title: Cytotoxic, apoptotic and anti-α-glucosidase activities of 3,4-di-O-caffeoyl quinic acid, an antioxidant isolated from the polyphenolic-rich extract of Elephantopus mollis Kunth.
abstract: BACKGROUND
  The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes.
  
  
  OBJECTIVE
  This study was initiated to determine whether the most effective antioxidant compound isolated from the whole plant of Elephantopus mollis can also contribute to its claimed traditional values as anticancer and antidiabetes agents.
  
  
  METHODS
  An active antiradical phenolic compound (3,4-di-O-caffeoyl quinic acid) was isolated from the methanol extract (with the highest in polyphenolic content) and their antioxidant activities were compared using four different assays, that are DPPH, FRAP, metal chelating, and β-carotene bleaching tests. The compound was also evaluated for its cytotoxic activity, apoptotic induction and anti-glucosidase efficacies using methylene blue, DeadEnd™ assay and α-glucosidase assays, respectively.
  
  
  RESULTS
  The compound acted as a greater primary antioxidant than its methanol extract, by having higher ferric reducing activity (EC(50) 2.18±0.05 μg/ml), β-carotene bleaching activity (EC(50) 23.85±0.65 μg/ml) and DPPH scavenging activity (EC(50) 68.91±5.44μg/ml), whereas the methanol extract exhibited higher secondary antioxidant activity as a metal chelator with lower EC(50) value (49.39±3.68 μg/ml) than the compound. Cytotoxicity screening of this compound exhibited a remarkable dose-dependent inhibitory effect on NCI-H23 (human lung adenocarcinoma) cell lines (EC(50) 3.26±0.35 μg/ml) and was found to be apoptotic in nature based on a clear indication of DNA fragmentation. This compound also displayed a concentration-dependent α-glucosidase inhibition with EC(50) 241.80±14.29 μg/ml.
  
  
  CONCLUSIONS
  The findings indicate the major role of 3,4-di-O-caffeoyl quinic acid to antioxidant capacities of Elephantopus mollis extracts. The compound also exerted apoptosis-mediated cytotoxicity and α-glucosidase inhibitory effects and is thus a promising non toxic agent in treating cancer and type 2 diabetes mellitus.
authors.affiliation: School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Kheng Leong
authors.initials: KL
authors.lastname: Ooi
authors.forename: Tengku Sifzizul Tengku
authors.initials: TS
authors.lastname: Muhammad
authors.forename: Mei Lan
authors.initials: ML
authors.lastname: Tan
authors.forename: Shaida Fariza
authors.initials: SF
authors.lastname: Sulaiman
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D019659:Asteraceae / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005290:Ferric Compounds / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010851:Picrates / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use; D019207:beta Carotene / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D001713:Biphenyl Compounds; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D065089:Glycoside Hydrolase Inhibitors; D010851:Picrates; D010936:Plant Extracts; D059808:Polyphenols; D019207:beta Carotene; D002726:Chlorogenic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl; C478100:3,4-di-O-caffeoylquinic acid