Berberine is a plant alkaloid with multiple pharmacological effects, including anti-diarrheal activity, and secretion is Cl in the distal colon to inhibit shown. The objectives of this study were to determine the molecular signaling mechanisms of berberine on secretion and ion transporters Cl goals. culture monolayers of human
T84 bearing permeable colon carcinoma cells were placed in Ussing chambers and measured short-circuit current in response to secretagogues and berberine. current records of whole cells were carried out in T84 cells using the patch clamp. Berberine reduces the short-circuit current induced by forskolin in a manner dependent on the concentration (IC 50 80 ± 8 pM). In monolayers permeabilized apically and current records of whole cells, berberine inhibited cAMP-dependent and chromanol 293B sensitive basolateral membrane K + current by 88%, suggesting inhibition of KCNQ1 K + channels. Berberine did not affect apical or basolateral conductance Cl + -K + -ATPase Na. Berberine stimulates p38 MAPK and PKA PKC, but had no effect on p42 / p44 MAPK and PKCô. However berberine pretreatment prevented the stimulation of p42 / p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl- secretion was partially offset by HBDDE (~ 65%), an inhibitor of PKC and blocked to a lesser extent by the inhibition of p38 by SB202190 (~ 15%) . treatment with berberine increased association between PKC and PKA with KCNQ1 and produces the induced phosphorylation of channels. We conclude that berberine on Cl secretion by inhibiting colon channels KCNQ1 basolateral exerts its inhibitory action responsible for the K + recycling a PKC-dependent pathway.
