Subhash C. Lakhotia | Search bioRxiv

bioRxiv2016

Ayurvedic Amalaki Rasayana promotes improved stress tolerance and thus has anti-aging effects in Drosophila melanogaster

Ethnopharmacological relevanceAmalaki Rasayana (AR) is a common Ayurvedic herbal formulation of Phyllanthus emblica fruits and other ingredients and is used for general good health and healthy aging. We earlier reported it to improve life history traits and to suppress neurodegeneration as well as induced apoptosis in Drosophila.\n\nAim of the studyTo examine effects of dietary AR supplement on cell stress responses in Drosophila melanogaster.\n\nMaterials and methodsLarvae/flies, reared on normal food or on that supplemented with 0.5% (w/v) AR, were exposed to crowding, thermal or oxidative stress and examined for survival, stress tolerance and levels of lipid peroxides, SOD and HSPs.\n\nResultsWild type larvae/flies reared on AR supplemented food survived the various cell stresses much better than those reared on normal food. AR-fed mutant park13 or DJ-1{beta}Delta93 (Parkinsons disease model) larvae, however, showed only partial or no protection, respectively, against paraquat-induced oxidative stress, indicating essentiality of DJ-1{beta} for AR mediated oxidative stress tolerance. AR feeding reduced the accumulation of reactive oxygen species (ROS) and lipid peroxidation even in aged (35 day old) wild type flies while enhancing superoxide dismutase (SOD) activity. We show for the first time that while Hsp70 or Hsp83 expression under normal or stress conditions was not differentially affected by AR feeding, Hsp27 levels were elevated in AR fed wild type control as well as heat shocked larvae. Therefore, besides the known anti-oxidant activity of Phyllanthus emblica fruits, dietary AR also enhances cellular levels of Hsp27.\n\nConclusionIn the context of the reported \"anti-aging\" and \"healthy-aging\" effects of AR, the present in vivo study on a model organisms shows that AR feeding significantly improves tolerance to a variety of cell stresses through reduced ROS and lipid peroxidation and enhanced SOD activity and Hsp27. Such improved cellular defences following dietary AR provide better homeostasis and thereby improve the life-span and quality of organisms life.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC=\"FIGDIR/small/050476_figu1.gif\" ALT=\"Figure 1\">\nView larger version (36K):\norg.highwire.dtl.DTLVardef@4452a8org.highwire.dtl.DTLVardef@18eb595org.highwire.dtl.DTLVardef@33533aorg.highwire.dtl.DTLVardef@19d4590_HPS_FORMAT_FIGEXP M_FIG C_FIG

Cell Biology↗

bioRxiv2016

Activated Ras expression in eye discs with altered levels of hsrω lncRNA causes JNK-induced Dilp8 secretion and reduces post-pupal ecdysone leading to early pupal death in Drosophila

BackgroundDilp8-mediated inhibition of ecdysone synthesis and pupation in holometabolous insects maintains developmental homeostasis through stringent control of timing and strength of moulting signals. We examined reasons for normal pupation but early pupal death observed in certain cases.\n\nResultsOver-expression of activated Ras in developing eye/wing discs inhibited Ptth expression in brain via up-regulated JNK signaling mediated Dilp8 secretion from imaginal discs, which inhibited ecdysone synthesis in prothoracic gland after pupariation, leading to death of ~25-30 Hr old pupae. Inhibition of elevated Ras signaling completely rescued early pupal death while post-pupation administration of ecdysone to organisms with elevated Ras signaling in eye discs partially rescued their early pupal death. Unlike the earlier known Dilp8 action in delaying pupation, hyperactivated Ras mediated elevation of pJNK signaling in imaginal discs caused Dilp8 secretion after pupariation. Ectopic expression of certain other transgene causing pupal lethality similarly enhanced pJNK and early pupal Dilp8. Sub-optimal ecdysone levels after 8 Hr of pupation prevented the early pupal metamorphic changes and caused organismal death.\n\nConclusionsOur results reveal early pupal stage as a novel Dilp8 mediated post-pupariation checkpoint and provide further evidence for inter-organ signaling during development, wherein a peripheral tissue influences the CNS driven endocrine function.

Developmental Biology↗