Plant adaptogens increase lifespan and stress resistance in C. elegans

Wiegant, F. A. C.; Surinova, S.; Ytsma, E.; Langelaar-Makkinje, Miriam; Wikman, G.; Post, Jan Andries

doi:10.1007/s10522-008-9151-9

Cited by 165 publications

(147 citation statements)

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“…The root and rhizome of A. senticosus showed neuroprotective effect on dopaminergic neurons in the model mice of Parkinson's disease, one of age-related neurodegenerative diseases (Liu et al, 2012). The extracts from A. senticosus root increased resistance to oxidative stress and lifespan in C. elegans (Wiegant et al, 2009). In this study, we examined the anti-oxidant activity of the extracts from A. sessiliflorus leaves using C. elegans as a model system.…”

Section: Resultsmentioning

confidence: 99%

Effect of Acanthopanax sessiliflorus Extracts on Stress Response and Aging in Caenorhabditis elegans

Kim

2013

FSTR

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Acanthopanax sessiliflorus has been used as traditional medicine in many diseases. The extracts from Acanthopanax sessiliflorus leaves were examined for their anti-oxidant activity in vivo. Resistance to oxidative stress was significantly increased by Acanthopanax sessiliflorus extracts. Since increased resistance to oxidative stress is commonly positively correlated with lifespan extension, we determined the effect of Acanthopanax sessiliflorus on lifespan of C. elegans. Both mean and maximum lifespan were markedly increased by Acanthopanax sessiliflorus extracts. In addition, the treatment of Acanthopanax sessiliflorus enhanced the survival of worms under heat stress. However, the reduced fertility or delayed reproduction period frequently accompanied with increased lifespan were not observed in Acanthopanax sessiliflorustreated animals. These findings suggest that Acanthopanax sessiliflorus leaves can confer longevity phenotype without reduced fertility, possibly through their anti-oxidant activity.Keywords: Acanthopanax sessiliflorus, Caenorhabditis elegans, oxidative stress, thermotolerance, aging *To whom correspondence should be addressed. E-mail: skpark@sch.ac.kr IntroductionCells produce free radicals as a byproduct of metabolism. Free radical theory of aging suggests that oxidative damages by free radicals in cellular macromolecules accumulate with aging and cause cellular dysfunction, tissue damage, and eventually organism's death (Harman, 1956; Beckman and Ames, 1998). Major cellular free radicals are reactive oxygen species (ROS) produced mainly from mitochondrial electron transport chain reaction. Cellular antioxidants can scavenge these ROS and prevent oxidative damage in DNA, protein, and lipid molecules. Based on ROS-scavenging activity of anti-oxidants, many antioxidants have been studied for their effect on aging. Resveratrol, a polyphenol compound found in red wine, extends lifespan in yeast, C. elegans, and drosophila (Howitz et al., 2003;Wood et al., 2004;Valenzano et al., 2006). Green tea polyphenols also conferred increased lifespan and reduced incidence of age-related diseases (Kitani et al., 2004). Supplementation of vitamin E significantly inhibited age-related transcriptional changes in mouse heart and brain (Park et al., 2008). Different anti-oxidants showed tissue-specific effects on the expression of transcriptional biomarkers of aging in mice (Park et al., 2009).Acanthopanax species belongs to Araliaceae plant family and is mainly found in Korea, Japan, and China. Previous studies identified biological active components of Acanthopanax species which include phenylpropanoids, lignins, sterols, coumarins, vitamins, minerals and mono-and polysaccharides (Jones and Albersheim, 1972;Jeong et al., 2006). Acanthopanax species have been used as traditional medicine to various diseases, including diabetes, gastric ulcer, tumors, hypertension, and rheumatoid arthritis (Jung and Shin, 2003;Fujikawa et al., 1996). The extracts from Acanthopanax sessiliflorus (A. sessiliflorus) showed immuno-...

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Section: Resultsmentioning

confidence: 99%

Effect of Acanthopanax sessiliflorus Extracts on Stress Response and Aging in Caenorhabditis elegans

Kim

2013

FSTR

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“…The expression of the HSP-16.2 small chaperone protein needs joint activity of transcription factors HSF-1 and DAF-16 (Hartwig et al 2009;Hsu et al 2003;Soti and Csermely 2007;Walker and Lithgow 2003;Wiegant et al 2009), both regulated, in turn, by the IIS pathway (Baumeister et al 2006;Chiang et al 2012;Murphy and Hu 2013;Yen et al 2011). This suggests that GABA A inactivation influences the IIS pathway and consequently the stress response.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic manipulations to overexpress individual chaperones, like Hsp90 and Hsp70, resulted in a subtle extension of life span (Morley and Morimoto 2004); however, the small chaperone Hsp16 seemed to be more efficient in worms (Soti and Csermely 2007), particularly HSP-16.2 that is often used as an indicator of increases in thermal and oxidative stress (Hartwig et al 2009;Rea et al 2005;Strayer et al 2003;Wiegant et al 2009;Wu et al 2006;Xiao et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans

Camargo

Elizalde

Trujillo

et al. 2016

Cell Stress and Chaperones

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The mechanisms underlying oxidative stress (OS) resistance are not completely clear. Caenorhabditis elegans (C. elegans) is a good organism model to study OS because it displays stress responses similar to those in mammals. Among these mechanisms, the insulin/IGF-1 signaling (IIS) pathway is thought to affect GABAergic neurotransmission. The aim of this study was to determine the influence of heat shock stress (HS) on GABAergic activity in C. elegans. For this purpose, we tested the effect of exposure to picrotoxin (PTX), gammaaminobutyric acid (GABA), hydrogen peroxide, and HS on the occurrence of a shrinking response (SR) after nose touch stimulus in N2 (WT) worms. Moreover, the effect of HS on the expression of UNC-49 (GABA A receptor ortholog) in the EG1653 strain and the effect of GABA and PTX exposure on HSP-16.2 expression in the TJ375 strain were analyzed. PTX 1 mM-or H 2 O 2 0.7 mM-exposed worms displayed a SR in about 80 % of trials. GABA exposure did not cause a SR. HS prompted the occurrence of a SR as did PTX 1 mM or H 2 O 2 0.7 mM exposure. In addition, HS increased UNC-49 expression, and PTX augmented HSP-16.2 expression. Thus, the results of the present study suggest that oxidative stress, through either H 2 O 2 exposure or application of heat shock, inactivates the GABAergic system, which subsequently would affect the oxidative stress response, perhaps by enhancing the activity of transcription factors DAF-16 and HSF-1, both regulated by the IIS pathway and related to hsp-16.2 expression.

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“…Thus, most of PAK1 blockers such as CAPE and curcumin activate FOXO through these two distinct routes in a concerted manner. At least two PAK1 blockers = AMPK activators, salidroside and curcumin, were shown to extend the life span of C. elegans and the fruit fl y Drosophila, respectively (56,57 Table 2. Anti-PAK1 and AMPK activating activity of anti-PAK1 products worm by 50% (58).…”

Section: Pak1 Blockers = Ampk Activatorsmentioning

confidence: 99%

“…These phenotypes are precisely the same as those of the PAK1-deficient mutant (RB689) of this worm (6). Since the more HSP16 is activated, the longer this worm lives (63), it is most likely that like salidroside and curcumin (56,57), all these PAK1 blockers would extend significantly the life span of this worm. Furthermore, as described earlier, CA is a precursor of CAPE, and blocks PAK1 by downregulating its activator RAC (14).…”

Section: A ''Fl Uorescent'' In Vivo Screening For Nf Therapeuticsmentioning

confidence: 99%

Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1

Miyata

2011

DD&T

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Neurofibromatosis (NF) is a family of genetic diseases which are caused by dysfunction of either NF1 gene or NF2 gene. One in 3,000 people suffer from this tumor-carrying NF. NF1 gene product is a RAS GTPase activating protein (GAP) of 2,818 amino acids, which normally attenuates the GTPdependent signal transducing activity of the G protein RAS. Dysfunction of this GAP leads to the abnormal activation of RAS, and eventually an oncogenic kinase called PAK1 as well. NF2 gene product is ''Merlin'' which directly inactivates PAK1. Thus, dysfunction of Merlin causes the abnormal activation of PAK1. In other words, dysfunction of NF1 gene (causing type 1 NF) is basically the same as dysfunction of NF2 gene (causing type 2 NF). In fact the growth of both NF1 and NF2 tumors requires PAK1, and all PAK1 blockers, synthetic chemicals or natural products, suppress the growth of these NF tumor cells both in vitro (cell culture) and in vivo (mice).However, until recently, no FDA-approved effective NF therapeutics is available on the market. Here a series of anti-PAK1 products shall be introduced, which would be potentially useful for the life-long treatment of NF patients in the future. These include the most potent HDAC (histone deacetylase) inhibitor FK228 (IC 50 : around 1 nM), that eventually blocks PAK1, the direct PAK1 inhibitor PF3758309 (IC 50 : around 10 nM), a CAPE (caffeic acid phenethyl ester)-based propolis extract called ''Bio 30'' from NZ (New Zealand), and an ARC (artepillin C)-based green propolis extract (GPE) from Brazil. Although the first two drugs are potent, none of them is available on the market as yet. The last two natural (bee-made) products are available on the market, and have been used for the therapy of NF and tuberous sclerosis (TSC) as well as many PAK1-dependent solid cancers such as breast and pancreatic cancers as well as glioma, which altogether represent more than 70% of all human cancers. Since PAK1 is not essential for the normal cell growth, propolis extracts cause no side effects.

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Plant adaptogens increase lifespan and stress resistance in C. elegans

Cited by 165 publications

References 51 publications

Effect of Acanthopanax sessiliflorus Extracts on Stress Response and Aging in Caenorhabditis elegans

Effect of Acanthopanax sessiliflorus Extracts on Stress Response and Aging in Caenorhabditis elegans

Inactivation of GABAA receptor is related to heat shock stress response in organism model Caenorhabditis elegans

Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1

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