GASTROMILK ® RAZIONALE SCIENTIFICO
1) COMPOSIZIONE FUNZIONALE DI Gastromilk.
1.1) COLOSTRO: caratteristiche della materia prima impiegata ed up-to date di fisiopatologia e razionale di impiego, come integratore dell'alimentazione, nel trattamento della patologia gastroduodenale acuta e cronica.
Il colostro utilizzato nella formulazione di Gastromilk è di origine bovina e proveniente da animali cresciuti in allevamenti biologici.
Per assicurare la massima concentrazione delle sostanze biologicamente attive, viene utilizzato il colostro prelevato solamente dalla prima e seconda mungitura. Il colostro è successivamente scremato, pastorizzato e quindi ridotto in polvere attraverso un tecnica di freeze drying in cui la bassa temperatura permette il mantenimento dell’integrità, e quindi dell’attività funzionale, delle biomolecole in esso presenti (in particolare immunoglobuline e fattori di crescita).
COMPONENTI DEL COLOSTRO UTILIZZATO IN Gastromilk
| NUTRIENTI & MINERALI | |
|---|---|
Proteine totali |
65-75 g/100 g
|
Grassi totali |
< 1,0 g/100 g
|
Lattosio |
5-8 g/100 g
|
Calcio* |
11,61 mg/g
|
Sodio* |
8,93 mg/g
|
Magnesio* |
2,28 mg/g
|
Potassio* |
21,74 mg/g
|
Ferro* |
0,029 mg/g
|
Zinco* |
0,022 mg/g
|
Cromo* |
0,0002 mg/g
|
Selenio* |
0,00004 mg/g
|
Rame* |
0,00059 mg/g
|
Ac. fosforico* |
11,12 mg/g
|
Cloro* |
17,97 mg/g
|
* Valori Medi |
|
| IMMUNOGLOBULINE & FATTORI DI CRESCITA |
|
|---|---|
IgG |
20-35 g/100g
|
IgA |
1,5-3,5 g/100g
|
IgM |
0,5-1,0 g/100g |
IGF-1 |
1,35-2,02 μg/g |
| VITAMINE (μg/100 g) | |
|---|---|
Vitamina A |
1400-1600
|
Tiamina (Vit. B1) |
600-700
|
Riboflavina (Vit. B2) |
2500-3500
|
Vitamina B6 |
150-200
|
Acido folico |
60-70
|
Vitamina C |
3100-3300
|
Colecalciferolo (Vit. D3) |
3,1-3,5
|
Cobalamina (Vit. B12) |
0,5-0,8
|
Tocoferolo (Vit. E) |
300-350
|
Ubichinone (Q10) |
50-80
|
| AMMINOACIDI LIBERI (mg/100g) | ||||
|---|---|---|---|---|
Alanina |
8,0-9,0
|
Arginina |
7,0-8,0
|
|
Acido aspartico |
3,0-4,0
|
β-Alanina |
0,2-0,5
|
|
Ac. β-aminoisobutirrico |
1,2-1,5
|
Citrullina |
1,2-1,6
|
|
Cistina |
0,2-0,4
|
Glutammina |
9,0-10,0
|
|
Acido glutammico |
40-55
|
Glicina |
6,0-7,0
|
|
Istidina |
1,5-2,5
|
Isoleucina |
6,0-7,0
|
|
Leucina |
12-13
|
Lisina |
10-11
|
|
Metionina |
1,2-1,8
|
Ornitina |
0,6-1,1
|
|
Fenilalanina |
6,5-7,0
|
Fosfoetanolammina |
30-35
|
|
Fosfoserina |
10-15
|
Prolina |
7-12
|
|
Serina |
5-8
|
Taurina |
120-240
|
|
Treonina |
3,5-5,0
|
Triptofano |
8-12
|
|
Tirosina |
3,5-5,5
|
Valina |
12-16
|
| ANALISI MICROBIOLOGICHE | |
|---|---|
Totale aerobi |
<1,0 x 103 / g |
| Muffe | <1,0 x 102 / g
|
Lieviti |
<1,0 x 102 / g
|
E. coli |
<1,0 x 0 / g
|
Coliformi |
<1,0 x 0 / g
|
Stafilococco aureo |
<1,0 x 0 / g
|
Salmonella |
Negativo / 25 g
|
Il colostro è il precursore del latte, la cui secrezione declina a partire dalla 48^ ora del puerperio e la cui funzione, estremamente complessa, ha come risultato lo sviluppo funzionale integrato dell’apparato digerente neonatale in tempi estremamente rapidi: negli equini e nei bovini infatti la piena maturità funzionale si acquisisce in poche settimane.
Dal contesto della composizione del colostro, una vera e propria panacea multimolecolare di composti ad attività trofoblastica, immunomodulatrice, auxologica, focalizzeremo la nostra attenzione prevalentemente sui fattori regolatori della crescita e maturazione cellulare della mucosa intestinale, onde potere dar conto della possibilità di una razionale indicazione all’uso alimentare di questo alimento nel favorire il ripristino della funzionalità del tratto gastroenterico alto dell’uomo, quando esso sia stato alterato e sovvertito da momenti esogeni (tossici o flogogeni o infettivi) o endogeni (disencrinie o turbe secretive).
Il tratto gastrointestinale è continuamente sottoposto ad attacchi di acidi, enzimi proteolitici, e agenti nocivi, quali alcool, aspirina e altri farmaci istolesivi/citolesivi, causanti danni iatrogeni. La presenza di meccanismi di difesa multipli, incluso il rapido turnover della mucosa, e una buona vascolarizzazione assicurano che la mucosa rimanga intatta. Se viene lesa una piccola parte della mucosa, nel contesto di una situazione alimentare e funzionale non patologica, sono sufficienti i normali meccanismi di cicatrizzazione naturale endogena per riparare i danni. In situazioni patologiche in cui invece questi meccanismi sono alterati o comunque non sono sufficienti al mantenimento o al ripristino dell’integrità della mucosa gastrica, può essere utile l’utilizzo quotidiano di Gastromilk.
Il colostro infatti risulta essere ricco di fattori di crescita che:
- stimolano la crescita tissutale
- modulano il turn-over del tessuto muscolare, nervoso e cartilagineo
- bilanciano l’utilizzo degli zuccheri sia nell’iper che nell’ipoglicemia
- stimolano l’utilizzo dei grassi
- rallentano i processi catabolici.
Studi recenti (1) suggeriscono che i fattori di crescita contenuti nel colostro:
- EPIDERMAL GROWTH FACTOR (EGF)
- INSULIN LIKE GROWTH FACTOR-I (O SOMATOMEDINA C) che nel colostro è presente tra 50 e 2000 mgr/l contro i 4-8 del latte (IGF 1)
- INSULIN LIKE GROWTH FACTOR-II che nel colostro è tra 200 e 600 mgr/l (IGF 2)
- TRANSFORMING GROWTH FACTOR b-1 (TGF b-1)
- TRANSFORMING GROWTH FACTOR b-2 (TGF b-2)
- GROWTH HORMON (GH)
e sembrerebbero implicati nel trattamento di un’ampia varietà di condizioni gastrointestinali, che includono i disturbi gastro-intestinali, infiammazioni indotte da farmaci e mucositi indotte da chemioterapia. L’integrità della mucosa intestinale dipende dall’equilibrio tra la produzione cellulare, la migrazione e la perdita di cellule (inclusa l’apoptosi). I fattori di crescita del latte e del colostro possono influenzare tutti questi aspetti, per esempio l’EGF stimola la proliferazione e la migrazione cellulare, promuovendo una rapida riepitelizzazione e turn over cellulare nei tessuti epidermici (62-63).
Tratto da “Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders.” Playford R, Macdonald CE, Johnson W. Am J Clin Nutr 2000;72:5-14.
I fattori immunologici contenuti nel colostro e necessari per combattere le infezioni, sono rappresentati da immunoglobuline (2-59-60-61), citochine, lattoferrina, lisozima, interferone e PRP (polipeptide ricco di prolina).
Le citochine sono proteine attive sul metabolismo cellulare in condizioni di infiammazione, in quanto stimolano risposte acute quali chemiotassi, sintesi proteica e differenziazione cellulare. In particolare:
- IL-4 (interleukin-4) è una glicoproteina multifunzionale prodotta da linfociti T, mastociti e granulociti in grado di ridurre i processi infiammatori mediante diminuzione della produzione locale di IL-6 e IL-1.
- IL-1Ra (interleukin-1 receptor antagonist) è una proteina di secrezione in grado di antagonizzare IL-1 proinfiammatoria sul sito recettoriale, bloccando il recettore stesso (58).
Il lisozima, la lattoferrina, le immunoglobuline (IgA secretorie e IgG) e l’interferone sono invece responsabili dell’azione difensiva ed antinfettiva rivolta a corroborare l’integrità della mucosa del primo tratto del tubo digerente, attraverso un meccanismo antibatterico, antivirale, antiprotozoario. Il lisozima (42-43-44) è un enzima naturale in grado di lisare la parete batterica e di inibire la chemiotassi e l’attivazione dei neutrofili.
La lattoferrina ha un’azione battericida (dovuta alla sottrazione di ferro ai batteri sensibili e all’aumento della permeabilità della parete), fungicida e viricida, nonché potenziante i linfociti natural killer.
Le IgA, coadiuvate dalla componente non-immunoglobulinica costituita prevalentemente da glicolipidi, glicoproteine ed oligosaccaridi liberi, inibiscono l’adesione batterica alle cellule epiteliali della mucosa intestinale e svolgono un’azione antiflogistica (inibendo la chemiotassi dei neutrofili). Questa proprietà del colostro è estremamente importante dal momento che il fenomeno dell’adesività batterica costituisce il “primum movens” per l’instaurarsi di un’infezione batterica.
1.2) Liquirizia estratto secco (Glycyrrhiza glabra, radici)
Il razionale dell’uso dell’estratto di liquirizia è convalidato dalla presenza di principi attivi che interagiscono favorevolmente con patologie gastriche a sfondo infiammatorio o ulcerativo, aumentando l’efficienza della barriera mucosa contro la diffusione dell’acido, senza inibire la secrezione acida, ma semplicemente aumentando la secrezione del muco gastrico e modificandone la composizione (viscosità).
I principi attivi contenuti nell’estratto di liquirizia sono:
- l’acido glicirrizico, noto come glicirrizina, presente dal 4% al 7% negli estratti di radice e contenente carbenoxolone; la glicirrizina è una saponina triterpenica in grado di incrementare la secrezione di muco e di incrementarne la viscosità
- l’acido liquiritico, glabrico e 28-idrossiglicirretico, con proprietà antinfiammatoria; questi componenti infatti, legandosi ai recettori dei glucocorticoidi, esplicano un’azione antiflogistica
- i glicosidi flavonoidi liquiritina ed isoliquiritina con spiccata attività antispastica e antimicrobica (64-65-67).
Nella composizione dell’estratto sono presenti anche fitosteroli e 17-chetosteroidi, onde la controindicazione nella patologia ipertensiva dei prodotti a base di liquirizia. Nel Gastromilk l’inclusione della liquirizia non comporta rischi particolari per il soggetto iperteso, in quanto la dose di glicirrizina introitata per ogni compressa è mediamente pari a 15 mg: le raccomandazioni in argomento quantificano in 100 mg giornalieri di glicirrizina il livello da non superare.
- Glycyrrhetic acid
- Glycyrrhetinic acid
- 3beta,20beta)-3-Hydroxy-11-oxo-olean-12-en-29-oic acid
- Enoxolone
Formula: C30-H46-O4
Synonyms:
- 18-beta-Glycyrrhetic acid
- 18-beta-Glycyrrhetinic acid
- Glycyrrhetin
- Uralenic acid
- Alpha-Glycyrrhetinic acid
- 3-Glycyrrhetinic acid
- 3-beta-Hydroxy-11-oxoolean-12-en-30-oic acid
- 3beta-Hydroxy-11-oxoolean-12-en-30-oic acid
- Glycyrrhizic acid
- Glycyrrhizin
- Glycyrrhizinic acid
- (3beta,20beta)-20-Carboxy-11-oxo-30-norlean-12-en-3-yl-2-O-beta-1-7-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid
Formula: C42-H62-O16
Synonyms:
- 18-beta-Glycyrrhizic acid
- 20beta-Carboxy-11-oxo-30-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid
- Glycyron
- Glycyrrhetinic acid glycoside
- Glycyrrizin
- Alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl-2-O-beta-D-glucopyranuronosyl-
1.3) Psyllium (polvere di cuticola pura al 99%).
Si utilizza in questa formulazione la cuticola polverizzata del seme della Plantago Ovata, ricca in mucillagini costituite essenzialmente da xilosio, arabinosio e acidi galatturinici. E’ utilizzata come emolliente, come lassativo di massa e per le infiammazioni ed irritazioni intestinali, che causano diarrea e dissenteria. In Gastromilk lo Psyllium ha la duplice funzione di proteggere la mucosa in funzione del suo elevato contenuto in mucillagini (“effetto verniciante”) e di conglutinare ed inglobare l’eccesso di acidità presente nello stomaco, consentendo agli altri ingredienti funzionali, colostro e liquirizia, di espletare appieno la loro interazione con la mucosa di rivestimento.
2) Conclusioni e Indicazioni alla Supplementazione.
Il colostro, inteso come alimento integrale multifattoriale, è un induttore di molteplici meccanismi preventivi e riparativi della mucosa gastrica; i composti principalmente implicati nei citati meccanismi sono: fattori di crescita, lattoferrina, lattoperossidasi, immunoglobuline, lisozima, interferone, fattori trofici non peptidici (glutammina, poliamina, nucleotidi, aminoacidi, oligoelementi, vitamine, citochine immunomodulatrici).
Il collaterale utilizzo di due “botanicals” quali l’estratto secco di liquirizia e la fibra “verniciante” di psyllium appare ragionevole alla luce della loro documentata attività pro-antinfiammatoria (55,56,57), protettiva e pro-cicatrizzante sulle mucose gastroenteriche.
1) Gastromilk trova applicazione nella prevenzione e nel trattamento delle gastriti da FANS (farmaci antinfiammatori non steroidei, es. aspirina) (1-20-46-66) e da altri farmaci gastrolesivi. Nonostante i numerosi farmaci di protezione mucosa, non si è ancora riusciti a neutralizzare completamente l’insulto patogenetico causato da farmaci gastro-lesivi, che può condurre a severe alterazioni della mucosa gastrica. Il meccanismo con cui i FANS agiscono è stato ampiamente indagato e si concretizza in: riduzione dei livelli di prostaglandine nella mucosa, riduzione del flusso ematico della parete, induzione del rilascio lisosomiale dei neutrofili e possibile aumento dell’apoptosi cellulare.
2) Il ricorso a farmaci anti-H2 o ad inibitori della pompa protonica appare ragionevole ma non privo di effetti collaterali a loro volta innescati. Appare quindi assai ragionevole tentare di ridurre la posologia di un farmaco a favore di un alimento, per interrompere il circolo vizioso dei side-effects ed iniziare il circolo virtuoso di una induzione terapeutica-riparativa, multifattoriale. E’ fin troppo logico curare l’intestino con un alimento proprio come razionale di fisiologia naturale dell’uomo.
Tratto da “Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders.” Playford R, Macdonald CE, Johnson W. Am J Clin Nutr 2000;72:5-14.
3) Gastromilk trova applicazione, in ragione della sua frazione EGF (50), anche nella riparazione della parete intestinale danneggiata da farmaci chemioterapici, quali per esempio il metotrexato, che induce mucositi, come dimostrato da studi sul ratto (50).
4) Gastromilk può essere utilizzato nel trattamento delle patologie da reflusso gastro-esofageo e dei disturbi da Helicobacter pylori. Nel caso del reflusso il contatto tra Gastromilk e la parete mucosa irritata dall’acido o metaplastica favorisce la “restitutio ad integrum” epiteliale; Gastromilk favorisce inoltre il ripristino della motilità dello sfintere esofageo inferiore (LES), grazie all’effetto antinfiammatorio e cicatrizzante, che consentono la rigenerazione della fibre muscolari dissociate dall’edema conseguente la flogosi. Nel caso dell’Helicobacter prevale il concetto di meccanismo antinfettivo mediato dai composti del colostro provvisti di attività immunocompetente, in grado quindi di impedirne la impregnazione intracitoplasmatica, sia in prevenzione che dopo l’eradicazione, nel trattamento a medio-lungo termine. Oltre ai principi antinfettivi del colostro è da citare anche la documentata attività antimicrobica in vitro dei flavonoidi contenuti nell’estratto di liquirizia (glabridina, glabrene, licocalcone A, licoricidina e licoisoflavone B); questi flavonoidi si sono dimostrati efficaci nell’inibire la crescita anche dei ceppi di H. pylori claritromicina e amoxicillina resistenti (64-65).
APPENDICE BIBLIOGRAFICA IN ABSTRACTS
American Journal of Clinical Nutrition, Vol. 72, No. 1, 5-14, July 2000
Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders 1,2,3,4
Raymond J Playford, Christopher E Macdonald and Wendy S Johnson
1From the Department of Gastroenterology, Imperial College School of Medicine, Hammersmith Hospital, London; Leicester General Hospital, Leicester, United Kingdom; and SHS International Ltd, Liverpool, United Kingdom.
Colostrum is the specific first diet of mammalian neonates and is rich in immunoglobulins, antimicrobial peptides, and growth factors. In this article we review some of these constituents of human and bovine colostrum in comparison with those of mature milk. Recent studies suggest that colostral fractions, or individual peptides present in colostrum, might be useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, nonsteroidal antiinflammatory drug–induced gut injury, and chemotherapy-induced mucositis. We therefore discuss the therapeutic possibilities of using whole colostrum, or individual peptides present in colostrum, for the treatment of various gastrointestinal diseases and the relative merits of the 2 approaches. Key Words: Gastrointestinal tract • gastrointestinal disease • intestinal injury • repair • colostrum • milk • peptide growth factor • nutrition • nonsteroidal antiinflammatory drugs • review
Gut 1999 May;44(5):653-8
Bovine colostrum is a health food supplement which prevents NSAID induced gut damage.
Playford RJ, Floyd DN, Macdonald CE, Calnan DP, Adenekan RO, Johnson W, Goodlad RA, Marchbank T.
University Division of Gastroenterology, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for arthritis but cause gastrointestinal injury. Bovine colostrum is a rich source of growth factors and is marketed as a health food supplement. AIMS: To examine whether spray dried, defatted colostrum or milk preparations could reduce gastrointestinal injury caused by indomethacin. METHODS: Effects of test solutions, administered orally, were examined using an indomethacin restraint rat model of gastric damage and an indomethacin mouse model of small intestinal injury. Effects on migration of the human colonic carcinoma cell line HT-29 and rat small intestinal cell line RIE-1 were assessed using a wounded monolayer assay system (used as an in vitro model of wound repair) and effects on proliferation determined using [3H]thymidine incorporation. RESULTS: Pretreatment with 0.5 or 1 ml colostral preparation reduced gastric injury by 30% and 60% respectively in rats. A milk preparation was much less efficacious. Recombinant transforming growth factor beta added at a dose similar to that found in the colostrum preparation (12.5 ng/rat), reduced injury by about 60%. Addition of colostrum to drinking water (10% vol/vol) prevented villus shortening in the mouse model of small intestinal injury. Addition of milk preparation was ineffective. Colostrum increased proliferation and cell migration of RIE-1 and HT-29 cells. These effects were mainly due to constituents of the colostrum with molecular weights greater than 30 kDa. CONCLUSIONS: Bovine colostrum could provide a novel, inexpensive approach for the prevention and treatment of the injurious effects of NSAIDs on the gut and may also be of value for the treatment of other ulcerative conditions of the bowel.
Clin Sci (Lond) 2001 Jun;100(6):627-33
Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability.
Playford RJ, MacDonald CE, Calnan DP, Floyd DN, Podas T, Johnson W, Wicks AC, Bashir O, Marchbank T.
Department of Gastroenterology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W120NN, UK. r.playford@ic.ac.uk
Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. We therefore examined whether spray-dried, defatted colostrum could reduce the rise in gut permeability (a non-invasive marker of intestinal injury) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons. Healthy male volunteers (n=7) participated in a randomized crossover trial comparing changes in gut permeability (lactulose/rhamnose ratios) before and after 5 days of 50 mg of indomethacin three times daily (tds) per oral with colostrum (125 ml, tds) or whey protein (control) co-administration. A second study examined the effect of colostral and control solutions (125 ml, tds for 7 days) on gut permeability in patients (n=15) taking a substantial, regular dose of an NSAID for clinical reasons. For both studies, there was a 2 week washout period between treatment arms. In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.
Publication Types: Clinical Trial; Randomized Controlled Trial
Pediatr Res 1993 Aug;34(2):208-12
Human colostrum has anti-inflammatory activity in a rat subcutaneous air pouch model of inflammation.
Murphey DK, Buescher ES.
Department of Pediatrics, University of Texas Medical School at Houston.
An animal model was used to examine the effect of human colostrum on an acute inflammatory process in vivo. Subcutaneous air pouches on the backs of outbred rats were injected with carrageenan as an inflammatory challenge, normal saline, pooled aqueous human colostrum, or carrageenan plus colostrum concurrently. Oral dexamethasone or indomethacin was administered to some animals before and during challenge as anti-inflammatory agents. Polymorphonuclear leukocyte (PMN) counts in pouch fluid were determined 6 h postchallenge. Carrageenan challenge resulted in a significant acute inflammatory response [48.8 +/- 4.9 x 10(6) PMN/pouch (mean +/- SEM, n = 46)] compared with normal saline controls [0.9 +/- 0.2 x 10(6) (n = 31, p < 0.001 versus carrageenan)] or with colostrum [4.3 +/- 0.8 x 10(6) PMN/pouch (n = 11, p < 0.001 versus carrageenan)]. The concurrent injection of colostrum plus carrageenan challenge significantly reduced the PMN response compared with carrageenan alone [18.8 +/- 2.9 versus 48.8 +/- 4.9 x 10(6) PMN/pouch (carrageenan plus colostrum versus carrageenan, n = 41 versus 46, p < 0.001)]. This degree of suppression of PMN influx was not significantly different from that seen with indomethacin treatment but was significantly more than that seen with dexamethasone treatment. The decreases in PMN counts observed most likely reflect suppression of the acute inflammatory response because a significant amount of PMN lysis in colostrum was not observed in vitro and the accumulation of PMN granule contents was not seen in pouch fluid from colostrum-treated animals in vivo. These data directly demonstrate for the first time that human colostrum has a biologically significant effect on the inflammatory process in vivo.
Life Sci 2002 Aug 9;71(12):1449-63
Anti-Helicobacter pylori flavonoids from licorice extract.
Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T
Department of Physico-chemical Analysis, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. fukai@phar.toho-u.ac.jp
Licorice is the most used crude drug in Kampo medicines (traditional Chinese medicines modified in Japan). The extract of the medicinal plant is also used as the basis of anti-ulcer medicines for treatment of peptic ulcer. Among the chemical constituents of the plant, glabridin and glabrene (components of Glycyrrhiza glabra), licochalcone A (G. inflata), licoricidin and licoisoflavone B (G. uralensis) exhibited inhibitory activity against the growth of Helicobacter pylori in vitro. These flavonoids also showed anti-H. pylori activity against a clarithromycin (CLAR) and amoxicillin (AMOX)-resistant strain. We also investigated the methanol extract of G. uralensis. From the extract, three new isoflavonoids (3-arylcoumarin, pterocarpan, and isoflavan) with a pyran ring, gancaonols A[bond]C, were isolated together with 15 known flavonoids. Among these compounds, vestitol, licoricone, 1-methoxyphaseollidin and gancaonol C exhibited anti-H. pylori activity against the CLAR and AMOX-resistant strain as well as four CLAR (AMOX)-sensitive strains. Glycyrin, formononetin, isolicoflavonol, glyasperin D, 6,8-diprenylorobol, gancaonin I, dihydrolicoisoflavone A, and gancaonol B possessed weaker anti-H. pylori activity. These compounds may be useful chemopreventive agents for peptic ulcer or gastric cancer in H. pylori-infected individuals.
Planta Med 2002 May;68(5):416-9
In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots.
Friis-Moller A, Chen M, Fuursted K, Christensen SB, Kharazmi A
Department of Clinical Microbiology, Hvidovre Hospital, Copenhagen, Denmark. alice.friis-moeller@hh.hosp.dk
Licochalcone A, extracted and purified from Chinese licorice roots, showed in vitro inhibitory effect on human pathogenic Mycobacteria species and Legionella species. M. tuberculosis, M. bovis and BCG were inhibited by < 20 mg/l licochalcone A, whereas all non- M. tuberculosis complex species were resistant to > 20 mg/l Legionella pneumophila (serogroups 1 - 7) and L. bozemanii, L. dumoffii, L. feelei, L. longbeacheae and L. wadsworthii were inhibited by licochalcone A 1 - 4 mg/l, whereas L. gormanii and L. micdadei were inhibited by licochalcone A 500 - 1000 mg/l. These data indicate that licochalcone A might be of interest as a new class of antibacterial drug in the treatment of severe lung-infections.
Int Immunopharmacol 2002 Mar;2(4):545-55
Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines.
Barfod L, Kemp K, Hansen M, Kharazmi A
Department of Clinical Microbiology, Centre for Medical Parasitology, Copenhagen University Hospital (Rigshospitalet), Denmark.
Licochalcone A (LicA), an oxygenated chalcone, has been shown to inhibit the growth of both parasites and bacteria. In this study, we investigated the effect of LicA and four synthetic analogues on the activity of human peripheral blood mononuclear cell proliferation and cytokine production. Four out of five chalcones tested inhibited the proliferation of lymphocytes measured by thymidine incorporation and by flow cytometry. The production of pro- and anti-inflammatory cytokines from monocytes and T cells was also inhibited by four of five chalcones. Furthermore, intracellular detection of cytokines revealed that the chalcones inhibited the production rather than the release of the cytokines. Taken together, these results indicate that LicA and some analogues may have immunomodulatory effects, and may thus be candidates not only as anti-microbial agents, but also for the treatment of other types of diseases.
Nutrition 2002 Mar;18(3):268-73
Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: increased resistance of LDL to atherogenic modifications, reduced plasma lipid levels, and decreased systolic blood pressure.
Fuhrman B, Volkova N, Kaplan M, Presser D, Attias J, Hayek T, Aviram M
Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel.
OBJECTIVE: We previously demonstrated the beneficial effects of dietary flavonoids derived from the ethanolic extract of licorice root against atherosclerotic lesion development in association with inhibition of low-density lipoprotein (LDL) oxidation in atherosclerotic mice. Administration of licorice extract to normolipidemic subjects also inhibited LDL oxidation. In the present study, we extended our investigation to analyze the antiatherogenic effects of licorice-root extract consumption in moderately hypercholesterolemic patients. METHODS: Supplementation of licorice root extract (0.1 g/d) to patients for 1 mo was followed by an additional 1 mo of placebo consumption. RESULTS: Licorice consumption 1) reduced patients' plasma susceptibility to oxidation (by 19%); 2) increased resistance of plasma LDL against three major atherogenic modifications: oxidation (by 55%), aggregation (by 28%), and retention, estimated as chondroitin sulfate binding ability (by 25%); 3) reduced plasma cholesterol levels (by 5%), which was due to a 9% reduction in plasma LDL cholesterol levels; and 4) reduced (by 14%) plasma triacylglycerol levels. After the 1 mo of placebo consumption, these parameters reversed toward baseline levels. Licorice extract supplementation also reduced systolic blood pressure by 10%, which was sustained during the placebo consumption. CONCLUSIONS: Dietary consumption of licorice-root extract by hypercholesterolemic patients may act as a moderate hypocholesterolemic nutrient and a potent antioxidant agent and, hence against cardiovascular disease.
J Pharm Pharmacol 1994 Feb;46(2):148-9
The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats.
Dehpour AR, Zolfaghari ME, Samadian T, Vahedi Y
Darou Pakhsh Pharmaceutical Research Center, Tehran, Iran.
We have examined the protective effect of liquorice or its derivatives against gastric ulcer induced by aspirin. A granular mixture of aspirin alone and coated with liquorice or its derivatives including the deglycyrrhized form, a high glycyrrhized form, carbenoxolone, and enoxolone were studied. Aspirin coated with liquorice reduced the number and size of ulcers, reducing the ulcer index from 1.5 +/- 0.12 to 0.5 +/- 0.12 and the incidence from 96% to 46%. Coating with derivatives was less effective (ulcer index, 0.70-0.94; incidence 62-76%).
BIBLIOGRAFIA
1. Playford R, Macdonald CE, Johnson W. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. Am J Clin Nutr 2000;72:5-14.
2. Brussow H, Hipler H et al. Bovine milk immunoglobulins for passive immunity to infantile rotavirus gastroenteritis. Journal of clinical microbiology 1989;25:982-6.
3. Klagsbrun M, Neumann J. The serum-free growth of Balb/c 3T3 cells in medium supplemented with bovine colostrum. Journal of Supramolecular Structure 1979;11:349-359.
4. Baumrucker C, Hadsell DL et al. Insulin-like growth factors and IGF binding proteins in mamm mammary secretions: origins and implications in neonatal physiology. Mechanism Regulation Lactation and Infant Nutrient Utilization Eds.M.F: Picciano and B. Lonnerdal 1992: 285-307, Wiley-Liss New York.
5. Baxter RC, Zaltsamn Z, Turtle JR. Immunoreactive somatomedin-C/insulin-like growth factor I and its binding pretein in human milk. J Clin Endocrinol Metab 1984; 58: 955-9.
6. Vacher PY, Blum JW. Age dependency of insulin like growth factor-I, insulin protein and immunoglobulin concentrations and gamma glutamyl transferase activity in first colostrum of dairy cows. Milch-wissenschaft 1993; 48: 423-5.
7. Collier RJ, Miller MA, Hidebrant JR, et al. Factors affecting insulin-like growth factor I concentration in bovine colostrum. J Dairy Sci 1991; 74: 2905-11.
8. Francis GL, Upton FM et al. Insuline-like growth factors 1 and 2 in bovine colostrum. Biochemical Journal 1988; 251: 95-103.
9. Ross M, Francis G et al. Insulin-like growth factor (IGF) binding proteins inhibit the biological activities of IGF-1 and IGF II but does not des-(1-3) IGF I, a potent IGF analogue, on growth hormone and IGF binding protein secretion from cultured rat anterior pituitary Cells. Journal of Endocrinology 1990; 130: 93-9.
10. Ballard FJ. Cell culture as a tool for identifying nutritional disease therapies. Journal of nutrition 1994; 24: S1540-S1545.
11. Mero A. A dietary supplement based on bovine colostrum increases the serum IGF-I concentration in male athletes during a short-term strenght and speed training period. Congress Abstract: The VIIIth FIMS European Congress of Sport Medicine 1995; Granada, Spain, p.292.
12. Tamm I, Kikuchi T. Insuline-like growth factor-I (IGF-I9), insulin and epidermal growth Factor (EGF) are survival factors for density-inhibited, quiscent Balb/c-3T3 murine fibroblasts. Journal of Cellular Physiology 1990; 143: 494-500.
13. Gluckman PD, Mellor DJ. Use of growth factor IGF-II. International patent application 1993: 252-27.
14. Suh DS, Rechler MM. Hepatocyte nuclear factor I and the glucocorticoid receptor synergistical activate transcription of the rat insulin-like growth factor binding protein-I gene. Mol Endocrinol 1997; 11: 1822-31.
15. Aranda P et al. Insulin in bovine colostrum and milk: Evolution throughout lactation and binding to caseins. Journal of dairy Science 1991; 74: 4320-5.
16. Fernandez Moreno MD, Serrano-Riosm Prieto J.C. Identification of insulin-receptors in epithelial cells from duodenum jejunum, ileum, caecum, colon and rectum in the rat. Diabetes Metabolism 1987; 13: 135-9.
17. Sporn MB, Roberts AB. Transforming growth factor Beta: recent progress and new challenges. Journal of Cell Biology 1992, 119: 1017-21.
18. Coffman RL, Lebman DA et al. Transforming Growth Factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. Journal of Experimental Medicine 1989, 170: 1039-44.
19. Chen SS and Li Q. Transforming growth factor b-1 is a bifunctional immune regulator for mucosal IgA responses. Cellular immunology 1990; 128: 353-61.
20. Marchbank T, Palyford RJ. Bovine colostrum or TGF-beta (a major bioactive constituent of colostrum) are prophylactic against indomethacin induced injury. Gut 1998; 42 (suppl): A68 (abstr).
21. Carpenter G, Cohen S. Epidermal frowth factor. Journal of Biology Chemistry 1990; 265: 7709-12.
22. Murray MJ, Schauies RP et al. Epidermal Growth Factor-like activity in mare’s milk. American Journal of Veterinary Research 1992; 53 (10): 729-31; 28 ref.
23. Forsyth IA, Rossdale PD et al. Studies in milk composition and lactogenic hormones in the mare. Journal Reprod Fert 1975; Suppl., 23: 631-5.
24. Stowe HD. Vitamine A profiles of equine serum and milk. Journal of animal science 1982; 54(1): 76-81.
25. Minieri I, Intrieri F. Ricerche elettroforetiche sulle frazioni proteiche del colostro e del latte di cavalla di razza avelignese, in rapporto alla distanza dal parto. Acta Med 1970 Napoli, 16: 73-88.
26. Salimei E, Capalbo R. Componenti azotate del latte di giumenta nei primi giorni post partum. Atti 2°Convegno Nuove acquisizioni in materia i alimentazione, allevamento e allenamento del cavallo sportivo. Campobasso 13-14 ottobre 2000.
27. Peltoten T, Kossila V et al. Effect of protein supplementation on milk composition of the mare and growth rate of thier foals. Proc. 31st Annu.Meet, EAAP, Munchen n° 6, 1980.
28. Bouwman I, Van der Schee W. Composition and production of milk from Dutch warm-blooded hose mares. Z. Tierphysiol Tierern u. Futtermittelk 1978, 40: 39-53.
29. Doreau M, Boulot S et al. Yeld and composition of milk from lactating mares: effect of lactation stage and individual differences. Journal Dairy Research 1990; 57: 449-54.
30. Davies DT, Holt C et al. The composition of milk. Biochemistry of Lactation Ed. Mepham LB, Elsevier Amsterdam, 1983.
31. Ulshen MH, Dowling RH, Fuller CR, Zimmermann EM, Lund PK. Enhanced growth of small bowel in transgenic mice overexpressing bovine growth hormone. Gastroenterology 1993; 104: 973-80.
32. Delehaye-Zervas MC, Mertani H, martini JF, Nihoul-fekete C, Morel G, Postel-Vinay MC. Expression of the growth hormone receptore gene in human digestive tissues. J Clin Endocrinol Metab 1994; 78: 1473-80.
33. Bano M, Worland P, Kidwell WR, Lippman ME, Dickson RB. Receptor induced phosphorylation by mammary derived growth factor I in mammary epithelial cell lines. J Biol Chem 1992; 267: 10389-92.
34. Talhouk RS, Neiswander RL, Schanbacher FL. Developmental regulation and partial chraracterization of growth factors in the bovine mammary gland. J Reprod Fertil 1996; 106: 221-30.
35. Reiter B, Marshall VM et al. Nonspecific bactericidal activity of the lactoperoxidase-thiocyyanate-hydrogen peroxide system of milk against Escherichia Coli and some Gram-pathogens. Infection and Immunity 1976; 13: 800-7.
36. Tsuji S, Hirata Y et al. Comparison of lactoferrin content in colostrum between different cattle breeds. Journal of Dairy Science 1990; 73: 125-8.
37. Griffiths E, Hymphreys J. Bacteriostatic effect of human milk and bovine colostrum on Escherichia Coli: importance of bicarbonate. Infection and Immunity 1977; 15: 396-401
38. Naidu AS, Arnold RR. Lactoferrin interaction with Salmonellae potentiates antibiotic Susceptibility in vitro. Diagnostic Microbiology and Infectious Disease 1994, 20: 69-75.
39. Erdei I, Forsgren A et al. Lactoferrin binds to porins Ompf and
Ompe in Escherichia Coli. Infection and Immunity 1994; 62: 1236-40.
40. Jones EM, Smart A et al. Lactoferricin, a new antimicrobial peptide. Journal of Applied Bacteriology 1994; 77: 208-14.
41. Fleet JC. A new role for lactoferrin: DNA binding and transcription activation. Nutrition Reviews 1995; 53: 226-7.
42. Fleming A. Proceedings of the Royal Society 1922, B 93: 306.
43. Ito Y, Yamada H et al. The primary structures and properties of non-stomach lysozymes of sheep and cow, and implication for functional divergence of lysozyme. European Journal of Biochemistry 1993, 213: 649-58.
44. Pellegrini A, Thomas U et al. Bactericidal activities of lysozyme and aprotinin against Gram-negative and Gram-positive bacteria related to their basic character. Journal of Applied Bacteriology 1992; 72: 180-187.
45. Przemioslo RT, Ciclitira PJ. Cytokines and gastrointestinal disease mechanisms. Baillieres Clin Gastroenterol 1996; 10: 17-32.
46. Playford RJ, Floyd DN, Macdonald CE, et al. Bovine colostrum is a health food supplement wich prevents NSAID-induced gut damage. Gut 1999; 44: 653-8.
47. Dinarello CA. The interleukin-I family: 10 years of discovery. FASEB J 1994; 8: 1314-25.
48. Koldovsky O. Hormonally active peptides in human milk. Acta paediatr 1994; 402(suppl): 89-93.
49. Koldovsky O, Britton J, Davis D et al. The developing gastrointrstinal tract and milk-borne epidermal growth factor. In: Mestecky J, ed Immunology of milk and the neonate. New York: Plenum Press, 1991: 99-105.
50. Hirano M, Iweakiri R, Fujimoto K et al. Epidermal growth factor enhances repair of rat intestinal mucosa damaged after oral administration of methotrexate. J gastroenterol 1995; 30: 169-76.
51. Sullivan PB, Brueton MJ, Tabara Z et al. Epidermal growth factor necrotizing enterocolitis. Lancet 1991; 338: 53-4.
52. Playford RJ, Boulton R, Ghatei MA, Bloom SR, Wright NA, Goodlad RA. Comparison of hte effects of TGF and EGF on gastrointestinal proliferation and hormone release. Digestion 1996; 57: 362-7.
53. O’Loughlin W, Winter M, Shun A et al. Structural and functional adaptation following jejunal resection in rabbits: effect of epidermal growth factor. Gastroenterology 1994; 107: 57-93.
54. Kelly D, King TP, McFadyen M, Coutts AGP. Effect of preclosure colostrum intake on the development of the intestinal epithelium of artificially reared piglets. Biol Neonate 1993; 64: 235-44.
55. Harrison - Principi di Medicina Interna
56. Goodman & Gilman – Le Basi Farmacologiche della Terapia
57. A. Bruni – Farmacognosia Generale ed Applicata – I Farmaci Naturali
58. Buescher ES, et al. Soluble receptors and cytokine antagonists in human milk. Pediatr Res. 1996 Dec;40(6):839-44.
59. Nonnecke BJ, et al. Biochemical and antibacterial properties of bovine mammary secretion during mammary involution and at parturition. J Dairy Sci. 1984 Dec;67(12):2863-72.
60. Morris DD, et al. Passive transfer failure in horses: incidence and causative factors on a breeding farm. Am J Vet Res. 1985 Nov;46(11):2294-9.
61. Lavoie JP, et al. Colostral volume and immunoglobulin G and M determinations in mares. Am J Vet Res. 1989 Apr;50(4):466-70.
62. Murray MJ, et al. Epidermal growth factor-like activity in mares' milk. Am J Vet Res. 1992 Oct;53(10):1729-31.
63. Savage CR Jr, et al. Human epidermal growth factor/urogastrone: rapid purification procedure and partial characterization. Anal Biochem. 1981 Feb;111(1):195-202.
64. Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T. Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci 2002 Aug 9;71(12):1449-63.
65. Kamiya S, Taguchi H. [Prospect of the development of new bactericidal drugs against Helicobacter pylori for eradication therapy.] Nippon Rinsho 2002 Feb;60 Suppl 2:751-5.
66. Dehpour AR, Zolfaghari ME, Samadian T, Vahedi Y. The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats. J Pharm Pharmacol 1994 Feb;46(2):148-9.
67. Friis-Moller A, Chen M, Fuursted K, Christensen SB, Kharazmi. A In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots. Planta Med 2002 May;68(5):416-9.
68. Barfod L, Kemp K, Hansen M, Kharazmi A. Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines. Int Immunopharmacol 2002 Mar;2(4):545-55.
69. Guo N.[Protective effect of glycyrrhizine in mice with systemic Candida albicans infection and its mechanism.] Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1991 Oct;13(5):380-3.









