Valproic Acid and Its Amidic Derivatives as New Antivirals against Alphaherpesviruses

Andreu, Sabina; Ripa, Inés; Bello-Morales, Raquel; López-Guerrero, José Antonio

doi:10.3390/v12121356

Cited by 18 publications

(14 citation statements)

References 67 publications

(90 reference statements)

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“… 2 Studies raise the possibility of the therapeutic anti-viral potential of VPA. 3 , 4 The virus replication and survival depend on the produced mitochondrial energy; thus, the anti-viral therapy tactics may involve medicine preparations that change energetic mitochondrial functions and activate anti-inflammatory mechanisms. 5 As a simple fatty acid, VPA is a substrate for the fatty acid β -oxidation pathway.…”

Section: Introductionmentioning

confidence: 99%

The effect of valproic acid on SLC5A8 expression in gonad-intact and gonadectomized rat thymocytes

Juknevičienė

Balnytė

Valančiūtė

et al. 2022

Int J Immunopathol Pharmacol

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Background Valproic acid (VPA) pharmacological mechanisms are related to the anti-inflammatory and anti-viral effects. VPA is a histone deacetylases inhibitor and serves a role in its immunomodulatory impacts. VPA has complex effects on immune cell’s mitochondrial metabolism. The SLC5A8 transporter of short fatty acids has an active role in regulating mitochondrial metabolism. The study aimed to investigate whether SLC5A8 expresses the sex-related difference and how SLC5A8 expression depends on gonadal hormones, VPA treatment, and NKCC1 expression in rat thymocytes. Methods Control groups and VPA-treated gonad-intact and gonadectomized Wistar male and female rats were investigated ( n = 6 in a group). The VPA 300 mg/kg/day in drinking water was given for 4 weeks. The SLC5A8 ( Slc5a8 gene) and NKCC1 ( Slc12a2 gene) RNA expressions were determined by the RT-PCR method. Results The higher Slc5a8 expression was found in the gonad-intact males than respective females ( p = 0.004). VPA treatment decreased the Slc5a8 expression in gonad-intact and castrated males ( p = 0.02 and p = 0.03, respectively), and increased in gonad-intact female rats compared to their control ( p = 0.03). No significant difference in the Slc5a8 expression between the ovariectomized female control and VPA-treated females was determined ( p > 0.05). VPA treatment alters the correlation between Slc 5a8 and Slc12a2 gene expression in thymocytes of gonad-intact rats. Conclusion VPA effect on the Slc5a8 expression in rat thymocytes is gender- and gonadal hormone-dependent.

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Section: Introductionmentioning

confidence: 99%

The effect of valproic acid on SLC5A8 expression in gonad-intact and gonadectomized rat thymocytes

Juknevičienė

Balnytė

Valančiūtė

et al. 2022

Int J Immunopathol Pharmacol

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“…Antiviral natural products have gained immense consideration in herpesvirus research after the Nobel Prize in Physiology or Medicine (in 2015) was awarded for the discovery of the natural anti-malarial drug artemisinin. Thus, natural anti-infective agents might pave the road for defeating the problem of drug resistance as well as provide effective and safe treatment of infections caused by herpesviruses [ 13 , 14 , 15 , 16 ]. Curcumin, a natural phenolic compound found in the Curcuma longa L. ( Zingiberaceae ) (turmeric), could help eliminate certain viruses by various mechanisms of action ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

Šudomová¹,

Hassan

2021

Microorganisms

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Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

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“…VPA has additional activities beyond inhibition of HDACs [17]. Clinically, VPA is a widely and frequently used anti-epileptic drug since 1963, owing to its activities in inhibition of GABA transaminase and blocking voltage-gated sodium channels and T-type calcium channels [18,19], and it has potential for the treatment of other neurological diseases, cancer and virus infection with unclear mechanisms [20][21][22]. VPA has been used to promote the differentiation of human stem cells into different types of somatic cells.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid promotes the in vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells

Wang

et al. 2021

Stem Cell Res Ther

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Background Studying human germ cell development and male infertility is heavily relied on mouse models. In vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells (SSCLCs) can be used as a model to study human germ cells and infertility. The current study aimed to develop the SSCLC induction protocol and assess the effects of the developed protocol on SSCLC induction. Methods We examined the effects of valproic acid (VPA), vitamin C (VC) and the combination of VPA and VC on the SSCLC induction efficiency and determined the expression of spermatogonial genes of differentiated cells. Haploid cells and cells expressed meiotic genes were also detected. RNA-seq analysis was performed to compare the transcriptome between cells at 0 and 12 days of differentiation and differently expressed genes were confirmed by RT-qPCR. We further evaluated the alteration in histone marks (H3K9ac and H3K27me3) at 12 days of differentiation. Moreover, the SSCLC induction efficiency of two hiPSC lines of non-obstructive azoospermia (NOA) patients was assessed using different induction protocols. Results The combination of low concentrations of VPA and VC in the induction medium was most effective to induce SSCLCs expressing several spermatogonial genes from human pluripotent stem cells at 12 days of differentiation. The high concentration of VPA was more effective to induce cells expressing meiotic genes and haploid cells. RNA-seq analysis revealed that the induction of SSCLC involved the upregulated genes in Wnt signaling pathway, and cells at 12 days of differentiation showed increased H3K9ac and decreased H3K27me3. Additionally, two hiPSC lines of NOA patients showed low SSCLC induction efficiency and decreased expression of genes in Wnt signaling pathway. Conclusions VPA robustly promoted the differentiation of human pluripotent stem cells into SSCLCs, which involved the upregulated genes in Wnt signaling pathway and epigenetic changes. hiPSCs from NOA patients showed decreased SSCLC induction efficiency and Wnt signaling pathway gene expression, suggesting that SSC depletion in azoospermia testes might be associated with inactivation of Wnt signaling pathway. Our developed SSCLC induction protocol provides a reliable tool and model to study human germ cell development and male infertility.

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Valproic Acid and Its Amidic Derivatives as New Antivirals against Alphaherpesviruses

Cited by 18 publications

References 67 publications

The effect of valproic acid on SLC5A8 expression in gonad-intact and gonadectomized rat thymocytes

The effect of valproic acid on SLC5A8 expression in gonad-intact and gonadectomized rat thymocytes

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

Valproic acid promotes the in vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells

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