Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans.
Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene and is a FDA approved food additive, found as an active ingredient in essential oils of numerous edible plants. It possesses a wide range of biological activities including anti-oxidant, anti-inflammatory, anti-cancerous and local anesthetic actions. We used the well established Caenorhabditis elegans model system to elucidate the stress modulatory and lifespan prolonging action of BCP. The present study for the first time reports the lifespan extension and stress modulation potential of BCP in C. elegans. Upon evaluation, it was found that 50μM dose of BCP increased the lifespan of C. elegans by over 22% (P≤0.0001) and significantly reduced intracellular free radical levels, maintaining cellular redox homeostasis. Moreover, the results suggest that BCP modulates feeding behavior, pharyngeal pumping and body size effectively. Further, this compound also exhibited significant reduction in intestinal lipofuscin levels. In the present investigation, we have predicted possible biological molecular targets for BCP using molecular docking approaches and BCP was found to have interaction with SIR-2.1, SKN-1 and DAF-16. The prediction was further validated in vivo using mutants and transgenic strains unraveling underlying genetic mechanism. It was observed that BCP increased lifespan of mev-1 and daf-16 but failed to augment lifespan in eat-2, sir-2.1 and skn-1 mutants. Relative quantification of mRNA demonstrated that several genes regulating oxidative stress, xenobiotic detoxification and longevity were modulated by BCP treatment. The study unravels the involvement of multiple signaling pathways in BCP mediated lifespan extension.
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow - 226 015, India.
Aakanksha
A
Pant
Vikas
V
Mishra
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow - 226 015, India.
Shilpi K
SK
Saikia
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow - 226 015, India.
Virendra
V
Shukla
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow - 226 015, India.
Jyotsna
J
Asthana
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow - 226 015, India.
Bashir A
BA
Akhoon
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow - 226 015, India. Electronic address: r.pandey@cimap.res.in.
Rakesh
R
Pandey
D000818:Animals; D049628:Body Size / Q000187:drug effects; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D008062:Lipofuscin / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D062105:Molecular Docking Simulation; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage*; D000081223:Polycyclic Sesquiterpenes; D017382:Reactive Oxygen Species / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D012717:Sesquiterpenes / Q000008:administration & dosage*; D013312:Stress, Physiological / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D008062:Lipofuscin; D010936:Plant Extracts; D000081223:Polycyclic Sesquiterpenes; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; C024714:caryophyllene; C525107:Sod-3 protein, C elegans; D013482:Superoxide Dismutase
Anti-aging; Beta-caryophyllene; Caenorhabditis elegans; Lifespan; Phytomolecule