TY - JOUR
T1 - Iridoid compound 10-O-trans-p-Coumaroylcatalpol extends longevity and reduces alpha synuclein aggregation in Caenorhabditis elegans
AU - Shukla, Virendra
AU - Phulara, Suresh C.
AU - Yadav, Deepti
AU - Tiwari, Sudeep
AU - Kaur, Supinder
AU - Gupta, M. M.
AU - Nazir, Aamir
AU - Pandey, Rakesh
PY - 2012/12/1
Y1 - 2012/12/1
N2 - Aging, the major cause of several ailments has led to intense exploration of potential drugs that delay aging and its associated effects. We mined the information on traditional Indian medicines and identified an iridoid, 10-O-trans-p- Coumaroylcatalpol (OCC), a major ingredient of Premna integrifolia Linn. (syn: Premna serratifolia). OCC forms an important constituent of famous herbal formulation "Dashmula", a ten herb formulation, commonly used for its various medicinal properties. Employing model system C. elegans, the effect of OCC on life span, stress resistance, chemotaxis, the content of reactive oxygen species (ROS) and on the aggregation of alpha synuclein was studied. OCC extended the mean life span of nematodes, increased their tolerance against chemical induced stress, improved the chemotaxis index and reduced the ROS content. Further, the aggregation of Parkinson's disease (PD) associated protein, alpha synuclein (asyn), was decreased when transgenic a-syn expressing worms were raised on OCC mixed diet. We extended the studies further to explore the possible genetic mechanism that mediates the observed effects of OCC. Employing the genetic knockout mutants TK22 [mev-1(kn1)III]; GR1307 [daf-16(mgDf50)I]; VC199 [sir-2.1(ok434)IV] and transgenic GFP expressing strain TJ356 [zls356; DAF-16::GFP], our studies revealed that the effects were mediated by daf-16 and not by sir-2.1 or mev-1. Our results indicate that OCC has the ability to ameliorate a-syn aggregation, reduce oxidative stress and promote longevity in C. elegans via activation of longevity promoting transcription factor DAF-16. Thus, OCC may serve as a lead compound of plant origin for important nutraceutical intervention against aging and age associated PD.
AB - Aging, the major cause of several ailments has led to intense exploration of potential drugs that delay aging and its associated effects. We mined the information on traditional Indian medicines and identified an iridoid, 10-O-trans-p- Coumaroylcatalpol (OCC), a major ingredient of Premna integrifolia Linn. (syn: Premna serratifolia). OCC forms an important constituent of famous herbal formulation "Dashmula", a ten herb formulation, commonly used for its various medicinal properties. Employing model system C. elegans, the effect of OCC on life span, stress resistance, chemotaxis, the content of reactive oxygen species (ROS) and on the aggregation of alpha synuclein was studied. OCC extended the mean life span of nematodes, increased their tolerance against chemical induced stress, improved the chemotaxis index and reduced the ROS content. Further, the aggregation of Parkinson's disease (PD) associated protein, alpha synuclein (asyn), was decreased when transgenic a-syn expressing worms were raised on OCC mixed diet. We extended the studies further to explore the possible genetic mechanism that mediates the observed effects of OCC. Employing the genetic knockout mutants TK22 [mev-1(kn1)III]; GR1307 [daf-16(mgDf50)I]; VC199 [sir-2.1(ok434)IV] and transgenic GFP expressing strain TJ356 [zls356; DAF-16::GFP], our studies revealed that the effects were mediated by daf-16 and not by sir-2.1 or mev-1. Our results indicate that OCC has the ability to ameliorate a-syn aggregation, reduce oxidative stress and promote longevity in C. elegans via activation of longevity promoting transcription factor DAF-16. Thus, OCC may serve as a lead compound of plant origin for important nutraceutical intervention against aging and age associated PD.
KW - 10-O-trans-p-Coumaroylcatalpol
KW - Aging
KW - Caenorhabditis elegans
KW - Lifespan
KW - Parkinson's disease
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=84875041132&partnerID=8YFLogxK
U2 - 10.2174/1871527311211080007
DO - 10.2174/1871527311211080007
M3 - Article
C2 - 23244417
AN - SCOPUS:84875041132
SN - 1871-5273
VL - 11
SP - 984
EP - 992
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
IS - 8
ER -