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Macleya cordata and Prunella vulgaris in oral hygiene products - their efficacy in the control of gingivitis

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Abstract

A double-blind, placebo-controlled clinical trial was performed to investigate the effectiveness of a herbal-based dentifrice in the control of gingivitis. Forty volunteers completed the 84-day study. All subjects were balanced for parameters measured - plaque index (PI), community periodontal index of treatment needs (CPITN) and papillary bleeding index (PBI). The dentifrice was effective in reducing symptoms of gingivitis as evaluated by the CPITN and PBI indexes.
103
MACLEYA CORDATA AND PRUNELLA VULGARIS IN ORAL HYGIENE PRODUCTS
– THEIR EFFICACY IN THE CONTROL OF GINGIVITIS
Hana Adámková
a
, Jaroslav Vičar
b
, Jiřina Palaso
c
, Jitka Ulrichová
b
, Vilím Šimánek
b*
a
1
st
Clinic of Dentistry, Faculty of Medicine, Palacký University, Czech Republic
b
Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University, 775 15 Olomouc,
vilim@tunw.upol.cz
c
Dental Surgery, Mikulášská 27, 794 01 Krnov
Received: May 12, 2004; Accepted July 6, 2004
Key words: Macleya cordata/Prunella vulgaris/Dentifrice/Antimicrobial/Anti-infl ammatory/Gingivitis
A double-blind, placebo-controlled clinical trial was performed to investigate the eff ectiveness of a herbal-based
dentifrice in the control of gingivitis. Forty volunteers completed the 84-day study. All subjects were balanced for
parameters measured – plaque index (PI), community periodontal index of treatment needs (CPITN) and papillary
bleeding index (PBI). The dentifrice was eff ective in reducing symptoms of gingivitis as evaluated by the CPITN and
PBI indexes.
INTRODUCTION
In oral hygiene preparations, toothpastes, massage
gels, mouthrinses, prevailing active components are syn-
thetic substances such as antimicrobially active benzy-
damine hydrochloride (1-benzyl-[3-(dimethyl amino)
pro poxyl]-1H-indazole), cetylpyridinium chloride, chlor -
hexidine digluconate (1,6-di(4’-chlorophenyl diguanido)
hexane digluconate), triclosan (5-chloro-2-2,4-dichloro-
phenoxy)phenol) and zinc chloride or stannous fl uoride.
Another important market segment is formed by prepara-
tions containing as active components, medicinal plants
reputed for their anti-infl ammatory and antimicrobial
activity. Herbal products of this kind traditionally contain
plant extracts and/or pure components including chamo-
mile, echinacea, peppermint oil, sage, myrrh, green tea
biofl avonoids, gallotannins and substances such as allan-
toin, coenzyme Q
10
, bisabolol, guaiazulene, eugenol, and
eucalyptus essential oil (thymol and eucalyptol, mixed
with menthol and methyl salicylate) (ref.
1
). In comparison
to the above-mentioned synthetic products, however plant
extracts and/or components are less effi cient following
single application.
Recently, we have studied the biological activity of an
extract of Prunella vulgaris L. (Labiatae), and we found
marked cytoprotective, antioxidant/radical scavenging,
antiviral and anti-infl ammatory eff ects both in vitro and
in vivo
2
. This plant, known as the “self-heal”, was popular
in traditional European medicine during the 17
th
century
as a remedy for alleviating sore throat, reducing fever,
and accelerating wound healing
3
. A major constituent
of P. vulgaris is rosmarinic acid, a phenolic antioxidant
whose content can be as high as 6 % (ref.
4
). Phytochemi-
cal studies indicate that P. vulgaris further contains olea-
nolic, betulinic, ursolic, 2α,3α-dihydroxyurs-12-en-28-oic
and 2α,3α-ursolic acids, triterpenoids, fl avonoids, tannins
and anionic polysaccharide prunelline
5
. Isoquinoline al-
kaloids from Macleya cordata R. Br. (Papaveraceae) are
another group of biologically active components studied
recently in this laboratory. The main alkaloids of this
plant, quaternary benzo[c]phenanthridines (QBA) san-
guinarine and chelerythrine are among the antimicrobi-
ally most active of natural substances. These alkaloids
display a plethora of species- and tissue-specifi c actions
but the molecular basis of their pharmacological activi-
ties remains obscure
6
. They exhibit antimicrobial, anti-
infl ammatory, antimitotic, adrenolytic, sympatholytic,
cytostatic and local anesthetic eff ects
7
. Medicinal plants
Sanguinaria canadensis and Chelidonium majus (Papav-
eraceae) containing both alkaloids were in the past, uti-
lized in traditional medicine (North America, Europe,
China). QBA fractions from S. canadensis sanguinaria
and M. cordata – sanguiritrin are used in toothpastes and
mouthwashes as antiplaque agents. Sanguinarine as well
as extracts containing benzo[c]phenanthridine alkaloids
exhibit very low acute oral toxicity (LD
50
1.7, and 1.4 g/
kg, resp.; rat); in subchronic studies, minor evidence of
treatment-related toxicity of QBA (doses > 30 mg/kg/day;
rat, monkey) has been reported (summarized in ref.
7
).
The cytotoxicity of sanguinarine was assessed on human
S-G gingival cells and human HGF-1 gingival fi broblasts
in an in vitro experiment; the 24 hours cytotoxicity was
comparable to that of chlorhexidine
8
. The available data
do not predict a health hazard to humans when QBA-
containing oral hygiene products are used. On the other
hand, it has been reported by a single group of authors
that long-term use (5 years) of oral products containing
0.03 % of sanguinaria is compromised by increased preva-
lence of maxillary vestibule leukoplakia
9
.
Biomed. Papers 148(1), 103–105 (2004)
© H. Adámková, J. Vičar, J. Palasová, J. Ulrichová, V. Šimánek
104
H. Adámková, J. Vičar, J. Palasová, J. Ulrichová, V. Šimánek
The aim of this study was to assess the effi cacy of
a dentifrice containing M. cordata and P. vulgaris extracts
in the control of gingivitis.
MATERIAL AND METHODS
Ethical approval for the clinical trial was provided by
the Ethical Committee of the Teaching Hospital, Olo-
mouc. A total of 40 subjects (18 female and 22 male) aged
between 34 and 58 years were selected for the study. They
had to manifest gingivitis as defi ned by bleeding on gentle
probing at more than 60% of the sites examined and no
periodontal pockets greater than 3 mm. Informed written
consent to participate in the study was obtained from
each subject. All subjects were healthy and none were
undergoing antibiotic or anti-infl ammatory therapy or
had undergone such therapy in the previous six months.
Female subjects were neither pregnant nor taking the con-
traceptive pill. No subject had a history of known sensi-
tivity or oral mucosal tissue reaction to toothpaste. The
tested toothpaste contained P. vulgaris extract (0.5 %), M.
cordata extract (0.005 %), a silica abrasive system, humect-
ants and surfactants, but no fl uoride. The placebo did not
contain plant extracts. Since gingivitis subjects complain
of over-sensitivity of periodontal tissues, the evaluation
of subjective sensations was also included in the study.
At baseline examination, the condition of the periodon-
tium was evaluated using indexes CPITN (Community
Periodontal Index of Treatment Needs – states the pres-
ence of bleeding, calculus, local irritating factors and the
depth of periodontal pockets), PBI (Papillary Bleeding
Index – degree of gingival bleeding around all teeth), and
the level of oral hygiene was assessed using the PI index
(Plaque Index – amount of plaque on the tooth surface).
The subject’s sensations were recorded. All subjects were
then divided randomly to two equal groups. At baseline,
they were instructed in detail to follow the guidelines of
good oral hygiene. After scaling, they received the tooth-
paste, test sample or placebo according to a random code
by which double blinding was maintained and two tooth-
brushes. On the fi rst follow-up visit (day 14), the condi-
tion of periodontium and oral cavity was evaluated, and
subjective sensations of the participant were recorded.
The second and third follow-up visits (day 42 and 84,
resp.) took place in the same way. Prior to the fi nal clini-
cal assessment, the subjects were asked not to discuss the
characteristics of the dentifrice that they had used with
the examiner (J.P.). Data are expressed as mean ± S.D.
The signifi cance of diff erences among four visits for each
index (PI, CPITN and PBI) was analyzed by a one-way
analysis variance (ANOVA). The level of confi dence re-
quired for signifi cance was selected at p < 0.05 .
*
0.0
0.5
1.0
1.5
2.0
2.5
*
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
*
*
Fig. 1. The mean (standard deviation) of community peri-
odontal index of treatment needs (CPITN). * Sig-
nifi cant decrerase from baseline to fi nal (12-week)
examination p < 0.05.
Fig. 2. The mean (standard deviation) of papillary bleeding
index (PBI). * Signifi cant decrease from baseline
to second and fi nal (6- and 12-week) examination
p < 0.05.
105
Macleya cordata and Prunella vulgaris in oral hygiene products – their effi cacy in the control of gingivitis
RESULTS AND DISCUSSION
The PI values both in mandible and maxilla decreased
in the test group from 0.47 to 0.10 (average of both jaws);
in the placebo group they decreased as well, from 0.381 to
0.16. We ascribe the improvement in the PI index, which
is comparable in both groups, to better oral hygiene all
patients applied in the course of the study. In indexes
CPTIN (Fig. 1) and PBI (Fig. 2), there was a statistically
signifi cant (p < 0.05) improvement in the test group, for
the CPITN from 1.86 to 0.98 and for the PBI from 1.38
to 0.52. In the placebo group, there was also an improve-
ment in both indexes (CPITN from 1.41 to 1.12; PBI from
0.95 to 0.73), again this can be ascribed to better oral
hygiene in the course of the study, but the improvement
in this case was not statistically signifi cant. Subjective
sensation and tolerance of the herbal-based toothpaste
by the participants were good.
The professional community generally accepts the
fact that a mechanical tooth brushing eff ect is positively
aff ected by dentifrice components with antimicrobial,
anti-infl ammatory and healing eff ects. However, studies
confi rm oriented to evidence this often bring in mixed
results, particularly if a concomitant use of a dentifrice
and a mouthrinse is clinically studied
10
. Most dentifrices
containing an active component claim an antiplaque ef-
fect. This is true particularly for synthetic components
with the exception of chlorhexidine whose antimicrobial
effi ciency is eliminated by necessary detergents. Oral
hygiene preparations containing herbal components are
generally less effi cient than those containing synthetic
substances. On the other hand, their advantage is that
they frequently combine several positive eff ects such as
anti-infl ammatory, antimicrobial and healing. The compo-
sition of the tested dentifrice originated in the long-known
antimicrobial activity of sanguinarine and chelerythrine
11
and in in vitro and in vivo evidenced antioxidative and
anti-infl ammatory eff ects of P. vulgaris
12
. The results of
this clinical study demonstrate a statistically confi rmed
anti-infl ammatory eff ect of the herbal-based dentifrice;
but not demonstrated antiplaque eff ect.
CONCLUSION
In the current population, a growing percentage of
people prefer oral hygiene preparations containing me-
dicinal plant extracts and/or their components. This study
showed that the combination of M. cordata and P. vulgaris
extracts was effi cient in the control of gingivitis. It was
concluded therefore that our herbal based preparation
may off er an effi cacious alternative to conventional denti-
frice formulations in a market where there is an increasing
interest in naturally based medicinal products.
ACKNOWLEDGEMENT
Supported by grant MSM 151100003.
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Chapter
Oral hygiene plays a crucial role in the prevention of oral diseases, including periodontitis, tooth decay, and oral candidiasis. In addition, many scientific studies show a relationship between oral health and cardiovascular diseases, diabetes, and even death. In order to prevent caries formation and periodontal diseases, effective oral hygiene should be performed and plaques should be removed, plaque formation should be prevented, and strains should be removed. Patients and dentists are faced with different oral hygiene products containing active and inactive ingredients. Although chemical‐based products are good at oral hygiene, there are many adverse effects of dental hygiene products, which are sold in the market. Effective usage of toothbrush, floss, or rinse is found very important for making oral hygiene even without using any chemicals. In addition, although popular herbal products have helped to control dental plaque and gingivitis, their safety and efficacy is not researched in detail. Herbal products may offer significant advantages over the chemical ones with less side effects and high antimicrobial potential. In addition, people are aware of the effects of herbal products for oral care, and their interest in these products has increased recently. Traditional herbal‐based treatments provide reduced adverse reactions of chemical counterparts such as resistance to antibiotics, corrosion, or staining of teeth. Herbal products such as clove and clove oil, coconut oil, pomegranate, green tea, Salvadora persica (meswak), Aloe vera, Acacia arabica, Melaleuca alternifolia (tea tree), Azadirahta indica (neem), and licorice are used to promote oral hygiene, and their inhibitory effect on biofilm formation is shown in different studies. According to bioactivity studies on these species, antibacterial, anti‐inflammatory, anticariogenic, and astringent properties were observed for their components and/or extracts. If such herbal products can be formulated effectively, this may lead to an improvement in the general dental health of the population. Summarized here are such natural products, which may be used effectively in the commercial formulations and/or personal product.
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The review concerns occurrence, isolation, properties, methods of determination, and biological activities of rosmarinic acid. Rosmarinic acid is a phenolic acid found mostly in plants of the families Lamiaceae, Boraginaceae and Apiaceae which exhibits significant antioxidant, antiinflammatory and antimicrobial activities. The antioxidant activity is higher than that of vitamin E making rosmarinic acid attractive for pharmaceutical and cosmetic industries. The antiinflammatory activity has been proved both in vitro and in vivo and may be used in the therapy of allergic inflammations.
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Quarternary benzo[c]phenanthridine alkaloids (QBA) are a small class of compounds commonly isolated from Caprifoliaceae, Fumariaceae, Meliacea, Papaveraceae and Rutaceae plants. QBA belong to the elicitor-inducible secondary metabolites and are considered phytoalexines because of their antifungal and nematocidal activities. Quaternary benzo[c]phenanthridine alkaloids whose most studied representatives are sanguinarine (SA), chelerythrine (CHE), and fagaronine (FA) (Fig. 1) display a wide spectrum of non-specific biological activities and affect basic molecular targets common to mammalian cells [1]. They are the subject of sustained practical and research interests because of their pronounced widespread physiological effects [2].
Article
Hydroalcholic extracts from four native medicinal Lamiaceae, Lycopus europaeus L., Melissa officinalis L., Origanum vulgare L. and Prunella vulgaris L. have shown significant antioxidative activities, by free radical scavenger effect on DPPH, compared with those of Rosmarinus officinalis L. and Salvia officinalis L. extracts. The antioxidative activity was partly in relation to the rosmarinic acid content. The major hydroxycinnamic compound, quantitatively determinated by HPLC, was present in large amount. The content in Prunella vulgaris L. spikes average 6.1%, based on dry weight.
Article
The Seal of Acceptance of the American Dental Association's Council on Dental Therapeutics has been awarded to Listerine and chlorhexidine gluconate (Peridex). The mechanism of action of Listerine involves bacterial cell wall destruction, bacterial enzymatic inhibition, and extraction of bacterial lipopolysaccharides. Chlorhexidine has the property of substantivity, i.e. the ability to bind to hard and soft tissue with slow release. Antibacterial mouthrinses/dentifrices containing triclosan hold promise for the reduction of plaque and gingivitis but are not yet available in the United States. The quaternary ammonium compounds and sanguinarine compounds (Viadent) have some merit, but studies of their efficacy in plaque and gingivitis reduction are mixed. New products containing various fluorides and oxygenating agents may have potential for the future as antiplaque and antigingivitis agents.
Article
Several dentifrices are available in the market for the control of calculus, plaque, and gingivitis. The anticalculus activity of the pyrophosphate dentifrice formulation has been convincingly demonstrated. Recently, dentifrices containing 0.3% triclosan and 2.0% Gantrez have been shown to possess some anticalculus activity, in addition to their antiplaque and antigingivitis properties. Similarly, sequential application of sanguinarine-containing dentifrice with a brush, followed by a rinse of 30 to 60 seconds, also provides sustained antiplaque and antigingivitis effects. However, other dentifrices have had much less convincing clinical results. It is therefore important for dentists to interpret the therapeutic claims of various antiplaque and antigingivitis dentifrices cautiously before recommending these products to patients.
This article reviews chemical, pharmacological, and toxicological research relating to two principal benzo[c]phenanthridine alkaloids, namely sanguinarine and chelerythrine, in the period 1980-1994. The medical applications of these alkaloids in relation to their biological activities are discussed.
Article
The in vitro cytotoxicity of sanguinarine chloride, a dental product used in the treatment of gingivitis and plaque, was compared using cell lines and primary cells from oral human tissues. For the established cell lines, sanguinarine chloride exhibited similar potencies to S-G gingival epithelial cells and to KB carcinoma cells, whereas HGF-1 gingival fibroblasts were more tolerant. However, a gingival primary cell culture was more sensitive to sanguinarine chloride than were the established cell lines. Detailed studies were performed with the S-G cells. The 24-hr midpoint (NR50) cytotoxicity value towards the S-G cells was 7.6 microM, based on the neutral red cytotoxicity assay; vacuolization and multinucleation were noted. When exposed to sanguinarine chloride for 3 days, a lag in growth kinetics was first observed at 1.7 microM. Damage to the integrity of the plasma membrane was evident, as leakage of lactic acid dehydrogenase occurred during a 3 hr exposure to sanguinarine chloride at 0.1275 mM and greater. The cytotoxicity of sanguinarine chloride to the S-G cells was lessened in the presence of an S9 hepatic microsomal fraction from Aroclor-induced rats or by including fetal bovine serum (15%) in the exposure medium. Progressively increasing the pH from 6.0 to 7.8 enhanced the potency of sanguinarine chloride, presumably due to the enhanced uptake of the lipophilic alkanolamine form, as compared to that of the cationic iminium form.
Article
In the past, the self-heal (Prunella vulgaris L.) was primarily used as a remedy alleviating pains in the throat, fevers and accelerating wound healing. A high content of rosmarinic acid, immunomodulation effects of the polysaccharide prunelline and antiviral activity of some constituents make the plant interesting from the viewpoint of therapeutical applications. The paper summarizes the contemporary phytochemical knowledge about the self-heal and the results of pharmacological studies of the extracts and pure substances from this plant.
Article
This review considers the main agents which have been used as antibacterial agents in mouthwashes and other vehicles to inhibit the growth of supragingival plaque. The agents discussed are bisguanide antiseptics, quaternary ammonium compounds, phenolic antiseptics, hexetidine, povidone iodine, triclosan, delmopinol, salifluor, metal ions, sanguinarine, propolis and oxygenating agents. The plaque inhibitory, anti-plaque and anti-gingivitis properties of these agents are considered along with their substantivity, safety and possible clinical usefulness. Clinical trials of these agents that have been published are also reported. The possible clinical uses of antiseptic mouthwashes are finally considered along with some advice about assessing manufacturers claims. Throughout this review the terms plaque inhibitory, anti-plaque and anti-gingivitis have been used according to the clarification of terminology suggested by the European Federation of Periodontology at its second workshop. This defines a plaque inhibitory effect as one reducing plaque to levels insufficient to prevent the development of gingivitis; an anti-plaque effect as one which produces a prolonged and profound reduction in plaque sufficient to prevent the development of gingivitis; and anti-gingivitis as an anti-inflammatory effect on the gingival health not necessarily mediated through an effect on plaque.