Celastrol as a Novel Cardioprotective Drug

Sarkissian, Shant Der; Cailhier, J.; Borie, M.; Mansour, Samer; Hamet, Pavel; Stevens, Lesley A.; Noiseux, N.

doi:10.1016/j.cjca.2013.07.563

Cited by 7 publications

(4 citation statements)

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“…The quinone methide triterpene celastrol is derived from the traditional Chinese medicinal plant Celastrol is a potent inhibitor of nuclear factor kB (NF‐kB) (Corson and Crews 2007; Sethi et al 2007) and activates heat shock gene transcription synergistically with other stresses providing cytoprotection (Der Sarkissian et al 2014). In mice, celastrol administration significantly attenuated the loss of dopaminergic neurons and the depletion in dopamine concentration following MPTP treatment (Cleren et al 2005).…”

Section: Pharmacological Activators Of the Keap1/nrf2/are Pathwaymentioning

confidence: 99%

Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes

Calabrese

Scapagnini

Davinelli

et al. 2014

J. Cell Commun. Signal.

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Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones, such as cortisol and thyroid hormones which remain stable and hormones with anabolic effects (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Deficiencies in multiple anabolic hormones have been shown to predict health status and longevity in older persons.Unlike female menopause, which is accompanied by an abrupt and permanent cessation of ovarian function (both folliculogenesis and estradiol production), male aging does not result in either cessation of testosterone production nor infertility. Although the circulating serum testosterone concentration does decline with aging, in most men this decrease is small, resulting in levels that are generally within the normal range. Hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with HT treatment. Stress-response hormesis from a molecular genetic perspective corresponds to the induction by stressors of an adaptive, defensive response, particularly through alteration of gene expression. Increased longevity can be associated with greater resistance to a range of stressors. During aging, a gradual decline in potency of the heat shock response occur and this may prevent repair of protein damage. Conversely, thermal stress or pharmacological agents capable of inducing stress responses, by promoting increased expression of heat-shock proteins, confer protection against denaturation of proteins and restoration of proteome function. If induction of stress resistance increases life span and hormesis induces stress resistance, hormesis most likely result in increased life span. Hormesis describes an adaptive response to continuous cellular stresses, representing a phenomenon where exposure to a mild stressor confers resistance to subsequent, otherwise harmful, conditions of increased stress. This biphasic dose-response relationship, displaying low-dose stimulation and a high-dose inhibition, as adaptive response to detrimental lifestyle factors determines the extent of protection from progression to metabolic diseases such as diabetes and more in general to hormonal dysregulation and age-related pathologies. Integrated responses exist to detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed vitagenes. Vitagenes encode for heat shock proteins (Hsps), thioredoxin and sirtuin protein systems. Nutritional antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways under control of Vitagene protein network. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against functional defects leading to degeneration and cell death with consequent impact on longevity processes.

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Section: Pharmacological Activators Of the Keap1/nrf2/are Pathwaymentioning

confidence: 99%

Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes

Calabrese

Scapagnini

Davinelli

et al. 2014

J. Cell Commun. Signal.

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“…Notably, 1 exhibits a multitude of beneficial properties, including anti-inflammatory [1], antioxidant [2], cardioprotective [3], and anti-rheumatic activities [4]. Additionally, celastrol has demonstrated anticancer activity [5], as well as efficacy in combating neuronal degeneration [6] and addressing obesity [7].…”

Section: Introductionmentioning

confidence: 99%

(2R,4aS,6aS,12bR,14aS,14bR)-N-(2-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethyl)-10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide

Yuzhu,

Anyanwu,

Yang

et al. 2024

Molbank

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In this report, we discuss the synthesis of a compound obtained from the derivatization of the natural compound celastrol. This derivative is connected to PEG azide moiety through an amide linkage. The linkage was achieved through the activation of the carboxylic acid using HOBt/EDC. The compound was fully characterized by proton (1H), carbon-13 (13C), heteronuclear single quantum coherence (HSQC), correlation spectroscopy (1H-1H-COSY), and distortionless enhancement by polarization transfer (DEPT) NMR. Ultraviolet (UV), Fourier-transform infrared (FTIR), and high-resolution mass spectrometry (HRMS) were also adopted. Computational investigations were conducted to forecast the binding mode between the synthesized compound and sarco-endoplasmic reticulum (SR) Ca2+ transport ATPase (SERCA), a known target for the development of novel therapeutics for rheumatoid arthritis. Additionally, the drug-likeness of the synthesized compound was assessed by predicting its pharmacokinetic properties.

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“…In fact, it exhibits a wide range of beneficial properties, including anti-inflammatory [1], antioxidant [2], cardioprotective [3], anti-osteoarthritis, and anticancer activity [4], and it has been shown to combat neuronal degeneration [5] and obesity [6]. Thus, these properties have sparked intense research efforts to explore the therapeutic potential of celastrol in conditions such as cancer, neurodegenerative diseases, obesity, and metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

(2R,4aS,6aS,12bR,14aS,14bR)10-Hydroxy-N-(4-((6-methoxyquinolin-8-yl)amino)pentyl)-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide

Xie,

Kuan,

Wei

et al. 2023

Molbank

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We herein report the synthesis of a derivative of the natural compound celastrol linked to the antimalarial drug primaquine through an amide obtained by the activation of the carboxylic acid with HOBt/EDC. The chemical structure of the new molecule was fully characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), heteronuclear single quantum coherence (HSQC), correlation spectroscopy (1H-1H-COSY), distortionless enhancement by polarization transfer (DEPT), mass spectrometry, Fourier-transform infrared (FTIR), and ultraviolet (UV) spectroscopies. Computational studies were enrolled to predict the interaction of the synthesized compound with sarco-endoplasmic reticulum (SR) Ca2+ transport ATPase (SERCA), a target of relevance for developing new therapeutics against arthritis. The drug-likeness of the compound was also investigated by predicting its pharmacokinetic properties.

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Celastrol as a Novel Cardioprotective Drug

Cited by 7 publications

References 0 publications

Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes

Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes

(2R,4aS,6aS,12bR,14aS,14bR)-N-(2-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethyl)-10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide

(2R,4aS,6aS,12bR,14aS,14bR)10-Hydroxy-N-(4-((6-methoxyquinolin-8-yl)amino)pentyl)-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide

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