Y-3

Paclitaxel (PTX) is an anticancer drug used to treat solid tumors, but one of its common adverse effects is chemotherapy-induced peripheral neuropathy (CIPN). Currently, there is limited understanding of neuropathic pain associated with CIPN and effective treatment strategies are inadequate. Previous studies report the analgesic actions of Naringenin, a dihydroflavonoid compound, in pain. Here we observed that the anti-nociceptive action of a Naringenin derivative, Trimethoxyflavanone (Y3), was superior to Naringenin in PTX-induced pain (PIP). An intrathecal injection of Y3 (1 μg) reversed the mechanical and thermal thresholds of PIP and suppressed the PTX-induced hyper-excitability of dorsal root ganglion (DRG) neurons. PTX enhanced the expression of ionotropic purinergic receptor P2X7 (P2X7) in satellite glial cells (SGCs) and neurons in DRGs. The molecular docking simulation predicts possible interactions between Y3 and P2X7. Y3 reduced the PTX-enhanced P2X7 expression in DRGs. Electrophysiological recordings revealed that Y3 directly inhibited P2X7-mediated currents in DRG neurons of PTX-treated mice, suggesting that Y3 suppressed both expression and function of P2X7 in DRGs post-PTX administration. Y3 also reduced the production of calcitonin gene-related peptide (CGRP) in DRGs and at the spinal dorsal horn. Additionally, Y3 suppressed the PTX-enhanced infiltration of Iba1-positive macrophage-like cells in DRGs and overactivation of spinal astrocytes and microglia. Therefore, our results indicate that Y3 attenuates PIP via inhibiting P2X7 function, CGRP production, DRG neuron sensitization, and abnormal spinal glial activation. Our study implies that Y3 could be a promising drug candidate against CIPN-associated pain and neurotoxicity.

In this study, 21 strains of aroma-producing yeast were isolated from Sichuan paocai juice of farmers in western, eastern and southern Sichuan. One strain, Y3, with the best aroma-producing characteristics, was screened using an olfactory method and a total ester titration method, and was identified as Wickerhamomyces anomalus. The total ester content of Y3 fermentation broth was as high as 1.22 g/L, and there was no white colonies or film on the surface. Meanwhile, the Y3 strain could tolerate 14% salt concentration conditions and grow well in a pH range of 3-4. Through sensory analysis, the fermented mustard with a ratio of Lactiplantibacillus plantarum to Y3 of 1:1 showed the highest overall acceptability. Ethyl acetate with its fruit and wine flavor was also detected in the fermented Sichuan paocai juice with a mixed bacteria ratio of 1:1, analyzed with SPME-GC-MS technology, as well as phenylethyl alcohol, isobutyl alcohol, isothiocyanate eaters, myrcene and dimethyl disulfide. These contributed greatly to the unique flavor of Sichuan paocai. In general, Wickerhamomyces anomalus Y3 enhanced the aroma of the fermented Sichuan paocai.