Plasma membrane as the target site of cholic acid analogs

Abstract

Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and mediated by the muscarinic receptor (M-receptor) or the relaxation induced by adrenaline and mediated by the β-adrenergic receptor (β-receptor) was inhibited by CAAs. They also had similar rank-order of potency and the effects on the plasma membrane. Collectively, the plasma membrane may be a target for the CAAs to exert the multiple pharmacological effects which are mediated by the alteration of the membrane mobility and the function of integral membrane proteins.

Development of a rapid and simple LC-MS/MS method for identification and quality control of natural Calculus bovis and Calculus bovis sativus

“…1) such as cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), taurocholic acid (TCA), and glycocholic acid (GCA), bilirubin as well as some inorganic salts. 22 Therefore, whether the structural (compositions and contents) differences of conjugated BAs affect their therapeutic values remains elusive, and it is of great signicance to propose a quality control method that simultaneously determines more components such as taurine and conjugated BAs in CBS. 17 Being in accordance with the herbal quality guidelines of the European Medicines Evaluation Agency (EMEA), 18 CA and bilirubin have already been used as the 'active markers' for quality control in the China Pharmacopoeia (2010 edition).…”

“…19 Furthermore, although conjugated BAs have low contents and poor absorption, their effects are comparable to those of unconjugated BAs. 22 Therefore, whether the structural (compositions and contents) differences of conjugated BAs affect their therapeutic values remains elusive, and it is of great signicance to propose a quality control method that simultaneously determines more components such as taurine and conjugated BAs in CBS. This strategy helps partially explain why CBS is an ideal substitute for natural CB by comparing their material compositions.…”