====== Protocatechuic Acid (PCA) ====== {{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1ZIrvZUsS726d1stbarfnptS9RYy0Xv3U6qoIiPlCG_M-RvkKJ/?limit=15&utm_campaign=pubmed-2&fc=20250427081910}} ---- ---- Protocatechuic [[Acid]] (PCA) is a natural phenolic compound found in many plants, fruits, and vegetables. It belongs to the family of hydroxybenzoic acids and acts as a potent antioxidant. ===== Chemical Structure ===== * 3,4-dihydroxybenzoic acid * Benzene ring with two hydroxyl groups (-OH) and one carboxylic acid group (-COOH) ===== Properties ===== ^ Property ^ Effect ^ | Antioxidant | Neutralizes free radicals and reduces oxidative stress | | Anti-inflammatory | Lowers inflammation in tissues | | Antimicrobial | Inhibits certain bacteria and fungi | | Anticancer potential | May inhibit cancer cell growth (under investigation) | | Neuroprotective | Protects nerve cells from oxidative and toxic damage | ===== Natural Sources ===== * Green tea * Olives and olive oil * Berries (e.g., blueberries, blackberries) * Nuts * Hibiscus flowers ===== Medical and Research Interest ===== Protocatechuic Acid is being researched for its potential protective role against: * Cancer development * Cardiovascular diseases * Diabetes * Neurodegenerative diseases (such as Alzheimer's disease) > **Note:** Current evidence is mostly based on in vitro (cell culture) and animal studies; clinical trials in humans are limited. ---- A study aimed to investigate whether [[pyroptosis]] can be activated by PCA in glioma cells. Different concentrations of PCA were used to treat [[glioma cell line]]s [[U87]] and [[U251]] for varying durations.[[ Cell proliferation]] was quantified using the Cell Counting Kit-8 (CCK-8) assay. The Transwell chamber assay was employed to evaluate [[cell invasion]], while [[cell migration]] was assessed via the scratch assay. [[Pyroptosis]] levels were determined through immunofluorescence staining. Additionally, the protein and mRNA expression levels of nucleotide-binding and oligomerization domain-like receptor thermal protein domain-associated protein 3 (NLRP3), cysteinyl aspartate-specific proteinase (caspase-1), and gasdermin D (GSDMD) were analyzed using Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Intervention with PCA resulted in a significant suppression of viability, invasion, and migration of glioma cells in a dose-dependent manner (p < 0.05). Additionally, the GSDMD positivity rate, as well as the protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD, showed significant increases in glioma cells (p < 0.05). Further intervention with NLRP3-specific inhibitor MCC950 reversed the effects of PCA and resulted in a significant increase in cell viability and number of invading cells (p < 0.01), a significant decrease in GSDMD positivity (p < 0.01), and a significant decrease in the protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD in glioma cells (p < 0.01). PCA mediates pyroptosis in glioma cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway ((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. doi: 10.24976/Discov.Med.202537195.57. PMID: 40287802.)) ---- This study provides promising preliminary evidence that PCA induces pyroptosis in glioma cells via activation of the NLRP3/caspase-1/GSDMD pathway, inhibiting their proliferation, invasion, and migration. However, translational and mechanistic gaps remain, particularly the need for [[in vivo]] studies, dose [[optimization]], and [[validation]] across more [[glioma model]]s. Overall, the research is well-conceived, methodologically solid for an [[in vitro]] study, and lays important groundwork for future preclinical investigations.