Analysis of lifespan-promoting effect of garlic extract by an integrated metabolo-proteomics approach.
The beneficial effects of garlic (Allium sativum) consumption in treating human diseases have been reported worldwide over a long period of human history. The strong antioxidant effect of garlic extract (GE) has also recently been claimed to prevent cancer, thrombus formation, cardiovascular disease and some age-related maladies. Using Caenorhabditis elegans as a model organism, aqueous GE was herein shown to increase the expression of longevity-related FOXO transcription factor daf-16 and extend lifespan by 20%. By employing microarray and proteomics analysis on C. elegans treated with aqueous GE, we have systematically mapped 229 genes and 46 proteins with differential expression profiles, which included many metabolic enzymes and yolky egg vitellogenins. To investigate the garlic components functionally involved in longevity, an integrated metabolo-proteomics approach was employed to identify metabolites and protein components associated with treatment of aqueous GE. Among potential lifespan-promoting substances, mannose-binding lectin and N-acetylcysteine were found to increase daf-16 expression. Our study points to the fact that the lifespan-promoting effect of aqueous GE may entail the DAF-16-mediated signaling pathway. The result also highlights the utility of metabolo-proteomics for unraveling the complexity and intricacy involved in the metabolism of natural products in vivo.
Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Chun-Hao
CH
Huang
Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Fang-Yu
FY
Hsu
Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Yuan-Heng
YH
Wu
Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Linda
L
Zhong
Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 112, Taiwan; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
Mu-Yun
MY
Tseng
Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Chao-Jen
CJ
Kuo
Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan. Electronic address: aolinhsu@med.umich.edu.
Ao-Lin
AL
Hsu
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: liang0615@kmu.edu.tw.
Shih-Shin
SS
Liang
Quantitative Proteomics Center and Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: shchiou@kmu.edu.tw.
Shyh-Horng
SH
Chiou
D000111:Acetylcysteine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D015536:Down-Regulation; D019143:Evolution, Molecular; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005737:Garlic / Q000737:chemistry*; D008136:Longevity / Q000187:drug effects*; D037601:Mannose-Binding Lectin / Q000378:metabolism; D055432:Metabolomics / Q000379:methods*; D008969:Molecular Sequence Data; D010936:Plant Extracts / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D037601:Mannose-Binding Lectin; D010936:Plant Extracts; D014819:Vitellogenins; C108831:daf-16 protein, C elegans; D000111:Acetylcysteine
Aging; C. elegans; DAF-16; Garlic extract; Mannose-binding lectin; Metabolo-proteomics; N-Acetylcysteine