Page 265 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-82

Mechanistic and behavioral evidence for betulinic acid as a novel

antidepressant targeting mTOR pathways in mice hippocampus

3
1
1
Han-Wen Chuang, Jou-Hua Ren, Yen-Yu Kuo, Kuang-Ti Chen, Mang-Hung Tsai, I-
1
2
Hua Wei*
,1

1 Department of Anatomy, China Medical University, Taichung 404328, Taiwan
2 School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan
3 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404328,
Taiwan
* E-mail: ihwei@mail.cmu.edu.tw

Abstract
Major depressive disorder (MDD) is a prevalent mental health condition and a leading cause
of disability worldwide. Despite the availability of pharmacological treatments, their
therapeutic efficacy remains limited, and significant side effects often accompany them.
Consequently, there is growing interest in exploring novel therapeutic targets, such as the
mTOR-mediated signaling pathway. Recent studies have also highlighted the potential of
betulinic acid, a compound with diverse biological and pharmacological activities, in improving
depressive symptoms. However, the mechanisms underlying its antidepressant effects remain
unclear. This study investigates the potential of betulinic acid as an antidepressant agent. Mice
were treated with 5mg/kg, 10 mg/kg and 30 mg/kg intraperitoneal injections of betulinic acid.
The depression-like behavior was evaluated using the forced swimming test, which revealed a
significant reduction in immobility time in the treated groups compared to the controls.
Molecular analysis via western blotting also demonstrated that betulinic acid activated key
signaling molecules, including mTOR, AMPAR, Akt, AMPK, and ERK, and increased levels
of BDNF in the hippocampus. These molecular changes were consistent with observed
behavioral improvements, confirming the compound’s potential antidepressant effects. The
findings suggest that betulinic acid may represent a promising therapeutic candidate for MDD,
meriting further exploration in future studies.

Keywords: Depression; Betulinic acid; mTOR; BDNF; FST