Effects of ginsenosides from Panax ginseng C. A. Meyer on gap junctional intercellular communication were investigated. Ginsenoside $Rh_2$ drastically inhibited a PMA-induced closure of gap junction channel of clone 9 cells while other ginsenosides had no effects. As the phosphorylation states of connexin43 were revealed by Western blotting analysis, connexin43 proteins were evenly distributed among connexin43-NP, -$P_1$, -$P_2$ in the subconfluent cultures whereas connexin43-NP was mainly expressed in the confluent cultures of clone 9 cells. When ginsenoside $Rh_2$ was treated in the subconfluent cultures, connexin43-$P_2$ was increased with concomittent decreases of connexin43-NP and connexin43-$P_1$. In the confluent cultures, ginsenoside $Rh_2$ strongly increased connexin43-$P_2$ which is barely detected in the normal cells. With the presence of PMA, a well-known tumor promoter, connexin43-$P_2$ was increased with a total expense of connexin43-NP and connexin43-$P_1$ in the subconfluent cultures while connexin43-$P_2$ was strongly increased with a slight decrease of connexin43-NP in the confluent cultures. However, the pretreatment of ginsenoside $Rh-2$ did not affect the PMA-induced phosphorylation of connexin43 either in the subconfluent or confluent cultures. The inhibitory effect of ginsenoside $Rh_2$ on the PMA-induced disruption of gap junctional intercellular communication is not seemed to be mediated by protein kinase C signaling pathway.
