Beta Caryophyllene and Caryophyllene Oxide, Isolated from Aegle Marmelos, as the Potent Anti-inflammatory Agents against Lymphoma and Neuroblastoma Cells
Soumyadeep Sain, Pravin K. Naoghare, S. Saravana Devi, Atul Daiwile, K. Krishnamurthi, P. Arrigo and T. Chakrabarti
Affiliation: Environmental Health Division, National Environmental Engineering Research Institute (NEERI), CSIR, Nagpur, India.
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 (50µg/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.
Keywords: Apoptotic genes, caryophyllene, 15-lipoxygenase, lymphoma, neuroblastoma cells.
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