Sweet-bitter taste interactions in binary mixtures of sweeteners: Relationship between taste receptor activities and sensory perception.

This study investigated the effects of various binary sweetener mixtures on sweetness enhancement and their interactions with sweet or bitter taste receptors, focusing on sensory perception and receptor activity. Acesulfame K or saccharin was mixed with allulose, aspartame, erythritol, fructose, glucose, or sucrose to match a target sucrose sweetness. The effects of the mixtures on sweet and bitter taste receptors (in the human embryonic kidney -293 cells) and sensory taste intensities were evaluated. Sweetness enhancement at the sweet taste receptor level was observed in some cases, with several monosaccharides reducing the acesulfame K- or saccharin-induced bitter taste receptor activity. Combining acesulfame K or saccharin with any of the six sweeteners perceptually enhanced sweetness (60% âˆ¼ 100% in 50:50 ratio), correlating with a reduction in inherent bitterness (-35% âˆ¼ -63% in 50:50 ratio). This finding suggests that sweetness perception likely increased because the monosaccharides mitigate the activation of bitter receptors caused by high-potency sweeteners.

Bitter Taste Receptor 46 (hTAS2R46) Protects Monocytes/Macrophages from Oxidative Stress.

Bitter taste receptors (TAS2Rs) are not only responsible for taste perception in the oral cavity, but are spread throughout the body, generating a widespread chemosensory system. In humans, 25 subtypes have been identified and are differentially expressed in tissues and organs, including in the immune system. In fact, several TAS2R subtypes have been detected in neutrophils, lymphocytes, B and T cells, NK cells, and monocytes/macrophages, in which they regulate various protective functions of the innate immune system. Given its recognized anti-inflammatory and antioxidant activity, and the generally protective role of bitter taste receptors, in this work, we studied TAS2R46's potential in the protection of human monocyte/macrophage DNA from stress-induced damage. Through both direct and indirect assays and a single-cell gel electrophoresis assay, we demonstrated that absinthin, a specific TAS2R46 agonist, counteracts the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and reduces DNA damage in both cell types. Even though the release of ROS from monocytes/macrophages is fundamental for contrast pathogen agents, supraphysiological ROS production impairs their function, finally leading to cell death. Our results highlight TAS2R46 as a novel player involved in the protection of monocytes and macrophages from oxidative stress damage, while simultaneously supporting their antimicrobial activity.

Comprehensive Analysis of the Function and Prognostic Value of TAS2Rs Family-Related Genes in Colon Cancer.

In the realm of colon carcinoma, significant genetic and epigenetic diversity is observed, underscoring the necessity for tailored prognostic features that can guide personalized therapeutic strategies. In this study, we explored the association between the type 2 bitter taste receptor (TAS2Rs) family-related genes and colon cancer using RNA-sequencing and clinical datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Our preliminary analysis identified seven TAS2Rs genes associated with survival using univariate Cox regression analysis, all of which were observed to be overexpressed in colon cancer. Subsequently, based on these seven TAS2Rs prognostic genes, two colon cancer molecular subtypes (Cluster A and Cluster B) were defined. These subtypes exhibited distinct prognostic and immune characteristics, with Cluster A characterized by low immune cell infiltration and less favorable outcomes, while Cluster B was associated with high immune cell infiltration and better prognosis. Finally, we developed a robust scoring system using a gradient boosting machine (GBM) approach, integrated with the gene-pairing method, to predict the prognosis of colon cancer patients. This machine learning model could improve our predictive accuracy for colon cancer outcomes, underscoring its value in the precision oncology framework.

Docking analysis of phenolic acid and flavonoids with selected TAS2R receptors and in vitro experiment.

Cornelian cherry fruits contain a wide range of phenolic acids, flavonoids, and other secondary metabolites. Selected flavonoids may inhibit the perceiving of bitterness, however, the full mechanism with all TAS2R bitter taste receptors is not known. The aim of the study was to determine the inhibitory effect of Cornus mas phenolics against the bitterness receptors TAS2R13 and TAS2R3 through functional in vitro assays and coupling studies. The overall effect was validated by analysing the inhibition of the receptors activity in cells treated with tested cornelian cherry extracts. The strength of interaction with both TAS2R receptors varied between studied compounds with different binding affinity. Most compounds bonded with the TAS2R3 receptor through a long-distant hydrophobic interaction with Trp89A and π-π orbital overlapping-between phenolic and tryptophane aromatic rings. For TAS2R13 observed were various mechanisms of interaction with the compounds. Nonetheless, naringin and quercetin had most similar binding affinity to chloroquine and denatonium-the model agonists for the receptor.

From the genesis to the present: The evolution of sublingual immunotherapy for cedar pollinosis.

In 2004, we started the initial attempt to evaluate the efficacy of SLIT for Japanese cedar pollinosis (JCP) using Japanese cedar (JC) pollen extract solution through a multicenter, placebo-controlled, double-blind comparative study. Based on its success in demonstrating the substantial efficacy of SLIT, we next conducted a larger-scale study by administering JC pollen to all JCP patients recruited. It was because of aiming to ascertain the effectiveness and safety of SLIT and its underlying mechanisms by comparing high- and non-responder patients. Despite limitations posed by liquid medication, significant effectiveness and safety demonstrated by the 2-year treatment served as the foundation for launching the first SLIT medicine for JCP, in 2014. Furthermore, in addition to the clearer Th1/Th2-imbalanced property in the high-responders, the possible involvement of bitter taste receptors in CD4+ T cells, apoptosis pathways in CD4+ T cells and basophils, and inducing a mast cell degranulation inhibitory molecule in the effect of SLIT was demonstrated. To solve the limitations posed by liquid medication, clinical trials evaluating JC pollen sublingual tablets started in 2014. Due to the minimal side effects, ease of administration, and convenient storage, the sublingual tablet medicine was launched in 2018. Giving the ongoing rise in demand for SLIT and considering that more than 1% of JCP patients are currently undergoing SLIT, the practical use of this treatment for multiple allergens is becoming increasingly important.

Influence of dietary bitter orange peel powder on growth, body composition, blood parameters, gut morphometry, and thermal tolerance of Nile tilapia (Oreochromis niloticus).

The potential of bitter orange peel powder (BOPP) as a nutritional strategy for fish was investigated in Nile tilapia. A total of 120 juveniles with an average initial weight of 9.8 ± 0.7 g were divided into four groups, replicated three times, resulting in 12 experimental units (60 L each) at a stocking density of 1.63 g of fish per liter. Productive parameters, whole-body composition, blood biochemistry, erythroid morphometry, intestinal histology, and heat tolerance were assessed in the juveniles subjected to one of the following treatments: non-supplemented basal diet (control group); basal diet with BOPP at 10 g/kg (BOPP10 group); basal diet with BOPP at 20 g/kg (BOPP20 group); and basal diet with BOPP at 40 g/kg (BOPP40 group). The BOPP additive had a positive influence on Nile tilapia growth, as final weight and weight gain were greater in all BOPP-treated fish, despite the reduction in crude protein in BOPP10 and BOPP20 groups. Fish receiving BOPP40 had an increase in total lipids and showed the highest levels of triglycerides and total cholesterol. Villi development was greater in the tilapia given BOPP10. It may be concluded that BOPP presented the most promising results for Nile tilapia juveniles when used at 10 g/kg diet. Regarding the erythroid morphometry, there was a general increase in nuclear and cytoplasmic areas in BOPP-fed tilapia; this seems to be the first report on the direct impact of the inclusion of functional additives in fish diet upon such parameters. As concerns the thermal tolerance evaluated at the end of the feeding trial, no differences were registered among the experimental groups. Thus, BOPP represents a feasible alternative ingredient to be explored in fish nutrition, since orange peel is a natural low-cost source of essential nutrients and valuable bioactive compounds.

Tongue-on-a-Chip: Parallel Recording of Sweet and Bitter Receptor Responses to Sequential Injections of Pure and Mixed Sweeteners.

A microfluidic tongue-on-a-chip platform has been evaluated relative to the known sensory properties of various sweeteners. Analogous metrics of typical sensory features reported by human panels such as sweet taste thresholds, onset, and lingering, as well as bitter off-flavor and blocking interactions were deduced from the taste receptor activation curves and then compared. To this end, a flow cell containing a receptor cell array bearing the sweet and six bitter taste receptors was transiently exposed to pure and mixed sweetener samples. The sample concentration gradient across time was separately characterized by the injection of fluorescein dye. Subsequently, cellular calcium responses to different doses of advantame, aspartame, saccharine, and sucrose were overlaid with the concentration gradient. Parameters describing the response kinetics compared to the gradient were quantified. Advantame at 15 µM recorded a significantly faster sweetness onset of 5 ± 2 s and a longer lingering time of 39 s relative to sucrose at 100 mM with an onset of 13 ± 2 s and a lingering time of 6 s. Saccharine was shown to activate the bitter receptors TAS2R8, TAS2R31, and TAS2R43, confirming its known off-flavor, whereas addition of cyclamate reduced or blocked this saccharine bitter response. The potential of using this tongue-on-a-chip to bridge the gap with in vitro assays and taste panels is discussed.

Gut tumors in flies alter the taste valence of an anti-tumorigenic bitter compound.

The sense of taste is essential for survival, as it allows animals to distinguish between foods that are nutritious from those that are toxic. However, innate responses to different tastants can be modulated or even reversed under pathological conditions. Here, we examined whether and how the internal status of an animal impacts taste valence by using Drosophila models of hyperproliferation in the gut. In all three models where we expressed proliferation-inducing transgenes in intestinal stem cells (ISCs), hyperproliferation of ISCs caused a tumor-like phenotype in the gut. While tumor-bearing flies had no deficiency in overall food intake, strikingly, they exhibited an increased gustatory preference for aristolochic acid (ARI), which is a bitter and normally aversive plant-derived chemical. ARI had anti-tumor effects in all three of our gut hyperproliferation models. For other aversive chemicals we tested that are bitter but do not have anti-tumor effects, gut tumors did not affect avoidance behaviors. We demonstrated that bitter-sensing gustatory receptor neurons (GRNs) in tumor-bearing flies respond normally to ARI. Therefore, the internal pathology of gut hyperproliferation affects neural circuits that determine taste valence postsynaptic to GRNs rather than altering taste identity by GRNs. Overall, our data suggest that increased consumption of ARI may represent an attempt at self-medication. Finally, although ARI's potential use as a chemotherapeutic agent is limited by its known toxicity in the liver and kidney, our findings suggest that tumor-bearing flies might be a useful animal model to screen for novel anti-tumor drugs.

The Growing Complexity of Human Bitter Taste Perception.

Human bitter perception is important for the identification of potentially harmful substances in food. For quite some years, research focused on the identification of activators for ∼25 human bitter taste receptors. The discovery of antagonists as well as increasing knowledge about agonists of different efficacies has substantially added to the intricacy of bitter taste perception. This article seeks to raise awareness for an underestimated new level of complexity when compound mixtures or even whole food items are assessed for their bitter taste.

Modulation of bitter taste receptors by yeast extracts.

Yeast extracts (YEs) are used in foods because of their flavour properties and ability to reduce bitterness. The adenosine 5'-monophosphate (AMP) found in YEs is known to decrease the bitterness of some compounds. This study aimed to investigate the ability of YEs to inhibit bitter taste receptors (TAS2Rs) using in vitro cell-based assays. A screen of TAS2Rs activated by AMP and YEs revealed that AMP and the AMP-rich YE activated more TAS2Rs. The inhibitory effect of the AMP-rich YE on seven TAS2Rs activated by bitter agonists was studied. YE reduced TAS2R activation, increased the EC50 value and decreased the maximum amplitude, demonstrating competitive and non-competitive inhibitions. Amongst the nineteen TAS2Rs tested, seven showed 40 % or greater inhibition after treatment of AMP-rich YE. Our data provide a better understanding of the TAS2R inhibition mechanism of AMP-rich YEs and promote their use as a strategy to reduce bitterness in foods and medicines.

Comparison of α and ß-acid isomerization in hops and beer using HPLC, confocal microscopy, spectrofluorimetry and chemical analysis of metabolites and essential oils in flowers of different hop cultivars produced in Brazil.

We used confocal microscopy and spectrofluorescence to characterize the emission spectra in hop flowers, to follow the isomerization processes in different hop preparations, and beers, to compare with HPLC extracted samples. Flowers of different hop cultivars produced in three regions of Brazil, were quantitated by HPLC and GC-MS. The fluorescence spectra showed two characteristic emission bands evaluated from different preparations. The isomerization process leads to a gradual decrease in fluorescence intensity as the reaction progresses. This demonstrates the valuable use of confocal microscopy and fluorescence spectroscopy for analysis of the correlation between bitter acid indices with fluorescence intensity and lifetime microscopy. Such techniques can be used directly in the flowers allowing rapid monitoring of the brewing process. Twenty-nine substances were characterized in the essential oils and some cultivars presented quantities of bitter acids and essential oil levels close to those expected for plants after more than three years of cultivation.

TAS2R38 bitterness receptor genetic variation is associated with diet quality in Koreans.

Genetic variation in the bitter taste receptor gene taste receptor type 2, member 38 (TAS2R38) is associated with an individual's bitter taste sensitivity, food preference and consumption, which may also influence overall diet quality. This study aims to determine whether the TAS2R38 bitter taste receptor genetic variation is associated with overall diet quality using the Korean Healthy Eating Index (KHEI). A total of 41,839 individuals from the Korean Genome and Epidemiology Study were analyzed for their TAS2R38 diplotypes (rs713598, rs1726866, and rs10246939), general characteristics, and KHEI scores by obesity status. Results revealed that in the non-obese group, individuals with the AVI/AVI diplotype had a significantly higher score of 'ratio of white meat to red meat' than individuals with the PAV/* diplotype (3.89 ± 3.23 vs. 3.79 ± 3.18, adjusted p = 0.029). However, obese individuals with the PAV/* diplotype showed a significantly higher level of the mean score of 'moderation' (19.32 ± 5.82 vs. 18.92 ± 5.80, adjusted p = 0.026) and total KHEI score (61.07 ± 12.19 vs. 60.52 ± 12.29, adjusted p = 0.008) than those with the AVI/AVI diplotype. Finally, an interactive effect between bitterness genetic variation and obesity level was observed in those scores of 'ratio of white meat to red meat' (adjusted p = 0.007), 'moderation' (adjusted p = 0.013), and total KEHI (adjusted p = 0.007). In conclusion, TAS2R38 genetic variation is associated with overall diet quality in Koreans, which is more evident in the obese group.

Human Sensory, Taste Receptor, and Quantitation Studies on Kaempferol Glycosides Derived from Rapeseed/Canola Protein Isolates.

Beyond the key bitter compound kaempferol 3-O-(2‴-O-sinapoyl-ß-d-sophoroside) previously described in the literature (1), eight further bitter and astringent-tasting kaempferol glucosides (2-9) have been identified in rapeseed protein isolates (Brassica napus L.). The bitterness and astringency of these taste-active substances have been described with taste threshold concentrations ranging from 3.3 to 531.7 and 0.3 to 66.4 µmol/L, respectively, as determined by human sensory experiments. In this study, the impact of 1 and kaempferol 3-O-ß-d-glucopyranoside (8) on TAS2R-linked proton secretion by HGT-1 cells was analyzed by quantification of the intracellular proton index. mRNA levels of bitter receptors TAS2R3, 4, 5, 13, 30, 31, 39, 40, 43, 45, 46, 50 and TAS2R8 were increased after treatment with compounds 1 and 8. Using quantitative UHPLC-MS/MSMRM measurements, the concentrations of 1-9 were determined in rapeseed/canola seeds and their corresponding protein isolates. Depending on the sample material, compounds 1, 3, and 5-9 exceeded dose over threshold (DoT) factors above one for both bitterness and astringency in selected protein isolates. In addition, an increase in the key bitter compound 1 during industrial protein production (apart from enrichment) was observed, allowing the identification of the potential precursor of 1 to be kaempferol 3-O-(2‴-O-sinapoyl-ß-d-sophoroside)-7-O-ß-d-glucopyranoside (3). These results may contribute to the production of less bitter and astringent rapeseed protein isolates through the optimization of breeding and postharvest downstream processing.

Ultra-high-performance liquid chromatography-mass spectrometry combined with molecular docking and molecular dynamics simulation reveals the source of bitterness in the traditional Chinese medicine formula Runchang-Tongbian.

The Runchang-Tongbian (RCTB) formula is a traditional Chinese medicine (TCM) formula consisting of four herbs, namely Cannabis Fructus (Huomaren), Rehmanniae Radix (Dihuang), Atractylodis Macrocephalae Rhizoma (Baizhu), and Aurantii Fructus (Zhiqiao). It is widely used clinically because of its beneficial effect on constipation. However, its strong bitter taste leads to poor patient compliance. The bitter components of TCM compounds are complex and numerous, and inhibiting the bitter taste of TCM has become a major clinical challenge. Here, we use ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) and high-resolution mass spectrometry to identify 59 chemical components in the TCM compound RCTB formula. Next, four bitter taste receptors, TAS2R39, TAS2R14, TAS2R7, and TAS2R5, which are tightly bound to the compounds in RCTB, were screened as molecular docking receptors using the BitterX database. The top-three-scoring receptor-small-molecule complexes for each of the four receptors were selected for molecular dynamics simulation. Finally, seven bitter components were identified, namely six flavonoids (rhoifolin, naringin, poncirin, diosmin, didymin, and narirutin) and one phenylpropanoid (purpureaside C). Thus, we proposed a new method for identifying the bitter components in TCM compounds, which provides a theoretical reference for bitter taste inhibition in TCM compounds.

Evaluation of Gustatory Function in Patients with Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the mucosa of the nasal cavity and nasal sinuses. Many patients with CRS complain of gustatory dysfunction which affects their quality of life. To assess the gustatory function and acuity in patients with chronic rhinosinusitis using taste strips. This is a case control study carried out at our institute from May 2021 to June 2022 on 63 Patients with chronic rhinosinusitis with nasal polyposis and 63 normal controls. All patients of the study and control group will be subjected to full medical history taking including SNOT-22-Questionnaire, sinuscopic examination, computed tomography scan nose and paranasal sinuses using Lund-Mackay score. Taste strips representing five tastes (sweet, sour, salty, bitter and umami) were used to assess gustatory function in CRS patients and controls. 63 patients with CRS and 63 healthy controls were involved in our study, age 42.05 ± 14 years old for cases and 40.9 ± 13.6 years old for controls. There was a highly significant difference between cases and controls as regard SNOT-22-Questionnaire scores and Meltzer-scores with higher mean scores among cases. There was a highly significant difference between cases and controls as regard Sweet, Salt Sour, Bitter, Umami and Total Taste score, with lower mean scores among cases. This is most evident in bitter taste. There was a significant negative Correlation between each of SNOT-22-Questionnaire score, Meltzer-score and Lund-Mackay score and total taste score. Patients with chronic rhinosinusitis exhibited decreased gustatory function compared to healthy controls. The effect was most pronounced for bitter taste.

Bitter melon extract mitigates heterocyclic aromatic amine formation in chicken thigh meat.

The purpose of the present research was to study the impact of bitter melon extract (BME) on the generation of heterocyclic aromatic amines (HAAs) in chicken thigh meat. Raw chicken samples were marinated overnight with various levels (0%, 0.5%, and 1%) of BME, and pan-fried at 150, 200, and 250°C for a total of 10 min. IQx, IQ, MeIQx, MeIQ, 7,8-DiMeIQx, 4,8-DiMeIQx, PhIP, AαC, and MeAαC were detected in quantities that varied according to the cooking temperature and the concentration of BME. Notably, IQx, MeIQx, MeIQ, 7,8-DiMeIQx, 4,8-DiMeIQx, and AαC levels were reduced through the application of the marinade. Cooking at higher temperatures led to elevated levels of total HAAs. Total HAA levels were 0.98 ± 1.12 ng/g, 3.82 ± 2.12 ng/g, and 6.25 ± 3.35 ng/g in samples cooked at 150, 200, and 250°C, respectively (p < .01). BME demonstrated its effectiveness in mitigating total HAA levels, showing reductions ranging from 25.9% to 69.9%. The most effective concentration of BME in reducing total HAAs was 1% for all cooking temperatures, which might be attributed to its antioxidant activity. These results carry substantial implications for potentially incorporating natural extracts such as BME into chicken products as a viable strategy to reduce HAAs, thus enhancing the safety and quality of meat products.

Insights into the identification of bitter peptides from Jinhua ham and its taste mechanism by molecular docking and transcriptomics analysis.

In order to identify the peptides responsible for bitter defects and to understand the mechanism of bitterness in dry-cured ham, the peptides were identified by LC-MS/MS, and the interaction between bitter peptides and receptor proteins were evaluated by molecular docking and molecular dynamics simulation; the signal transduction mechanism of bitter peptides was investigated using the model of HEK-293T cells by calcium imaging and transcriptomics analysis. The results of LC-MS/MS showed that 11 peptides were identified from the high bitterness fraction of defective ham; peptides PKAPPAK, VTDTTR and YIIEK derived from titin showed the highest bitterness values compared with other peptides. The results of molecular docking showed that lower CDOCKER energy was observed in the interaction between these peptides and hT2R16 in comparison with these receptors of hT2R1, hT2R4, hT2R5, hT2R8 and hT2R14, and the interaction of hT2R16 and peptides was stabilized by hydrophobic interaction and hydrogen bond. The average RMSF values of VTDTTR were higher than that of YIIEK and PKAPPAK, while EC50 values of VTDTTR were lower compared with PKAPPAK and YIIEK. Transcriptomics analysis showed that 529 differentially expressed genes were identified in HEK-293T cells during the stimulating by VTDTTR and were mainly enriched into neuroactive ligand-receptor interaction, MAPK pathway, cAMP pathway and calcium signaling pathway, which were mainly responsible for the bitter signal transduction of VTDTTR. These results could provide evidence for understanding the bitter defects of dry-cured ham and the taste mechanism of bitter peptide.

Exploring bitter characteristics of blue honeysuckle (Lonicera caerulea L.) berries by sensory-guided analysis: Key bitter compounds and varietal differences.

The taste of blue honeysuckle (Lonicera caerulea L.) berries is wrapped in bitterness, and awareness about the essence of bitterness is lacking. In the current study, 7-ketologanin, sweroside and loganin were isolated and identified as key bitter compounds using sensory-guided analysis. The bitterness thresholds of these compounds were determined to be 11.9 µg/mL, 33.5 µg/mL and 60.2 µg/mL. Subsequently, the differences in bitterness among 16 blue honeysuckle varieties were evaluated. The wild varieties A1 and A2 exhibited the highest bitter intensity. 7-Ketologanin, with the highest concentration of 34.70-37.11 mg/100 g and taste activity values of 29.16-31.18 in A1 and A2, was first identified as a bitter contributor in blue honeysuckle. There was no significant difference in bitter intensity between the reconstitution model and the original sample, confirming the contribution of the three bitter compounds. This study lays the foundation for the bitter improvement and variety selection of blue honeysuckle resources.

Intestinal Taste Receptor Expression and Its Implications for Health: An Integrative Analysis in Female Rats after Chronic Insect Supplementation.

Taste receptors are found in the gastrointestinal tract, where they are susceptible to dietary modulation, a key point that is crucial for diet-related responses. Insects are sustainable and good-quality protein sources. This study analyzed the impact of insect consumption on the modulation of taste receptor expression across various segments of the rat intestine under healthy or inflammatory conditions. Female Wistar rats were supplemented with Tenebrio molitor (T) or Alphitobius diaperinus (B), alongside a control group (C), over 21 days under healthy or LPS-induced inflammation. The present study reveals, for the first time, that insect consumption modulates taste receptor gene expression, mainly in the ascending colon. This modulation was not found under inflammation. Integrative analysis revealed colonic Tas1r1 as a key discriminator for insect consumption (C = 1.04 ± 0.32, T = 1.78 ± 0.72, B = 1.99 ± 0.82, p-value <0.05 and 0.01, respectively). Additionally, correlation analysis showed the interplay between intestinal taste receptors and metabolic and inflammatory responses. These findings underscore how insect consumption modulates taste receptors, influencing intestinal function and broader physiological mechanisms.

Activation of TAS2R4 signaling attenuates podocyte injury induced by high glucose.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C ß2 (PLCß2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCß2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gßγ inhibitor Gallein, or a PLCß2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.