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Cranberry juice constituents affect influenza virus adhesion and infectivity


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Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM's potential for inhibiting influenza virus adhesion to cells, and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes (H1N1)and H3N2) and the B type was inhibited by NDM at concentrations of 125 microg/ml or lower, which is at least 20-fold lower than that usually found in cranberry juice. A dose-response effect of NDM on HA was demonstrated. The infectivity of the A and B types was significantly reduced by preincubation with NDM (250 microg/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.
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Antiviral Research 66 (2005) 9–12
Cranberry juice constituents affect influenza
virus adhesion and infectivity
E.I. Weissa,, Y. Houri-Haddada, E. Greenbaumb, N. Hochmana,
I. Ofekc, Z. Zakay-Ronesb
aDepartment of Prosthodontics, Faculty of Dental Medicine, Hebrew University-Hadassah, Jerusalem, Israel
bDepartment of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
cDepartment of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel
Received 26 July 2004; accepted 2 December 2004
Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation
of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM’s potential for inhibiting influenza virus adhesion to cells,
and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes
(H1N1and H3N2) and the B type was inhibited by NDM at concentrations of 125g/ml or lower, which is at least 20-fold lower than
that usually found in cranberry juice. A dose–response effect of NDM on HA was demonstrated. The infectivity of the A and B types was
significantly reduced by preincubation with NDM (250g/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney
(MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were
allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect
was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory
effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.
© 2005 Elsevier B.V. All rights reserved.
Keywords: Influenza; Cranberry; NDM; Antiviral effect
Influenza, a highly communicable acute respiratory dis-
ease, predisposes to a number of complications, resulting in
a severe worldwide economic burden. Prevention and con-
trol of both the annual influenza epidemics and its infrequent
but severe pandemic outbreaks are achieved by the use of
vaccines and newly emerging antiviral drugs.
These vaccines provide sometimes lower than desirable
protection, particularly in the immunocompromised and the
elderly, the two most susceptible subpopulations (Keren et
al., 1988; Admon et al., 1997). Furthermore, the vaccines
currently available are designated for intramuscular injec-
tion, resulting mainly in serum antibodies. It follows that a
negligible amount of mucosal antibodies are present at the
access site of the virus. In addition, vaccines are generally
Corresponding author. Tel.: +972 2 6776142; fax: +972 2 6429683.
E-mail address: (E.I. Weiss).
unavailable in the early stages of a pandemic (WHO, 1999)
and antiviral drugs may be the only means of intervention.
Two classes of antiviral drugs are used:
(i) Anti-M2 inhibitors amantadine and rimantadine, effec-
tive against A strains only (WHO, 1980). A reduction
in the severity and duration of the signs and symptoms
is recorded when they are administered within 48h of
disease onset (ACIP, 1996).
(ii) Neuraminadase inhibitors, effective against both A and
B viruses and better tolerated than the former. To date,
strains resistant to the drugs are not clinically important,
probably because they are not as virulent as the parental
strains. As prophylactics, these inhibitors are 70–90%
effective and may shorten the duration of illness by 1.5
days when used within the first 48 h (Treanor and Falsey,
1999; Hayden et al., 1999). Therefore, there is a need
0166-3542/$ – see front matter © 2005 Elsevier B.V. All rights reserved.
10 E.I. Weiss et al. / Antiviral Research 66 (2005) 9–12
for novel approaches and a new class of substances to
prevent and contain influenza outbreaks.
Physicians have long recommended consumption of cran-
berry juice to avoid urinary tract infections. It was hypoth-
esized that the prevention of such infections is due to the
inhibition of E. coli adhesion to uroepithelial cells by cran-
berry constituents (Ofek et al., 1991). Studies have shown
that cranberries contain high and low molecular weight con-
stituents [nondialyzable material (NDM) and proanthocyani-
dins, respectively], which act in vitro to inhibit the adhesion
of diverse microbial species (Ahuja et al., 1998; Burger et
al., 2000; Foo et al., 2000; Weiss et al., 1998; Zafriri et al.,
1989). Although it has been suggested that cranberry proan-
thocyanidins are one of the active anti-adhesion agents (Foo
et al., 2000), we found that NDM was at least six times more
dins in inhibiting bacterial adhesion and co-aggregation of
various representative bacteria (unpublished data).
Since NDM exhibits a broad anti-adhesion activity, it was
of interest to determine whether it inhibits the attachment
study we addressed this issue by testing the activity of NDM
on influenza virus-mediated red blood cell (RBC) hemagglu-
tination (HA) as well as on in vitro replication of the virus.
Cranberry juice from the American cranberry, Vaccinium
macrocarpon, and a proanthocyanidin-rich fraction were ob-
tained from Ocean Spray, Inc. The juice was dialyzed at 4C
for 10 days against distilled water, changed 10 times, in dial-
ysis bags of 15,000MW cut-off and lyophilized. The non-
dialyzable material exhibits tannin-like properties, is highly
soluble in water, devoid of proteins, carbohydrates and fatty
acids and contains 56.6% carbon and 4.14% hydrogen (Ofek
et al., 1996). As opposed to proanthocyanidins, the chemical
ular weight (>15,000) and because attempts to degrade it
by conventional chemical means into lower-sized molecules
no information was obtained using nuclear magnetic res-
onance (NMR) as well as matrix-assisted laser desorption
ionization (MALDI) or electrospray ionization (ESI) mass
spectrometry and chromatographic procedures to resolve its
The following influenza virus strains were used:
1. A/PR/8/34H1N1grownin the allantoic sac of 10–11-day-
old eggs to a 1:1024–2048 HA titer, or grown in Madine-
Darby canine kidney (MDCK) cells to a 1:128 HA titer.
2. A/H1N1(1:128 HA titer) and A/H3N2(1:256 HA titer),
clinical isolates grown in MDCK cells.
3. A/Panama 2007/99 H3N2adapted to MDCK cells (1:256
HA titer).
4. B/Yamanashi/166/98, grown in MDCK cells (1:256–512
HA titer). To evaluate replication inhibition, viruses cul-
tivated in MDCK cells were used.
Table 1
Effect of cranberry juice constituents (NDM) on viral hemagglutination and
replication in MDCK cells
Viral strain HAUaMDCK cells (log10)b
Nontreated Treated Nontreated Treated
Egg 16 <1 NP NP
MDCK 16 2–4 6.5 1.5c
A/H3N216 4–8 6.5 1.5c
A/H1N116 4–8 6.0 1.5c
B/Yamanashi 16 <1 7.5 1.5c
aHemagglutination units of treated virus (preincubated with 125g/ml
of NDM), compared with those of nontreated virus.
bTCID50 in MDCK cells of treated virus (preincubated with 250g/ml
of NDM), compared with that of nontreated virus.
cSignificantly different from the corresponding nontreated virus
(p<0.001,Fisher’sExactTest).Eachexperimentwas repeated at least twice.
To determine HA, 0.1 ml of twofold dilutions of each virus
suspension in phosphate-buffered-saline (PBS) was mixed
with 0.1ml of a 0.5% chicken RBC or 1% sheep RBC or
human 1% O RBC suspension and scored after 30 min incu-
bation at room temperature (Sever, 1962).
At 500g/ml, NDM did not cause hemolysis or sponta-
neous HA of any of the RBC tested. The HA data are sum-
marized in Table 1. Preincubation of NDM (125 g/ml) with
A/PR/8(egg-grown)orB/Yamanashi(grownin MDCK cells)
strains inhibited virus-induced HA. This was reduced from
16HA units (HAU) to <1 in NDM-containing virus suspen-
sions (100%). NDM at 125g/ml reduced the 16 HAU of
the two clinical isolates A/H1N1and A/H3N2to 4–8 units.
A/PR/8grown in MDCKcellswasless sensitiveto 125 g/ml
NDM; the 16 HAU were reduced to 2–4 HAU (Table 1). A
higherNDM concentration(400g/ml)was neededtoreduce
the HAU of the MDCK cell-grown A/PR/8 strain from 16 to
<1 units (not shown). Chess board titration of virus densities
and decreasing NDM concentrations revealed that as little as
4, 16, 64 and 128 g/ml NDM were needed to completely in-
hibit HA induced by 8, 16, 32, 64, respectively, HAU of virus
A/PR8/34. The results indicate a highly significant r2=0.980
correlation between HAU and NDM concentration required
to completely inhibit HA (Fig. 1). HA inhibition was also ob-
servedusing sheep or human RBC, consistent with the notion
that the target for NDM is the virus.
To test inhibition of virus replication, MDCK cells were
grown in DMEM medium supplemented with 10% inac-
tivated FCS and antibiotics (100g/ml penicillin G and
100g/ml streptomycin). For the assay, cells were grown
in 12-well culture plates (Nunc, Roskilde, Denmark) in a hu-
midified atmosphere with 5% CO2at 37C, and used when
confluent monolayers had formed (48 h). NDM inhibition of
virus infectivity in vitro was tested by incubating 250g/ml
NDM with virus for 2h at room temperature. Tenfold serial
dilutions in medium without serum were inoculated in trip-
licate wells containing MDCK monolayers. The virus was
allowed to adsorb for 1h at 37 C. The inoculum was re-
moved and the medium was supplemented with 1% serum
E.I. Weiss et al. / Antiviral Research 66 (2005) 9–12 11
Fig. 1. NDM concentration causing 100% inhibition of virus HA activity.
Eachof thevirus titers(A/PR8/34), expressedas log2of HAU,wasincubated
with twofold serial dilutions of NDM in order to determine the minimal
concentrationrequired forcomplete inhibition of virus HA. Each experiment
was performed in triplicate.
and trypsin, 2 g/ml (2×crystallized), was added. Following
4 days incubation at 37 Cina5%CO
2incubator, the mono-
layers were examined for cytopathic effect (CPE) (Fig. 2)
and the respective supernatants were assayed for HA. HA
was evident at a dilution of up to 107in the control wells,
whereas in wells infected with the virus-NDM suspension,
hemagglutination was observed only at 101. For the CPE,
the monolayers were washed with PBS to remove dead cells
and debris, fixed with cold methanol and stained with crys-
tal violet to determine the integrity of the monolayer. The
CPE was observed in all the control wells (Fig. 2 rows A,
B and C) at a 107viral dilution whereas in the virus-NDM
suspension the CPE was observed at 101(Fig. 1 rows D,
E and F). The observed CPE correlated with the HA results
(not shown), allowing calculation of tissue culture infective
dose (TCID50,Reed and Muench, 1938). NDM reduced the
B/Yamanashi titer from 107.5 to 101.5 (Table 1). Significant
Fig. 2. Prevention of virus-induced cytopathic effect by NDM. MDCK
monolayers were inoculated in triplicate with 10-fold dilutions (columns
1 to 8) of a B/Yamanashi virus suspension (rows A, B and C) or with a mix-
ture of NDM (250g/ml) and B/Yamanashi virus, in triplicate (rows D, E
and F). Following 1 h adsorption, the inoculum was removed, fresh medium
was added and the cultures were incubated for 4 days. The monolayers were
then fixed and stained for CPE. Blue staining indicates that the cells are
intact; staining is not obtained if the cells are destroyed. (For interpretation
of the references to color in this figure legend, the reader is referred to the
web version of the article.)
inhibition of infectivity by NDM was demonstrated for all
the virus strains tested (p<0.001, Fisher’s Exact Test): the
A/H3N2was reduced from 106.5 to 101.5, A/H1N1from 106.0
to 101.5 and A/PR8 (grown in MDCK cells) from 106.5 to
101.5 (Table 1). When A/H3N2and NDM were added si-
multaneously, TCID50 dropped from 106.5 to 102.0 and from
106.0 to 101.5 when A/PR8 was tested. These data suggest
that the NDM-virus interaction was virtually instantaneous
and that preincubation is not required. Inhibition of infectiv-
ity in MDCK cells was similar for the A strains (4.5–5 logs),
B/Yamanashi appeared to be more sensitive (6logs).
Although in our previous studies we observed very little
batch-to-batch variation in the ability of NDM to inhibit bac-
terial adhesion, further experiments are required to confirm
such variations in the virus system, as all experiments in this
study were performed with one batch of NDM.
To evaluate the potential of the NDM in the therapy of
viral infection, the cells were first exposed to viral suspen-
sions to allow adsorption followed by penetration into the
cells for 1h. NDM (100g/ml) was added at various post-
infection time intervals as indicated (Table 2). Viral TCID50
was determined in the treated cultures following 4 days and 6
days incubation by assaying the supernatants for HA activity,
as described above. The results show that NDM reduced the
virusTCID50 for the entire time of the follow-up(6dayspost-
infection). This effect was most accentuated when the NDM
was added several times to the infected MDCK monolayer
(Table 2). These results demonstrate that NDM can reduce
or inhibit virus replication indicating inactivation of newly
formed virus.
We also compared the effect of cranberry proanthocyani-
dins with that of NDM. A four- to fivefold higher proantho-
cyanidin concentration was required to completely inhibit 16
HA units of A/PR8 (grown in egg), confirming our previ-
ous observation that NDM is significantly more potent than
cranberry proanthocyanidins (unpublished data).
To be clinically effective, an antiviral drug should pre-
vent infection, arrest viral growth, eliminate the virus from
the cell or suppress viral multiplication, allowing an effective
hostreaction(WHO,1969).However,the use of the currently
available antiviral drugs such as anti-M2 inhibitors and neu-
Table 2
Effect of NDM added after infection on virus replication in MDCK cells
Viral strain Control Time (h) of NDM treatment
post-viral adsorptiona
1 6 24 1+6+24
A/Panama H3N2 3.5/3.5 <1/3 1.5/2.5 2/2.5b<1/<1c
B/Yamanashi 4.5/4.5 2.5/3 2/3b3/>3b<1/1.5c
The numbers indicate the viral log10 TCID50, determined following 4/6 days
incubation by assaying the supernatants for HA as described in the text. The
values are the averages of triplicates of two independent experiments.
aNDM, 100 g/ml, was added in each treatment.
bLogistic regression at a confidence interval of 95% yielded odds of
cLogistic regression at a confidence interval of 95% yielded odds of
12 E.I. Weiss et al. / Antiviral Research 66 (2005) 9–12
raminadase inhibitors is limited, owing to their low effective-
ness, strain specificity, side effects and the emergence of re-
sistant strains (Hayden et al., 1991). Since NDM is prepared
from cranberries and its antiviral effect was demonstrated
at concentrations lower than that found in cranberry juice
cocktail, it is unlikely to cause any significant side effects.
NDM may belong to a class of natural antiviral substances.
It appears that NDM interacts directly with the virus, as pre-
treatment of MDCK cells or RBC with NDM followed by
rinsing, had little or no effect on the virus-induced HA or
TCID50. NDM probably exerts its effect by preventing viral
adsorption onto the cells because it inhibited viral HA, which
is mediated by the sialic acid-specific hemagglutinin. More-
over, its effect on the infectivity of the virus was more pro-
nouncedwhenaddedseveraltimes post-infection, suggesting
that it prevented the adsorption of viral progeny released by
infected cells onto new cells. Based on our cumulative find-
ings, it is possible that NDM could be used as an aerosol or
for intranasal administration to control influenza viral infec-
tion. The anti-bacterial adhesion effects of NDM on bacte-
rial adhesion and aggregation might have an important added
value in preventing bacterial infections secondary to viral
This study was performed in part at the R. Goldstein Re-
search Center, Faculty of Dentistry, Hadassah-Hebrew Uni-
versity. The work was partially supported by a grant from
Ocean Spray, Inc.
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Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry’s polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.
... Une autre étude a montré des résultats similaires sur le virus de la grippe. Une réduction de l'adhésion et de la réplication du virus a été observée sur des cellules de foie de chien (MDCK) [124]. ...
L’infection urinaire (IU) est un problème majeur de Santé publique. La cystite aiguë touchant principalement les femmes est la plus fréquente des IU. La bactérie la plus fréquemment isolée au cours de ces IU est Escherichia coli. Une des particularités de la cystite est sa propension à récidiver. Le traitement préconisé pour ces infections est la prise d’antibiotiques, qui peut être fréquente en cas de cystites récidivantes. C’est dans ce contexte que de nouvelles stratégies doivent être développées afin de prévenir et traiter les IU récidivantes. Parmi ces différentes stratégies, l’utilisation de produits naturels tels que la canneberge (Vaccinium macrocarpon) apparaît comme prometteuse. En effet, des études précédentes ont montré que la canneberge a un effet négatif sur l’adhésion des bactéries aux cellules superficielles de l’épithélium vésical facilitant l’élimination des bactéries par le flux urinaire. Cette activité est portée par la proanthocyanidine de type A (PAC-A). D’autre part, une étude menée par notre équipe a montré que l’effet de la canneberge sur l’adhésion et la virulence de souches d’E. coli uropathogènes pouvait être potentialisé par l’ajout d’un autre composé naturel : la propolis. Depuis l’Antiquité ses propriétés anti-bactériennes sont reconnues et des études plus récentes ont démontré son impact sur des bactéries à Gram positif mais également sur deux bactéries à Gram négatif : E. coli et Pseudomonas aeruginosa. Ce travail de thèse a permis : i) de décrire l’impact de la canneberge, de la propolis et de leur association sur le transcriptome d’une souche clinique d’E. coli uropathogène (G50). Cette analyse transcriptomique a montré que la canneberge entrainait une sous-expression de gènes liés à l’adhésion, mais également de gènes liés à la mobilité et à la formation de biofilm. En revanche, la canneberge augmentait l’expression des gènes liés au métabolisme du fer ainsi qu’à la réponse au stress. Ces effets étaient potentialisés par l’ajout de la propolis. En parallèle, des tests phénotypiques menés sur une collection de souches d’E. coli uropathogènes sur la mobilité et la formation de biofilm ont confirmé les résultats précédents ; ii) de développer un test, basé sur les précédents travaux de transcriptomique, permettant une évaluation standardisée de l’effet de la PAC-A sur E. coli, indépendamment de sa concentration car il n’existe pas de techniques standardisées pour doser cette molécule. C’est ainsi que 4 gènes (tsr, ftnA, fecB, feoB) ont été sélectionnés, le suivi de leur expression permettant une mesure de l’activité anti-bactérienne de la canneberge; iii) de mesurer l’effet potentialisateur de la propolis sur l’activité des antibiotiques utilisés dans le traitement des IU. C’est ainsi qu’il a été montré que l’ajout de la propolis permettait d’augmenter l’activité bactéricide des antibiotiques testés et de diminuer les concentrations minimales inhibitrices de ces antibiotiques.
... In addition, inhibition of hemagglutinin occurred at a 20% concentration of CJ that was treated with simian rotavirus SA-11 (Lipson et al., 2007). In another study, CJ inhibited InfV A and B adhesion to cells, and subsequent infectivity (Weiss et al., 2005). As an antiviral agent, CJ suggested being considered as an effective viral system to that of a mammalian enteric virus. ...
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As the leading cause of death worldwide, viruses significantly affect global health. Despite the rapid progress in human healthcare, there are few viricidal and antiviral therapies that are efficient enough. The rapid emergence of resistance, and high costs, as well as the related side effects of synthetic antiviral drugs, raise the need to identify novel, effective, and safe alternatives against viral diseases. Nature has been of the most exceptional help and source of inspiration for developing novel multi-target antiviral compounds, affecting several steps of the viral life cycle and host proteins. For that matter and due to safety and efficacy limitations, as well as high resistance rate of conventional therapies, hundreds of natural molecules are preferred over the synthetic drugs. Besides, natural antiviral agents have shown acceptable antiviral value in both preclinical and clinical trials.This is the first review regarding molecular and cellular pathways of the virus life cycle, treatment strategies, and therapeutic targets of several viral diseases with a particular focus on anthocyanins as promising natural compounds for significant antiviral enhancements. Clinical applications and the need to develop nano-formulation of anthocyanins in drug delivery systems are also considered.
... NDM inhibited the hemagglutinin activity of influenza type A and B viruses, thus preventing virus attachment and penetration into cells. When NDM was added to infected cells, it reduced or inhibited in vitro virus replication (Weiss, Houri-Haddad, Greenbaum, Hochman, Ofek, & Zakay-Rones, 2005). The effect of NDM on glycoproteins is not limited to hemagglutinins, but it also includes neuraminidases. ...
Influenza is a highly dangerous disease, as it is connected with a risk of complications and in extreme cases – also death. Treatment based on virustatic drugs is not always effective, as mutations lead to the development of drug-resistant viruses. A relatively efficacious protection against influenza is provided by vaccinations; however, they are not very popular due to the common distrust in their efficacy and concerns over their supposed adverse effects. Phytotherapy uses several raw materials which may be applied in the prevention and treatment of influenza. Plant origin materials of particular interest include berry fruits containing considerable amounts of bioactive compounds. The multifaceted health-promoting action of berry fruits is connected first of all with the presence of polyphenols. Antiviral activity against influenza viruses results from the presence of anthocyanins and other classes of flavonoids, proanthocyanidins and phenolic acids. An important group of compounds other than polyphenols, which may be readily used in influenza infections comprises polysaccharides. Research indicates that components of berry fruits may inhibit replication of the virus both directly and indirectly, e.g. by blocking surface glycoproteins of influenza virus and stimulating the immune system of the organism. In consequence to their properties berry fruits are raw materials of potential use in the prevention and treatment of influenza.
Excessive activation and proliferation of hepatic stellate cells (HSCs) is the most critical factor in liver fibrosis. Cranberry (Vaccinium macrocarpon) is berry-bearing with potential health benefits. Here, we reported the inhibitory effects of cranberry phytochemicals (CPS) on HSC activation and liver fibrogenesis. The results showed that CPS reduced cell viability and inhibited the TGFβ/Smad signaling pathway of HSCs in vitro. The therapeutic effects of CPS on HSC activation were further linked to the amelioration of CCl4-induced liver fibrosis in rats. CPS treatment reduced liver fibrosis, revived liver function (HYP, MDA, ALB, ALP, ALT, AST, and TBIL), and decreased inflammatory cytokines (IL-1, IL-6, and TNF-α) in a dose-dependent manner. Moreover, the expression levels of the TGFβ/Smad signaling pathway related genes, including TGF-β1, Smad2/3, p-Smad2/3, Col1α1, and α-SMA, were down-regulated by CPS. It is suggested that CPS may inhibit HSC activation and liver fibrosis by reducing the expression of inflammatory cytokines and inhibiting the TGFβ/Smad signaling pathway.
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Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.
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For many decades, cranberry juice has been recommended by physicians in North America for the treatment or prevention of urinary tract infections (UTI). However, until recently, no experimental evidence has been presented for the purported beneficiary effect of the juice, nor for its mechanism of action. For a while, it was believed that the antibacterial effect of the juice is due to its ability to acidify urine and thus to inhibit bacterial growth but no support for this was found (Kunin, 1987; Bodel et al., 1959).
Dental plaque stability depends on bacterial adhesion to acquired pellicle, and on interspecies adhesion (or coaggregation). A high-molecular-weight cranberry constituent at 0.6 to 2.5 milligrams per milliliter reversed the coaggregation of 49 (58 percent) of 84 coaggregating bacterial pairs tested. It acted preferentially on pairs in which one or both members are gram-negative anaerobes frequently involved in periodontal diseases. Thus, the anticoaggregating cranberry constituent has the potential for altering the subgingival microbiota, resulting in conservative control of gingival and periodontal diseases. However, the high dextrose and fructose content of the commercially available cranberry juice makes it unsuitable for oral hygiene use, and the beneficial effect of the high-molecular-weight constituent requires animal and clinical studies.
A microtechnique (modified Takatsy) is described which can be applied to complement fixation, hemagglutination, hemagglutination inhibition and metabolic inhibition tests. The system permits an 8-fold saving of reagents and rapid performance of microdilutions. The specific methods and modifications of equipment necessary to obtain reliable results are presented in detail. Comparative data obtained with the micro- and standard systems establish the reliability and validity of the microsystem.
A cohort of 127 nursing home residents aged 60–98 years were vaccinated during the winter of 1985–86 with the A-Chile 1/83 (C), A-Philippines 2/82 (P), and B-USSR (B) commercial influenza vaccines. Before vaccination 40%, 23%, and 69% were susceptible to influenza Ac, Ap, and B, respectively [hemagglutinin inhibition (H.I.) titer <1:40]. One month following initial vaccination, 32 patients [25%] remained unprotected against two or all three vaccine strains. These patients were revaccinated with the same influenza vaccine and followed up. At five months 11 %, 19%, and 23% of the initial cohort were still unprotected against Ac, Ap, and B strains, respectively. We conclude that two conventional influenza vaccines administered one month apart leave unprotected 30% of healthy elderly people who are initial influenza vaccine failures.
Ethyl acetate extracts of Sephadex LH20-purified proanthocyanidins of American cranberry (Vaccinium macrocarpon Ait.) exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing α-Gal(1 → 4)β-Gal receptor sequences similar to those on epithelial cells in the urinary tract. The chemical structures of the proanthocyanidins were determined by NMR, electrospray mass spectrometry, matrix-assisted laser absorption time-of-flight mass spectrometry and by acid catalyzed degradation with phloroglucinol. The proanthocyanidin molecules consisted predominantly of epicatechin units with mainly DP of 4 and 5 containing at least one A-type linkage. The procyanidin A2 was the most common terminating unit occurring about four times as frequently as the epicatechin monomer.
The therapeutic activity of rimantadine and its relationship to the shedding of drug-resistant influenza A virus were assessed in two randomized, double-blind, placebo-controlled trials involving patients with laboratory-documented influenza A virus (H3N2 subtype) illness of 2 days' duration or less. In a family-based study, rimantadine treatment for 10 days (24 children and adults) was associated with significant decreases in the number of days to a 50% reduction in symptoms (mean difference, 2.5 days), days of fever (1.6 days), and days of restricted activity (1.5 days) compared with the results obtained with placebo-treated patients (32 children and adults). Drug-resistant virus was recovered from eight (33%) of the rimantadine recipients on day 5. No differences in patient demographics or illness severity at the time of enrollment in the study were apparent between those who shed resistant virus and those who did not. Illness resolution tended to be slower in those who shed resistant virus compared with that in those who did not. In a study of adults treated for 5 days (six treated with rimantadine, six treated with placebo), resistant virus was recovered in three rimantadine recipients by day 3 of treatment. The results indicate that drug-resistant influenza A virus (H3N2) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment, but that rimantadine retains a net therapeutic benefit compared with that of placebo.