Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity

Abstract

Background:Forsythoside A (FTA), one of the main active ingredients in Shuang–Huang–Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously.Materials and Methods:In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation.Results:The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control.Conclusion:Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.

Using Bioinformatics Approach to Explore the Pharmacological Mechanisms of Multiple Ingredients in Shuang-Huang-Lian

“…Studies have already demonstrated that SHL had the pharmacological actions of antimicrobial, antiviral, antipyretic, anti-inflammatory, antioxidant, antiarrhythmic, and enhanced immunity [ 16 – 19 ], but they only focused on individual component, pharmacological action, or pathway. The component they studied could be extracted and was with a high content.…”

Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract

“…The transport study across Caco-2 monolayer was investigated by a modified version of a previously published method . 19 Briefly, 0.4 mL of PD solution (0.45 μg/mL) or PRE solution (corresponding equivalent PD) in hanks's balanced salt solution (HBSS) was loaded on apical side of the cell monolayer and 0.6 mL of blank HBSS onto the basolateral side. Aliquots of 0.1 mL and 0.15 mL of samples were taken sequentially at time points 0, 30, 60, 90, 120 min from doner and receiver side of the cell monolayer respectively.…”

The Relationship of Antioxidant or Antibacterial Effects of Key Components of Shuang-Huang-Lian Oral Liquid

“…The minimum inhibitory concentration (MIC) was determined using 96-well plates [16]. The experimental configuration of the bacterial solution, comprised activated Streptococcus hemolyticus-β, Staphylococcus.…”