# Effects of Toki Shakuyaku San on Olfactory Function in a Postmenopausal Mouse Model

## TL;DR

This study investigates whether Toki Shakuyaku San improves olfactory function in postmenopausal mice, finding that its effects may depend on estrogen levels.

## Contribution

The study explores the potential of Toki Shakuyaku San as a treatment for postmenopausal olfactory dysfunction, highlighting its estrogen-dependent efficacy.

## Key findings

- TSS-fed sham-operated mice showed significantly longer odor aversion time compared to controls.
- TSS-fed mice had more OMP-positive cells in the superior nasal septum.
- OVX mice showed no significant improvement in olfactory function with TSS.

## Abstract

Objective: This study aimed to evaluate the effects of Toki Shakuyaku San (TSS) on olfactory function in a mouse model of sensorineural olfactory dysfunction, with a focus on the estrogen-deficient state. We investigated whether TSS promotes olfactory neuronal regeneration and recovery of odor-evoked behavior in both sham-operated and ovariectomized (OVX) mice to clarify its potential therapeutic value in postmenopausal olfactory impairment.

Methods: Female BALB/c mice underwent ovariectomy or sham surgery, followed by methimazole administration to induce olfactory epithelial injury. Mice were fed either a control diet or a diet containing 0.5% TSS. Odor aversion behavior was evaluated using a light-dark box, and olfactory marker protein (OMP) expression in the nasal epithelium was analyzed by immunohistochemistry on Day 14. Statistical analysis was performed using the Mann-Whitney U test.

Results: In sham-operated mice, those fed a TSS-containing diet exhibited significantly longer odor aversion time at day 14 when compared to the mice fed a control diet (P = 0.007). A significantly higher number of OMP-positive cells was observed in the superior nasal septum (R1) of TSS-fed mice than in control-fed mice (P = 0.03). In OVX mice, no significant differences were observed between the TSS-fed and control-fed groups in odor aversion behavior (P = 0.11) or in the number of OMP-positive cells in any of the four regions of the olfactory epithelium (P > 0.05).

Conclusion: Our results suggest that the effects of TSS on olfactory recovery may depend on the presence of estrogen, and its efficacy could be influenced by the hormonal status.