Nuclear Factor κB (NF‐κB) Pathway
NF‐κB is one of the transcription factors, which is abnormally regulated in disease like cancer. Activation of NF‐κB has been documented in various cancers, including liver, colon, pancreas, breast, prostrate, ovarian, leukemia, and lymphoma cancers and others also. DNA damaging also activates NF‐κB, which in turn activates and regulates a number of NF‐κB‐influenced target genes, including inducible nitric oxide synthase, and COX‐2. Furthermore, binding of TNF‐α to TNFR leads to homotrimerization of receptors and adaptor proteins resulting in cell proliferation and survival by increasing the expression of NF‐κB and activator protein 1 target genes, including vascular cell adhesion molecule‐1 (VCAM‐1). NF‐κB activation triggers the activation of chemokines and its related receptors, including C‐X‐C chemokine receptor 4 (CXCR4) and CCR7, which play crucial role in cancer cells’ migration to target organs. These genes play major roles in antiapoptosis process. Vanilla‐containing foods have the potential of therapeutic efficacy against cancer by inhibiting NF‐κB pathway activation in cancer cells. In lipopolysaccharide‐induced MCF‐7 cells, Z138 cells, T24, and THP1 cells, vanilla inhibits proliferation, adhesion, migration, and invasion by regulating the NF‐κB pathway. In the NF‐κB pathway, vanilla also reported to inhibit the expression of inflammatory factors TNF‐α and IL‐6 and abnormal NF‐κB activation through inhibition of phospho‐IκBα, p65 and upregulation of miR16 (Lirdprapamongkol et al., 2010). Vanilla also showed the inhibition of the NF‐κB nuclear translocation leading to the inhibition of mRNA expression and COX‐2, VCAM, and ICAM proteins.
2.5.4 Anti‐sickling Activity
Sickle cell disease (SCD) is a genetic disorder caused by a point mutation in the β‐globin gene, where glutamic acid is replaced by valine at the sixth position of the β‐chain of hemoglobin (Hb). In 1991, vanillin, a natural flavoring agent, has been reported as anti‐sickling agent (Abraham et al., 1991). The results have shown that vanillin covalently binds with HbS and helps in increasing its oxygen carrying affinity and thus vanillin has a moderate anti‐sickling property. However, vanillin showed poor oral bioavailability and thus demands for other mode of administration into the body. To overcome this issue, Zhang et al. (2004) synthesized a vanillin prodrug, MX‐1520, which can be biotransformed into vanillin in vivo. Oral administration of MX‐1520 prior to hypoxia exposure in the transgenic sickle mice exhibited significant reduction in the number of sickled cells, which clearly evidenced the potential of MX1520 as a safe antisickling agent for SCD patients.
2.5.5 Hypolipidemic Activity
Vanillin has exerted significant reduction in the levels of serum triglyceride, VLDL‐C, and total cholesterol in high‐fat diet‐induced hyperlipidemic rats (Belagali et al., 2013). Likewise, vanillin‐containing foods showed positive results in reducing obesity in high‐fat diet‐induced obese mice, wherein vanillin reduced abnormal elevation of inflammatory factors including IL‐6 and TNF‐α in plasma and liver tissue results from obesity in high‐fat‐induced mice (Guo et al., 2018).
2.6 Conclusion
The organoleptic compound vanillin has a wide application in number of industries. Among them, vanillin has received much attention by food industry due to its flavoring property. There are three modes of production of vanillin: natural, chemical, and biotechnological synthesis. Only natural and biotechnological vanillin is recommended by food‐safety authorities worldwide. The annual production of vanillin in global market is reported to be 5361 metric tons among which the contribution of natural vanillin is much low. In order to meet the world’s requirement, many advanced biotechnological methods such as strain development, metabolic engineering, genetic engineering, and enzymatic production have been widely investigated. Yet, only very less biotechnological methods have been employed in industries. Thus, applying metabolically engineered strains in industrial production would greatly increase the annual production rate of vanillin.
Acknowledgments
The authors gratefully acknowledge the Indian Council of Medical Research (ICMR), India [No. 5/4/5‐4/Diab.‐16‐NCD‐II], for the financial support to BA. The authors also thank DST‐PURSE, UGC‐UPE, and UGC‐SAP programs of Madurai Kamaraj University for their infrastructure and other facilities.
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