Vanillic acid is a natural phenolic acid compound with antioxidant, anti-inflammatory, neuroprotective, cardioprotective, hypoglycemic and anticancer pharmacological effects. Vanillic acid scavenges free radicals and reactive oxygen species, inhibits COX-2 and iNOS expression, downregulates pro-inflammatory cytokines such as TNF-α and IL-1β, and modulates signaling pathways including NF-κB, MAPK and Nrf2/HO-1. Vanillic acid can be used in research on cardiovascular diseases, diabetes and its complications, neurodegenerative diseases and cancer[1-4].
In vitro, treatment of H₂O₂-induced H9c2 cells with 50-200µM Vanillic acid for 3 hours reduced apoptosis rate and lactate dehydrogenase release, decreased reactive oxygen species and malondialdehyde levels, attenuated mitochondrial membrane potential depolarization, and improved autophagic flux and mitophagy[5]. Treatment of SH-SY5Y cells with 300µM Vanillic acid for 18-24 hours elevated PGC-1α and TFAM mRNA expression, and increased mitochondrial DNA copy number and mitochondrial mass[6]. Treatment of D.Mel-2 cells with 250µg/mL Vanillic acid for 24 hours elevated catalase activity, superoxide dismutase activity, glutathione peroxidase activity and glutathione level[7].
In vivo, oral gavage of 50-100mg/kg Vanillic acid once daily for 2 weeks to arsenic-exposed NMRI mice. Vanillic acid reduced fasting blood glucose and glucose tolerance test area under curve, decreased serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities, and alleviated liver pathological changes including inflammatory infiltration and erythrocyte accumulation[8]. Daily intraperitoneal injection of 20mg/kg Vanillic acid to Swiss albino mice for 30 days, followed by a single intraperitoneal injection of 80mg/kg N-ethyl-N-nitrosourea on day 31. Vanillic acid increased survival rate within 120 days and delayed death time[9]. Oral gavage of 12.5-50mg/kg Vanillic acid once daily for 7 days to DSS-induced colitis C57BL/6 mice. Vanillic acid reduced body weight loss and colon shortening, decreased disease activity index score, and alleviated colonic mucosal damage and inflammatory cell infiltration[10].
References:
[1] Yalameha B, Nejabati HR, Nouri M. Cardioprotective potential of vanillic acid. Clin Exp Pharmacol Physiol. 2023 Mar;50(3):193-204.
[2] Lashgari NA, Roudsari NM, Momtaz S, et al. Regulatory Mechanisms of Vanillic Acid in Cardiovascular Diseases: A Review. Curr Med Chem. 2023;30(22):2562-2576.
[3] Shekari S, Khonsha F, Rahmati-Yamchi M, et al. Vanillic Acid and Non-Alcoholic Fatty Liver Disease: A Focus on AMPK in Adipose and Liver Tissues. Curr Pharm Des. 2021;27(46):4686-4692.
[4] Gong J, Zhou S, Yang S. Vanillic Acid Suppresses HIF-1α Expression via Inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK Pathways in Human Colon Cancer HCT116 Cells. Int J Mol Sci. 2019 Jan 22;20(3):465.
[5] Mei M, Sun H, Xu J, et al. Vanillic acid attenuates H2O2-induced injury in H9c2 cells by regulating mitophagy via the PINK1/Parkin/Mfn2 signaling pathway. Front Pharmacol. 2022 Sep 7;13:976156.
[6] Ay M. Vanillic acid induces mitochondrial biogenesis in SH-SY5Y cells. Mol Biol Rep. 2022;49(7):4443-9.
[7] Taqvi S, Bhat EA, Sajjad N, et al. Protective effect of vanillic acid in hydrogen peroxide-induced oxidative stress in D.Mel-2 cell line. Saudi J Biol Sci. 2021;28(3):1795-800.
[8] Shariati S, Khodayar MJ, Azadnasab R, et al. Protective Effects of Vanillic Acid on Arsenic-Induced Hepatotoxicity and Diabetes in Mice; the Role of PPARγ and NF-κB Signaling. Rep Biochem Mol Biol. 2025 Jan;13(4):549-60.
[9] Salimi A, Haddadi S, Khezri S, et al. Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia. Toxicol Rep. 2024;12:389-96.
[10] Nia J, Zhang L, Feng G, et al. Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis. Pharmacol Res. 2024;202:107128.