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.
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.


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.


CONCLUSIONS
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.
College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing, PR China ; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing PR China ; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, Nanjing, PR China.
Wei
W
Zhou
Department of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, PR China.
Xuan Xuan
XX
Zhu
College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing, PR China.
Ai Ling
AL
Yin
College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing, PR China.
Bao Chang
BC
Cai
Department of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, PR China.
Hai Dan
HD
Wang
College of Pharmacy, Nanjing University of Chinese Medicine; Nanjing, PR China ; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing PR China ; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, Nanjing, PR China.
Liuqing
L
Di
First Medicine College, Nanjing University of Chinese Medicine, Nanjing, PR China.
Jin Jun
JJ
Shan
Absorption enhancers; Forsythoside A; Shuang-Huang-Lian; antivirus activity; tight junction