Structure–activity relationship of Baifuzi-cerebrosides on BKCa channel activation

• We isolated 5 cerebrosides from Baifuzi and determined their chemical structures.
• Four cerebrosides significantly activated the BK channel.
• Acyl chain lengths of the cerebrosides potently affect the channel activation.
• Double bond configuration of the cerebrosides weakly affected the channel.

Our previous study reported that a mixture of cerebrosides from traditional Chinese medicine Baifuzi could activate BKCa channel. It is curious to know the effect of each single cerebroside on the channel. Here we isolated 5 pure cerebrosides from the mixture and determined their chemical structures. The most potent one increased the single channel open probability 6 folds with EC50 value of 1.0 μM. The structure–activity relationship revealed that acyl chain length of cerebrosides has potent effect, while configuration of double bond at C8–C9 on their long chain base has weak effect on the channel activity. Thus, this research provides a guide for design and synthesis of a lead cerebroside with more potent effect on the BKCa channel.

The longer the acyl chain length, the more efficient the cerebrosides to activate the BKCa channel.Figure optionsDownload as PowerPoint slide