Purpose: In a prior study, we found that giving licorice and dried ginger decoction (LGD) to mice with activity-based anorexia (ABA) enhanced their behavior by increasing their activity during mealtime and improving their survival rate. This study aims to uncover the detailed mechanism of LGD in treating ABA by examining changes in the central nervous system, systemic blood, hippocampus, and intestinal microbiomes.

Methods: The radical scavenging abilities of LGD were assessed using DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid). Murine hippocampal HT22 cells were treated with H2O2 and LGD, and cell survival rates were analyzed to confirm cell protection efficacy. ABA was induced in mice through food restriction and provision of a wheel, followed by oral administration of LGD. Changes in neurotransmitters, neurotrophins, and molecules involved in neural activity in the brain, hippocampus, and blood serum were analyzed using western blot and quantitative analysis tools. Intestinal microbiome diversity was assessed using Ezbiocloud, MTP, and LefSe.

Results: LGD demonstrated concentration-dependent DPPH and ABTS radical scavenging abilities and protective effects against oxidative stress in HT22 cells. In ABA mice, LGD increased dopamine levels in brain tissue and blood and

elevated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. ABA reduced intestinal microbiome diversity, but LGD restored this diversity, particularly increasing Akkermansia, Prevotella, and Muribaculum strains.

Conclusion: LGD improved dopamine and BDNF levels and restored intestinal microbial balance in mice with ABA.

Keywords: Activity based anorexia, anorexia nervosa, licorice and dried ginger decoction, Gamchogeongang-Tang, dopamine, BDNF, microbiome