Ardipusilloside-I stimulates gastrointestinal motility and phosphorylation of smooth muscle myosin by myosin light chain kinase

Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The experiment of smooth muscle contraction directly monitored the contractions of the isolated jejunal segment (IJS) in different contractile states, and the effects of ardipusilloside-I on myosin were measured in the presence of Ca²⁺-calmodulin using the activities of 20 kDa myosin light chain (MLC₂₀) phosphorylation and myosin Mg²⁺-ATPase. The effects of ardipusilloside-I on gastro emptying and intestinal transit in constipation-predominant rats were observed, and the MLCK expression in jejuna of constipated rats was determined by western blot. The results showed that, ardipusilloside-I increased the contractility of IJS in a dose-dependent manner and reversed the low contractile state (LCS) of IJS induced by low Ca²⁺, adrenaline, and atropine respectively. There were synergistic effects on contractivity of IJS between ardipusilloside-I and ACh, high Ca²⁺, and histamine, respectively. Ardipusilloside-I could stimulate the phosphorylation of MLC₂₀ and Mg²⁺-ATPase activities of Ca²⁺- dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric emptying and intestinal transit in normal and constipated rats in vivo, respectively, and increased the MLCK expression in the jejuna of constipation-predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could effectively excite gastrointestinal motility in vitro and in vivo.

Synthesis and cytotoxic activities of ardipusilloside I derivatives / 中草药

Objective: To seek novel compounds with better antineoplastic activities by modifying the structure of ardipusilloside I (ADS I) isolated from Ardisia pusilla. Methods: A series of ADS I derivatives were synthesized through oxidation, reduction, and condensation on C-30 aldehyde group, and the antineoplastic activities of these compounds against nine kinds of human cancer cells were evaluated by MTT assay. Results: Four derivatives a, b, d, and c were respectively named as hydrogenated ardipusilloside I, ardipusilloside I oxide, ardipusilloside 4-benzyl-3-thiosemicarbazide, ardipusilloside methyl hydrazinecarbodithioate. Compound a and c had lower IC50 than the lead compound on nine kinds of human cancer cells (P < 0.05), which indicated that they could enhance the antineoplastic activities when compared with ADS I. Four derivatives of ADS I were synthesized, among which compounds a and c had lower IC50 than the lead compound (P < 0.05). Conclusion: Through structural modification of ADS I, the antineoplastic activities are enhanced.