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Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells.

Abstract
Aegle marmelos (Indian Bael) is a tree which belongs to the family of Rutaceae. It holds a prominent position in both Indian medicine and Indian culture. We have screened various fractions of Aegle marmelos extracts for their anticancer properties using in vitro cell models. Gas chromatography-Mass spectrometry (GC-MS) was employed to analyze the biomolecules present in the Aegle marmelos extract. Jurkat and human neuroblastoma (IMR-32) cells were treated with different concentrations of the fractionated Aegle marmelos extracts. Flow cytometric analysis revealed that optimal concentration (50 µg/ml) of beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract can induce apoptosis in Jurkat cell line. cDNA expression profiling of pro-apoptotic and anti-apoptotic genes was carried out using real time PCR (RT-PCR). Down-regulation of anti-apoptotic genes (bcl-2, mdm2, cox2 and cmyb) and up-regulation of pro-apoptotic genes (bax, bak1, caspase-8, caspase-9 and ATM) in Jurkat and IMR-32 cells treated with the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract revealed the insights of the downstream apoptotic mechanism. Furthermore, in-silico approach was employed to understand the upstream target involved in the induction of apoptosis by the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract. Herein, we report that beta caryophyllene and caryophyllene oxide isolated from Aegle marmelos can act as potent anti-inflammatory agents and modulators of a newly established therapeutic target, 15-lipoxygenase (15-LOX). Beta caryophyllene and caryophyllene oxide can induce apoptosis in lymphoma and neuroblastoma cells via modulation of 15-LOX (up-stream target) followed by the down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes.
AuthorsSoumyadeep Sain, Pravin K Naoghare, S Saravana Devi, Atul Daiwile, K Krishnamurthi, P Arrigo, T Chakrabarti
JournalAnti-inflammatory & anti-allergy agents in medicinal chemistry (Antiinflamm Antiallergy Agents Med Chem) Vol. 13 Issue 1 Pg. 45-55 (Mar 2014) ISSN: 1875-614X [Electronic] United Arab Emirates
PMID24484210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Apoptosis Regulatory Proteins
  • Plant Extracts
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • caryophyllene
  • Arachidonate 15-Lipoxygenase
  • caryophyllene oxide
Topics
  • Aegle
  • Anti-Inflammatory Agents (pharmacology)
  • Apoptosis (drug effects)
  • Apoptosis Regulatory Proteins (genetics, metabolism)
  • Arachidonate 15-Lipoxygenase (metabolism)
  • Chemical Fractionation
  • Computer Simulation
  • Humans
  • India
  • Jurkat Cells
  • Lymphoma (drug therapy)
  • Molecular Targeted Therapy
  • Neuroblastoma (drug therapy)
  • Plant Extracts (pharmacology)
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes (pharmacology)
  • Transcriptome

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