Vanillic acid as a novel specific inhibitor of snake venom 5′-nucleotidase: A pharmacological tool in evaluating the role of the enzyme in snake envenomation

Dhananjaya, B. L.; Angaswamy, Nataraju; Gowda, Chandrika; Sharath, B. K.; D'Souza, Cletus J. M.

doi:10.1134/s0006297909120037

Cited by 40 publications

(24 citation statements)

References 34 publications

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“…Vanillic acid has been associated with a variety of pharmacologic activities such as inhibiting snake venom activity (32,33), carcinogenesis (34), apoptosis (35,36) and inflammation (37) but it has become most popular for its pleasant creamy odour that is widely used in fragrances and licensed as a food additive (FAO/WHO Expert Committee on Food Additives, JECFA no. 959).…”

Section: Introductionmentioning

confidence: 99%

The food additive vanillic acid controls transgene expression in mammalian cells and mice

Gitzinger

Kemmer

Fluri

et al. 2011

Nucleic Acids Research

105

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Trigger-inducible transcription-control devices that reversibly fine-tune transgene expression in response to molecular cues have significantly advanced the rational reprogramming of mammalian cells. When designed for use in future gene- and cell-based therapies the trigger molecules have to be carefully chosen in order to provide maximum specificity, minimal side-effects and optimal pharmacokinetics in a mammalian organism. Capitalizing on control components that enable Caulobacter crescentus to metabolize vanillic acid originating from lignin degradation that occurs in its oligotrophic freshwater habitat, we have designed synthetic devices that specifically adjust transgene expression in mammalian cells when exposed to vanillic acid. Even in mice transgene expression was robust, precise and tunable in response to vanillic acid. As a licensed food additive that is regularly consumed by humans via flavoured convenience food and specific fresh vegetable and fruits, vanillic acid can be considered as a safe trigger molecule that could be used for diet-controlled transgene expression in future gene- and cell-based therapies.

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Section: Introductionmentioning

confidence: 99%

The food additive vanillic acid controls transgene expression in mammalian cells and mice

Gitzinger

Kemmer

Fluri

et al. 2011

Nucleic Acids Research

105

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“…Vanillic acid abolished the deleterious effect of oxidative stress induced by STZ on learning and memory in mice and exerted specific anti-inflammatory and anti-oxidant effects that down-regulated the neuroinflammatory process, suggesting that the long-term administration of VA could delay the progression of AD20. These findings are in line with another report21 describing the beneficial effects of VA. Vanillic acid has been associated with multiple pharmacologic activities such as the inhibition of snake venom activity and antifilarial, antimicrobial, anti-inflammatory and antioxidant functions212223242526.…”

mentioning

confidence: 99%

Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice

Amin

Shah

Kim

2017

Sci Rep

152

110

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Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer’s disease (AD). The aims of the present study were to determine and explore the antioxidant nature and potential mechanism of vanillic acid (VA) in Aβ1-42-induced oxidative stress and neuroinflammation mediated cognitive impairment in mice. An intracerebroventricular (i.c.v.) injection of Aβ1-42 into the mouse brain triggered increased reactive oxygen species (ROS) levels, neuroinflammation, synaptic deficits, memory impairment, and neurodegeneration. In contrast, the i.p. (intraperitoneal) administration of VA (30 mg/kg, for 3 weeks) after Aβ1-42-injection enhanced glutathione levels (GSH) and abrogated ROS generation accompanied by an induction of the endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) via the activation of Akt and glycogen synthase kinase 3β (GSK-3β) in the brain mice. Additionally, VA treatment decreased Aβ1-42-induced neuronal apoptosis and neuroinflammation and improved synaptic and cognitive deficits. Moreover, VA was nontoxic to HT22 cells and increased cell viability after Aβ1-42 exposure. To our knowledge, this study is the first to reveal the neuroprotective effect of VA against Aβ1-42-induced neurotoxicity. Our findings demonstrate that VA could potentially serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.

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“…On similar lines, we demonstrated the involvement of Naja naja venom 5′NUC in inducing anticoagulant effect by the use of specific inhibitor . Further, we had exemplified that the specific inhibitor of snake venom 5′NUC could be used as a pharmacological tool to decipher the role of 5′NUC in envenomation and also use it as a molecular tool for development of new therapeutic agents in the treatment of ophidian accidents . In the earlier studies, we had demonstrated the potential of vanillin analogs to inhibit snake venom 5′NUC, and reported that vanillic acid was potent with selective inhibition .…”

Section: Introductionmentioning

confidence: 57%

“…Further, we had exemplified that the specific inhibitor of snake venom 5′NUC could be used as a pharmacological tool to decipher the role of 5′NUC in envenomation and also use it as a molecular tool for development of new therapeutic agents in the treatment of ophidian accidents . In the earlier studies, we had demonstrated the potential of vanillin analogs to inhibit snake venom 5′NUC, and reported that vanillic acid was potent with selective inhibition . Further continuing on these aspects, here we report vanillin mandelic acid (VMA) as non‐nucleoside specific and potent inhibitor of snake venom 5′NUC.…”

Section: Introductionmentioning

confidence: 68%

Vanillin Analog – Vanillyl Mandelic Acid, a Novel Specific Inhibitor of Snake Venom 5′‐Nucleotidase

Arun

Arafat

D'Souza

et al. 2014

Archiv der Pharmazie

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Snake venom 5'-nucleotidase (5'NUC) plays a very important role in envenomation strategies; however, apart from its modulation of hemostatic functions, its other pharmacological effects are not yet well characterized. Several studies have used specific inhibitors of enzyme toxins as a biochemical or pharmacological tool to characterize or establish its mechanism of action. We report here for the first time vanillin mandelic acid (VMA), an analog of vanillin, to potentially, selectively, and specifically inhibit venom 5'NUC activity among other enzymes present in venoms. VMA is much more potent in inhibiting 5'NUC activity than vanillyl acid (VA). The experimental results obtained are in good agreement with the in silico molecular docking interaction data. Both VA and VMA are competitive inhibitors as evident by the inhibition-relieving effect upon increasing the substrate concentration. VMA also dose-dependently inhibited the anticoagulant effect in Naja naja venom. In this study, we report novel non-nucleoside specific inhibitors of snake venom 5'NUC and experimentally demonstrate their involvement in the anticoagulant activity of N. naja venom. Hence, we hypothesize that VMA can be used as a molecular tool to evaluate the role of 5'NUC in snake envenomation and to develop prototypes and lead compounds with potential therapeutic applications against snake bites.

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Vanillic acid as a novel specific inhibitor of snake venom 5′-nucleotidase: A pharmacological tool in evaluating the role of the enzyme in snake envenomation

Cited by 40 publications

References 34 publications

The food additive vanillic acid controls transgene expression in mammalian cells and mice

The food additive vanillic acid controls transgene expression in mammalian cells and mice

Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice

Vanillin Analog – Vanillyl Mandelic Acid, a Novel Specific Inhibitor of Snake Venom 5′‐Nucleotidase

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