title: Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells.
abstract: Berberine (B1), isolated from stems of Coscinium fenestratum (Goetgh.) Colebr, was used as a principle structure to synthesize three phenolic derivatives: berberrubine (B2) with a single phenolic group, berberrubine chloride (B3) as a chloride counter ion derivative, and 2,3,9,10-tetra-hydroxyberberine chloride (B4) with four phenolic groups, to investigate their direct and indirect antioxidant activities. For DPPH assay, compounds B4, B3, and B2 showed good direct antioxidant activity (IC50 values=10.7±1.76, 55.2±2.24, and 87.4±6.65 μM, respectively) whereas the IC50 value of berberine was higher than 500 μM. Moreover, compound B4 exhibited a better DPPH scavenging activity than BHT as a standard antioxidant (IC50=72.7±7.22 μM) due to the ortho position of hydroxyl groups and its capacity to undergo intramolecular hydrogen bonding. For cytotoxicity assay against human fibrosarcoma cells (HT1080) using MTT reagent, the sequence of IC50 value at 7-day treatment stated that B1<B4<B2 (0.44±0.03, 2.88±0.23, and 6.05±0.64 μM, respectively). Berberine derivatives, B2 and B4, showed approximately the same level of CAT expression and significant up-regulation of SOD expression in a dose-dependent manner compared to berberine treatment for 7-day exposure using reverse transcription- polymerase chain reaction (RT-PCR) assays. Our findings show a better direct-antioxidant activity of the derivatives containing phenolic groups than berberine in a cell-free system. For cell-based system, berberine was able to exert better cytotoxic activity than its derivatives. Berberine derivatives containing a single and four phenolic groups showed improved up-regulation of SOD gene expression. Cytotoxic action might not be the main effect of berberine derivatives. Other pharmacological targets of these derivatives should be further investigated to confirm the medical benefit of phenolic groups introduced into the berberine molecule.
authors.affiliation: Natural Products Research Unit, Department of Chemistry, Chulalongkorn University, Pathumwan, Thailand E-mail : roongs@swu.ac.th.
authors.forename: Veerachai
authors.initials: V
authors.lastname: Pongkittiphan
authors.forename: Warinthorn
authors.initials: W
authors.lastname: Chavasiri
authors.forename: Roongtawan
authors.initials: R
authors.lastname: Supabphol
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000737:chemistry; D002374:Catalase / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry*; D010851:Picrates / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D001713:Biphenyl Compounds; D010636:Phenols; D010851:Picrates; D010936:Plant Extracts; D012333:RNA, Messenger; D001599:Berberine; C115958:berberrubine; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D013482:Superoxide Dismutase