Periodontitis and gingivitis are the two forms of periodontal disease, which is also called pyorrhea. Gingivitis results from the buildup of plaque and calculus on the teeth.
The main cause of periodontitis is plaque. This consists of certain components of saliva, food residues and above all bacteria and their decomposition products. This special form of an infectious disease is caused in most cases by Porphyromonas gingivalis, Bacteroides forsythus and Actinobacillus actinomycetemcomitans. The continuous release of bacterial toxins, especially of lipopolysaccharides, presumably triggers the distribution of proinflammatory mediators, such as IL-1beta, TNF-alpha and PGE2 for example, in the patient's affected tissues. These signal substances stimulate the infiltration of immunocompetent cells into the populated tissue.
The migration of neutrophilic granulocytes and macrophages then subsequently leads to inflammation of the gums (gingivitis) and to the release of proinflammatory mediators such as IL-1 and IL-6, for example. These in turn activate in the skin and mucous membranes the synthesis of matrix-degrading metalloproteinases (matrix metalloproteinases, MMPs), which destroy the extracellular matrix of the surrounding connective tissue. This allows bacteria, which initially interacted with the free gingiva, to penetrate further into the underlying connective tissue, continuing inflammation processes and the synthesis of MMPs there and finally loosening the connection between the uppermost layer of the epithelium and the root of the tooth. A gingival pocket is formed as a consequence. The reaction of the body is the inflammation of the gingiva and the periodontium with damage to the alveolar bone. In the final stage of periodontitis the affected person is at risk of a massive loss of teeth.
MMPs also have an important role to play in the development of caries and
non-caries-related losses of hard tooth structure, such as erosions for example.
The teeth are constructed mainly from a bonelike substance called dentine. In
the area of the crown which protrudes from the gum, the dentine is covered with
the protective enamel. Dentine is made up of around 30% of a cell-free basic
substance consisting largely of glycoproteins.
The development of caries and erosions is accompanied by the demineralisation of
the teeth. Mineral substances are critically responsible for the hardness of the
tooth. The formation of acids by oral bacteria after consumption of sugary foods
on the one hand, but also through frequent contact with highly acidic drinks
(e.g. fruit juices) and highly acidic food (citrus and tropical fruits,
pineapple, etc.) leads to demineralisation of the enamel and, if it continues,
of the dentine too. The demineralised dentine is susceptible to degradation.
Maintaining the health or slowing the degradation of the connective tissue of
the periodontium and the collagen fibres of the teeth by preventing damage due
to MMPs is therefore an important aim in the development of new active
ingredients for the area of oral care and oral hygiene. A number of plant extracts have also already been described as inhibitors of various MMPs.
It has been found that an extract of the
leaves of the blackberry (Rubus fruticosus) exhibits an outstanding MMP-9- and
MMP-1-inhibiting action. Extraction of the blackberry leaves with the extractant for up to 72 hours have proved to be particularly effective in inhibiting the metalloproteinases MMP-1 and MMP-9, even in low concentrations. It was also established that in comparison to the leaf extract, a blackberry fruit extract or juice concentrate which was also tested
displays a markedly lower anti-MMP-1 and -9 activity. Rraspberry leaf extract in comparison to blackberry leaf extract in the same concentration displays a 28 times lower anti-MMP-9 activity and a 6 times lower anti-MMP-1 activity (see the appended examples), even though the raspberry (Rubus idaeus) is a member of the same plant species as the blackberry . The extract has a slight, pleasant, herbal, green, tea-like inherent flavor reminiscent of camomile and peppermint.
Pure water or ethanol extracts have a lower anti-MMP action than extracts produced using ethanol/water blends. Particularly preferred blackberry leaf extracts are obtained with an extractant consisting of ethanol and water in the ratio of 2:8 (2 parts by weight of ethanol mixed with 8 parts by weight of water) to 8:2, preferably in the ratio of 3:7 to 7:3.