Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans

Free Radic Biol Med. 2018 Dec;129:310-322. doi: 10.1016/j.freeradbiomed.2018.09.035. Epub 2018 Sep 25.

Abstract

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 μg/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 μg/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp-16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-E significantly delayed amyloid β-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 μg/mL chlorogenic acid, 15 μg/mL 1,5-dicaffeoylquinic acid and 7.5 μg/mL 1,3-dicaffeoylquinic acid) of 500 μg/mL LJ-E could significantly delay paralysis in CL4176 worms caused by Aβ toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.

Keywords: Caenorhabditis elegans; Lifespan; Lonicera japonica; RNA-sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / growth & development
  • Adipose Tissue / metabolism
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Chlorogenic Acid / pharmacology
  • Cinnamates / pharmacology
  • Cytochromes b / genetics
  • Cytochromes b / metabolism
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental / drug effects*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Longevity / drug effects*
  • Longevity / genetics
  • Lonicera / chemistry*
  • Metallothionein / genetics
  • Metallothionein / metabolism
  • Paralysis / prevention & control
  • Quinic Acid / analogs & derivatives
  • Quinic Acid / pharmacology
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Stress, Physiological
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • 1,3-dicaffeoylquinic acid
  • Amyloid beta-Peptides
  • Caenorhabditis elegans Proteins
  • Cinnamates
  • Drugs, Chinese Herbal
  • Forkhead Transcription Factors
  • Heat-Shock Proteins
  • MEV-1 protein, C elegans
  • MTL-1 protein, C elegans
  • Reactive Oxygen Species
  • Transcription Factors
  • Vesicular Transport Proteins
  • bec-1 protein, C elegans
  • daf-16 protein, C elegans
  • heat shock factor-1, C elegans
  • hsp-16.2 protein, C elegans
  • Quinic Acid
  • Chlorogenic Acid
  • cynarine
  • Cytochromes b
  • Metallothionein
  • Sod-3 protein, C elegans
  • Superoxide Dismutase
  • DAF-2 protein, C elegans
  • Receptor, Insulin