulcere gastriche

per il suo riconosciuto effetto citoprotettivo ed antiossidante sulle mucose gastriche.

The susceptibility of Helicobacter pylori to disinfectants was compared to that

of Escherichia coli. H. pylori is more resistant than E. coli to chlorine and

ozone but not monochloramine. H. pylori may be able to tolerate

disinfectants in distribution systems and, therefore, may be transmitted by

a waterborne route.

Vopr Kurortol Fizioter Lech Fiz Kult. 2006 Nov-Dec;(6):34-7.[Ozone therapy in gastroduodenal pathology associated

with Helicobacter pylori].[Article in Russian]

Fedorov AA, Gromov AS, Sapronenok SV, Kurochkin VIu, Zhernakova ZM.

Three methods of ozone therapy (intravenous injection of ozonized

physiologic saline, oral intake of ozonized low-mineral water and

combination of the two treatments) were compared by efficacy in 215

patients with gastroduodenal pathology associated with

Helicobacter pilori. All the techniques of ozone therapy proved

effective in relation to regress of clinical symptoms, regeneration

processes, eradication of Helicobacter pylori, but the combined

regimen was the best.

Eksp Klin Gastroenterol. 2007;(5):81-5, 165.[Optimization of the treatment of stomach ulcer in patients subjected

to perforated gastroduodenal ulcer closure].[Article in Russian]

Lelianov AD, Budrin VA, Novikov AS, Guseva ED, Nesterov AA, Kirsov PP.

The organized benchmark analysis result treatments 152 sick with

taken in perforated gastroduodenal ulcers. In the main group (87

sick) in complex treatment are used methods of ozonotherapy. In

group of the comparison (65 sick) used standard scheme of the

treatment to peptic ulcer. Methods of ozonotherapy promote more

early and more full recovering the structure gastroduodenal

mucous and provide efficient eradication of Helicobacter pylori,

reduces the time of the healing the ulcers and reduces the risk of

the relapse ulcers.

Digestion. 2014;90(1):10-7. The influences of pepsin concentrations and pH levels on the disinfective activity

of ozone nanobubble water against helicobacter pylori.Kawara F1, Inoue J, Takenaka M, Hoshi N, Masuda A, Nishiumi S, Kutsumi H, Azuma

T, Ohdaira T.

AIMS: To investigate the utility of ozone nanobubble water (NBW3) for the treatment of Helicobacter pylori in

the stomach, authors tested the influence of pepsin concentrations and pH levels on the disinfective activity of

NBW3, and the cytotoxicity of NBW3 against mammalian cells and mucosa.

METHODS: Different concentrations of pepsin were dissolved in NBW3, and the bactericidal activity was tested on

H. pylori. NBW3 was adjusted to different pH levels (2.0-7.4) and the bactericidal activity on H. pylori was also

tested. To examine the cytotoxicity of NBW3, AGS cells, human gastric epithelial cells, were treated with NBW3

and the viability of the cells was evaluated in vitro. Furthermore, NBW3 was administered to mice and gastric

mucosal damage was evaluated by histology.

RESULTS: Pepsin reduced the disinfective activity of NBW3 on H. pylori in a pepsin concentration-dependent

manner. NBW3 showed stable disinfective activity at all pH levels examined. Cytotoxicity of NBW3 against

human gastric epithelial cells and gastric mucosa was not observed in our experimental setting.

CONCLUSIONS: NBW3 can sustain its disinfective activity in wide range of pH levels and show no cytotoxicity on

mammalian cells and tissue. Pepsin can inhibit NBW3 activity in a dose-dependent manner.

FITOTERAPICI

To determine the frequency of medicinal herb use, the species consumed and the profile of medicinal herb consumers among patients with gastrointestinal disorders, patients attending the gastroenterology outpatient clinic of the Francesc de Borja district hospital (Gandía, Spain) over a 5-month period were interviewed and 539 valid questionnaires were obtained. A total of 34.7% of the interviewees had taken medicinal herbs at some time and 26.9% had used them in the last year. Self-prescription was reported by 67.1%. Medicinal herbs were mainly obtained in the pharmacy or herbalist's (74.7%). The results of medicinal herb therapy were considered good or excellent by 80.3% of the interviewees, average by 18.6% and poor by 1.1%. In the univariate analysis, medicinal herb consumption was positively associated with female sex (p < 0.001), a university education (p < 0.05), consumption of psychotropic drugs (p < 0.005), functional gastrointestinal disorders (p < 0.005) and a diagnosis of lower gastrointestinal disorder (p < 0.01). 57 botanical varieties were used. The most frequent varieties were Santolina chamaecyparissus (18.8%), Tilia platyphyllos (6.5%), Thymus vulgaris (6%), Equisetum ramosissimum (4.7%), Mentha pulegium (4.4%) and Valeriana officinalis (4.4%).

The results show that consumption of medicinal herbs is frequent among patients attending the gastroenterology outpatient clinic of a district hospital. The probable profile of those showing maximum consumption is: female sex, university education, lower gastrointestinal disorder, functionalgastrointestinal disorder, psychotropic drug consumption and use of TE.

FINOCCHIO (Foeniculum vulgare)

COMPONENTI: il componente principale è rappresentato dall’ olio essenziale, costituito prevalentemente da

trans-anetolo, di sapore dolciastro (non meno del 80%); fencone, dal sapore amaro canforato (circa l’1% e non

superiore al 7.5%); metilcavicolo; anilsaldeide ed alcuni idrocarburi terpenici, tra cui alfa-pinene, alfa-

fellandrene, limonene. I frutti contengono inoltre olio grasso, proteine, carboidrati, acidi organici,

flavonoidi e cumarine. Tra i flavonoidi presenti nel Foeniculum vulgare, i più rappresentati solo la quercetina 3-

glucuronide, la isoquercitrina, la quercetina 3-arabinoside, il kempferolo 3-glucuronide ed il kaempferolo 3-

arabinoside, ed isoramnetina glucoside.

Attività farmacologica

Attività spasmolitica intestinale e antimeteorica. Azione galattogena.

Azione espettorante. Azione antimicrobica. Blando diuretico.

Impiego clinico

Dispepsie e atonie digestive. Meteorismo e coliche gassose dei

bambini.

FINOCCHIO (Foeniculum vulgare)

Attività antispasmolitica. L’olio essenziale di Finocchio agisce sulla

muscolatura liscia dell’apparato digerente, regolarizzando la motilità e

riducendo al tempo stesso la produzione intestinale di gas in eccesso, utilizzato

anche come coadiuvante nella terapia del colon irritabile. Da solo ed in

associazione con altri fitocomplessi, il Foeniculum vulgare trova indicazione nel

trattamento dei disturbi gastrointestinali di tipo spastico; in alcune forme di

colite cronica, e nelle dispepsie da atonia gastrointestinale.

Attività antimicrobica. L’olio essenziale di

Finocchio ha inibito la crescita di microrganismi

come l’Escherichia coli, lo Staphylococcus aureus, Salmonella typhimurium, Helicobacter Pylori e Candida albicans, in vitro.

Treatment Study design Sample Results Mechanism of action

Constipation Randomized, crossover, placebo-

controlled, single-blinded

trial;

20 constipated

patients

Improvement of the colonic transit time (P < 0.001) and of the patient perception

of bowel function (p < 0.01)

Activation of the peristalsis, with

antispasmodic action

Treatment Study design Method Results Mechanism of action

Evaluation of the secretion of IL-8 and

generation of ROS in a bid to rationalize their

medicinal use and to examine the anti-inflammatory and

cytoprotective effects in gastric epithelial cells.

AGS cells and clinically isolated

Helicobacter pylori strain (193C).

Anti-Helicobacter pylori activity and cytotoxic effects of the selected

plants were determined by serial dilution method and DNA fragmentation assay respectively. ELISA and flow cytometry were

performed to evaluate the effect on IL-8

secretion and ROS generation in

Helicobacter pylori-infected cells.

At 100μg/ml, extracts exhibited strong inhibitory activity against IL-8 secretion. Of

these extracts of Cinnamomum cassia, Myrtus communis, Syzygium aromaticum, and

Terminalia chebula markedly inhibited IL-8 secretion at both 50 and 100μg/ml. Achillea

millefolium, Berberis aristata, Coriandrum sativum, Foeniculum vulgare, Matricaria

chamomilla and Prunus domestica demonstrated significant suppression of ROS

from Helicobacter pylori-infected cells (p<0.01).

Anti-oxidant and anti-microbial activity

METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the

dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour

after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole

blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and beta-

carotene levels were measured in all the groups.

RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect

of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 +/- 2.81 vs

13.15 +/- 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly

increased GSH, nitrite, nitrate, ascorbic acid, retinol and beta-carotene levels.

MECHANISM OF ACTION: Reduction in lipid peroxidation and augmentation in the antioxidant activity.

CAMOMILLA (Chamomile recutitia)

COMPONENTI: terpenoidi, α-bisabololo ed ossidi di azulene (tra cui

ciamazulene ed i derivati dell’acetilene), composti fenolici (tra cui i

flavonoidi apigenina, quercetina, patuletina) e glicosidi.

Impiego clinico

Treatment Study design

Sample Results Mechanism of action

Functional dyspepsia

double-blind,

randomized,

placebo-controlled, multicenter

trial

120 patients

43.3% of the actively treated

patients and 3.3% on placebo

reported complete relief of

symptoms. (p < 0.001)

Antispasmodic and sedating properties

Digestion. 2004;69(1):45-52. Epub 2004 Jan 30. Treatment of functional dyspepsia with a herbal preparation. A double-

blind, randomized, placebo-controlled, multicenter trial. Madisch A, Holtmann G, Mayr G, Vinson B, Hotz J.

J Med Food. 2009 Dec;12(6):1403-6. Bisabolol-induced gastroprotection against acute gastric lesions: role

of prostaglandins, nitric oxide, and KATP+ channels. Bezerra SB, Leal LK, Nogueira NA, Campos AR.

The effects of Matricaria recutita and alpha-bisabolol, a bioactive component from Chamomile species, were investigated against gastric damage induced by absolute ethanol (96%, 1 mL per animal) in rats. The effects of M. recutita extract and alpha-bisabolol on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area. Mechanistic studies were carried out at with 100 mg/kg alpha-bisabolol. We further examined the possible participation of prostaglandins, nitric oxide, and KATP+ channels in its mechanism. M. recutita reduced gastricd amage in all doses tested. Alpha-bisabolol at oral doses of 50 and 100 mg=kg markedly attenuated the gastric lesions induced by ethanol to the extent of 87% and 96%, respectively. Pretreatments with the nitric oxide antagonist N-nitro-l-arginine methyl ester (10 mg/kg, i.p.) or with indomethacin, an inhibitor of cyclooxygenase, failed to block effectively the gastroprotective effect of alpha-bisabolol. Furthermore, the alpha-bisabolol effect was significantly reduced in rats pretreated with glibenclamide, an inhibitor of KATP+ channel activation. Thus we

provide evidence that alpha-bisabolol reduces the gastric damage induced by ethanol, at least in part, by the mechanism of activation of KATP+ channels.

Inhibition of cAMP- and cGMP-phosphodiesterases (PDE) is one of the mechanisms operated by spasmolytic drugs. In this study, the effect of chamomile on PDE was investigated. Human platelet cAMP-PDE and recombinant PDE5A1 were assayed in the presence of infusions prepared from sifted flowers and capitula. LC-ESI-MS/MS analysis showed different compositions in infusions made with sifted flowers and capitula. Chamomile inhibited cAMP-PDE activity (IC50 = 17.9-40.5 microg/mL), while cGMP-PDE5 was less affected (-15% at 50 microg/mL). Among the individual compounds tested, only flavonoids showed an inhibitory effect (IC50 = 1.3-14.9 microM), contributing to around 39% of the infusion inhibition; other compounds responsible for cAMP-PDE inhibition still remain unknown. Although experimental evidence supporting the use of chamomile for gastrointestinal minor spasms dates back to the fifties, cAMP-PDE inhibition as a likely mechanism underlying the spasmolytic activity is reported for the first time.

TIGLIO (Tilia platyphyllos)

COMPONENTI: oli essenziali, flavonoidi, glicosidi (astragalina, quercetina,

tiliroside)

Impiego clinico

SANTOLINA (Santolina chamaecyparissus)

COMPONENTI: santolinone, tannini, resine, alcaloidi, terpeni.

Impiego clinico

Spasmolytic studies: Rat duodenum. Extract at 90 ug/ml showed complete blockage of contractions

induced by acetylcholine. Extracts C and A were found to be less potent than H. Extracts M and L only

presented a slight anti-cholinergic action.

Spasmolytic studies: Guinea-pig ileum. All extracts were found to antagonize the contractions

of the guinea-pig ileum induced by histamine in a concentration-dependent way, although higher

concentrations of M and L were needed to inhibit these contractions.

Different concentrations of the extracts (H, C, A; 12.5,25 and 50 pg/ml; M, L: 50,100 and 200 pg/ml)

COMPONENTI: oli essenziali, vitamina C, vitamine del gruppo B. Contiene

inoltre timolo, linaiolo e sali minerali. Sali minerali (manganese, ferro,

potassio, calcio e magnesio).

Impiego clinico

TIMO (Thymus vulgaris)

Acta Vet Hung. 2013 Jun;61(2):197-208. Effect of thyme oil on small intestine integrity and antioxidant status, phagocytic activity

and gastrointestinal microbiota in rabbits.Placha I, Chrastinova L, Laukova A, Cobanova K, Takacova J, Strompfova V, Chrenkova M, Formelova

Z, Faix S.

TIMO (Thymus vulgaris)

The effects of 0.5 g thyme oil per kg dry matter (DM) of diet on duodenal tissue integrity, antioxidant status,

phagocytic activity and selected microbiota in the caecum and faeces of rabbits were studied. 24 rabbits were

divided into two groups and were fed a commercial granulated diet for growing rabbits (CD) with access to water

ad libitum. The first group was fed the CD, while to the CD of the second group thyme oil was added. Intestinal

integrity was tested by measuring the transepithelial electrical resistance (TEER). Thyme oil significantly

increased the value of total antioxidant status (TAS) in the blood plasma and glutathione peroxidase (GPx)

activity in the liver, and it decreased malondialdehyde (MDA) concentration in the duodenal tissue. Thyme oil

resulted in strengthened intestinal integrity, as the essential oil supplementation significantly increased TEER

values in the experiment. The faecal microbiota of rabbits was almost completely balanced in both groups, and

only a slight decrease was found in the microbial population at day 42 of the trial. In both groups, the bacterial

counts were generally lower in the caecum than in the faecal samples. In conclusion, dietary supplementation

with 0.5 g/kg DM thyme oil may improve intestinal integrity, and it may have an antioxidant effect. A tendency was

also found for thyme oil to stimulate the abundance of some microbes beneficial in the rabbit gut.

METHODS: The anti-H. pylori activities of six native Iranian plants (Glycyrrhiza aspera, Juglans regia,

Ligustrum vulgare, Thymus kotschyanus, Trachyspermum copticum and Xanthium brasilicum) and seven

antibiotics were determined against 70 clinical isolates from children using the disk susceptibility assay. Minimum

inhibitory concentrations were also measured for the biologically active extracts. One extract with the best anti-H.

pylori activity was fractionated by silica gel and thin layer chromatography and the active compounds were

identified by hydrogen nuclear magnetic resonance ((1)HNMR) spectroscopy.

RESULTS: All plant extracts showed anti-H. pylori activity by the disk sensitivity method, but the most active

extracts were those from X. brasilicum and T. copticum. In fact, the anti-H. pylori activities of the two extracts

were superior to the disk antibiotic susceptibility profile. Minimum inhibitory concentrations were within the

range of 31.25-250 micro g/ml. Fractionation and chemical identification of the extract from X. brasilicum

showed the presence of two substances, a flavonoid and a xanthanolide.

CONCLUSIONS: Due to the rise in antibiotic resistance, new sources of anti-H. pylori drugs are needed. The use

of medicinal plants and/or their chemical components may have potential benefit in eradicating such problems.

COMPONENTI: L’olio essenziale, contiene 35-55% MENTOLO, esteri di mentolo, acetato ed

isovalerianato di mentolo, mentofurano, acidi monoterpenici, acido acetico e valerianico, mentofurano,

TANNINI, sostanze amare, triterpeni, acido ursolico e oleanolico, 10-35% MENTONE, PINENE,

FELLANDRENE, L-LIMONENE, TERPINENE, CADINENE, 1-8 CINEOLO, ENZIMI ossidasi e

perossidasi, VITAMINA C, acido FERULICO, CEFFEINICO, CLOROGENICO, FUMARICO, FLAVONOIDI,

TANNINI. Le FOGLIE contengono FLAVONOIDI, ACIDI FENOLICI e TRITERPENICI.

Impiego clinico

MENTA (Mentha pulegium)

J Smooth Muscle Res. 2010;46(2):107-17.Spasmolytic effect of Mentha pulegium L. involves ionic flux

regulation in rat ileum strips.Estrada-Soto S, González-Maldonado D, Castillo-España P, Aguirre-

Crespo F, Sánchez-Salgado JC.

Mentha pulegium is common known as "poleo" and used for the treatment of diarrhea, headache

and cough in Mexican traditional medicine. Organic extracts from aerial parts were evaluated

to determine their spasmolytic action on rat isolated ileum test. Hexanic (HEMp),

dichloromethanic (DEMp) and methanolic (MEMp) extracts induced a concentration-

dependent (0.97 to 1000 microg/mL) antispasmodic effect on spontaneous contractions.

DEMp was the most active extract; therefore, spasmolytic mechanism was investigated. This

extract (200 microg/mL) induced a significant depression on cumulative concentration-

response curve for carbachol and serotonin (P<0.05). Besides, extract decreased and shifted to

the right KCl- and CaCl2-induced contraction curves. Moreover, pre-incubation with

chlorpromazine (0.001 mM) shifted to the left the relaxant curve. Pre-treatment with L-NAME (1

mM), papaverine (0.01 mM), teophylline (0.01 mM), TEA (1 mM) and glybenclamide (0.1 mM) did

not produced any changed of the relaxant curves of DEMp. Findings indicate that

dichloromethanic extract of M. pulegium induced its spasmolytic effect through Ca2+-influx

blockade, which may explain its traditional use against diarrhea.

COMPONENTI: Acidi valerenici: acido valerenico, acido acetossivalerenico, acido idrossivalerenico.

Impiego clinico

VALERIANA (Valeriana Officinalis)

Zhongguo Zhong Yao Za Zhi. 2011 May;36(9):1235-8. Influence of iridoid from Valeriana jatamansi on 5-HT and 5-HIAA in rats with irritable bowel

syndrome.Yan X, Hong Y, Shi J, Qin Y, Zhang J, Lin Q, Chen Z, Zhao R, Cui X, Gao X

METHOD: 60 male rats were equally divided into 6 groups (2 controls, 1 model and 3 treatment

doses) with 10 rats per group. The test groups were administered with iridoid (24.92, 12.46, 6.

23 mg x kg(-1)) while the control groups were administered with fluoxetine (2.5 mg x kg(-1),

positive control) or distilled water (negative control). The model was established by chronic stress

and independent feeding. The influence of iridoid from V. jatamansi on 5-HT and 5-HIAA in colon,

serum and hypothalamic were observed in all groups.

RESULT: In the model group, the content of 5-HT in colon and serum increased significantly, but

the content of 5-HT in hypothalamic decreased significantly. The content of 5-HIAA and the

value of 5-HT/5-HIAA had no significant change. In three iridoid-treated groups, the content of

5-HT in colon and serum decreased, but the content of 5-HT in hypothalamic increased. The

content of 5-HIAA had no significant change. The value of 5-HT/5-HIAA in colon and serum

reduced.

CONCLUSION: The mechanism of iridoid from V. jatamansi treating irritable bowel syndrome

may be related to the regulation effect to the levels of 5-HT from Gastrointestinal to central

nervous system.

Arch Int Pharmacodyn Ther. 1982 Jun;257(2):274-87.Antispasmodic effects of valeriana compounds: an in-vivo and in-vitro study on the

guinea-pig ileum.Hazelhoff B, Malingré TM, Meijer DK.

The valepotriates isovaltrate and valtrate, and the essential oil compound valeranone caused a

suppression of rhythmic contractions in a closed part of the guinea-pig ileum in-vivo. The same

compounds and didrovaltrate relaxed potassium stimulated contractures and inhibited BaCl2

contractions in guinea-pig ileum preparations in-vitro. Guinea-pig stomach fundic strips stimulated by

carbachol were also relaxed by these substances. Potassium stimulated smooth muscle cells were also

relaxed by the valeriana compounds (10-5-10-4 M) even, when autonomic receptors were blocked by

appropriate antagonists. In lower concentrations (10-6-10-5 M), the compounds did not affect the dose-

response curves of carbachol and isoprenaline. In some experiments valeranone at 4.10-6 M produced an

increased isoprenaline relaxation of the guinea-pig ileum. Valeranone and didrovaltrate were about

equipotent to papaverine in inhibiting BaCl2 contractions.

It is concluded that the valeriana compounds probably relax stimulated smooth

muscle cells by acting as musculotropic agents and not by interacting with receptors of

the autonomic nervous system.

COMPONENTI: antrachinoni (derivati idrossiantracenici, antroni e diantroni - emodina, fiscione,

crisofanolo, aloeemodina, reina (glicosidi 60-80%), sennosidi), acido ossalico, tannini (costituiscono

peculiarità lassativa del rabarbaro), flavoni e catechine, resine, amidi e pectine, sali.

RABARBARO (Rheum spp.)

Attività farmacologica

Il rabarbaro ha proprietà colagoghe, lassative e, in piccole dosi,

toniche e stomachiche.

Impiego clinico

Stipsi, affezioni in cui sia indicata una facile

evacuazione, insufficienza digestiva, flogosi

orofaringee.

RABARBARO (Rheum spp.)

L'effetto lassativo differisce infatti da quello degli altri noti lassativi vegetali a base antrachinonica per la presenza dei tannini che,

esercitando una azione astringente, mitigano l'azione purgante degli idrossiantraceni. Infatti il rabarbaro a basse dosi è ritenuto un

antidiarroico, per effetto dei tannini, mentre a dosaggi più alti è un forte purgante, anche più potente di cascara e senna.

RABARBARO (Rheum spp.)

I derivati 1,8-idrossiantracenici hanno effetto lassativo per l'influenza sulla motilità del colon mediante inibizione delle contrazioni stazionarie e contemporanea stimolazione delle contrazioni propulsive. Ne risulta quindi un accelerato passaggio intestinale con concomitante riduzione dell'assorbimento di liquidi, a causa del diminuito tempo di contatto con

la mucosa.

RABARBARO (Rheum spp.)

METHODS: After orally administering rhubarb extract or its major component (sennoside A) to rats, the fecal water content, AQP3 expression and prostaglandin E2 (PGE2) concentrations in the colon were examined. The mechanism by which sennoside A decreases the expression of AQP3 was examined using the human colon cancer HT-29 cells and macrophage-derived Raw264.7 cells.

RESULTS: During diarrhea by rhubarb extract administration, the PGE2 levels in the colon increased while the AQP3 expression significantly decreased. Similar changes were also observed when sennoside A was administered. When sennoside A or its metabolites, rheinanthrone and rhein were added to Raw264.7 cells, a significant increase in the PGE2 concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE2 to the HT-29 cells, the AQP3 expression decreased to approximately 40% of the control. When pretreated with indomethacin, sennoside A neither decreased the AQP3 expression nor induced diarrhea.

CONCLUSIONS: Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to a laxative effect. The decreases in the levels of AQP3 are caused by rheinanthrone, which is a metabolite of sennoside A, this metabolite activates the macrophages in the colon and increases the secretion of PGE2; PGE2 acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells.

RABARBARO (Rheum spp.)

Composti antracenici, in forma ridotta ed ossidata, in parte liberi ed in parte combinati in forma glucosidica:

1) Crisofaneina, C21H20O9, che per idrolisi produce crisofanolo ed una molecola di glucosio, la cui posizione nel

glucoside non è stata definita.

2) Crisofanolo (acido crisofanico, rumicina, archinina), C15H10O4, nella quantità del 3-4% .

3) Alizarina, C14H8O4, trovata in piccole quantità.

4) Emodina (frangula-emodina, reum-emodina, acido frangulinico, archina), C15H10O5, ottenuta da rizomi di

Rabarbaro officinale e dal Rheum palmatum.

5) Isoemodina (rabarberone), C15H10O5, identificata nel Rheum palmatum e nel Rh. Officinale.

6) Aloemodina (rottlerina), C15H10O5, l'antrachinone tipico dell'Aloe, è stato trovato anche nei rizomi del

Rabarbaro cinese.

7) Reocrisina, C22H22O10, monoglucoside del fiscione, la cui presenza nel Rabarbaro cinese deve essere

confermata da più recenti ricerche.

8) Fiscione (metiletere dell'emodina, metilemodina, parietina, reocrisidina, «acido metilcrisofanico», acido fiscico)

, C16H12O5 separato dal Rabarbaro con il nome di acido metilcrisofanico e di reocrisidina, è stato recentemente

trovato nel Rheum palmatum

9) Reina (acido cassinico), C15H8O6, estratta da rizomi di Rabarbaro di origine cinese e del Rheum palmatum.

La presenza della reina come dimero («direina») segnalata da Wagner e Kohler (12) è stata negata e la

struttura di acido 1,8-diossi-antrachinone-3-carbossilico è stata confermata da Nawa e coll.

10) Glucosidi dell’emodina, dell’aloemodina, del fiscione e della reina, dei quali non è stata sinora precisata

la composizione. Quali componenti dei glucosidi sono stati identificati gli zuccheri, glucosio, fruttosio e ramnosio.

RABARBARO (Rheum spp.)

Risultati analisi spettrofotometriche del contenuto di composti antracenici liberi e

combinati in rizomi di Rheum palmatum.

RABARBARO (Rheum spp.)

Risultati analisi spettrofotometriche del contenuto di reina, crisofanolo ed emodina in

rizomi di Rheum palmatum.

A 4 years-old boy presented to emergency department with symptoms of

acute intestinal obstruction. Upright plain abdominal radiography revealed

multiple air fluid levels. Ultrasound showed no abnormalities, and because of

worsening symptoms computed tomography of abdomen was performed. It

showed intraluminal obstruction of the terminal ileum. Exploratory

laparotomy revealed a phytobezoar consisting of undigested rhubarb. The

mass was milked through the large bowel and out the anus. Although rare in

humans, bezoars are a well-documented cause of small bowel obstruction and

should be considered when intraluminal bowel obstruction occurs. Bezoars

causing small bowel obstruction may require surgical treatment.

OLI VEGETALI

In an ideal diet, the daily consumption of fats should not exceed 15-20% of

total caloric intake. Approximately one-third of these fats should be the

essential fatty acids in their proper ratio. For a 2500 calorie/day diet,

Linoleic Acid intake should be 9-18 grams/day, and alfa-linolenic acid

intake should be 6-7 g/day.

Anti-inflammatory and immune activity

OLIO DI SEMI DI CANAPA

Hemp seed oil contains linoleic acid

(LA) and alfa-linolenic acid (LNA) as

its major omega-6 and omega-3

polyunsaturated fatty acids (PUFA),

respectively. These fatty acids

comprise the most desirable contents

of the oil, especially due to the ratios

in which they exist (3:1).

Cannabidiol. Pharmacological Properties of Cannabidiol. Cannabidiol (CBD) has been shown to

possess several desirable pharmacological propertties which are exhibited in absence of the psychoactive

properties of THC, which are usually associated with the cannabinoids. Although the levels of CBD detected in

the oil were low at 10 mg/kg, its presence could still provide some benefit.

CBD has demonstrated the capability to mediate a strong inhibition of neutrophil chemotaxis and

proliferation (Sacerdote et al., 2005), and this has been considered at the basis of its great efficacy as an

anti-inflammatory drug, described both in acute and chronic animal models of inflammation (Costa et al.,

2004).

Such antioxidant activity has been reported to markedly inhibit colon injury, inducible nitric oxide synthase

expression (but not cyclooxygenase-2), and IL-1b, IL-10 (Borrelli et al., 2009); further effects of CBD on

immune cells include the inhibition of release of interferon-gamma by mononuclear cells (Formukong et al.,

1988; Watzl et al., 1991) and the suppression of chemokine production by human B cells (Srivastava et

al., 1998).

CBD has a so potent efficacy in decreasing the severity of experimental colitis in rodents (Borrelli et al.,

2009; Schicho and Storr, 2012).

The in-depth analysis of CBD-related pharmacology during gut disorders demonstrated that CBD may reduce

intestinal inflammation severity through the control of neuro-immune axis (De Filippis et al., 2011). This

study demonstrated that CBD appears as a key modulator of enteric glia-mediated neuroinflammation in

the gut because of its capability to activate peroxisome proliferator-activated receptor-gamma (PPARg).

Activation of PPARg is in fact accompanied to massive inhibition of the activity of pro-inflammatory transcription

factors such as nuclear factor kappa-light-chain-enhancer of activated B cells, signal transducer and activator of

transcription (STAT) and activator protein-1. For these reasons, CBD-mediated modulation of PPARg activation may

result not only a beneficial approach in the management of ulcerative colitis or Crohn’s disease but also a

chemopreventive pharmacological tool capable to reduce the risk of and other pathologies related to

persistent inflammation of the colon, such as colon cancer.

Therefore the rationale of this study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an its well documented increased glial cell activation

and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirmingeffect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway.

Plant sterols have been known to affect plasma cholesterol levels by blocking cholesterol absorption through crystallization and coprecipitation (Mattson et al., 1982). Within the intestinal lumen, phytosterols reduce cholesterol solubility by excluding it from micelles, thereby preventing its absorption.

Β-sitosterol.

Tocopherols

Antioxidant properties of tocopherols have been known and exploited for some time.

Tocopherol may induce increased membrane fluidity through intercalation between fatty acyl chains in the

membrane bilayer (Berlin et al., 1992).

Perhaps the most interesting activity of tocopherol which has not yet been widely studied, is its ability

to act as an anticancer agent, specifically with respect to colon cancer. Because tocopherol is

secreted via the bile into the intestine and fecal material, it can inhibit lipid peroxidation and reduce

the formation of mutagenic peroxidation products in the bowel (Stone & Papas, 1997). Ultimately,

by being excreted into the colon, as opposed to being active in the plasma, tocopherol is able to

minimize DNA damage caused by reactive nitrogen oxide species (Stone & Papas, 1997).