Withanolide A offers neuroprotection, ameliorates stress resistance and prolongs the life expectancy of Caenorhabditis elegans

Akhoon, Bashir Akhlaq; Pandey, Swapnil; Tiwari, Sudeep; Pandey, Rakesh

doi:10.1016/j.exger.2016.03.004

Cited by 62 publications

(37 citation statements)

References 70 publications

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“…The WA was also found to get absorbed in a lymphoid organ (spleen) in significant amounts which may be agreed with the potent immunostimulatory activity of WA and its therapeutic application in augmenting the immune response in diseases such as tuberculosis, cancer, leishmaniasis, leprosy, and AIDS (Malik et al, ). Meanwhile, WA concentration was also found in the brain, suggesting that WA can cross the blood–brain barrier which is consistent with the results of pharmacological studies that WA possesses the significant neuroprotective/modulatory effect (Akhoon, Pandey, Tiwari, & Pandey, ).…”

Section: Resultssupporting

confidence: 87%

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Singh

Valicherla

Joshi

et al. 2018

Drug Development Research

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Preclinical Research & Development Withanolide A (WA), a steroidal lactone is a major bioactive constituent of Withania somnifera (L.) with remarkable neuropharmacological activity. In this study, we investigated the permeability, plasma protein binding (PPB), blood partitioning, intravenous (i.v.), and oral pharmacokinetics as well as i.v. tissue distribution (TD) of pure WA in a rat model. The PPB, RBCs partitioning, and permeability of WA were determined by Ultra Performance Liquid Chromatography (UPLC) method. However, the pharmacokinetics and TD of WA were evaluated by validated and sensitive liquid chromatography coupled mass spectrometry (LC‐ESI‐MS/MS) method. The PPB and permeability of WA were determined by equilibrium dialysis and parallel artificial membrane permeability assay method, respectively. The results demonstrated that WA has high PPB and passive permeability. Furthermore, WA was found to have fast equilibration between RBCs and plasma. Following i.v. (2 mg/kg) and per‐oral (25 mg/kg) administration of WA, the max concentration (Cmax) in plasma was found as 85.53 ± 6.54 and 48.04 ±5.78 ng/mL, respectively. The TD study results indicated that WA has a rapid and wide TD. The maximum concentration in various tissues was found in following order: Clung > Cliver > Ckidney ≈ Cspleen > Cheart > Cbrain. The preclinical in vitro, as well as pharmacokinetics and TD results, are anticipated to support the future preclinical and clinical application of WA.

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Section: Resultssupporting

confidence: 87%

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Singh

Valicherla

Joshi

et al. 2018

Drug Development Research

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show abstract

“…Our results showed that GNC failed to further extend the longevity of the mutant daf-2 (e1370), age-1 (hx546), and daf-16 (mu86) worms, suggesting that GNC extends the lifespan of C. elegans by regulating the insulin/IGF-1 signalling pathway. Many compounds, such as Withanolide A [ 32 ] and Chlorogenic Acid [ 4 ], exert the prolongevity properties in the same way.…”

Section: Discussionmentioning

confidence: 99%

Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

Meng

Rao

et al. 2018

Oxidative Medicine and Cellular Longevity

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Gengnianchun (GNC), a traditional Chinese medicine (TCM), is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against Aβ-induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans. However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance. Moreover, chemotaxis increased after GNC treatment. RNA-seq analysis showed that GNC regulated genes associated with longevity. We also conducted lifespan assays with a series of worm mutants. The results showed that GNC significantly extended the lifespan of several mutant strains, including eat-2 (ad465), rsks-1 (ok1255), and glp-1 (e2144), suggesting that the prolongevity effect of GNC is independent of the function of these genes. However, GNC failed to extend the lifespan of daf-2 (e1370), age-1 (hx546), and daf-16 (mu86) mutant strains. Our findings suggest that GNC extends the lifespan of C. elegans via the insulin/IGF-1 signalling pathway and may be a potential antiageing agent.

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“…Withaferin-A and withanone (withanolides), are the major biologically active constituents of Ashwagandha leaves [ 22 , 23 ] and believed to be involved in majority of biological functions of Ashwagandha. Withanolides are involved in various bodily functions such as anti-cancer activity [ 22 ], neuroprotection and anti-stress activity [ 24 ], recovery from amnesia [ 14 ], anti-mutagenic [ 25 ]. However, in our study, ethanol extract that contain high ratio of withaferin A and withanone, failed to induce sleep in mice, indicating that withanolides might not be involved in sleep promotion ( Fig 1A ).…”

Section: Discussionmentioning

confidence: 99%

Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction

et al. 2017

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Insomnia is the most common sleep complaint which occurs due to difficulty in falling asleep or maintaining it. Most of currently available drugs for insomnia develop dependency and/or adverse effects. Hence natural therapies could be an alternative choice of treatment for insomnia. The root or whole plant extract of Ashwagandha (Withania somnifera) has been used to induce sleep in Indian system of traditional home medicine, Ayurveda. However, its active somnogenic components remain unidentified. We investigated the effect of various components of Ashwagandha leaf on sleep regulation by oral administration in mice. We found that the alcoholic extract that contained high amount of active withanolides was ineffective to induce sleep in mice. However, the water extract which contain triethylene glycol as a major component induced significant amount of non-rapid eye movement sleep with slight change in rapid eye movement sleep. Commercially available triethylene glycol also increased non-rapid eye movement sleep in mice in a dose-dependent (10–30 mg/mouse) manner. These results clearly demonstrated that triethylene glycol is an active sleep-inducing component of Ashwagandha leaves and could potentially be useful for insomnia therapy.

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Withanolide A offers neuroprotection, ameliorates stress resistance and prolongs the life expectancy of Caenorhabditis elegans

Cited by 62 publications

References 70 publications

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone

Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction

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