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Journal of Healthcare Engineering 2022Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate...
Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate the effect of sodium valproate on the invasion and metastasis of glioma cells and its mechanism. Glioma cell lines were stimulated with VPA at different concentrations and for different durations of action. U87 glioma cells were transfected with Smad4 plasmid and small interfering RNA, and the changes of EMT-related protein indexes in U87 cells after up- or downregulation of Smad4 were detected by Western blotting. Immunohistochemistry was used to detect the differences in the expression of Smad4, TIF1-, and TGF- proteins in 39 glioma clinical specimens from the Department of Pathology of our hospital. Based on the regulation of EMT-related transcription factors by VPA, our study indicates that VPA inhibits the EMT process of glioma by altering the expression level of Smad4, which is induced by TGF-1 to form a Smad3/4 complex, thus inducing the EMT process of the tumor and acting as an antitumor target to inhibit the invasive ability of glioma cells. Sodium valproate inhibits glioma invasion and metastasis through the regulation of Smad4 expression.
Topics: Brain Neoplasms; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Glioma; Humans; Valproic Acid
PubMed: 35251569
DOI: 10.1155/2022/4985781 -
Bipolar Disorders Mar 2023
Topics: Humans; Lithium; Bipolar Disorder; Antimanic Agents; Valproic Acid; Lithium Compounds
PubMed: 36907971
DOI: 10.1111/bdi.13306 -
Molecules (Basel, Switzerland) Dec 2021Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and... (Review)
Review
Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.
Topics: Amides; Animals; Anticonvulsants; Drug Monitoring; Epilepsy; Humans; Molecular Structure; Structure-Activity Relationship; Teratogens; Urea; Valproic Acid
PubMed: 35011339
DOI: 10.3390/molecules27010104 -
Issues in Mental Health Nursing Jul 2018
Review
Topics: Antimanic Agents; Humans; Schizophrenia; Valproic Acid
PubMed: 30111200
DOI: 10.1080/01612840.2018.1494987 -
Brazilian Journal of Biology = Revista... 2022Valproic acid in association with sodium valproate (VPA) is an important anticonvulsant drug used for decades to treat neurological disorders. VPA also acts as an... (Review)
Review
Valproic acid in association with sodium valproate (VPA) is an important anticonvulsant drug used for decades to treat neurological disorders. VPA also acts as an epigenetic modulator by inhibiting histone deacetylases, permitting histone acetylation, affecting the DNA and histone methylation status and gene expression, and inducing chromatin remodeling. Insects represent an important animal model for studies in several areas of science. Their high phenotypic plasticity makes them alternative models for epigenetic studies. This brief review emphasizes recent reports on insect epigenetics and the contribution of studies on the VPA action in insects, including effects on epigenetic markers, extending the pharmacological understanding of the potential of this drug, and demonstrating the usefulness of insects as an alternative animal model to drug studies.
Topics: Acetylation; Animals; Disease Models, Animal; Epigenesis, Genetic; Histones; Insecta; Valproic Acid
PubMed: 35416850
DOI: 10.1590/1519-6984.256045 -
Viruses Nov 2020Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67%... (Review)
Review
Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.
Topics: Alphaherpesvirinae; Amides; Animals; Antiviral Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Valproic Acid
PubMed: 33256172
DOI: 10.3390/v12121356 -
Stem Cells (Dayton, Ohio) Aug 2023Cytochrome P450 3A4 (CYP3A4) is involved in first-pass metabolism in the small intestine and is heavily implicated in oral drug bioavailability and pharmacokinetics. We...
Cytochrome P450 3A4 (CYP3A4) is involved in first-pass metabolism in the small intestine and is heavily implicated in oral drug bioavailability and pharmacokinetics. We previously reported that vitamin D3 (VD3), a known CYP enzyme inducer, induces functional maturation of iPSC-derived enterocyte-like cells (iPSC-ent). Here, we identified a Notch activator and CYP modulator valproic acid (VPA), as a promotor for the maturation of iPSC-ent. We performed bulk RNA sequencing to investigate the changes in gene expression during the differentiation and maturation periods of these cells. VPA potentiated gene expression of key enterocyte markers ALPI, FABP2, and transporters such as SULT1B1. RNA-sequencing analysis further elucidated several function-related pathways involved in fatty acid metabolism, significantly upregulated by VPA when combined with VD3. Particularly, VPA treatment in tandem with VD3 significantly upregulated key regulators of enterohepatic circulation, such as FGF19, apical bile acid transporter SLCO1A2 and basolateral bile acid transporters SLC51A and SLC51B. To sum up, we could ascertain the genetic profile of our iPSC-ent cells to be specialized toward fatty acid absorption and metabolism instead of transporting other nutrients, such as amino acids, with the addition of VD3 and VPA in tandem. Together, these results suggest the possible application of VPA-treated iPSC-ent for modelling enterohepatic circulation.
Topics: Humans; Valproic Acid; Cholecalciferol; Induced Pluripotent Stem Cells; Enterocytes; Cells, Cultured
PubMed: 37228023
DOI: 10.1093/stmcls/sxad042 -
Journal of Molecular Neuroscience : MN Jun 2022Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism. But, to... (Review)
Review
Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism. But, to date, its validation, suitability, and applicability as a well defining autistic model are still questionable. Previous research efforts highlighted that this model shows various core defining features of autism and related pathways, hence it is very necessary to explore its authenticity as a well-suited model for autism. Therefore, in this review, we summarize the preclinical and neurobiological relevant validated features, involved etiological mechanism, biological markers, treatment responses, drawbacks, current approaches, and future perspectives of VPA-induced model of autism. This review would help in deciphering the validation of the VPA-induced autistic model and its suitability as an experimental model of autism. A thorough investigation of behavioral, molecular, and neurobiological processes in animal models of autism would help in investigating the exact causation and effective treatment for autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Female; Humans; Prenatal Exposure Delayed Effects; Rodentia; Valproic Acid
PubMed: 35635674
DOI: 10.1007/s12031-022-02033-7 -
Molecules (Basel, Switzerland) May 2023Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), the severe side effects and loss of anticancer activity caused by the lack of...
Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), the severe side effects and loss of anticancer activity caused by the lack of selectivity to cancer cells and hydrolysis of ring E prevent its clinical application. To address the issue, herein a multifunctional SN38 derivative (compound ) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound exhibited superior cytotoxicity than irinotecan against human cervical cancer HeLa cells, albeit it was inferior to SN38. More significantly, compound significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that, compared with irinotecan, compound induced similar apoptosis of cancer cells. Consequently, compound can not only improve its tumor-targeting ability mediated by biotin but also exert potent anticancer activity through the effect of SN38 and valproic acid, indicating that the design concept is an effective strategy for the structural modification of SN38.
Topics: Animals; Humans; Mice; Irinotecan; Valproic Acid; Biotin; HeLa Cells; NIH 3T3 Cells; Cell Line, Tumor; Fibroblasts; Camptothecin; Antineoplastic Agents, Phytogenic
PubMed: 37175346
DOI: 10.3390/molecules28093936 -
Kidney International Mar 2022
Topics: Humans; Kidney Diseases; Kidney Tubules, Proximal; Valproic Acid
PubMed: 35190045
DOI: 10.1016/j.kint.2021.08.005