Silymarin Extends Lifespan and Reduces Proteotoxicity in C. elegans Alzheimer&amp;#8217;s Model

Kumar, Jitendra; Park, Kyung-Chae; Awasthi, Anjali; Prasad, Birendra

doi:10.2174/1871527314666150116110212

Cited by 53 publications

(41 citation statements)

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“…In the case of the flavolignan isomers silymarin, the effect appeared to be dose dependent, since 25 and 50 µM increased the worm's lifespan, while 100 µM shortened it (49) .…”

Section: Flavonoids and The Lifespan Of The Worm Caenorhabditis Elegansmentioning

confidence: 97%

A literature review of flavonoids and lifespan in model organisms

Pallauf¹,

Duckstein²,

Rimbach³

2016

Proc. Nutr. Soc.

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Epidemiological data on consumption of flavonoid-containing food points to the notion that some of these secondary plant metabolites may favour healthy ageing. The aim of the present paper was to review the literature on lifespan extension by flavonoids in worms, flies and mice. In most studies, worms and flies experienced lifespan extension when supplemented with flavonoids either as extracts or single compounds. Studies with mutant worms and flies give hints as to which gene products may be regulated by flavonoids and consequently enhance longevity. We discuss the data considering putative mechanisms that may underlie flavonoid action such as energy-restriction-like effects, inhibition of insulin-like-growth-factor signalling, induction of antioxidant defence mechanisms, hormesis as well as antimicrobial properties. However, it remains uncertain whether human lifespan could be prolonged by increased flavonoid intake.

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“…In the case of the flavolignan isomers silymarin, the effect appeared to be dose dependent, since 25 and 50 µM increased the worm's lifespan, while 100 µM shortened it (49) .…”

Section: Flavonoids and The Lifespan Of The Worm Caenorhabditis Elegansmentioning

confidence: 97%

A literature review of flavonoids and lifespan in model organisms

Pallauf¹,

Duckstein²,

Rimbach³

2016

Proc. Nutr. Soc.

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“…A previous study has shown silibinin to inhibit anaplastic large cell lymphoma through suppressing pathways involving STAT3, MEK/ERK and AKT (33). Additionally, silymarin treatment has also been reported to increase the lifespan in Caenorharbditis elegans (34). It is important to mention here that silymarin is an extract from milk thistle seed containing silibinin, isosilibinin, silychristin, silydianin and others, but silibinin is considered the prominent active ingredient (35).…”

Section: Discussionmentioning

confidence: 95%

Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis

Rigby

Roy

Deep

et al. 2016

CARCIN

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Non-melanoma skin cancers (NMSC) are a growing problem given that solar ultraviolet B (UVB) radiation exposure is increasing most likely due to depletion of the atmospheric ozone layer and lack of adequate sun protection. Better preventive methods are urgently required to reduce UV-caused photodamage and NMSC incidence. Earlier, we have reported that silibinin treatment activates p53 and reduces photodamage and NMSC, both in vitro and in vivo; but whether silibinin exerts its protective effects primarily through p53 remains unknown. To address this question, we generated p53 heterozygous (p53 +/− ) and p53 knockout (p53 −/− ) mice on SKH-1 hairless mouse background, and assessed silibinin efficacy in both short-and long-term UVB exposure experiments. In the chronic UVB-exposed skin tumorigenesis study, compared to p53 +/+ mice, p53 +/− mice developed skin tumors earlier and had higher tumor number, multiplicity and volume. Silibinin topical treatment significantly reduced the tumor number, multiplicity and volume in p53 +/+ mice but silibinin' protective efficacy was significantly compromised in p53 +/− mice. Additionally, silibinin treatment failed to inhibit precursor skin cancer lesions in p53 −/− mice but improved the survival of the mice. In short-term studies, silibinin application accelerated the removal of UVB-induced DNA damage in p53 +/+ mice while its efficacy was partially compromised in p53 −/− mice. Interestingly, silibinin treatment also inhibited the UVB-induced inflammatory markers in skin tissue. These results further confirmed that absence of the p53 allele predisposes mice to photodamage and photocarcinogenesis, and established that silibinin mediates its protection against UVB-induced photodamage, inflammation and photocarcinogenesis partly through p53 activation.

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“…The beneficial effects of NDS are probably due to the well-documented anti-oxidative actions of curcumin, although a synergistic action of all polyphenolic compounds contained in NDS has to also be considered. In fact, antioxidant and neuroprotective effects have been reported for silymarin and chlorogenic acid as well [72,73]. Figure 1 summarizes the main actions responsible for the neuroprotective effects of curcuminoids.…”

Section: Curcuminoidsmentioning

confidence: 99%

“…The ability to slow the progression of neurodegeneration was also tested in CL4176 Caenorhabditis elegans, a model for AD. The results demonstrated that silymarin treatment significantly reduced the expression of amyloid β-protein (Aβ1-42) in muscle tissues of C. elegans via enhancing resistance to oxidative stress [72]. In rats, silymarin administration can improve ethanol- Nevertheless, clinical trials revealing any beneficial effects of curcuminoid administration for the treatment of AD are few and controversial [77][78][79].…”

Section: Silymarinmentioning

confidence: 99%

Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer’s Disease

2019

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The positive role of nutrition in chronic neurodegenerative diseases (NDs) suggests that dietary interventions represent helpful tools for preventing NDs. In particular, diets enriched with natural compounds have become an increasingly attractive, non-invasive, and inexpensive option to support a healthy brain and to potentially treat NDs. Bioactive compounds found in vegetables or microalgae possess special properties able to counteract oxidative stress, which is involved as a triggering factor in neurodegeneration. Here, we briefly review the relevant experimental data on curcuminoids, silymarin, chlorogenic acid, and compounds derived from the microalga Aphanizomenon flos aquae (AFA) which have been demonstrated to possess encouraging beneficial effects on neurodegeneration, in particular on Alzheimer's disease models. and intracellular neurofibrillary tangles (NFTs) [4,5]. Intracellular neurofibrillary tangles are composed of hyperphosphorylated Tau proteins in neurons located particularly in the hippocampus and cerebral cortex regions of the brain. The reduced expression of the brain-derived neurotrophic factor (BDNF), important for neuronal growth and memory functions, also plays a crucial role in AD pathogenesis via formation of senile plaque of Aβ and NFTs. At the molecular level, Aβ induces oxidative stress, inflammation, and mitochondrial dysfunction associated with apoptosis [6,7].Parkinson's disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and formation of Lewy bodies, abnormal intraneuronal aggregates of proteins that include α-synuclein, ubiquitin, and neurofilaments [8]. The pathogenic mechanisms of PD include oxidative stress, mitochondrial and protein dysfunction, inflammation, and apoptosis [9]. In particular, oxidative stress generates ROS which activates glial cells, and activated glial cells generate inflammation that results in mitochondrial dysfunction, and, consequently, dysfunctional mitochondria activate cell death machinery [10].Hence, oxidative stress and mitochondrial damage are common factors involved in the etiopathology of these neurodegenerative diseases [11-13]. Oxidative Stress and NeurodegenerationOxidative stress is characterized by an overproduction of ROS-oxygen-containing molecules known to be highly reactive.Reactive oxygen species are formed in mitochondria during oxidative phosphorylation as a byproduct of normal metabolism. Therefore, modest levels of ROS are normally expected and are considered essential for the regulation of normal cell functions, while excessive ROS production can damage various biological targets, such as DNA, lipids, and proteins, causing serious neurological injury. Because the brain consumes a large amount of molecular oxygen to function properly, the accumulation of damaged biomolecules caused by ROS is high, especially with aging [14]. To limit these cellular damages, brain neurons produce antioxidant defense enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catala...

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Silymarin Extends Lifespan and Reduces Proteotoxicity in C. elegans Alzheimer’s Model

Cited by 53 publications

References 0 publications

A literature review of flavonoids and lifespan in model organisms

A literature review of flavonoids and lifespan in model organisms

Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis

Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer’s Disease

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