# Harnessing Odorant Receptor Activation to Suppress Real Malodor
## 2 Results and Discussions
### Sensory Deodorization of Cat Urine Odor Using TAAR5 Antagonists
Furthermore, ALD9 (also known as helional) and ALD7 (also known as cinnamaldehyde) significantly reduced malodor intensity, and ethyl maltol improved pleasantness. When a higher concentration of fragrance solution was used, more fragrance compounds exhibited odor-suppressing effects (Figure 4C). A relative ranking of odor-suppressing effects at the 0.01% concentration indicated that ALD6 (bourgeonal) exerted the highest malodor-suppressing effect (red in Figure 4D). Bourgeonal is a fragrance compound with a fresh, floral muguet scent and a watery green character and is commonly used in toiletries and alcoholic fragrances. ALD6 (bourgeonal) showed significant inhibition at relatively high concentrations compared to other aldehydes in the in vitro TAAR5 antagonist screening (Figures 3C and S3). The inhibition of urinary odor in the sensory evaluation does not seem to necessarily correspond to the strength of the antagonist action of TAAR5. Our results suggest that bourgeonal effectively suppresses urine odor by acting as a TAAR5 antagonist. Remarkably, several human and mouse ORs respond to bourgeonal as an agonist, supporting that bourgeonal does not work as a universal inhibitor of odorant-responsive receptors [22; 30]. This may be attributed to not only the deactivation of TAAR5 but also the activation of ORs that respond to bourgeonal, which probably resulted in a particularly effective alteration of the combination code, thereby improving the suppression of unpleasant odors. Additionally, four other fragrances, ALD8 (floral butanal), KET2 (alpha-damascone), EST2 (ethyl safranate), and ESS1 (litsea cubeba fruit oil), that inhibited TAAR5 response also demonstrated cat urine odor suppression in sensory evaluation (Figure S4). The chemical structure of the fragrance summarizes the presence or absence of TAAR5 response inhibition effect on cat urine odor and its effect on sensory evaluation. A comparison of TAAR5 response suppression and cat urine odor suppression in sensory evaluation is summarized in Figure 5. Among the eleven fragrances that suppressed TAAR5 response, eight also exhibited malodor suppression, with six of them significantly shifting pleasantness toward a more positive perception. Conversely three fragrances that suppressed TAAR5 response showed no positive effect in sensory evaluations. Furthermore, the two fragrances that did not suppress TAAR5 responses failed to reduce malodor intensity. These findings indicate that selecting masking fragrances based on olfactory receptor responses to odors is a highly effective approach. Moreover, predicting effective fragrances solely from molecular structures remains challenging, as no clear structural commonalities were identified among the most effective compounds. As revealed by the GC-MS analysis, cat urine odor comprises multiple components, some of which act as agonists or antagonists for different receptors. It is challenging to predict molecules that exert antagonistic effects to positively influence the complex combination patterns of receptor activity. Of the hundreds of thousands of odor molecules, approximately 4000 are listed as fragrance compounds in The International Fragrance Association (IFRA) Transparency List that depicts the ingredients used by fragrance companies around the world ([[https://ifrafragrance.org/priorities/ingredients/ifra-transparency-list](https://ifrafragrance.org/priorities/ingredients/ifra-transparency-list)]([https://ifrafragrance.org/priorities/ingredients/ifra-transparency-list](https://ifrafragrance.org/priorities/ingredients/ifra-transparency-list)), accessed on 10 November 2024). However, it is impractical to investigate all these compounds solely through sensory tests. Therefore, a strategic approach that involves selecting specific ORs responsive to malodor sources and using receptor responses as indicators to narrow down effective antagonists is not only efficient but also reduces the exposure of sensory evaluators to malodors.