| Traditional Chinese medicine (TCM)play an important role in the prevention and treatment of a number of complex diseases. And formula is best performed in TCM, especially for decoction, which is normally administered to patients in this form.According to the combination principle of "monarch, minister, assistantand messenger", decoction is prepared by boiling two or more different herbsin the proper proportion. And because of the enhanced availability and lower side effects, decoction had attracted publicity a lot. Zhizi Bopi Decoction, derived from Zhang Zhongjing’s "Typhoid Theory", is a famous formula in TCM. according to the combination principle, Gardenia jasminoides Ellis, Cortex phellodendriand Glycyrrhizae Radix et Rhizomaare considered as "monarch, ministerand messenger" herb,respectively. In particularly, the best therapeutic ratio is 10:6:3, andit was considered to perform wonderful action in nourishing liver and treating damp heat jaundice. Although increasing evidence covers the pharmacologic actions of Zhizi Bopi Decoction, thecompatibility study, absorption characteristics of essential ingredients and the synergistic actions haven’t been under way, so the main investigations are summarized as follows:1. Therapeutical effects of Zhizi Bopi Decoction and its compatibility on hepatic fibrosis in miceThe model of mouse liver fibrosis was caused by carbon tetraehlofide (CCl4) and the micein experimental group were used to study the therapeutical effects of Zhizi Bopi Decoction by gavage, meanwhile, control group were given equivalent olive oil. Indicators of inflammation and hepatic fibrosis were assessed by automated biochemistry analyzer and liver fibrosis of the mice was investigated by Masson staining and HE staining. In addition, the protein levels of collagen type I and a-smooth muscle actin (a-SMA) were studied by Western blot analysis. It was found that Zhizi Bopi Decoction and its compatibility woulddecrease the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA) and hydroxyproline (Hyp)activitiesin different degrees, and improve the pathological changes of mouse livers. Furthermore, the therapeutic actions on liver fibrosis which were caused by CCl4 in mice were largely ascribed to the enhancement of Gardenia jasminoides Ellis, Cortex phellodendri and Glycyrrhizae Radix et Rhizoma,which were showed the best effects (P<0.01). And they also obviously decreased the protein expression levels of collagen type I and a-SMA, similarly, three kinds of drug compatibility group showed significant difference compare to the other group (P<0.01). On the other hand, Zhizi Bopi Decoction could also clearly reduced the increased contents of transforming growth factor-betal (TGF-β1). This part experiment was found thatZhizi Bopi Decoction and its compatibility almost exhibited obvious anti-fibrotic effects on the liver induced by CCl4 in mice in different degree, but the compatibility of Gardenia jasminoides Ellis, Cortex phellodendri and Glycyrrhizae Radix et Rhizomashowed the most apparently therapeutical effects among them, which may be because of the decreasedlevels of TGF-β1.2. The permeability characteristics and interaction of the main components fromZhizi BopiDecoction in the MDCK Cell ModelAlthough an increasing number of research reports demonstrate the pharmacological actions of Zhizi Bopi Decoction, the absorption characteristics of essential ingredients and the probable synergistic effects are poorly understood.In this section, MDCK cell model was appliedto study the permeability characteristicsandinteraction between the active ingredients(geniposide, berberine and glycyrrhizic acid) of Zhizi Bopi Decoction. It was found that thebi-directional transport of the key components all showed concentration-dependent in both directions. And when it performed at 4℃ or co-incubated with an ATP inhibitor, thePapp (AP-BL) values of berberine and glycyrrhizic acid were distinctly reduced. Additionally, uptake of berberine, glycyrrhizic acid were clearly inhibited by verapamil (a selective P-gp inhibitor), MK571 or probenecid (MRP2 inhibitors),which indicated that P-gpand MRP2 may beparticipate in the permeation of berberine and glycyrrhizic acid, respectively. However, it could be concluded thatgeniposide may transport through MDCK cell model by purely passive diffusion. What is more, when co-incubation geniposidewith berberine and glycyrrhizic acid, it revealed a obvious sorbefacient effect than use of a single ingredient alone which may because of the openof tight junctions. |
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