Abstract
Valproic acid or valproate (VPA) is an anticonvulsive drug used for treatments of epilepsy, bipolar disorder, and migraine headaches. VPA is also an epigenetic modulator, inhibiting histone deacetylase, and it has been subjected to clinical study for cancer treatment. During the investigation of VPA on a metabolite profile in a fungus, we found that VPA has significant effects on the production of some fatty acids. Further exploration of VPA on fatty acid profiles of microorganisms, fungi, yeast, and bacteria, as well as representative gut microbiome, revealed that VPA could enhance or reduce the production of some fatty acids. VPA was found to induce the production of trans-9-elaidic acid, a fatty acid that was previously reported to have cellular effects in human macrophages. VPA could also inhibit the production of some polyketides produced by a model fungus. The present work suggests that the induction or inhibition of fatty acid biosynthesis by VPA (100 µM) in gut microbiome could give effects to patients treated with VPA because high doses of VPA oral administration (up to 600 mg to 900 mg) are used by patients; the concentration of VPA in the human gut may reach a concentration of 100 µM, which may give effects to gut microorganisms.
Highlights
Valproic acid or valproate (VPA) is an anticonvulsive drug used for treatments of epilepsy, bipolar disorder, and migraine headaches
The present work revealed that an anticonvulsive drug, VPA, has effects on the fatty acid profile of fungi, bacteria, and yeast, suggesting that this drug affects the biosynthesis of fatty acids in microorganisms
We found that VPA with the concentration 100 μM has effects on the biosynthesis of fatty acids in certain representative gut microbiome
Summary
Valproic acid or valproate (VPA) is an anticonvulsive drug used for treatments of epilepsy, bipolar disorder, and migraine headaches. VPA was found to induce the production of trans-9-elaidic acid, a fatty acid that was previously reported to have cellular effects in human macrophages. Valproic acid (VPA) or valproate, an anticonvulsive drug, has been used as drug for the treatment of epilepsy, bipolar disorder, and for the prevention of migraine headaches. Drug repurposing of VPA has been intensively explored for the treatment of various diseases, for example, the treatment of breast cancer[17], colon cancer associated with diabetes mellitus[18], diffuse intrinsic pontine glioma[19], high-fat diet-induced hypertension[20], Fatty acid content (%), mean ± s.d. We report the effects of an anticonvulsive drug VPA on the production of fatty acids and polyketides in microorganisms. Preliminary study on the effects of VPA on representative gut yeast and fungal strains is investigated
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