Background. Quercus infectoria (QI) is a plant used in traditional medicines in Asia. The plant was reported to contain various active phytochemical compounds that have potential to stimulate bone formation. However, the precise mechanism of the stimulation effect of QI on osteoblast has not been elucidated. The present study was carried out to isolate QI semipurified fractions from aqueous QI extract and to delineate the molecular mechanism of QI semipurified fraction that enhanced bone formation by using hFOB1.19 human fetal osteoblast cell model. Methods. Isolation of QI semipurified fractions was established by means of column chromatography and thin layer chromatography. Established QI semipurified fractions were identified using Liquid Chromatography-Mass Spectrometry (LC-MS). Cells were treated with derived QI semipurified fractions and investigated for mineralization deposition and protein expression level of BMP-2, Runx2, and OPN by ELISA followed gene expression analysis of BMP-2 and Runx2 by RT-PCR. Results. Column chromatography isolation and purification yield Fractions A, B, and C. LC-MS analysis reveals the presence of polyphenols in each fraction. Results show that QI semipurified fractions increased the activity and upregulated the gene expression of BMP-2 and Runx2 at day 1, day 3, and day 7. OPN activity increased in cells treated with QI semipurified fractions at day 1 and day 3. Meanwhile, at day 7, expression of OPN decreased in activity. Furthermore, the study showed that combination of Fractions A, B, and C with osteoporotic drug (pamidronate) further increased the activity and upregulated the gene expression of BMP-2 and Runx2. Conclusions. These findings demonstrated that polyphenols from semipurified fractions of QI enhanced bone formation through expression of the investigated bone-related marker that is its potential role when combined with readily available osteoporotic drug.

The complicated pathology of current diseases requires an intricate treatment. Today, current application of individual single-target drugs or therapeutic approaches is inadequate to target these diseases not to mentioned perceived shortcomings and presented with numerous adverse effects. The extensive and successful documented findings in natural product researches urges the need to make use of these knowledge in the development of new generation of medicine. Polyphenols are compounds naturally derived from plants and have been describe in many research to have tremendous medical benefit. Therefore, a synergistic combination of readily available drugs or other therapeutic approaches is a favourable approach to enhance efficacy, overcome toxicity and optimize safety. The objective of this review is to describe the synergistic effects between the combination of a variety of polyphenols with synthetic drugs or other therapeutic approaches which can help to improve therapeutic efficacy subsequently minimize the adverse effects of a substance targeted in various diseases focusing mainly on cancer, diabetic, microbial infections and tissue regeneration along with their underlying mechanism.