Vanillin

Food Chem Toxicol. 2014 Jan;63:30-7.

Vanillin protects human keratinocyte stem cells against ultraviolet B irradiation.[Pubmed: 24184596]

Ultraviolet-B (UVB) irradiation is one of major factors which induce cellular damages in the epidermis.
METHODS AND RESULTS:
We investigated protective effects and mechanisms of Vanillin, a main constituent of vanilla beans, against UVB-induced cellular damages in keratinocyte stem cells (KSC). Here, Vanillin significantly attenuated UVB irradiation-induced cytotoxicity. The Vanillin effects were also demonstrated by the results of the senescence-associated β-galactosidase and alkaline comet assays. In addition, Vanillin induced production of pro-inflammatory cytokines. Attempts to elucidate a possible mechanism underlying the Vanillin-mediated effects revealed that Vanillin significantly reduced UVB-induced phosphorylation of ataxia telangiectasia mutated (ATM), serine threonine kinase checkpoint kinase 2 (Chk2), tumor suppressor protein 53 (p53), p38/mitogen-activated protein kinase (p38), c-Jun N-terminal kinase/stress-activated protein kinase (JNK), S6 ribosomal protein (S6RP), and histone 2A family member X (H2A.X). UVB-induced activation of p53 luciferase reporter was also significantly inhibited by Vanillin. In addition, while ATM inhibitor had no effect on the Vanillin effects, mouse double minute 2 homolog (MDM2) inhibitor significantly attenuated suppressive effects of Vanillin on UVB-induced activation of p53 reporter in KSC.
CONCLUSIONS:
Taken together, these findings suggest that Vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation.

J Biosci Bioeng. 2014 Sep;118(3):263-9.

Importance of glucose-6-phosphate dehydrogenase (G6PDH) for vanillin tolerance in Saccharomyces cerevisiae.[Pubmed: 24725964]

Vanillin is derived from lignocellulosic biomass and, as one of the major biomass conversion inhibitors, inhibits yeast growth and fermentation. Vanillin was recently shown to induce the mitochondrial fragmentation and formation of mRNP granules such as processing bodies and stress granules in Saccharomyces cerevisiae. Furfural, another major biomass conversion inhibitor, also induces oxidative stress and is reduced in an NAD(P)H-dependent manner to its less toxic alcohol derivative. Therefore, the pentose phosphate pathway (PPP), through which most NADPH is generated, plays a role in tolerance to furfural. Although Vanillin also induces oxidative stress and is reduced to vanillyl alcohol in a NADPH-dependent manner, the relationship between Vanillin and PPP has not yet been investigated.
METHODS AND RESULTS:
In the present study, we examined the importance of glucose-6-phosphate dehydrogenase (G6PDH), which catalyzes the rate-limiting NADPH-producing step in PPP, for yeast tolerance to Vanillin. The growth of the null mutant of G6PDH gene (zwf1Δ) was delayed in the presence of Vanillin, and Vanillin was efficiently reduced in the culture of wild-type cells but not in the culture of zwf1Δ cells. Furthermore, zwf1Δ cells easily induced the activation of Yap1, an oxidative stress responsive transcription factor, mitochondrial fragmentation, and P-body formation with the Vanillin treatment, which indicated that zwf1Δ cells were more susceptible to Vanillin than wild type cells.
CONCLUSIONS:
These findings suggest the importance of G6PDH and PPP in the response of yeast to Vanillin.

Food Chem Toxicol . 2016 Oct;96:62-9.

Vanillin attenuates negative effects of ultraviolet A on the stemness of human adipose tissue-derived mesenchymal stem cells[Pubmed: 27470612]

Abstract Ultraviolet A (UVA) irradiation induces various changes in cell biology. The objective of this study was to determine the effect of Vanillin on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). UVA-antagonizing mechanisms of Vanillin were also examined. The results revealed that Vanillin attenuated UVA-induced reduction of the proliferative potential and stemness of hAMSCs evidenced by increased proliferative activity in BrdU incorporation assay and upregulation of stemness-related genes (OCT4, NANOG and SOX2) in response to Vanillin treatment. UVA-induced reduction in mRNA level of hypoxia-inducible factor (HIF)-1α was significantly recovered by Vanillin. In addition, the antagonizing effect of Vanillin on UVA was found to be mediated by reduced production of PGE2 through inhibiting JNK and p38 MAPK. Taken together, these findings showed that Vanillin could improve the reduced stemness of hAMSCs induced by UVA. The effect of Vanillin is mediated by upregulating HIF-1α via inhibiting PGE2-cAMP signaling. Therefore, Vanillin might be used as an antagonizing agent to mitigate the effects of UVA. Keywords: HIF; Human adipose tissue-derived mesenchymal stem cells; PGE(2); Stemness gene; UVA toxicity; Vanillin.

Psychiatry Res . 2015 Feb 28;225(3):509-14.

Vanillin-induced amelioration of depression-like behaviors in rats by modulating monoamine neurotransmitters in the brain[Pubmed: 25595338]

Abstract Olfaction plays an important role in emotions in our daily life. Pleasant odors are known to evoke positive emotions, inducing relaxation and calmness. The beneficial effects of Vanillin on depressive model rats were investigated using a combination of behavioral assessments and neurotransmitter measurements. Before and after chronic stress condition (or olfactory bulbectomy), and at the end of Vanillin or fluoxetine treatment, body weight, immobility time on the forced swimming test and sucrose consumption in the sucrose consumption test were measured. Changes in these assessments revealed the characteristic phenotypes of depression in rats. Neurotransmitters were measured using ultrahigh-performance liquid chromatography. Our results indicated that Vanillin could alleviate depressive symptoms in the rat model of chronic depression via the olfactory pathway. Preliminary analysis of the monoamine neurotransmitters revealed that Vanillin elevated both serotonin and dopamine levels in brain tissue. These results provide important mechanistic insights into the protective effect of Vanillin against chronic depressive disorder via olfactory pathway. This suggests that Vanillin may be a potential pharmacological agent for the treatment of major depressive disorder. Keywords: Aromatherapy; Chronic unpredictable mild stress; Corticosterone; Major depressive disorder; Olfactory pathway; Ultrahigh performance liquid chromatography.

Bioresour Technol. 2014 Sep;167:324-30.

Inhibitory effect of vanillin on cellulase activity in hydrolysis of cellulosic biomass.[Pubmed: 24997375]

Pretreatment of lignocellulosic material produces a wide variety of inhibitory compounds, which strongly inhibit the following enzymatic hydrolysis of cellulosic biomass. Vanillin is a kind of phenolics derived from degradation of lignin.
METHODS AND RESULTS:
The effect of Vanillin on cellulase activity for the hydrolysis of cellulose was investigated in detail. The results clearly showed that Vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L. The inhibition kinetics of cellulase by Vanillin was studied using HCH-1 model and inhibition constants were determined. Moreover, investigation of three compounds with similar structure of Vanillin on cellulase activity demonstrated that aldehyde group and phenolic hydroxyl groups of Vanillin had inhibitory effect on cellulase.
CONCLUSIONS:
These results provide valuable and detailed information for understanding the inhibition of lignin derived phenolics on cellulase.

J Biosci Bioeng. 2014 Jan;117(1):33-8.

Vanillin causes the activation of Yap1 and mitochondrial fragmentation in Saccharomyces cerevisiae.[Pubmed: 23850265]

Vanillin and furfural are derived from lignocellulosic biomass and inhibit yeast growth and fermentation as biomass conversion inhibitors. Furfural has been shown to induce oxidative stress in Saccharomyces cerevisiae.
METHODS AND RESULTS:
Since there has been no report on the relationship between Vanillin and oxidative stress, we investigated whether Vanillin caused oxidative stress in yeast cells. We showed that Vanillin caused the nuclear accumulation of Yap1, an oxidative stress responsive transcription factor, and subsequent transcriptional activation of Yap1-target genes. The growth of the null mutant of the YAP1 gene (yap1Δ) was delayed in the presence of Vanillin, which indicated that Yap1 plays a role in the acquisition of tolerance to Vanillin. We also demonstrated that Vanillin facilitated the fragmentation of mitochondria.
CONCLUSIONS:
These findings suggest that the toxicity of Vanillin involves damage induced by oxidative stress.