LIQUORICE - REFERENCES
- Anti-Helicobacter pylori flavonoids from licorice extract.
- In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots.
- Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines.
- 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.
- The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats.
- Chemical modification of glycyrrhizic Acid as a route to new bioactive compounds for medicine.
- Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus.
- A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice.
- Opinion of The Scientific Committee On Food on glycyrrhizinic acid and its ammonium salt
- Licorice root. A natural sweetener and an important ingredient in Chinese medicine*
Life Sci 2002 Aug
9;71(12):1449-63
1.
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.
L’estratto di liquirizia rappresenta la droga grezza maggiormente
utilizzata dalla medicina orientale; è rimarcato il suo impiego nel
trattamento dell’ulcera peptica. Tra i numerosi componenti sono
riportati diversi flavonoidi che hanno mostrato in vitro capacità di
inibire la crescita di H. pylori. Tale azione è stata osservata anche
verso ceppi di H. pylori claritromicina ed amoxicillina-resistenti. In
particolare, è stato esaminato l’estratto in metanolo di Glycyrrhiza
uralensis. Da questo estratto sono stati isolati 15 flavonoidi già
conosciuti e 3 non ancora noti. Tra tutte queste molecole, alcune sono
state riconosciute maggiormente attive di altre nei confronti di H.
pylori claritro e amoxi-resistente. Si indicano tali composti per
un loro utile impiego come agenti chemo-preventivi verso l’ulcera
peptica e l’insorgenza di cancro allo stomaco nei soggetti con H.
pylori.
^ Inizio
Planta Med 2002 May;68(5):416-9
2. 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.
^ Inizio
Int Immunopharmacol 2002 Mar;2(4):545-55
3. 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
^ Inizio
Nutrition 2002 Mar;18(3):268-73
4. 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.
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J Pharm Pharmacol 1994 Feb;46(2):148-9
5. 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%).
E’ stato esaminato l’effetto della
liquirizia e dei suoi derivati contro l’ulceragastrica indotta da
aspirina nei ratti.
L’aspirina rivestita con liquirizia ha mostrato una riduzione nel
numero e nella dimensione delle ulcere da essa provocate.
Il rivestimento con i soli derivati della liquirizia si sono mostrati in
tal senso meno efficaci.
^ Inizio
Curr Med Chem 2003 Jan;10(2):155-71
6. Chemical modification of glycyrrhizic Acid as a route to new bioactive compounds for medicine.
Baltina LA.
Institute of Organic Chemistry Ufa Research Centre of RAS, 71 Prospect Oktyabrya, Ufa, 450054, Russian Federation. baltina@anrb.ru
Glycyrrhizic Acid (GL) is the major bioactive triterpene glycoside of licorice root (Glycyrrhiza Radix) extracts possessing a wide range of pharmacological properties (anti-inflammatory, anti-ulcer, anti-allergic, anti-dote, anti-oxidant, anti-tumor, anti-viral etc.). Official sources of GL are Glycyrrhiza glabra L. and Gl. uralensis Fish. (Leguminosae). The content of GL in licorice root is 2-24% of the dry weight. GL is one of the leading natural compounds for clinical trials of chronic active viral hepatitis and HIV infections (preparation Stronger Neo-Minophagen C, SNMC), and its monoammonium salt (glycyram, tussilinar) is used as an anti-inflammatory and anti-allergic remedy. The synthetic transformations of GL on carboxyl and hydroxyl groups were carried out to produce new bioactive derivatives for medicine. GL esters were produced containing fragments of bioactive acids (4-nitrobenzoic, cinnamic, salycilic, acetylsalycilic, nicotinic, isonicotinic). Bioactive amides of GL were synthesized using chloroanhydride technique and N,N'-diciclohexylcarbodiimide (DCC) method. The synthesis of acylthioureids and semicarbazones was carried out via the reaction of triacylisothiocianate of penta-O-acetyl-GL with primary amines and hydrazines. The chain of transformations of trichloranhydride of penta-O-acetyl-GL was made with the introduction of diazoketone groups in the molecule. A new group of GL derivatives to be triterpene glycopeptides was prepared by the activated esters method (N-hydrohysuccinimide-DCC or N-hydroxybenzotriazol-DCC) using alkyl (methyl, ethyl, propyl, butyl, tert-butyl) or benzyl (4-nitrobenzyl) esters of amino acids. The glycyrrhizyl analogs of the known immunostimulator, N-acetyl-muramoyldipeptide (MDP), were synthesized using Reagent Woodward K. A series of ureids and carbamates of GL was synthesized containing 5-amino-5-desoxy-D-xylopyranose units. The synthesis of 4-nitro-4-desoxy-glycosides, modified analogs of GL, was carried out by the oxidative splitting of the carbohydrate part of GL with NaIO(4). Triterpene 2-desoxy-D-glycosides, analogs of GL, were prepared by the glycal method in the presence of iodine-containing promoters or sulfonic acid cation-exchange resin KU-2-8 (H+) and LiBr. New anti-inflammatory and anti-ulcer agents were found among GL derivatives such as esters, amides, ureids, carbamates, thioureids and glycopeptides. GL glycopeptides are of interest as immunomodulators. Some of the chemically modified GL derivatives (salts, amides, glycopeptides) were potent HIV-1 and HIV-2 inhibitors in vitro. Preparation niglizin (penta-O-nicotinate of GL) was studied clinically as an anti-inflammatory agent and is of interest for studies as hepatoprotector and HIV inhibitor.
L’acido glicirrizico è il più importante glicoside triterpenico con attività biologica presente nella radice di liquirizia. I suoi estratti posseggono un’ampio range di proprietà farmacologiche ampiamente riconosciute (antinfiammatorie, anti-ulcera, antiossidanti, antivirali ecc.). L’acido glicirrizico è estratto dalle radici di Glycyrrhiza glabra L. e Glycyrrhiza uralensis Fish. ed è contenuto in quantità variabile dal 2 al 24% sul peso secco.
L’acido glicirrizico è infatti la principale molecola naturale utilizzata nei trials clinici in corso di infezioni da HIV e di epatiti virali, i suoi sali d’ammonio sono impiegati come trattamento antinfiammatorio ed antiallergico.
Sono molteplici le modificazioni sintetiche che i gruppi carbossilico e ossidrilico dell’acido glicirrizico possono subire originando nuovi derivati biologicamente attivi con largo utilizzo in medicina. Per esempio, derivati quali esteri, ammidi, ureidi, carbammati, tioureidi, glicopeptidi e sali sono stati riconosciuti come nuovi agenti antinfiammatori, antiulcera ed immunomodulatori. In vitro, alcune di queste molecole hanno inoltre mostrato proprietà inibitorie verso i virus HIV-1 e HIV-2.
^ Inizio
Fitoterapia 2002 Oct;73(6):536-9
7. Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus.
Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T.
School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. fukai@pahr.toho-u.ac.jp
Nineteen flavonoids isolated from licorice (Glycyrrhiza glabra, G. inflata and G. uralensis) were tested for their antimicrobial activities against methicillin sensitive Staphylococcus aureus, methicillin resistant S. aureus, Micrococcus luteus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Copyright 2002 Elsevier Science B.V.
Diciannove flavonoidi sono stati isolate dalla liquirizia e ne sono state testate le proprietà antimicrobiche contro I seguenti germi: S.aureus meticillino-sensibile, S. aureus meticillino-resistente, M. luteus, B. subtilis, E. coli, K. Pneumonite e P. aeruginosa.
^ Inizio
Yakugaku Zasshi 2000 Oct;120(10):849-62
8. A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice.
Shibata S.
Shibata Laboratory of Natural Medicinal Materials, C/o Minophagen Pharmaceutical Co., Ltd., Tokyo, Japan.
Licorice, the root of Glycyrrhiza spp. (Fabaceae), has been used since ancient Egyptian, Greek, and Roman times in the West and since the Former Han era (the 2nd-3rd century B.C.) in ancient China in the East. In traditional Chinese medicine, licorice is one of the most frequently used drugs. In Japan, the oldest specimen of licorice introduced from China in the middle of the 8th century still exists in Shosoin, the Imperial Storehouse, in Nara. Extracts of licorice were recommended as a remedy for gastric ulcer by Revers of the Netherlands in 1946, which was soon withdrawn owing to its side effects. Carbenoxolon sodium, glycyrrhetinic acid (GA) hemisuccinate Na, was prepared from licorice to treat peptic ulcer in the UK. In Japan for the past 60 years, a glycyrrhizin (GL) preparation under the name of Stronger Neo-Minophagen C (SNMC) has been used clinically as an antiallergic and antihepatitis agent. GL and GA sometimes induce edema, hypertension, and hypokalemia in patients treated with higher doses and long-term administration. The mechanism of this side effect, pseudoaldosteronism, has been explained as due to the 11-hydroxy-steroid dehydrogenase inhibitory activity of GL and GA. The excess of endogenous cortisol produced combines with the renal mineral corticoid receptor, which promotes an aldosterone-like action. GL and GA reduce alanine transaminase (ALT) and aspartate transaminase (AST) values in the serum. This hepatoprotective effect has recently been explained as the inhibitory effects of GL and GA on immune-mediated cytotoxicity against hepatocytes and on nuclear factor (NF)-kappa B, which activates genes encoding inflammatory cytokines in the liver. To exclude the side effects and enhance the therapeutic activities, chemical modification of GL and GA has been performed. Deoxoglycyrrhetol (DG), homo- and heteroannular diene homologs of dihemiphthalates, showed a remarkable improvement in antiinflammatory, antiallergic, and antiulcer activities in animal experiments. Immunomodulating effects of GL, GA, and DG derivatives, which induce interferon-gamma and some other cytokines, have been demonstrated in relation with their antiviral activities. Antiinflammatory, antitumorigenic, and antimalarial effects of licorice flavonoids have also been investigated.
La liquirizia
estratta dalle redici di Glycyrrhiza è nota fin dall’antichità sia
alla medicina egiziana, greca e romana che alla medicina cinese per la
quale rappresentava uno dei rimedi più utilizzati.
Tutt’ora molti preparati sono ottenuti a partire da questo estratto e
molteplici sono le loro applicazioni: come antiallergico, agente
anti-epatite, nel trattamento dell’ulcera peptica.
Effetti collaterali, che possono essere indotti dall’acido
glicirrizico e dalla glicirrizina, sono rappresentati da edema,
ipertensione e iperkaliemia in pazienti trattati con elevati dosaggi e
somministrazioni a lungo termine. Al fine di eliminare tali effetti sono
state eseguite reazioni di sintesi che hanno modificato le molecole
responsabili. Effetti immunomodulatori di queste molecole derivate,
inducenti l’attività dell’Interferon-γ e di alcune altre
citochine, sono state osservati in relazione alla loro azione
antivirale. Sono stati, inoltre, esaminati i flavonoidi della liquirizia
relativamente alle proprietà antinfiammatorie, antitumorali e
antimalariche.
^ Inizio
Scientific Committee on Food
SCF/CS/ADD/EDUL/225 Final - 10 April 2003
9. Opinion of The
Scientific Committee On Food on glycyrrhizinic acid and its ammonium
salt
Clicca qui e apri il documento in formato PDF:
Conclusion
Previously, the Committee evaluated the toxicological information
for glycyrrhizinic acid and concluded that the data were inadequate to
derive an ADI (SCF, 1991). At that time, the Committee considered it
prudent that regular ingestion should not exceed 100 mg/day, while it
was explicitly mentioned that this was a provisional figure. Since then,
new toxicological information, including data from human volunteer
studies, has become available. Although these data provide a stronger
basis for the upper limit for regular ingestion of glycyrrhizinic acid
of 100 mg/day, the Committee still is of the opinion that an ADI for
glycyrrhizinic acid and ammonium glycyrrhizinate cannot be derived,
because the new human toxicity studies are too limited (small
experimental groups, short duration).
The Committee considers that this upper limit for regular ingestion of
100 mg/day provides a sufficient level of protection for the majority of
the population. It is noted that this upper limit includes the intake of
glycyrrhizinic acid via all products, liquorice confectionery as well as
glycyrrhizinic acid- or ammonium glycyrrhizinate-flavoured products.
Sebbene in questi ultimi anni nuovi studi abbiano fornito nuovi dati e
più solide basi per stabilire il limite massimo di ingestione
dell’acido glicirrizinico a 100mg/giorno, il Comitato scientifico per
l’alimentazione è ancora del parere che un valore di ADI per questo
acido e per il suo sale d’ammonio non possano ancora essere derivati a
causa di studi sulla tossicità ancora troppo limitati.
Il Comitato considera che il limite massimo di una ingestione regolare
di 100mg/giorno fornisca un sufficiente livello di protezione per la
maggior parte della popolazione (ciò, ovviamente, indipendentemente
dalla matrice di assunzione).
^ Inizio
Pure Appl. Chem. Vol. 74, No. 7, pp. 1189-1198 (2002)
10. Licorice root. A natural sweetener and an important ingredient in Chinese medicine*
Isao Kitagawa
School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
Abstract: This paper reviews our investigations on the chemical constituents of several kinds of botanically identified licorice roots, which led to the characterization of 13 then-new glucuronide-saponins named licorice-saponins (AL), apioglycyrrhizin, and araboglycyrrhizin, together with glycyrrhizin and 18a-glycyrrhizin and also of 49 kinds of phenolic compounds and their glycosides (11 then-new). The restoration-promoting activity of licorice-saponin B2 for CCl4-intoxicated hepatocyte function and the structuresweetness relationship of saponins were discussed. Biologically interesting, but isolable in minor quantities, several licorice-saponins were favorably synthesized from abundantly available glycyrrhizin. With 15 saponins and 49 phenolic compounds (including their glycosides) at hand, chemical evaluation of licorice root processings was undertaken. It was shown that the cortex contained a rich amount of phenolic compounds, whereas the xylem was rich in phenolic glycosides and the saponins contained were richer in the xylem than in the cortex. It was also found that roasted licorice root contained an increased amount of glycyrrhetic acid monoglucuronide, which was secondarily formed from glycyrrhizin through thermal hydrolysis and was known to taste 5 times sweeter than glycyrrhizin.
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AAPS PharmSciTech. 2005 Sep 20;6(1):E74-82.
Licorice: a possible anti-inflammatory and anti-ulcer drug.
Aly AM, Al-Alousi L, Salem HA.
Faculty of Pharmacy, Al-Isra University, Amman, Jordan. amaly50@yahoo.com
The purpose of this investigation was to study the anti-inflammatory activities of both glycerrhitinic acid (GA) and the aqueous licorice extract (ALE) in comparison with diclofenac sodium (DS) (10 mg/kg), using the carrageenan-induced paw edema model in male albino rats. In addition, the anti-ulcer activities of ALE, famotidine (FT), and a combination of ALE and FT using indomethacin-induced ulceration technique in rat stomach were investigated. Conventional DS tablets containing GA, as well as DS chewable tablets containing either GA or ALE with different tastes were prepared. Also, rapidly disintegrating FT tablets were prepared using direct compression and camphor sublimation methods. ALE or GA produced significant anti-inflammatory activity similar to DS, and when taken concomitantly, there is no possible antagonism. The anti-ulcer activity of licorice was found to be similar to that of FT in indomethacin-induced ulceration technique in rat stomach. Combination therapy of both FT and licorice showed higher anti-ulcer activity than either of them alone. Generally, tablets containing the crosslinked sodium carboxymethyl cellulose (AcDisol) showed more rapidly disintegrating effect than those including Sodium starch glycolate (Primojel). The oral disintegration was very rapid for all the tested formulations. Also, the amount of FT absorbed from the oral cavity was nearly 9 from 10 mg theoretically present in each formula. It could be concluded that both GA and ALE have anti-inflammatory activity comparable with DS. It may be recommended to add ALE to either FT or diclofinac for more effective anti-inflammatory or anti-ulcer formulations, respectively.
nota: in Gastromilk è utilizzato ALE.
^ Inizio