| One of the causes of the high cost of pharmaceuticals and the major obstacles to rapidly assessing the bioavailability and risk of a chemical is the lack of experimental model systems. A new pre-treatment technology, in vitro bionic digestion was designed, according to: (a) chemical bionic stomach and intestine, (b) medical bionics, i.e., the action of digestive enzymes, (c) whole medical effective, and (d) methods in molecular medicine, using trace metals as indicator. After in vitro bionic digestion, the chyme was close to the effective compounds, and trace metals were transformed into final coordinated complexes before being absorbed by biomembrane. The mechanism of absorption and transport of the decoction or powder of TCMs in stomach and intestine was simulated. The decoction or powder of TCMs was digested on body temperature, the acidity and digestive enzymes of stomach and intestine. The stirring was used to simulate the movement of stomach and intestine, and the stirring time was accorded with the stay time of decoction or powder of TCMs. The theory, which TCMs express their bioactivities by special characteristics of synergistic action of multiple compounds and multiple acting sites in vivo, was applied to the design of in vitro bionic digestion technology.Monolayer liposome, similar as the biomembrane between the gastrointestinal tract and blood vessels, was used as biomembrane model. Monolayer liposome-water system was adopted to study the metal distribution in the chyme, monolayer liposome-soluble metals (MLSMs) and water-soluble metals were used for speciation analysis of trace elements in TCMs. The concentration of MLSMs were used for the metal bioavailability assessment and then the action of gastrointestinal digestive enzymes was assessed, the metal main absorption organ was offered, and the safe dosage or tolerable upper intake level of TCMs for adults were proposed as follows:(1) The correlation between the monolayer liposome extraction model and the rat in situ stomach and single-pass duodenal intestinal absorption was studied. Monolayer liposome-soluble metals (MLSMs) compared with the rat in situ gastric absorbable metals (GAMs) in the decoction of Herba Anoectochili or Astrgalus Membranaceus demonstrated that MLSMs and GAMs were proportional to the metals in its chyme, suggesting that the passive diffusion of the agents was the major mechanism for the stomach or intestinal absorption. The frequency of the ratios between MLSMs and GAMs in the range of 0.8～1.2 and 0.8～1.4 were about 70% and 84%, respectively. If the low-frequency points were ignored, the frequency distribution of the ratios was closely normal. These results indicated that the monolayer liposome used as gastrointestinal biomembrane model was reasonable, particularly suitable for passive absorption model. This new gastrointestinal biomembrane model could be adopted for pharmaceutical analysis or toxicological testing, replacing the common animal studies.(2) Metal speciation and bioavailability in L. japonica were affected by the total metal contents, the gastrointestinal acidity, and the gastrointestinal compositions, including inorganic and organic components, especially for the digestive enzymes. The safe dosage and tolerable upper intake level of L. japonica for adults were proposed as 33.3 g/day and 230.8 g/day, respectively.(3) The best combination ratio of Radix Aconiti Preparata (A) and Radix Paeoniae Alba (B) was 1A:1B; In the decoction from herbs combined with 1A:1B, the safe dosage were 295.0 and 214.5 g/day for males and females, respectively, and the tolerable upper intake level was 1072.7 g/day for males and females.(4) Trace metals in lianhua qingwen capsules were absorbed mainly in intestine. The total concentrations of As, Cd, Pb in the capsule were 0.38, 0.07, 1.60 mg/kg, respectively. These contents were far less than the permissible dose, i.e., Import and export of medicinal plants and preparation of green industry standards. |
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