Sodium Phenylbutyrate is a histone deacetylase (HDAC) inhibitor. Sodium Phenylbutyrate is metabolized via β-oxidation to phenylacetate, which conjugates with glutamine to form phenylacetylglutamine. Sodium Phenylbutyrate exerts antitumor effects by inhibiting PDKs to upregulate PDHC activity and modulating HDAC activity. Sodium Phenylbutyrate can be used in research related to urea cycle disorders and amyotrophic lateral sclerosis[1-4].
In vitro, MGC-803 and BGC-823 gastric cancer cells were treated with Sodium Phenylbutyrate (0.5-10mM) for 16 hours. Sodium Phenylbutyrate induced epithelial-mesenchymal transition (EMT) and promoted cell migration by upregulating IL-8 expression and activating the Gab2-ERK pathway[5]. A scratched IPEC-J2 cell monolayer was treated with Sodium Phenylbutyrate (1.0mM) for 24 hours, which accelerated cell migration and barrier function recovery. When IPEC-J2 cell monolayers were co-treated with DON (2.0μg/mL) or LPS (5.0μg/mL) and Sodium Phenylbutyrate for 48 hours, Sodium Phenylbutyrate accelerated barrier function recovery and upregulated the expression of tight junction proteins ZO-1, occludin, and claudin-1[6].
In vivo, Sprague-Dawley rats exposed to a hypoxic environment at 5500 meters were intraperitoneally administered Sodium Phenylbutyrate (30mg/kg/day) for 10 days. Sodium Phenylbutyrate effectively alleviated hypoxia-induced lipolysis and improved hepatic lipid accumulation, liver injury, and apoptosis[7]. Female Sprague-Dawley rats with protamine/LPS-induced interstitial cystitis were administered Sodium Phenylbutyrate (500mg/kg/day) by gavage for 5 days. Sodium Phenylbutyrate improved bladder micturition function, inhibited endoplasmic reticulum stress, restored autophagic flux, and suppressed bladder oxidative stress, inflammatory reaction, and apoptosis[8].
References:
[1] Chang TH, Szabo E. Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin Cancer Res. 2002 Apr;8(4):1206-12.
[2] Frouco G, Freitas FB, Martins C, et al. Sodium phenylbutyrate abrogates African swine fever virus replication by disrupting the virus-induced hypoacetylation status of histone H3K9/K14. Virus Res. 2017 Oct 15;242:24-29.
[3] Park HJ, Son HJ, Sul OJ, et al. 4-Phenylbutyric acid protects against lipopolysaccharide-induced bone loss by modulating autophagy in osteoclasts. Biochem Pharmacol. 2018 May;151:9-17.
[4] Xiong F, Wang C, Lu J, et al. 4-PBA exerts brain-protective effects against sepsis-associated encephalopathy in a mouse model of sepsis. Exp Neurol. 2024 May;375:114738.
[5] Shi X, Gong L, Liu Y, et al. 4-phenylbutyric acid promotes migration of gastric cancer cells by histone deacetylase inhibition-mediated IL-8 upregulation. Epigenetics. 2020 Jun-Jul;15(6-7):632-645.
[6] Jiang Q, Yin J, Chen J, et al. 4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model. Anim Nutr. 2021 Dec;7(4):1061-1069.
[7] Xiong Y, Wang Y, Xiong Y, et al. 4-PBA inhibits hypoxia-induced lipolysis in rat adipose tissue and lipid accumulation in the liver through regulating ER stress. Food Sci Nutr. 2023 Feb 9;11(3):1223-1231.
[8] Jia L, Jingzhen Z, Xinliang Y, et al. 4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats. Sci Rep. 2023 Aug 28;13(1):14057.
Sodium Phenylbutyrate是一种组蛋白去乙酰化酶（HDAC）抑制剂。Sodium Phenylbutyrate通过β-氧化代谢为乙酸苯酯并与谷氨酰胺结合生成苯乙酰谷氨酰胺。Sodium Phenylbutyrate通过抑制PDKs上调PDHC活性及调控HDACs活性发挥抗肿瘤作用。Sodium Phenylbutyrate可用于尿素循环障碍和肌萎缩侧索硬化症的相关研究[1-4]。
在体外，Sodium Phenylbutyrate（0.5-10mM）处理MGC-803和BGC-823胃癌细胞16小时。Sodium Phenylbutyrate可诱导上皮-间质转化（EMT）并促进细胞迁移，通过上调IL-8表达并激活Gab2-ERK通路[5]。Sodium Phenylbutyrate（1.0mM）处理划伤的IPEC-J2细胞单层24小时，加速了细胞迁移和屏障功能恢复；与DON（2.0μg/mL）或LPS（5.0μg/mL）同时处理IPEC-J2细胞单层48小时。Sodium Phenylbutyrate加速了屏障功能的恢复，并上调了紧密连接蛋白ZO-1、occludin和claudin-1的表达[6]。
在体内，Sodium Phenylbutyrate（30mg/kg/day）腹腔注射处理暴露于5500米缺氧环境的Sprague-Dawley大鼠10天。Sodium Phenylbutyrate有效减轻了缺氧诱导的脂肪分解，同时改善了肝脏脂质积累、肝损伤和细胞凋亡[7]。Sodium Phenylbutyrate（500mg/kg/day）灌胃处理鱼精蛋白/LPS诱导的间质性膀胱炎雌性Sprague-Dawley大鼠5天。Sodium Phenylbutyrate改善了膀胱排尿功能，抑制了内质网应激，恢复了自噬流，并抑制了膀胱氧化应激、炎症反应和细胞凋亡[8]。