3,4-Dihydroxybenzoic acid (Protocatechuic acid) is a natural polyphenolic compound found in many edible and medicinal plants[1]. 3,4-Dihydroxybenzoic acid exhibits significant antioxidant activity[2], neuroprotective effects[3], and anticancer properties[4].
In vitro, treatment of human HepG2 hepatocellular carcinoma cells with 3,4-Dihydroxybenzoic acid (100μM) for 4 days induced cell death through a mechanism dependent on c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)[5]. Treatment of human glioma cell lines U87 and U251 with 3,4-Dihydroxybenzoic acid (2.5–10μM) for 24–48 hours significantly inhibited cell proliferation, invasion, and migration, and induced pyroptosis via a mechanism dependent on the NLRP3/caspase-1/GSDMD signaling axis[6].
In vivo, dietary supplementation with 3,4-Dihydroxybenzoic acid (0.025–0.1%w/w) for 12 weeks in high-fat diet-fed C57BL/6J mice significantly ameliorated metabolic-associated fatty liver disease (MAFLD) by inhibiting the growth of Enterococcus faecalis in the gut and modulating insulin signaling pathways[7]. Intramuscular administration of 3,4-Dihydroxybenzoic acid (100mg/kg/day) for 9 days in an isoproterenol (80mg/kg/day)-induced heart failure model using C57BL/6 mice significantly improved cardiac function and attenuated cardiac hypertrophy and fibrosis[8].
References:
[1] Khan AK, Rashid R, Fatima N, et al. PHARMACOLOGICAL ACTIVITIES OF PROTOCATECHUIC ACID. Acta Pol Pharm. 2015 Jul-Aug;72(4):643-50.
[2] Zhang X, Luo J, Bharati L, Hua Z, et al. Protocatechuic acid suppresses ferroptosis to protect against hypoxic-ischemic encephalopathy by targeting the HIF-1α/VEGFA axis. Phytomedicine. 2025 Jul 25;143:156900.
[3] Krzysztoforska K, Mirowska-Guzel D, Widy-Tyszkiewicz E. Pharmacological effects of protocatechuic acid and its therapeutic potential in neurodegenerative diseases: Review on the basis of in vitro and in vivo studies in rodents and humans. Nutr Neurosci. 2019 Feb;22(2):72-82.
[4] Cadena-Iñiguez J, Santiago-Osorio E, Sánchez-Flores N, et al. The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review. Molecules. 2024 Mar 23;29(7):1439.
[5] Yip EC, Chan AS, Pang H, et al. Protocatechuic acid induces cell death in HepG2 hepatocellular carcinoma cells through a c-Jun N-terminal kinase-dependent mechanism. Cell Biol Toxicol. 2006 Jul;22(4):293-302.
[6] Zhang W, Cai Y, Zheng H. Protective Role of Protocatechuic Acid in Glioma: Modulation of Cell Growth, Migration, and Pyroptosis via NLRP3/Caspase-1/GSDMD Axis. Discov Med. 2025 Apr;37(195):659-668.
[7] Tan J, Hu R, Gong J, et al. Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid. Gut Microbes. 2023 Jan-Dec;15(1):2238959.
[8] Bai L, Han X, Kee HJ, et al. Protocatechuic acid prevents isoproterenol-induced heart failure in mice by downregulating kynurenine-3-monooxygenase. J Cell Mol Med. 2023 Aug;27(16):2290-2307.
3,4-Dihydroxybenzoic acid (Protocatechuic acid)是一种天然的多酚类化合物，存在于许多食用和药用植物中[1]。3,4-Dihydroxybenzoic acid具有显著的抗氧化活性[2]、神经保护作用[3]、以及抗癌作用[4]。
在体外，3,4-Dihydroxybenzoic acid（100μM）处理人HepG2肝癌细胞4天，通过c-Jun N末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）依赖性机制诱导细胞死亡[5]。3,4-Dihydroxybenzoic acid（2.5–10μM）处理人胶质瘤细胞系U87和U251 24–48小时，通过NLRP3/caspase-1/GSDMD信号轴依赖性机制显著抑制细胞增殖、侵袭和迁移能力，并诱导细胞焦亡[6]。
在体内，3,4-Dihydroxybenzoic acid（0.025–0.1%w/w；膳食补充）干预高脂饮食喂养的C57BL/6J小鼠12周，通过抑制肠道粪肠球菌生长和调节胰岛素信号通路显著改善代谢相关脂肪肝病（MAFLD）[7]。3,4-Dihydroxybenzoic acid（100mg/kg/day）通过肌肉注射处理经异丙肾上腺素（80mg/kg/day）诱导的心力衰竭C57BL/6小鼠模型9天，显著改善心脏功能并减轻心肌肥厚和纤维化[8]。