A number of herbal extracts consisting of plant-derived herbs have been used in the treatment of inflammatory diseases, such as stomatitis due to their wide range of biological activities, including anti-inflammatory effects, few side-effects and low costs (3–5). For the clinical treatment of periodontitis, non-steroidal anti-inflammatory drugs (NSAIDs) are systemically administered for the treatment of gingival inflammations (4,8). However, NSAIDs often elicit side-effects, such as gastrointestinal dysfunction and bronchoconstriction (4). In human gingival cells, herbal extracts, such as kakkonto, shosaikoto and hangeshashinto have been shown to reduce the production of PGE₂, which plays an important role in the progression of the gingival tissue degradation and alveolar bone loss, through the suppression of arachidonic cascade, similar to NSAIDs (4). Sumac (Rhus coriaria) is a spice widely used as an herbal medicine (5) and its extract has been shown to inhibit alveolar bone loss via its antioxidant properties in rats with periodontitis (9). Thus, herbal extracts may be possible candidates which can be used, in place of NSAIDs, to attenuate and prevent periodontal diseases.

Green tea is known to contain 6 primary antioxidants, namely catechin, gallocatechin, epicatechin, epigallocatechin, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) (5). EGCG is a major polyphenol extracted from the leaves of Camellia sinensis (5) and is known to possess antioxidant and anti-bacterial activities (10). The O-methylated form of synthetic EGCG also exerts beneficial effects, such as the suppression of allergies (10). It has also been shown that ECG inhibits the biofilm formation of periodontal pathogens, such as P. gingivalis and Prevotella intermedia (11). It has been demonstrated that EGCG inhibits the resorption of alveolar bone induced by lipopolysaccharide (LPS) in mice suffering from periodontitis (12). In a preliminary clinical trial, the local application of green tea in the form of mouthwash or dentifrice was shown to produce an improved effect comparable to that of CHX on chronic periodontitis (13,14).

Theaflavin is a main polyphenol found in black tea made from the leaves of Camellia sinensis, and exerts anti-oxidant, anti-inflammatory and anti-tumor effects (15). In human gingival cells, theaflavin has been shown to decrease the secretion of interleukin (IL)-6 and IL-8 induced by LPS or tumor necrosis factor-α (TNF-α) (16,17). Recently, it was shown that theaflavin inhibited alveolar bone resorption in ligature-induced periodontitis rats, along with the reduction of immune cell infiltration and osteoclast formation in gingival tissues (15).

Turmeric is a yellow-orange spice derived from a rhizome of the plant Curcuma longa, and one of the main components in turmeric is curcumin (diferuloyl methane) (18). Clinical studies have demonstrated that curcumin exhibits a variety of therapeutic actions, such as anti-cancer, anti-platelet aggregation and vascular protective effects through its anti-inflammatory and anti-oxidant actions (18). Furthermore, curcumin has been shown to decrease blood cholesterol and triglyceride levels, despite its low bioavailability (18). In periodontitis, the oral administration of curcumin has been shown to reduce the levels of the inflammatory mediators, IL-6, TNF-α and PGE₂ in the gingival tissues of rats with both ligature- or LPS-induced periodontitis, whereas it was not shown to affect the resorption of alveolar bone (19,20). On the other hand, chemically modified curcumin, but not curcumin per se, has been shown to inhibit bone loss in rats with LPS-induced periodontitis (7). In addition, gel and mouthwash containing the extract of Curcuma longa or curcumin have been found to decrease the several indices of gingivitis and the number of periodontal pathogens in clinical trials, along with or without the mechanical treatments, such as scaling and root planing (3).

Garlic has been used since ancient times to suppress the growth of bacteria, fungi and viruses (21). It has been demonstrated that garlic extract and its components attenuate atherosclerosis (22) and hypertension (23), and exert immunomodulatory and anti-tumor effects (24). It has also been found that the aqueous extract of garlic (21,25) and its components, allicin (26) and diallyl sulfide (27), inhibit the growth of the periodontal pathogens, P. gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum in vitro. However, to date, at least to the best of our knowledge, no clinical study or in vivo experiment has been performed to determine whether garlic, the extracts of garlic and these garlic-derived substances can affect gingivitis or periodontitis. AGE, which is made by extracting and aging in water/ethanol solution for >10 months, contains a variety of pharmacologically active sulfur amino acids, such as S-allylcysteine (SAC), S−1-propenylcysteine (S1PC) and S-allylmercaptocysteine (SAMC) (28). AGE has been shown to attenuate atherosclerosis (29,30) and lower hypertension (31), possibly due to the anti-inflammatory (28,32) and antioxidant effects (33,34) of the sulfur compounds. Recently, the oral administration of AGE was shown to alleviate both the gingival index (GI) and gingival bleeding index (GBI) in a clinical trial (2), suggesting a promising application of AGE to relieve periodontal diseases. However, the mechanisms through which AGE attenuates gingivitis remain to be elucidated.