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The present article reviews the research progress of three major polyphenols (tannins, flavonoids and lignin carbohydrate complexes), chromone (backbone structure of flavonoids) and herbal extracts. Chemical modified chromone derivatives showed highly specific toxicity against human oral squamous cell carcinoma cell lines, with much lower toxicity against human oral keratinocytes, as compared with various anticancer drugs. QSAR analysis suggests the possible correlation between their tumor-specificity and three-dimensional molecular shape. Condensed tannins in the tea extracts inactivated the glucosyltransferase enzymes, involved in the biofilm formation. Lignin-carbohydrate complexes (prepared by alkaline extraction and acid-precipitation) and crude alkaline extract of the leaves of Sasa species (SE, available as an over-the-counter drug) showed much higher anti-HIV activity, than tannins, flavonoids and Japanese traditional medicine (Kampo). Long-term treatment with SE and several Kampo medicines showed an anti-inflammatory and anti-oxidant effects in small size of clinical trials. Although the anti-periodontitis activity of synthetic angiotensin II blockers has been suggested in many papers, natural angiotensin II blockers has not yet been tested for their possible anti-periodontitis activity. There should be still many unknown substances that are useful for treating the oral diseases in the natural kingdom.

Abstract.

Background/Aim: Very few studies are available about the biological activity of 3-styrylchromones. Our previous study demonstrated the importance of methoxy group at 6-position of the chromone ring and hydroxyl group at 4'position of phenyl group in styryl moiety. As a sequel of this study, we synthesized fourteen compounds that include eight 3-styrylchromones where methoxy group was introduced at 7position of chromone rings, and then evaluated their tumorspecificity. Materials and Methods: Tumor-specificity (TS) was calculated by relative cytotoxicity against human oral squamous cell carcinoma cell lines versus human normal oral cells. Apoptosis induction and growth arrest were monitored by cell-cycle analysis. Quantitative structure-activity relationship analysis of TS was performed with 3,167 chemical descriptors. Results and Discussion: Two compounds, 7methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one [7] and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1benzopyran-4-one [14] showed higher tumor-specificity than doxorubicin and 5-FU, suggesting the importance of methoxy group in 7-position of the chromone ring. These compounds induced the apoptosis and mitotic arrest in HSC-2 cells. The tumor-specificity of 3-styrylchromone derivatives were most correlated with descriptors for molecule shape and electronic charge. The present study suggested that modification by introducing methoxy group at 7-position, instead at 6-position, further increased the tumor-specificity of 3-styrylchromone. Chromone is a two-ring backbone structure contained in many flavonoids. 3-Chromone is a compound that has a styryl group attached at 3-position of chromone. We previously reported that (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound A) showed approximately 69-fold higher cytotoxicity against human oral squamous cell carcinoma (OSCC) cell lines as compared with human normal oral cells (1). On the other hand, natural polyphenols such as tannins and flavonoids showed only marginal tumor-specificity (2, 3). As far as we are aware, only five studies of biological activities of 3-styrylchromone derivatives have been reported so far. This includes antimicrobial activity (4), antipicornavirus activity (5), free radical scavenging and αglucosidase inhibitory activity (6), apoptosis induction (7) and tumor-specificity (1). Quantitative structure-activity relationship (QSAR) analysis demonstrated the importance of methoxy group at 6-position of the chromone ring and hydroxyl group at 4'position of phenyl group in styryl moiety (1). As a sequel of this study, we synthesized fourteen compounds that include eight 3-styrylchromones where methoxy group was introduced at 7-position of chromone ring, and then evaluated the tumor-specificity. We first investigated their cytotoxicity against four human oral squamous cell carcinoma (OSCC) cells lines (Ca9-22, derived from gingival tissue; HSC-2, HSC-3. HSC-4, derived from tongue) and three human normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal l...

Objectives:Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are antipyretic analgesics with established adverse effects (AEs); however, only a few studies have compared their AEs simultaneously. We aimed to compare the AEs of these medications to confirm the respective frequencies of both rare and major AEs.Methods:We used a high-quality database for spontaneous adverse drug event reporting in Japan. Data were extracted regarding the AEs of acetaminophen and NSAIDs to compare the tendency of the appearance of those AEs between the drugs. We also performed a principal component analysis using the AE data to assess the characteristics of major AEs.Results:Cutaneous disorders and hepatic disorders were the most common AEs induced by acetaminophen and NSAIDs, with gastrointestinal tract disorders also common with NSAID use. Principal component analysis quantitatively showed the tendencies of specific AEs, and it helped demonstrate the characteristics of AEs. Acetaminophen and NSAIDs showed different tendencies in the occurrence of AEs. Each NSAID was plotted based on the tendency of the appearance of major AEs, and AEs were classified by their likelihood of being pharmacological or idiosyncratic.Conclusions:These findings may help clinicians select an appropriate drug for patients considering their backgrounds, instead of choosing merely based on the class of the drug, for example, cyclooxygenase selectivity. This selection, based on the characteristic information on AEs occurring in clinical settings, might be more suitable for patients.