title: An antidiabetic polyherbal phytomedicine confers stress resistance and extends lifespan in Caenorhabditis elegans.
abstract: An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system. The effect on aging is evaluated by studying effect of PHE on mean survival in worms. The stress modulatory potential was assessed by quantification of intracellular ROS level, autofluorescent age pigment lipofuscin, oxidative and thermal stress assays. Additionally, stress response was quantified using gene reporter assays. The 0.01 µg/ml dose of PHE was able to enhance mean lifespan by 16.09% (P < 0.0001) in C. elegans. Furthermore, PHE treated worms demonstrated oxidative stress resistance in both wild type and stress hypersensitive mev-1 mutant along with upregulation of stress response genes sod-3 and gst-4. The delayed aging under stress can be attributed to its direct reactive oxygen species-scavenging activity and regulation of some age associated genes like daf-2, daf-16, skn-1, sod-3 and gst-4 in wild-type worms. Additonally, PHE delayed age related paralysis phenotype in CL4176 transgenic worms. Altogether, our results suggest PHE significantly improves the oxidative stress and life span in C. elegans. Overall the present study suggests this polyherbal formulation might play important role in regultaing aging and related complications like diabetes.
authors.affiliation: Microbial Technology and Nematology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Rathor
authors.affiliation: Microbial Technology and Nematology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India.
authors.forename: Aakanksha
authors.initials: A
authors.lastname: Pant
authors.affiliation: Department of Herbal Medicinal Products, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India.
authors.forename: Harshika
authors.initials: H
authors.lastname: Awasthi
authors.affiliation: Department of Herbal Medicinal Products, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India.
authors.forename: Dayanandan
authors.initials: D
authors.lastname: Mani
authors.affiliation: Microbial Technology and Nematology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226 015, India. r.pandey@cimap.res.in.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Pandey
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008136:Longevity / Q000187:drug effects* / Q000502:physiology*; D008515:Medicine, Ayurvedic; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010936:Plant Extracts / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D029742:Caenorhabditis elegans Proteins; D004338:Drug Combinations; D010936:Plant Extracts; D017382:Reactive Oxygen Species
keywords: Aging; Anti-diabetic; Caenorhabditis elegans; Neurodegenerative disease; Polyherbal extract