Exploring the pharmacological and adverse reaction mechanism of a drug by network pharmacology strategy: Using colchicine to treat Behcet syndrome as an example

Abstract

Colchicine (COLC) is a natural alkaloid used to treat Behcet syndrome (BS), but its adverse reactions limit its clinical application in treating BS. However, the adverse reaction mechanism of COLC in the treatment of BS remains unclear. Herein, a network pharmacology-based strategy was designed to analyze the pharmacological and adverse reaction mechanism of COLC in treating BS. The biological functions of COLC and BS pathogenesis were analyzed through a series of network construction and analysis. The data above predicted the pharmacological and adverse reaction mechanism of COLC in BS treatment. The pharmacological mechanism of COLC against BS was predicted to control inflammatory responses. Interleukin-8, interleukin-18, integrin alpha-4, integrin beta-2, and tubulin targets are crucial in treating BS. The adverse reactions of COLC in BS treatment were predicted as neurotoxicity and hepatotoxicity. The mechanism of hepatotoxicity may be related to the decrease of cytochrome P450 family 3 subfamily A activity caused by various factors, such as poor hepatic function, the dosage of COLC, and combination with inhibitors. The mechanism of neurotoxicity may be related to the disruption of microtubules in the nervous system by COLC transport across the blood-brain barrier. This study provided basic evidence for the medication safety management of COLC used in treating BS. Moreover, this study demonstrated that it is feasible to analyze the adverse reaction mechanisms of drugs using a network pharmacology strategy, which facilitates systematic drug safety management and evaluation.