Berberine, which is an extract of Coptis Rhizome, has been used in Chinese Medicine for the prevention and treatment of oral diseases. Recent studies have suggested that berberine is useful for inducing bone regeneration. It is known that undifferentiated mesenchymal stem cells in the periodontal ligament play an important role in the regeneration of periodontal tissue. However, little is known about the effects of berberine on the periodontal ligament cells. In this study, the effects of berberine on human periodontal ligament-derived fibroblasts (hPDL cells) and immortalized mouse cementoblasts were analyzed, and it was revealed that berberine induced proliferation of these cells. On the other hand, berberine significantly inhibited the gene expression and enzyme activity of alkaline phosphatase (ALP). No significant effect of berberine was seen on the gene expression of osteocalcin or bone sialoprotein. Berberine induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) in hPDL cells. However, SB203580 (p38 MAPK inhibitor) and PD98059 (ERK1/2 inhibitor), which are inhibitors of these two kinases, respectively, showed no significant inhibitory effect on the enhancement of cell proliferation mediated by berberine. In addition, pretreatment of the cells with PD98059 abrogated the suppressive effect of berberine on the gene expression and enzyme activity of ALP, suggesting that berberine suppresses ALP gene expression and enzyme activity via the ERK1/2 pathway. These results suggest that berberine promotes mesenchymal cell proliferation while keeping their differentiation level into periodontal ligament cells at a low level.

Periodontal tissues such as periodontal ligaments are known to have high alkaline phosphatase (ALP) activity, and the genotype of ALP in periodontal ligament is reported to the bone-type. Therefore, if periodontal tissues are damaged by periodontitis, bone-type ALP (BAP) may be released in gingival crevicular fluid (GCF). The aim of this study was to compare the values of BAP in the GCF in patients during supportive periodontal therapy (SPT) with clinical parameters, as a contribution to knowledge regarding early clinical diagnosis of the disease. Thus, we sampled GCF from healthy sites (probing depth (PD) ≤4 mm and bleeding on probing (BOP) (-) ) and diseased sites (PD ≥4 mm and BOP (+) ) from 76 patients receiving SPT. We then measured clinical parameters; plaque index (PI), amount of GCF, gingival index (GI), PD, clinical attachment level (CAL), BOP and alveolar bone resorption. Biochemical parameters included the amount of BAP, aspartate aminotransferase (AST) activity and amount of protein. In addition, we defined a cut-off value for the amount of BAP for analysis.

The results demonstrated that diseased sites were significantly higher for all clinical and biochemical parameters than healthy sites. Furthermore, in an analysis using the cut-off values, those above the cut-off value in healthy sites had significantly higher values of AST activity and amount of protein when compared those with less than the cut-off value. Therefore, the amount of BAP may be related to condition of periodontal health. Based on this study, the amount of BAP in GCF may be indicative of early periodontal tissue damage.