Andrographolide and Epigallocatechin Gallate (EGCG) Lower the Risk of Addiction Induced by Nicotine and Cigarette Smoke Extract (CSE) in Mice

Background: Nicotine, a psychoactive compound from the tobacco plant, produces a reward effect that potentially causes addiction. It is postulated that nicotine addiction occurs through increased reactive oxygen species production in nucleus accumbens, which causes damage to the endogenous antioxidant defense system resulting in an increased need for nicotine intake, which leads to addiction. The antioxidants, andrographolide and epigallocatechin gallate (EGCG), are expected as potential substances to decrease the risk of nicotine addiction. This study aimed to analyze the effect of andrographolide and EGCG on the risk of addiction induced by nicotine and cigarette smoke extract (CSE) in mice. Methods: Thirty-five Balb/c male mice, divided into seven groups, were used in this study. The administered drugs were normal saline 1.0 mL/kg BW as control group, nicotine 0.5 mg/kg BW, CSE 1.0 mg/kg BW, andrographolide 50 mg/kg BW, and EGCG 50 mg/kg BW as pre-treatment. Conditioned place preference (CPP) with a biased design method was used to evaluate the reward effects induced by nicotine and CSE. Several stages were carried out, namely preconditioning, conditioning, post-conditioning, extinction, and reinstatement tests. Results: Based on the CPP score, both nicotine (p<0.001) and CSE (p<0.001) groups increased the reward effect significantly compared to that of the normal saline group. The andrographolide + nicotine (p<0.001) and EGCG + nicotine (p<0.001) groups decreased the reward effect significantly compared to that of the nicotine group without pharmacological treatment. Similarly, the andrographolide + CSE (p<0.001) and EGCG + CSE (p<0.01) groups decreased the reward effect significantly compared to that of the CSE group without pharmacological treatment. Conclusion: Andrographolide and EGCG lower the risk of addiction induced by nicotine and CSE.