The metabolism of 20-hydroxyecdysone in mice: Relevance to pharmacological effects and gene switch applications of ecdysteroids

Kumpun, Saowanee; Girault, Jean‐Pierre; Dinan, Laurence; Blais, Catherine; Maria, Annick; Dauphin‐Villemant, Chantal; Yingyongnarongkul, Boon Ek; Suksamrarn, Apichart; Lafont, René

doi:10.1016/j.jsbmb.2011.03.016

Cited by 44 publications

(67 citation statements)

References 38 publications

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“…20E was isolated from the bark of Vitex glabrata using the literature-described procedure (21). The physical and spectroscopic (nuclear magnetic resonance and mass spectra) data of the isolated compound were found to be in accordance with the literature values (22,23).…”

Section: -supporting

confidence: 65%

Effect of 20-Hydroxyecdysone on Proteolytic Regulation in Skeletal Muscle Atrophy

Hirunsai

Yimlamai

Suksamrarn

2016

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Abstract. Skeletal muscle atrophy is a debilitating condition associated with a variety of pathological conditions (e.g. diabetes mellitus, cancer, chronic obstructive pulmonary disease, and chronic heart failure), physiological consequence of aging (sarcopenia), and disuse (e.g. casting-immobilization, microgravity, or tendon injury), subsequently leading to a decrease in mobility and reduced quality of life (1). Muscle atrophy is characterized by a decrease of protein content leading to a reduction in cross-sectional area (CSA) of muscle fibers and impairment of muscle force generation and fatigue resistance (2, 3). Skeletal muscle mass is determined by the balance of protein synthesis and protein breakdown. However, previous compelling evidence has indicated that disuse muscle atrophy is primarily caused by the increase in the rate of protein degradation rather than a decrease in the rate of protein synthesis (4). Although several proteolytic systems are involved in protein turnover in skeletal muscle, recent studies suggested that the ubiquitin-proteasome system (UPS) represents the major intracellular proteolysis machinery responsible for the degradation of major contractile proteins, and contributes significantly to muscle atrophy in both animal and human models (1, 5).To date, in spite of many attempts, there is no single effective method to completely cure muscle atrophy. Although several pharmacological agents such as β2-adrenergic agonist or proteasome inhibitors have been prescribed to combat muscle atrophy (5), these drugs do not come without side-effects. Therefore, a search for a nonpharmacological therapeutic strategy should be considered as an alternative approach to tackle these clinical problems. There is evidence that ecdysteroids, insect hormones, have an anabolic effect on skeletal muscle (6) with no side-effects in mammals, including humans (7).Ecdysteroids act as molting hormones in insects and also play a defensive role against insect herbivory in plants (8).There are a large number of structurally related ecdysteriods in plants (phytoecdysteriods). Of these, 20-hydroxyecdysone (20E) is the most commonly found and extensively studied. This compound is present at high concentration in the bark of blackberry tree (Vitex glabrata). 20E has low toxicity in mammals: the lethal dose 50 (LD 50 ) is 6.4 g/kg in mice for intraperitoneal injection and more than 9 g/kg when given orally (9). The pharmacokinetics of 20E depend on the mode of administration, for example, the half-time of elimination of this substance in lambs when administered via oral, intravenous, and intramuscular routes were 0.2, 0.4, and 2 h, respectively (10). It has been reported that the half-life of

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Section: -supporting

confidence: 65%

Effect of 20-Hydroxyecdysone on Proteolytic Regulation in Skeletal Muscle Atrophy

Hirunsai

Yimlamai

Suksamrarn

2016

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“…Their beneficial effects in mammals have been reviewed previously, particularly in the case of 20E, and refer mostly to their anabolic potential (Lafont and Dinan, 2003;Dinan and Lafont, 2006;Bathori et al, 2008;Kumpun et al, 2011a). Although there is very limited information on the effects of PEs in humans, both in vitro studies and animal models suggest that PEs have anabolic (Syrov, 2000), anti-diabetic (Kizelsztein et al, 2009), and anti-obesity (Foucault et al, 2011) properties.…”

Section: Physiologic Effects Of Phytoecdysteroids In Mammalsmentioning

confidence: 99%

“…2b and Table 4). As 20E is rapidly metabolized in mammals (Lafont and Dinan, 2003;Kumpun et al, 2011a), we also analyzed the potential binding of its known metabolites (Figure 2b) (Destrez et al, 2009;Kumpun et al, 2011a;Brandt, 2003).…”

Section: In Silico Modelingmentioning

confidence: 99%

Assessing Herbal Products with Health Claims

Lapenna

Gemen

Jan

et al. 2013

Critical Reviews in Food Science and Nutrition

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Herbs, herbal extracts, or phytochemicals are broadly used as foods, drugs, and as traditional medicines. These are well regulated in Europe, with thorough controls on both safety and efficacy or validity of health claims. However, the distinction between medicines and foods with health claims is not always clear. In addition, there are several cases of herbal products that claim benefits that are not scientifically demonstrated. This review details the European Union (EU) legislative framework that regulates the approval and marketing of herbal products bearing health claims as well as the scientific evidence that is needed to support such claims. To illustrate the latter, we focus on phytoecdysteroid (PE)-containing preparations, generally sold to sportsmen and bodybuilders. We review the limited published scientific evidence that supports claims for these products in humans. In addition, we model the in silico binding between different PEs and human nuclear receptors and discuss the implications of these putative bindings in terms of the mechanism of action of this family of compounds. We call for additional research to validate the safety and health-promoting properties of PEs and other herbal compounds, for the benefit of all consumers.

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“…instead of molecular oxygen, results in a more severe change in the structure of the starting ecdysteroid molecule, causing side-chain cleavage between C-20 and C-22, and gives poststerone (51) as major product [56,57,58]. As it was mentioned above, this compound was observed as a major metabolite of 20E [32], and therefore its bioactivity may be of particular interest.…”

Section: Selected Examples For the Semi-synthesis Of Ecdysteroidsmentioning

confidence: 93%

“…The metabolism of 20E in mice was studied by Kumpun et al -in their experiment, they injected 20E intraperitoneally to mice and collected urine and faeces to identify metabolites in them. They found that the metabolism of 20E involves dehydroxylation at C-14 and sidechain cleavage between C-20 and C-22 as major steps, thus yielding poststerone (51), 14-deoxy-20-hydroxyecdysone and 14-deoxypoststerone as main metabolites, which then undergo several metabolic steps of reduction [32]. Ramazanov et al gave 20E to rats (50 mg/kg) directly into their stomach with a special probe and collected urine over the following 10 days.…”

Section: Biological Activity and Potential Application Of Ecdysteroidsmentioning

confidence: 99%

Preparation of novel bioactive semi-synthetic ecdysteroid derivatives

József¹

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The metabolism of 20-hydroxyecdysone in mice: Relevance to pharmacological effects and gene switch applications of ecdysteroids

Cited by 44 publications

References 38 publications

Effect of 20-Hydroxyecdysone on Proteolytic Regulation in Skeletal Muscle Atrophy

Effect of 20-Hydroxyecdysone on Proteolytic Regulation in Skeletal Muscle Atrophy

Assessing Herbal Products with Health Claims

Preparation of novel bioactive semi-synthetic ecdysteroid derivatives

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